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Conserved domains on  [gi|569011688|ref|XP_006528762|]
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FYVE, RhoGEF and PH domain-containing protein 1 isoform X1 [Mus musculus]

Protein Classification

PH1_FGD1 and PH2_FGD1-4 domain-containing protein( domain architecture ID 10069120)

protein containing domains RhoGEF, PH1_FGD1, FYVE_FGD1_2_4, and PH2_FGD1-4

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH1_FGD1 cd01219
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin ...
421-528 4.20e-70

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 275392  Cd Length: 108  Bit Score: 225.29  E-value: 4.20e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd01219    1 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPKLRLIGQKFSVRARIDVEGMELKESSSLNLPRTFLVSGKQRSLELQ 80
                         90       100
                 ....*....|....*....|....*...
gi 569011688 501 ARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd01219   81 ARTEEEKKDWIQAIQATIQRHEQTLETF 108
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
645-750 7.52e-58

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270056  Cd Length: 105  Bit Score: 192.18  E-value: 7.52e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 645 ASVAAENSVICSFLHYMEKGgKGWHKAWFVVPENEPLVLYIYGAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQ 724
Cdd:cd13236    1 ASAVPENSLLCGFLQYSEKG-KTWQKVWCVIPRTEPLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEERLDGRHVFKLSQ 79
                         90       100
                 ....*....|....*....|....*.
gi 569011688 725 SHLSWYFSPETEELQRRWMAVLGRAG 750
Cdd:cd13236   80 SKQSHYFSAESEELQQRWLEALSRAA 105
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
206-389 4.99e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 173.64  E-value: 4.99e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 206 HIANELLQTEKAYVSRLHLLDQVFCARLLEEARNrssFPADVVHGIFSNICSIYCFHQQFLLPELEKRMEEWDRYPRIGD 285
Cdd:cd00160    3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP---LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIGD 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 286 ILQKLAPFLKMYGEYVKNFDRAVELVNTWTERSTQFKVIIHEVQKEeaCGNLTLQHHMLEPVQRIPRYELLLKDYLLKLP 365
Cdd:cd00160   80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                        170       180
                 ....*....|....*....|....
gi 569011688 366 HGSPDSKDAQKSLELIATAAEHSN 389
Cdd:cd00160  158 DGHEDREDLKKALEAIKEVASQVN 181
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
555-619 1.63e-37

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


:

Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 134.15  E-value: 1.63e-37
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 555 PTPIREKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15741    1 PRWVRDNEVTMCMRCKEPFNALTRRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCYVIL 65
 
Name Accession Description Interval E-value
PH1_FGD1 cd01219
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin ...
421-528 4.20e-70

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275392  Cd Length: 108  Bit Score: 225.29  E-value: 4.20e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd01219    1 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPKLRLIGQKFSVRARIDVEGMELKESSSLNLPRTFLVSGKQRSLELQ 80
                         90       100
                 ....*....|....*....|....*...
gi 569011688 501 ARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd01219   81 ARTEEEKKDWIQAIQATIQRHEQTLETF 108
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
645-750 7.52e-58

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270056  Cd Length: 105  Bit Score: 192.18  E-value: 7.52e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 645 ASVAAENSVICSFLHYMEKGgKGWHKAWFVVPENEPLVLYIYGAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQ 724
Cdd:cd13236    1 ASAVPENSLLCGFLQYSEKG-KTWQKVWCVIPRTEPLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEERLDGRHVFKLSQ 79
                         90       100
                 ....*....|....*....|....*.
gi 569011688 725 SHLSWYFSPETEELQRRWMAVLGRAG 750
Cdd:cd13236   80 SKQSHYFSAESEELQQRWLEALSRAA 105
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
206-389 4.99e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 173.64  E-value: 4.99e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 206 HIANELLQTEKAYVSRLHLLDQVFCARLLEEARNrssFPADVVHGIFSNICSIYCFHQQFLLPELEKRMEEWDRYPRIGD 285
Cdd:cd00160    3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP---LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIGD 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 286 ILQKLAPFLKMYGEYVKNFDRAVELVNTWTERSTQFKVIIHEVQKEeaCGNLTLQHHMLEPVQRIPRYELLLKDYLLKLP 365
Cdd:cd00160   80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                        170       180
                 ....*....|....*....|....
gi 569011688 366 HGSPDSKDAQKSLELIATAAEHSN 389
Cdd:cd00160  158 DGHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
207-390 2.67e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 160.54  E-value: 2.67e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   207 IANELLQTEKAYVSRLHLLDQVFCARLLEEARNrssFPADVVHGIFSNICSIYCFHQQFLLpELEKRMEEWDR-YPRIGD 285
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL---LSPNELETLFGNIEEIYEFHRDFLD-ELEERIEEWDDsVERIGD 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   286 ILQKLAPFLKMYGEYVKNFDRAVELVNTWTERStQFKVIIHEVQKEEACGNLTLQHHMLEPVQRIPRYELLLKDYLLKLP 365
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKKNP-RFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155
                          170       180
                   ....*....|....*....|....*
gi 569011688   366 HGSPDSKDAQKSLELIATAAEHSNA 390
Cdd:smart00325 156 EDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
207-389 9.65e-45

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 158.62  E-value: 9.65e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  207 IANELLQTEKAYVSRLHLLDQVFcarlLEEARNRSSFPADVVHGIFSNICSIYCFHQQFLLpelEKRMEEWDRYPRIGDI 286
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVF----LPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLL---EELLKEWISIQRIGDI 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  287 LQKLAPFLKMYGEYVKNFDRAVELVNTWTERSTQFKVIIHEVQKEEACGNLTLQHHMLEPVQRIPRYELLLKDYLLKLPH 366
Cdd:pfam00621  74 FLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP 153
                         170       180
                  ....*....|....*....|...
gi 569011688  367 GSPDSKDAQKSLELIATAAEHSN 389
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
555-619 1.63e-37

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 134.15  E-value: 1.63e-37
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 555 PTPIREKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15741    1 PRWVRDNEVTMCMRCKEPFNALTRRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCYVIL 65
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
554-621 1.60e-23

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 94.42  E-value: 1.60e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569011688   554 APTPIREKEVTMCMRCQEPFNsITKRRHHCKACGHVVCGKCSEFRARLIYD-NNRSNRVCTDCYVALHG 621
Cdd:smart00064   1 RPHWIPDEEVSNCMGCGKEFN-LTKRRHHCRNCGRIFCSKCSSKKAPLPKLgIERPVRVCDDCYENLNG 68
FYVE pfam01363
FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: ...
555-620 1.12e-21

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.


Pssm-ID: 426221 [Multi-domain]  Cd Length: 68  Bit Score: 88.98  E-value: 1.12e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688  555 PTPIREKEVTMCMRCQEPFNsITKRRHHCKACGHVVCGKCSEFRARLI--YDNNRSNRVCTDCYVALH 620
Cdd:pfam01363   1 PVWVPDSSATVCMICSKPFT-FFRRRHHCRNCGRVFCSACSSKKISLLpeLGSNKPVRVCDACYDTLQ 67
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
421-518 7.13e-17

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 76.82  E-value: 7.13e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   421 LIKEGHILKLSA-KNGTTQDRYLILFNDRLLYCVPRLRllGQKFSVRARIDVDGMELKES---SNLNMPRTF-LVSGKQR 495
Cdd:smart00233   1 VIKEGWLYKKSGgGKKSWKKRYFVLFNSTLLYYKSKKD--KKSYKPKGSIDLSGCTVREApdpDSSKKPHCFeIKTSDRK 78
                           90       100
                   ....*....|....*....|...
gi 569011688   496 SLELQARTEEEKKDWVQAINSTL 518
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKAI 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
653-749 9.21e-13

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 64.88  E-value: 9.21e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   653 VICSFLHYMEKGG-KGWHKAWFVVPENeplVLYIY---GAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKI-TQSHL 727
Cdd:smart00233   2 IKEGWLYKKSGGGkKSWKKRYFVLFNS---TLLYYkskKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIkTSDRK 78
                           90       100
                   ....*....|....*....|..
gi 569011688   728 SWYFSPETEELQRRWMAVLGRA 749
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKA 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
421-518 1.93e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.12  E-value: 1.93e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  421 LIKEGHILKLSAKNGTT-QDRYLILFNDRLLYCVPRLRllGQKFSVRARIDVDGMELKESSNLNM---PRTFLVSGKQ-- 494
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKDDKS--GKSKEPKGSISLSGCEVVEVVASDSpkrKFCFELRTGErt 78
                          90       100
                  ....*....|....*....|....*.
gi 569011688  495 --RSLELQARTEEEKKDWVQAINSTL 518
Cdd:pfam00169  79 gkRTYLLQAESEEERKDWIKAIQSAI 104
PH pfam00169
PH domain; PH stands for pleckstrin homology.
653-751 3.75e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 63.35  E-value: 3.75e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  653 VICSFLHYMEKG-GKGWHKAWFVVPENEpLVLYIYG-APQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQSHL--- 727
Cdd:pfam00169   2 VKEGWLLKKGGGkKKSWKKRYFVLFDGS-LLYYKDDkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGERtgk 80
                          90       100
                  ....*....|....*....|....*
gi 569011688  728 -SWYFSPETEELQRRWMAVLGRAGR 751
Cdd:pfam00169  81 rTYLLQAESEEERKDWIKAIQSAIR 105
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
210-455 1.49e-05

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 48.73  E-value: 1.49e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  210 ELLQTEKAYVSRLHLLDQVFcARLLEE-----ARNRSSFpadvVHGIFSNICSIYCFHQQFLlPELEKRMEEWDRYPRIG 284
Cdd:COG5422   491 EVIYTERDFVKDLEYLRDTW-IKPLEEsniipENARRNF----IKHVFANINEIYAVNSKLL-KALTNRQCLSPIVNGIA 564
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  285 DILQKLAPFLKMYGEYVKNFDRAVELVNTwtERST--QFKVIIHEVQKEEACGNLTLQHHMLEPVQRIPRYELLLKDYLL 362
Cdd:COG5422   565 DIFLDYVPKFEPFIKYGASQPYAKYEFER--EKSVnpNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLK 642
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  363 KLPHGSPDSKDAQKSLELIATAAEHSNAAIRKMERMHKLLKVYELLGGEEDIVS-----PTKELIKEGhILKLSAKNGT- 436
Cdd:COG5422   643 FTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVNlglndEYRKIIFKG-VLKRKAKSKTd 721
                         250       260
                  ....*....|....*....|..
gi 569011688  437 ---TQDRYLILFNDRLLYCVPR 455
Cdd:COG5422   722 gslRGDIQFFLLDNMLLFCKAK 743
 
Name Accession Description Interval E-value
PH1_FGD1 cd01219
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin ...
421-528 4.20e-70

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 1, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275392  Cd Length: 108  Bit Score: 225.29  E-value: 4.20e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd01219    1 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPKLRLIGQKFSVRARIDVEGMELKESSSLNLPRTFLVSGKQRSLELQ 80
                         90       100
                 ....*....|....*....|....*...
gi 569011688 501 ARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd01219   81 ARTEEEKKDWIQAIQATIQRHEQTLETF 108
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
645-750 7.52e-58

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270056  Cd Length: 105  Bit Score: 192.18  E-value: 7.52e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 645 ASVAAENSVICSFLHYMEKGgKGWHKAWFVVPENEPLVLYIYGAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQ 724
Cdd:cd13236    1 ASAVPENSLLCGFLQYSEKG-KTWQKVWCVIPRTEPLVLYLYGAPQDVRAQRTIPLPGCEVTVPPPEERLDGRHVFKLSQ 79
                         90       100
                 ....*....|....*....|....*.
gi 569011688 725 SHLSWYFSPETEELQRRWMAVLGRAG 750
Cdd:cd13236   80 SKQSHYFSAESEELQQRWLEALSRAA 105
PH1_FGD3 cd13387
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin ...
421-528 1.97e-51

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 3, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275422  Cd Length: 108  Bit Score: 174.77  E-value: 1.97e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd13387    1 LIKEGHIQKLSAKNGTAQDRYLYLFNSMVLYCVPKLRLMGQKFSVREKIDIAGMQVQEIVKQNVPHTFTITGKKRSLELQ 80
                         90       100
                 ....*....|....*....|....*...
gi 569011688 501 ARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd13387   81 ARTEEEKKEWIQVIQATIEKHKQNSETF 108
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
206-389 4.99e-50

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 173.64  E-value: 4.99e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 206 HIANELLQTEKAYVSRLHLLDQVFCARLLEEARNrssFPADVVHGIFSNICSIYCFHQQFLLPELEKRMEEWDRYPRIGD 285
Cdd:cd00160    3 EVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP---LSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGPRIGD 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 286 ILQKLAPFLKMYGEYVKNFDRAVELVNTWTERSTQFKVIIHEVQKEeaCGNLTLQHHMLEPVQRIPRYELLLKDYLLKLP 365
Cdd:cd00160   80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESE--CGRLKLESLLLKPVQRLTKYPLLLKELLKHTP 157
                        170       180
                 ....*....|....*....|....
gi 569011688 366 HGSPDSKDAQKSLELIATAAEHSN 389
Cdd:cd00160  158 DGHEDREDLKKALEAIKEVASQVN 181
PH1_FGD1-4_like cd13388
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, ...
421-514 6.96e-50

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 1-4 and similar proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. They play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275423  Cd Length: 94  Bit Score: 169.81  E-value: 6.96e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd13388    1 LIKEGKILKISARNGDTQERYLFLFNDMLLYCSPRLRLIGQKYKVRARFDVDGMQVLEGDNLETPHTFYVRGKQRSLELQ 80
                         90
                 ....*....|....
gi 569011688 501 ARTEEEKKDWVQAI 514
Cdd:cd13388   81 ASTQEEKAEWVDAI 94
PH1_FDG_family cd13328
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal ...
423-514 6.65e-48

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia family proteins, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275410  Cd Length: 92  Bit Score: 164.20  E-value: 6.65e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 423 KEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQAR 502
Cdd:cd13328    1 KEGQILKLSAKNGTPQPRYLFLFNDMLLYCVPKLSLVGQKFSVRNRLDVAGMKVREPVNENYPHTFKISGKERSLELQAS 80
                         90
                 ....*....|..
gi 569011688 503 TEEEKKDWVQAI 514
Cdd:cd13328   81 SAEEKDEWIQAI 92
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
207-390 2.67e-45

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 160.54  E-value: 2.67e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   207 IANELLQTEKAYVSRLHLLDQVFCARLLEEARNrssFPADVVHGIFSNICSIYCFHQQFLLpELEKRMEEWDR-YPRIGD 285
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKL---LSPNELETLFGNIEEIYEFHRDFLD-ELEERIEEWDDsVERIGD 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   286 ILQKLAPFLKMYGEYVKNFDRAVELVNTWTERStQFKVIIHEVQKEEACGNLTLQHHMLEPVQRIPRYELLLKDYLLKLP 365
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKLKKNP-RFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTP 155
                          170       180
                   ....*....|....*....|....*
gi 569011688   366 HGSPDSKDAQKSLELIATAAEHSNA 390
Cdd:smart00325 156 EDHEDREDLKKALKAIKELANQVNE 180
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
207-389 9.65e-45

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 158.62  E-value: 9.65e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  207 IANELLQTEKAYVSRLHLLDQVFcarlLEEARNRSSFPADVVHGIFSNICSIYCFHQQFLLpelEKRMEEWDRYPRIGDI 286
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVF----LPPNSKPLSESEEEIKTIFSNIEEIYELHRQLLL---EELLKEWISIQRIGDI 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  287 LQKLAPFLKMYGEYVKNFDRAVELVNTWTERSTQFKVIIHEVQKEEACGNLTLQHHMLEPVQRIPRYELLLKDYLLKLPH 366
Cdd:pfam00621  74 FLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPP 153
                         170       180
                  ....*....|....*....|...
gi 569011688  367 GSPDSKDAQKSLELIATAAEHSN 389
Cdd:pfam00621 154 DHPDYEDLKKALEAIKEVAKQIN 176
FYVE_FGD1_2_4 cd15741
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia ...
555-619 1.63e-37

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein facio-genital dysplasia FGD1, FGD2, FGD4; This family represents a group of Rho GTPase cell division cycle 42 (Cdc42)-specific guanine nucleotide exchange factors (GEFs), including FYVE, RhoGEF and PH domain-containing protein FGD1, FGD2 and FGD4. FGD1, also termed faciogenital dysplasia 1 protein, or Rho/Rac guanine nucleotide exchange factor FGD1 (Rho/Rac GEF), or zinc finger FYVE domain-containing protein 3, is a central regulator of extracellular matrix remodeling and belongs to the DBL family of GEFs that regulate the activation of the Rho GTPases. FGD1 is encoded by gene FGD1. Disabling mutations in the FGD1 gene cause the human X-linked developmental disorder faciogenital dysplasia (FGDY, also known as Aarskog-Scott syndrome). FGD2, also termed zinc finger FYVE domain-containing protein 4, is expressed in antigen-presenting cells, including B lymphocytes, macrophages, and dendritic cells. It localizes to early endosomes and active membrane ruffles. It plays a role in leukocyte signaling and vesicle trafficking in cells specialized to present antigen in the immune system. FGD4, also termed actin filament-binding protein frabin, or FGD1-related F-actin-binding protein, or zinc finger FYVE domain-containing protein 6, functions as an F-actin-binding (FAB) protein showing significant homology to FGD1. It induces the formation of filopodia through the activation of Cdc42 in fibroblasts. Those FGD proteins possess a similar domain organization that contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus. However, each FGD has a unique N-terminal region that may directly or indirectly interact with F-actin. FGD1 and FGD4 have an N-terminal proline-rich domain (PRD) and an N-terminal F-actin binding (FAB) domain, respectively. This model corresponds to the FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site. FGD1 possesses a FYVE-like domain that lack the N-terminal WxxD motif. Moreover, FGD2 is the only known RhoGEF family member shown to have a functional FYVE domain and endosomal binding activity.


Pssm-ID: 277280 [Multi-domain]  Cd Length: 65  Bit Score: 134.15  E-value: 1.63e-37
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 555 PTPIREKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15741    1 PRWVRDNEVTMCMRCKEPFNALTRRRHHCRACGYVVCWKCSDYKATLEYDGNKLNRVCKHCYVIL 65
PH1_FDG4 cd15791
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin ...
421-514 4.78e-37

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 4, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275434  Cd Length: 94  Bit Score: 133.97  E-value: 4.78e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd15791    1 LIKEGQILKLAARNTSAQERYLFLFNNMLLYCVPKFSLVGSKYTVRTRIGIDGMKVVETQNEDYPHTFQVSGKERTLELQ 80
                         90
                 ....*....|....
gi 569011688 501 ARTEEEKKDWVQAI 514
Cdd:cd15791   81 ASSEQDKEEWIKAL 94
PH1_FGD2 cd13386
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin ...
421-528 7.38e-37

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 2, N-terminal Pleckstrin homology (PH) domain; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275421  Cd Length: 108  Bit Score: 133.89  E-value: 7.38e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPRLRLLGQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQ 500
Cdd:cd13386    1 LLKEGPVLKISFRNNNPKERYLFLFNNMLLYCVPKVIQVGAKFQVHMRIDVDGMKVRELNDAEFPHSFLVSGKQRTLELQ 80
                         90       100
                 ....*....|....*....|....*...
gi 569011688 501 ARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd13386   81 ARSQEEMEAWIQAFQEAIDQNEKRTETF 108
FYVE smart00064
Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four ...
554-621 1.60e-23

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.


Pssm-ID: 214499 [Multi-domain]  Cd Length: 68  Bit Score: 94.42  E-value: 1.60e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569011688   554 APTPIREKEVTMCMRCQEPFNsITKRRHHCKACGHVVCGKCSEFRARLIYD-NNRSNRVCTDCYVALHG 621
Cdd:smart00064   1 RPHWIPDEEVSNCMGCGKEFN-LTKRRHHCRNCGRIFCSKCSSKKAPLPKLgIERPVRVCDDCYENLNG 68
FYVE pfam01363
FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: ...
555-620 1.12e-21

FYVE zinc finger; The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.


Pssm-ID: 426221 [Multi-domain]  Cd Length: 68  Bit Score: 88.98  E-value: 1.12e-21
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688  555 PTPIREKEVTMCMRCQEPFNsITKRRHHCKACGHVVCGKCSEFRARLI--YDNNRSNRVCTDCYVALH 620
Cdd:pfam01363   1 PVWVPDSSATVCMICSKPFT-FFRRRHHCRNCGRVFCSACSSKKISLLpeLGSNKPVRVCDACYDTLQ 67
FYVE_FGD3 cd15740
FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar ...
559-616 1.13e-20

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 3 (FGD3) and similar proteins; FGD3, also termed zinc finger FYVE domain-containing protein 5, is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) that undergoes the ubiquitin ligase SCFFWD1/beta-TrCP-mediated proteasomal degradation. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Due to this difference, FGD3 may play different roles from that of FGD1 to regulate cell morphology or motility. The FYVE domain of FGD3 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.


Pssm-ID: 277279 [Multi-domain]  Cd Length: 54  Bit Score: 85.82  E-value: 1.13e-20
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688 559 REKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRArliyDNNRSNRVCTDCY 616
Cdd:cd15740    1 REKEKQTCKGCNESFNSITKRRHHCKQCGAVICGKCSEFKD----LASRHNRVCRDCF 54
FYVE_endofin cd15729
FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE ...
551-619 1.61e-19

FYVE domain found in endofin and similar proteins; Endofin, also termed zinc finger FYVE domain-containing protein 16 (ZFY16), or endosome-associated FYVE domain protein, is a FYVE domain-containing protein that is localized to EEA1-containing endosomes. It is regulated by phosphoinositol lipid and engaged in endosome-mediated receptor modulation. Endofin is involved in Bone morphogenetic protein (BMP) signaling through interacting with Smad1 preferentially and enhancing Smad1 phosphorylation and nuclear localization upon BMP stimulation. It also functions as a scaffold protein that brings Smad4 to the proximity of the receptor complex in Transforming growth factor (TGF)-beta signaling. Moreover, endofin is a novel tyrosine phosphorylation target downstream of epidermal growth factor receptor (EGFR) in EGF-signaling. In addition, endofin plays a role in endosomal trafficking by recruiting cytosolic TOM1, an important molecule for membrane recruitment of clathrin, onto endosomal membranes.


Pssm-ID: 277268 [Multi-domain]  Cd Length: 68  Bit Score: 83.17  E-value: 1.61e-19
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569011688 551 GKRAPTPIREKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15729    1 GKVAPVWVPDSEAPNCMQCEVKF-TFTKRRHHCRACGKVLCSACCSLKARLEYLDNKEARVCVPCYQTL 68
PH1_FGD5_FGD6 cd13389
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal ...
410-528 4.48e-19

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275424  Cd Length: 124  Bit Score: 83.86  E-value: 4.48e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 410 GEEDIVSPTKELIKEGHILKLSAKNgtTQDRYLILFNDRLLYCVPrLRLLGQkFSVRARIDVDGMELKESSNLNMPRTFL 489
Cdd:cd13389    3 GQYNIVKPGRKLIKEGELMKVSRKE--MQPRYFFLFNDCLLYTTP-VQSSGM-LKLNNELPLSGMKVKLPEDEEYSNEFQ 78
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 569011688 490 VSGKQRSLELQARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd13389   79 IISTKRSFTLIASSEEERDEWVKALSRAIEEHTKKQRTF 117
FYVE_FGD6 cd15743
FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar ...
555-616 3.59e-18

FYVE domain found in FYVE, RhoGEF and PH domain-containing protein 6 (FGD6) and similar proteins; FGD6, also termed zinc finger FYVE domain-containing protein 24 is a putative Cdc42-specific guanine nucleotide exchange factor (GEF) whose biological function remains unclear. It is a homologue of FGD1 and contains a DBL homology (DH) domain and pleckstrin homology (PH) domain in the middle region, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. Moreover, the FYVE domain of FGD6 is a canonical FYVE domain, which has been found in many proteins involved in membrane trafficking and phosphoinositide metabolism, and has been defined by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCR patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding site.


Pssm-ID: 277282 [Multi-domain]  Cd Length: 61  Bit Score: 79.02  E-value: 3.59e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569011688 555 PTPIREKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15743    1 PIWIPDSRVTMCMICTSEF-TVTWRRHHCRACGKVVCGSCSSNKAPLEYLKNKSARVCDECF 61
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
421-518 7.13e-17

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 76.82  E-value: 7.13e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   421 LIKEGHILKLSA-KNGTTQDRYLILFNDRLLYCVPRLRllGQKFSVRARIDVDGMELKES---SNLNMPRTF-LVSGKQR 495
Cdd:smart00233   1 VIKEGWLYKKSGgGKKSWKKRYFVLFNSTLLYYKSKKD--KKSYKPKGSIDLSGCTVREApdpDSSKKPHCFeIKTSDRK 78
                           90       100
                   ....*....|....*....|...
gi 569011688   496 SLELQARTEEEKKDWVQAINSTL 518
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKAI 101
FYVE_like_SF cd00065
FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger ...
565-616 2.76e-15

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.


Pssm-ID: 277249 [Multi-domain]  Cd Length: 52  Bit Score: 70.64  E-value: 2.76e-15
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 569011688 565 MCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARL-IYDNNRSNRVCTDCY 616
Cdd:cd00065    1 RCMLCGKKF-SLFRRRHHCRRCGRVFCSKCSSKKLPLpSFGSGKPVRVCDSCY 52
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
657-742 1.75e-14

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270057  Cd Length: 91  Bit Score: 69.36  E-value: 1.75e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 657 FLHYMEKGGKGWHKAWFVVPENeplVLYIYGAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQSHLSWY-FSPET 735
Cdd:cd13237    4 YLQRRKKSKKSWKRLWFVLKDK---VLYTYKASEDVVALESVPLLGFTVVTIDESFEEDESLVFQLLHKGQLPIiFRADD 80

                 ....*..
gi 569011688 736 EELQRRW 742
Cdd:cd13237   81 AETAQRW 87
FYVE_PKHF cd15717
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), ...
558-616 2.86e-14

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1), 2 (phafin-2), and similar proteins; This family includes protein containing both PH and FYVE domains 1 (phafin-1) and 2 (phafin-2). Phafin-1 is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway. Phafin-2 is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.


Pssm-ID: 277257 [Multi-domain]  Cd Length: 61  Bit Score: 67.78  E-value: 2.86e-14
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 558 IREKEVTMCMRCQEP-FNSITkRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15717    3 VPDSEAPVCMHCKKTkFTAIN-RRHHCRKCGAVVCGACSSKKFLLPHQSSKPLRVCDTCY 61
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
657-749 8.19e-14

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 68.07  E-value: 8.19e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 657 FLHYMEKGG-KGWHKAWFVVPENeplVLYIYGAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQSHL-SWYFSPE 734
Cdd:cd13248   12 WLHKQGGSGlKNWRKRWFVLKDN---CLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANMrTYYFAAD 88
                         90
                 ....*....|....*
gi 569011688 735 TEELQRRWMAVLGRA 749
Cdd:cd13248   89 TAEEMEQWMNAMSLA 103
FYVE_PKHF2 cd15755
FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar ...
558-616 1.14e-13

FYVE domain found in protein containing both PH and FYVE domains 2 (phafin-2) and similar proteins; Phafin-2, also termed endoplasmic reticulum-associated apoptosis-involved protein containing PH and FYVE domains (EAPF), or pleckstrin homology domain-containing family F member 2 (PKHF2), or PH domain-containing family F member 2, or PH and FYVE domain-containing protein 2, or zinc finger FYVE domain-containing protein 18, is a ubiquitously expressed endoplasmic reticulum-associated protein that facilitates tumor necrosis factor alpha (TNF-alpha)-triggered cellular apoptosis through endoplasmic reticulum (ER)-mitochondrial apoptotic pathway. It is an endosomal phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) effector, as well as an interactor of the endosomal-tethering protein EEA1. It regulates endosome fusion upstream of Rab5. Phafin-2 also functions as a novel regulator of endocytic epidermal growth factor receptor (EGFR) degradation through a role in endosomal fusion.


Pssm-ID: 277294 [Multi-domain]  Cd Length: 64  Bit Score: 66.21  E-value: 1.14e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 569011688 558 IREKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15755    3 VPDSEATVCMRCQKAKFTPVNRRHHCRKCGFVVCGPCSEKKFLLPSQSSKPVRVCDFCY 61
FYVE_scVPS27p_like cd15760
FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 ...
561-616 2.48e-13

FYVE domain found in Saccharomyces cerevisiae vacuolar protein sorting-associated protein 27 (scVps27p) and similar proteins; scVps27p, also termed Golgi retention defective protein 11, is the putative yeast counterpart of the mammalian protein Hrs and is involved in endosome maturation. It is a mono-ubiquitin-binding protein that interacts with ubiquitinated cargoes, such as Hse1p, and is required for protein sorting into the multivesicular body. Vps27p forms a complex with Hse1p. The complex binds ubiquitin and mediates endosomal protein sorting. At the endosome, Vps27p and a trimeric protein complex, ESCRT-1, bind ubiquitin and are important for multivesicular body (MVB) sorting. Vps27p contains an N-terminal VHS (Vps27/Hrs/STAM) domain, a FYVE domain that binds PtdIns3P, followed by two ubiquitin-interacting motifs (UIMs), and a C-terminal clathrin-binding motif.


Pssm-ID: 277299 [Multi-domain]  Cd Length: 59  Bit Score: 65.01  E-value: 2.48e-13
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688 561 KEVTMCMRCQEPFNSiTKRRHHCKACGHVVCGKCSEFRARLIYDNNRSN--RVCTDCY 616
Cdd:cd15760    3 KPDSRCDVCRKKFGL-FKRRHHCRNCGDSFCSEHSSRRIPLPHLGPLGVpqRVCDRCF 59
PH1_FARP1-like cd01220
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
414-515 5.88e-13

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 1; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269928  Cd Length: 109  Bit Score: 65.80  E-value: 5.88e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 414 IVSPTKELIKEGHILKLSaKNGTtQDRYLILFNDRLLYcVPRLRLLGQKFSVRARIDVDGMELKESSN-LNMPRTFLVSG 492
Cdd:cd01220    1 LVQPGREFIREGCLQKLS-KKGL-QQRMFFLFSDVLLY-TSRSPTPSLQFKVHGQLPLRGLMVEESEPeWGVAHCFTIYG 77
                         90       100
                 ....*....|....*....|...
gi 569011688 493 KQRSLELQARTEEEKKDWVQAIN 515
Cdd:cd01220   78 GNRALTVAASSEEEKERWLEDLQ 100
FYVE_FGD5 cd15742
FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar ...
555-619 7.15e-13

FYVE-like domain found in FYVE, RhoGEF and PH domain-containing protein 5 (FGD5) and similar proteins; FGD5, also termed zinc finger FYVE domain-containing protein 23, is an endothelial cell (EC)-specific guanine nucleotide exchange factor (GEF) that regulates endothelial adhesion, survival, and angiogenesis by modulating phosphatidylinositol 3-kinase signaling. It functions as a novel genetic regulator of vascular pruning by activation of endothelial cell-targeted apoptosis. FGD5 is a homologue of FGD1 and contains a DBL homology (DH) domain, a pleckstrin homology (PH) domain, a FYVE domain, and another PH domain in the C-terminus, but lacks the N-terminal proline-rich domain (PRD) found in FGD1. The FYVE domain of FGD5 resembles a FYVE-like domain that is different from the canonical FYVE domains, since it lacks one of the three conserved signature motifs (the WxxD motif) that are involved in phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding and exhibits altered lipid binding specificities.


Pssm-ID: 277281 [Multi-domain]  Cd Length: 67  Bit Score: 64.19  E-value: 7.15e-13
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 555 PTPIREKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15742    1 PTLVPVSHVMMCMNCGSDF-TLTLRRHHCHACGKIVCRNCSRNKYPLKYLKDRPAKVCDGCFAEL 64
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
653-749 9.21e-13

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 64.88  E-value: 9.21e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688   653 VICSFLHYMEKGG-KGWHKAWFVVPENeplVLYIY---GAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKI-TQSHL 727
Cdd:smart00233   2 IKEGWLYKKSGGGkKSWKKRYFVLFNS---TLLYYkskKDKKSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIkTSDRK 78
                           90       100
                   ....*....|....*....|..
gi 569011688   728 SWYFSPETEELQRRWMAVLGRA 749
Cdd:smart00233  79 TLLLQAESEEEREKWVEALRKA 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
421-518 1.93e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 64.12  E-value: 1.93e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  421 LIKEGHILKLSAKNGTT-QDRYLILFNDRLLYCVPRLRllGQKFSVRARIDVDGMELKESSNLNM---PRTFLVSGKQ-- 494
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwKKRYFVLFDGSLLYYKDDKS--GKSKEPKGSISLSGCEVVEVVASDSpkrKFCFELRTGErt 78
                          90       100
                  ....*....|....*....|....*.
gi 569011688  495 --RSLELQARTEEEKKDWVQAINSTL 518
Cdd:pfam00169  79 gkRTYLLQAESEEERKDWIKAIQSAI 104
PH pfam00169
PH domain; PH stands for pleckstrin homology.
653-751 3.75e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 63.35  E-value: 3.75e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  653 VICSFLHYMEKG-GKGWHKAWFVVPENEpLVLYIYG-APQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKITQSHL--- 727
Cdd:pfam00169   2 VKEGWLLKKGGGkKKSWKKRYFVLFDGS-LLYYKDDkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFELRTGERtgk 80
                          90       100
                  ....*....|....*....|....*
gi 569011688  728 -SWYFSPETEELQRRWMAVLGRAGR 751
Cdd:pfam00169  81 rTYLLQAESEEERKDWIKAIQSAIR 105
FYVE_WDFY3 cd15719
FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar ...
558-619 4.25e-12

FYVE domain found in WD40 repeat and FYVE domain-containing protein 3 (WDFY3) and similar proteins; WDFY3, also termed autophagy-linked FYVE protein (Alfy), is a ubiquitously expressed phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein required for selective macroautophagic degradation of aggregated proteins. It regulates the protein degradation through the direct interaction with the autophagy protein Atg5. Moreover, WDFY3 acts as a scaffold that bridges its cargo to the macroautophagic machinery via the creation of a greater complex with Atg12, Atg16L, and LC3. It also functionally associates with sequestosome-1/p62 (SQSTM1) in osteoclasts. WDFY3 shuttles between the nucleus and cytoplasm. It predominantly localizes to the nucleus and nuclear membrane under basal conditions, but is recruited to cytoplasmic ubiquitin-positive protein aggregates under stress conditions. WDFY3 contains a PH-BEACH domain assemblage, five WD40 repeats and a PtdIns3P-binding FYVE domain.


Pssm-ID: 277259 [Multi-domain]  Cd Length: 65  Bit Score: 61.63  E-value: 4.25e-12
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 558 IREKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRA---RLiyDNNRSNRVCTDCYVAL 619
Cdd:cd15719    4 VKDEGGDSCTGCSVRF-SLTERRHHCRNCGQLFCSKCSRFESeirRL--RISRPVRVCQACYNIL 65
FYVE_EEA1 cd15730
FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed ...
560-616 4.50e-12

FYVE domain found in early endosome antigen 1 (EEA1) and similar proteins; EEA1, also termed endosome-associated protein p162, or zinc finger FYVE domain-containing protein 2, is an essential component of the endosomal fusion machinery and required for the fusion and maturation of early endosomes in endocytosis. It forms a parallel coiled-coil homodimer in cells. EEA1 serves as the p97 ATPase substrate and the p97 ATPase may regulate the size of early endosomes by governing the oligomeric state of EEA1. It can interact with the GTP-bound form of Rab22a and be involved in endosomal membrane trafficking. EEA1 also functions as an obligate scaffold for angiotensin II-induced Akt activation in early endosomes. It can be phosphorylated by p38 mitogen-activated protein kinase (MAPK) and further regulate mu opioid receptor endocytosis. EEA1 consists of an N-terminal C2H2 Zn2+ finger, four long heptad repeats, and a C-terminal region containing a calmodulin binding (IQ) motif, a Rab5 interaction site, and a FYVE domain. This model corresponds to the FYVE domain that is responsible for binding phosphatidyl inositol-3-phosphate (PtdIns3P or PI3P) on the membrane.


Pssm-ID: 277269 [Multi-domain]  Cd Length: 63  Bit Score: 61.65  E-value: 4.50e-12
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 560 EKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARlIYDNNRSNRVCTDCY 616
Cdd:cd15730    6 DEEVQNCMACGKGF-SVTVRKHHCRQCGNIFCNECSSKTAT-TPSSKKPVRVCDACF 60
PH1_FGD6 cd15793
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin ...
408-528 6.82e-12

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 6, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275436  Cd Length: 123  Bit Score: 63.12  E-value: 6.82e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 408 LGGEEDIVSPTKELIKEGHILKLSAKngTTQDRYLILFNDRLLYCVPrlrLLGQKFSVRARIDVDGMELKESSNLNMPRT 487
Cdd:cd15793    1 LNGHHEIVQPGRVFLKEGTLMKLSRK--VMQPRMFFLFNDALLYTTP---VQSGMYKLNNMLSLAGMKVSKPSQEAYQNE 75
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 569011688 488 FLVSGKQRSLELQARTEEEKKDWVQAINSTLLKHEQTLETF 528
Cdd:cd15793   76 LNIESVERSFILSASSATERDEWLEAISRAIEEYAKKKITF 116
FYVE_PKHF1 cd15754
FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar ...
558-619 1.49e-11

FYVE domain found in protein containing both PH and FYVE domains 1 (phafin-1) and similar proteins; Phafin-1, also termed lysosome-associated apoptosis-inducing protein containing PH (pleckstrin homology) and FYVE domains (LAPF), or pleckstrin homology domain-containing family F member 1 (PKHF1), or PH domain-containing family F member 1, or apoptosis-inducing protein, or PH and FYVE domain-containing protein 1, or zinc finger FYVE domain-containing protein 15, is a representative of a novel family of PH and FYVE domain-containing proteins called phafins. It is a ubiquitously expressed pro-apoptotic protein via translocating to lysosomes, facilitating apoptosis induction through a lysosomal-mitochondrial apoptotic pathway.


Pssm-ID: 277293 [Multi-domain]  Cd Length: 64  Bit Score: 60.36  E-value: 1.49e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569011688 558 IREKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15754    3 IPDKATDICMRCTQTNFSLLTRRHHCRKCGFVVCHECSRQRFLIPRLSPKPVRVCSLCYRKL 64
FYVE_RBNS5 cd15716
FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and ...
558-620 2.89e-11

FYVE domain found in FYVE finger-containing Rab5 effector protein rabenosyn-5 (Rbsn-5) and similar proteins; Rbsn-5, also termed zinc finger FYVE domain-containing protein 20, is a novel Rab5 effector that is complexed to the Sec1-like protein VPS45 and recruited in a phosphatidylinositol-3-kinase-dependent fashion to early endosomes. It also binds to Rab4 and EHD1/RME-1, two regulators of the recycling route, and is involved in cargo recycling to the plasma membrane. Moreover, Rbsn-5 regulates endocytosis at the apical side of the wing epithelium and plays a role of the apical endocytic trafficking of Fmi in the establishment of planar cell polarity (PCP).


Pssm-ID: 277256 [Multi-domain]  Cd Length: 61  Bit Score: 59.28  E-value: 2.89e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569011688 558 IREKEVTMCMRCQEPFNsITKRRHHCKACGHVVCGKCSEFRARLIydnnrsnRVCTDCYVALH 620
Cdd:cd15716    5 VNDSDVPFCPDCGKKFN-LARRRHHCRLCGSIMCNKCSQFLPLHI-------RCCHHCKDLLE 59
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
663-749 3.60e-11

FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin Homology (PH) domain, repeat 2; Members here include FARP1 (also called Chondrocyte-derived ezrin-like protein; PH domain-containing family C member 2), FARP2 (also called FIR/FERM domain including RhoGEF; FGD1-related Cdc42-GEF/FRG), and FARP6 (also called Zinc finger FYVE domain-containing protein 24). They are members of the Dbl family guanine nucleotide exchange factors (GEFs) which are upstream positive regulators of Rho GTPases. Little is known about FARP1 and FARP6, though FARP1 has increased expression in differentiated chondrocytes. FARP2 is thought to regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac. It is found in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FARP1 and FARP2 are composed of a N-terminal FERM domain, a proline-rich (PR) domain, Dbl-homology (DH), and two C-terminal PH domains. FARP6 is composed of Dbl-homology (DH), and two C-terminal PH domains separated by a FYVE domain. This hierarchy contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270055  Cd Length: 98  Bit Score: 60.41  E-value: 3.60e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 663 KGGKGWHKAWfVVPENepLVLYIYGAPQDVKAQRSLPLIGFEVGPPEAGERPDRRHVFKIT-QSHLsWYFSPETEELQRR 741
Cdd:cd13235   14 KNSNGWQKLW-VVFTN--FCLFFYKSHQDEFPLASLPLLGYSVGLPSEADNIDKDYVFKLQfKSHV-YFFRAESEYTFER 89

                 ....*...
gi 569011688 742 WMAVLGRA 749
Cdd:cd13235   90 WMEVIRSA 97
FYVE_RUFY1_like cd15721
FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; ...
560-616 5.47e-11

FYVE domain found in RUN and FYVE domain-containing protein RUFY1, RUFY2 and similar proteins; This family includes RUN and FYVE domain-containing protein RUFY1 and RUFY2. RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions. Both RUFY1 and RUFY2 contain an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.


Pssm-ID: 277261 [Multi-domain]  Cd Length: 58  Bit Score: 58.55  E-value: 5.47e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 560 EKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIyDNNRSNRVCTDCY 616
Cdd:cd15721    4 DKEVTHCQQCEKEF-SLSRRKHHCRNCGGIFCNSCSDNTMPLP-SSAKPVRVCDTCY 58
FYVE_LST2 cd15731
FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; ...
566-617 5.55e-11

FYVE domain found in lateral signaling target protein 2 homolog (Lst2) and similar proteins; Lst2, also termed zinc finger FYVE domain-containing protein 28, is a monoubiquitinylated phosphoprotein that functions as a negative regulator of epidermal growth factor receptor (EGFR) signaling. Unlike other FYVE domain-containing proteins, Lst2 displays primarily non-endosomal localization. Its endosomal localization is regulated by monoubiquitinylation. Lst2 physically binds Trim3, also known as BERP or RNF22, which is a coordinator of endosomal trafficking and interacts with Hrs and a complex that biases cargo recycling.


Pssm-ID: 277270 [Multi-domain]  Cd Length: 65  Bit Score: 58.51  E-value: 5.55e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 569011688 566 CMRCQEPFNSItKRRHHCKACGHVVCGKCSEFRARLI-YDNNRSNRVCTDCYV 617
Cdd:cd15731   14 CMACSAPFTVL-RRRHHCRNCGKIFCSRCSSNSVPLPrYGQMKPVRVCNHCFM 65
FYVE_ZFY26 cd15724
FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed ...
558-616 7.10e-11

FYVE domain found in FYVE domain-containing protein 26 (ZFY26 or ZFYVE26); ZFY26, also termed FYVE domain-containing centrosomal protein (FYVE-CENT), or spastizin, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that localizes to the centrosome and midbody. ZFY26 and its interacting partners TTC19 and KIF13A are required for cytokinesis. It also interacts with Beclin 1, a subunit of class III phosphatidylinositol 3-kinase complex, and may have potential implications for carcinogenesis. In addition, it has been considered as the causal agent of a rare form of hereditary spastic paraplegia. ZFY26 contains a FYVE domain that is important for targeting of FYVE-CENT to the midbody.


Pssm-ID: 277263 [Multi-domain]  Cd Length: 61  Bit Score: 58.30  E-value: 7.10e-11
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 569011688 558 IREKEVTMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15724    2 VPDEAVSVCMVCQVERFSMFNRRHHCRRCGRVVCSSCSTKKMLVEGYRENPVRVCDQCY 60
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
423-514 8.05e-11

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 59.09  E-value: 8.05e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 423 KEGHILKLSAKNGTT-QDRYLILFNDRLLYCVPRLRllgQKFSVRARIDVDG-MELKESSNLNMPRTF-LVSGKQRSLEL 499
Cdd:cd00821    1 KEGYLLKRGGGGLKSwKKRWFVLFEGVLLYYKSKKD---SSYKPKGSIPLSGiLEVEEVSPKERPHCFeLVTPDGRTYYL 77
                         90
                 ....*....|....*
gi 569011688 500 QARTEEEKKDWVQAI 514
Cdd:cd00821   78 QADSEEERQEWLKAL 92
FYVE_Hrs cd15720
FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) ...
561-619 1.22e-10

FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins; Hrs, also termed protein pp110, is a tyrosine phosphorylated protein that plays an important role in the signaling pathway of HGF. It is localized to early endosomes and an essential component of the endosomal sorting and trafficking machinery. Hrs interacts with hypertonia-associated protein Trak1, a novel regulator of endosome-to-lysosome trafficking. It can also forms an Hrs/actinin-4/BERP/myosin V protein complex that is required for efficient transferrin receptor (TfR) recycling but not for epidermal growth factor receptor (EGFR) degradation. Moreover, Hrs, together with STAM proteins, STAM1 and STAM2, and EPs15, forms a multivalent ubiquitin-binding complex that sorts ubiquitinated proteins into the multivesicular body pathway, and plays a regulatory role in endocytosis/exocytosis. Furthermore, Hrs functions as an interactor of the neurofibromatosis 2 tumor suppressor protein schwannomin/merlin. It is also involved in the inhibition of citron kinase-mediated HIV-1 budding. Hrs contains a single ubiquitin-interacting motif (UIM) that is crucial for its function in receptor sorting, and a FYVE domain that harbors double Zn2+ binding sites.


Pssm-ID: 277260 [Multi-domain]  Cd Length: 61  Bit Score: 57.40  E-value: 1.22e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 561 KEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARL-IYDNNRSNRVCTDCYVAL 619
Cdd:cd15720    3 KDGDECHRCRVQF-GVFQRKHHCRACGQVFCGKCSSKSSTIpKFGIEKEVRVCDPCYEKL 61
FYVE_ZF21 cd15727
FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ...
554-617 2.29e-10

FYVE domain found in zinc finger FYVE domain-containing protein 21 (ZF21) and similar proteins; ZF21 is phosphoinositide-binding protein that functions as a regulator of focal adhesions and cell movement through interaction with focal adhesion kinase. It can also bind to the cytoplasmic tail of membrane type 1 matrix metalloproteinase, a potent invasion-promoting protease, and play a key role in regulating multiple aspects of cancer cell migration and invasion. ZF21 contains a FYVE domain, which corresponds to this model.


Pssm-ID: 277266 [Multi-domain]  Cd Length: 64  Bit Score: 57.00  E-value: 2.29e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569011688 554 APTPIREKEVTMCMRCQEPFNsITKRRHHCKACGHVVCGKCSEFRARLiydnNRSN-----RVCTDCYV 617
Cdd:cd15727    1 EPPWVPDKECPVCMSCKKKFD-FFKRRHHCRRCGKCFCSDCCSNKVPL----PRMCfvdpvRVCNECAL 64
FYVE_ANFY1 cd15728
FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar ...
566-616 4.12e-10

FYVE domain found in ankyrin repeat and FYVE domain-containing protein 1 (ANFY1) and similar proteins; ANFY1, also termed ankyrin repeats hooked to a zinc finger motif (Ankhzn), is a novel cytoplasmic protein that belongs to a new group of double zinc finger proteins involved in vesicle or protein transport. It is ubiquitously expressed in a spatiotemporal-specific manner and is located on endosomes. ANFY1 contains an N-terminal coiled-coil region and a BTB/POZ domain, ankyrin repeats in the middle, and a C-terminal FYVE domain.


Pssm-ID: 277267 [Multi-domain]  Cd Length: 63  Bit Score: 56.28  E-value: 4.12e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569011688 566 CMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLI-YDNNRSNRVCTDCY 616
Cdd:cd15728   10 CYECGVKF-GITTRKHHCRHCGRLLCSKCSTKEVPIIkFDLNKPVRVCDVCF 60
FYVE_FYCO1 cd15726
FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar ...
560-616 6.16e-10

FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar proteins; FYCO1, also termed zinc finger FYVE domain-containing protein 7, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport. It acts as an effector of GTP-bound Rab7, a GTPase that recruits FYCO1 to autophagosomes and has been implicated in autophagosome-lysosomal fusion. FYCO1 also interacts with two microtubule motor proteins, kinesin (KIF) 5B and KIF23, and thus functions as a platform for assembly of vesicle fusion and trafficking factors. FYCO1 contains an N-terminal alpha-helical RUN domain followed by a long central coiled-coil region, a FYVE domain and a GOLD (Golgi dynamics) domain in C-terminus.


Pssm-ID: 277265 [Multi-domain]  Cd Length: 58  Bit Score: 55.64  E-value: 6.16e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 560 EKEVTMCMRCQEPFNSItKRRHHCKACGHVVCGKCSEFrARLIYDNNRSNRVCTDCY 616
Cdd:cd15726    4 DTDVTHCLDCKSEFSWM-VRRHHCRLCGRIFCYACSNF-YVLTAHGGKKERCCKACF 58
FYVE_RUFY1 cd15758
FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; ...
558-619 1.44e-09

FYVE domain found in RUN and FYVE domain-containing protein 1 (RUFY1) and similar proteins; RUFY1, also termed FYVE-finger protein EIP1, or La-binding protein 1, or Rab4-interacting protein (Rabip4), or Zinc finger FYVE domain-containing protein 12 (ZFY12), a human homologue of mouse Rabip4, an effector of Rab4 GTPase that regulates recycling of endocytosed cargo. RUFY1 is an endosomal protein that functions as a dual effector of Rab4 and Rab14 and is involved in efficient recycling of transferrin (Tfn). It is a downstream effector of Etk, a downstream tyrosine kinase of PI3-kinase that is involved in regulation of vesicle trafficking. RUFY1 contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between.


Pssm-ID: 277297 [Multi-domain]  Cd Length: 71  Bit Score: 55.07  E-value: 1.44e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569011688 558 IREKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIyDNNRSNRVCTDCYVAL 619
Cdd:cd15758    7 LKDDEATHCKQCEKEF-SISRRKHHCRNCGHIFCNTCSSNELALP-SYPKPVRVCDSCHTLL 66
FYVE_WDFY1_like cd15718
FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and ...
561-616 3.12e-09

FYVE domain found in WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2, and similar proteins; This family includes WD40 repeat and FYVE domain-containing protein WDFY1 and WDFY2. WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. Both WDFY1 and WDFY2 contain a FYVE domain and multiple WD-40 repeats.


Pssm-ID: 277258 [Multi-domain]  Cd Length: 70  Bit Score: 53.86  E-value: 3.12e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 561 KEVTMCMRCQEPF----------NSITKRRHHCKACGHVVCGKCSEFRARL-IYDNNRSNRVCTDCY 616
Cdd:cd15718    4 AESDNCQKCSRPFfwnfkqmwekKTLGVRQHHCRKCGKAVCDKCSSNRSTIpVMGFEFPVRVCNECY 70
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
654-743 3.49e-09

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270135  Cd Length: 91  Bit Score: 54.27  E-value: 3.49e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 654 ICSFLHYMEKGGKG---WHKAWFVVPENeplVLYIYGAPQDVKAQRSLPLIGFEVGPpeAGERPDRRHVFKITQSHLSWY 730
Cdd:cd13326    1 YQGWLYQRRRKGKGggkWAKRWFVLKGS---NLYGFRSQESTKADCVIFLPGFTVSP--APEVKSRKYAFKVYHTGTVFY 75
                         90
                 ....*....|...
gi 569011688 731 FSPETEELQRRWM 743
Cdd:cd13326   76 FAAESQEDMKKWL 88
FYVE_MTMR4 cd15733
FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also ...
563-616 3.63e-09

FYVE domain found in myotubularin-related protein 4 (MTMR4) and similar proteins; MTMR4, also termed FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2), or zinc finger FYVE domain-containing protein 11, is an dual specificity protein phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). It is localizes to early endosomes, as well as to Rab11- and Sec15-positive recycling endosomes, and regulates sorting from early endosomes. Moreover, MTMR4 is preferentially associated with and dephosphorylated the activated regulatory Smad proteins (R-Smads) in cytoplasm to keep transforming growth factor (TGF) beta signaling in homeostasis. It also functions as an essential negative modulator for the homeostasis of bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signaling. In addition, MTMR4 acts as a novel interactor of the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4) and may play a role in the biological process of muscle breakdown. MTMR4 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain.


Pssm-ID: 277272 [Multi-domain]  Cd Length: 60  Bit Score: 53.20  E-value: 3.63e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688 563 VTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARL----IYDnnrSNRVCTDCY 616
Cdd:cd15733    7 ASHCFGCDCEF-WLAKRKHHCRNCGNVFCADCSNYKLPIpdeqLYD---PVRVCNSCY 60
PH1_FGD5 cd15792
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin ...
409-533 5.62e-09

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 5, N-terminal Pleckstrin Homology (PH) domain; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275435  Cd Length: 123  Bit Score: 54.84  E-value: 5.62e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 409 GGEEDIVSPTKELIKEGHILKLSAKNgtTQDRYLILFNDRLLYCVPrlrLLGQKFSVRARIDVDGMELKESSNLNMPRTF 488
Cdd:cd15792    2 RGQRDLLQPGREFVKEGTLMKVSGKN--RHPRHLFLMNDVLLYTYP---QKDGKYRLKNTLAVSGMKVSRPVIEKAQNVL 76
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 569011688 489 LVSGKQRSLELQARTEEEKKDWVQAINSTLLKHEQTLETFKLLNS 533
Cdd:cd15792   77 KIEVSEVCLTLSASSCSERDEWYSCLSRTIPDDYKAQNASSSHSS 121
FYVE_WDFY1 cd15756
FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar ...
566-616 9.35e-09

FYVE domain found in WD40 repeat and FYVE domain-containing protein 1 (WDFY1) and similar proteins; WDFY1, also termed FYVE domain containing protein localized to endosomes-1 (FENS-1), or phosphoinositide-binding protein 1, or zinc finger FYVE domain-containing protein 17, is a novel single FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. WDFY1 to early endosomes requires an intact FYVE domain and is inhibited by wortmannin, a PI3-kinase inhibitor. In addition to FYVE domain, WDFY1 harbors multiple WD-40 repeats.


Pssm-ID: 277295 [Multi-domain]  Cd Length: 76  Bit Score: 52.76  E-value: 9.35e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569011688 566 CMRCQEPF----------NSITKRRHHCKACGHVVCGKCSEFRARL-IYDNNRSNRVCTDCY 616
Cdd:cd15756    9 CQKCEQPFfwnikqmwdtKTLGLRQHHCRKCGQAVCGKCSSKRSSYpIMGFEFQVRVCDSCF 70
FYVE2_Vac1p_like cd15737
FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed ...
562-615 1.07e-08

FYVE domain 2 found in yeast protein VAC1 (Vac1p) and similar proteins; Vac1p, also termed vacuolar segregation protein Pep7p, or carboxypeptidase Y-deficient protein 7, or vacuolar protein sorting-associated protein 19 (Vps19p), or vacuolar protein-targeting protein 19, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that interacts with a Rab GTPase, GTP-bound form of Vps21p, and a Sec1p homologue, Vps45p, to facilitate Vps45p-dependent vesicle-mediated vacuolar protein sorting. It also acts as a novel regulator of vesicle docking and/or fusion at the endosome and functions in vesicle-mediated transport of Golgi precursor carboxypeptidase Y (CPY), protease A (PrA), protease B (PrB), but not alkaline phosphatase (ALP) from the trans-Golgi network-like compartment (TGN) to the endosome. Vac1p contains an N-terminal classical TFIIIA-like zinc finger, two putative zinc-binding FYVE fingers, and a C-terminal coiled coil region. The family corresponds to the second FYVE domain that is responsible for the ability of Pep7p to efficiently interact with Vac1p and Vps45p.


Pssm-ID: 277276 [Multi-domain]  Cd Length: 83  Bit Score: 52.89  E-value: 1.07e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 562 EVTMCMRCQEPFNSITkRRHHCKACGHVVCG----KCSEF-----RARLIYDNNRSN--------------RVCTDC 615
Cdd:cd15737    7 SVTHCPICLRSFGLLL-RKHHCRLCGKVVCDdrrtKCSTEvpldlLSSALPDLPFVFkepqsdipddtksvRVCRDC 82
FYVE_ZFYV1 cd15734
FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar ...
562-616 1.41e-08

FYVE domains found in zinc finger FYVE domain-containing protein 1 (ZFYV1) and similar proteins; ZFYV1, also termed double FYVE-containing protein 1 (DFCP1), or SR3, or tandem FYVE fingers-1, is a novel tandem FYVE domain containing protein that binds phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) with high specificity over other phosphoinositides. The subcellular distribution of exogenously-expressed ZFYV1 to Golgi, endoplasmic reticulum (ER) and vesicular is governed in part by its FYVE domains but unaffected by wortmannin, a PI3-kinase inhibitor. In addition to C-terminal tandem FYVE domain, ZFYV1 contains an N-terminal putative C2H2 type zinc finger and a possible nucleotide binding P-loop.


Pssm-ID: 277273 [Multi-domain]  Cd Length: 61  Bit Score: 51.56  E-value: 1.41e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 562 EVTMCMRCQEPFNSiTKRRHHCKACGHVVCGKCSEFRaRLIYDNNRSN--RVCTDCY 616
Cdd:cd15734    7 EIKECSVCKRPFSP-RLSKHHCRACGQGVCDDCSKNR-RPVPSRGWDHpvRVCDPCA 61
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
654-746 1.57e-08

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270058  Cd Length: 97  Bit Score: 52.65  E-value: 1.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 654 ICSFLHYMEKGGKGWHKAWFVVPENepLVLYIYGAPQDVKAQRSLPLIGFEVGPPE------AGERPDRRHVFKITQSHL 727
Cdd:cd13238    1 LSGYLKLKTNGRKTWSRRWFALQPD--FVLYSYKSQEDKLPLTATPVPGFLVTLLEkgsavdPLNDPKRPRTFKMFHVKK 78
                         90
                 ....*....|....*....
gi 569011688 728 SWYFSPETEELQRRWMAVL 746
Cdd:cd13238   79 SYYFQANDGDEQKKWVLTL 97
FYVE_spVPS27p_like cd15735
FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 ...
565-616 1.87e-08

FYVE domain found in Schizosaccharomyces pombe vacuolar protein sorting-associated protein 27 (spVps27p) and similar proteins; spVps27p, also termed suppressor of ste12 deletion protein 4 (Sst4p), is a conserved homolog of budding Saccharomyces cerevisiae Vps27 and of mammalian Hrs. It functions as a downstream factor for phosphatidylinositol 3-kinase (PtdIns 3-kinase) in forespore membrane formation with normal morphology. It colocalizes and interacts with Hse1p, a homolog of Saccharomyces cerevisiae Hse1p and of mammalian STAM, to form a complex whose ubiquitin-interacting motifs (UIMs) are important for sporulation. spVps27p contains a VHS (Vps27p/Hrs/Stam) domain, a FYVE domain, and two UIMs.


Pssm-ID: 277274 [Multi-domain]  Cd Length: 59  Bit Score: 51.38  E-value: 1.87e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 569011688 565 MCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIYDN-NRSNRVCTDCY 616
Cdd:cd15735    8 VCMRCRTAF-TFTNRKHHCRNCGGVFCQQCSSKSLPLPHFGiNQPVRVCDGCY 59
FYVE_RABE_unchar cd15739
FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This ...
560-623 2.53e-08

FYVE domain found in uncharacterized rab GTPase-binding effector proteins from bilateria; This family includes a group of uncharacterized rab GTPase-binding effector proteins found in bilateria. Although their biological functions remain unclear, they all contain a FYVE domain that harbors a putative phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding site.


Pssm-ID: 277278 [Multi-domain]  Cd Length: 73  Bit Score: 51.19  E-value: 2.53e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688 560 EKEVTMCMRCQEPFNSiTKRRHHCKACGHVVCGKCSefrARLIYD--NNRSNRVCTDCYVAL--HGAP 623
Cdd:cd15739    7 EDDVDQCPNCKTPFSV-GKRKHHCRHCGKIFCSDCL---TKTVPSgpNRRPARVCDVCHTLLvkDSAP 70
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
655-749 5.61e-08

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 51.64  E-value: 5.61e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 655 CSFLHymEKGG-----KGWHKAWFVVPENeplVLYIYGAPQDVKAQRSLPLIGFEVgPPEAGERPDRRHVFKIT---QSH 726
Cdd:cd13308   12 SGTLT--KKGGsqktlQNWQLRYVIIHQG---CVYYYKNDQSAKPKGVFSLNGYNR-RAAEERTSKLKFVFKIIhlsPDH 85
                         90       100
                 ....*....|....*....|...
gi 569011688 727 LSWYFSPETEELQRRWMAVLGRA 749
Cdd:cd13308   86 RTWYFAAKSEDEMSEWMEYIRRE 108
PH_Collybistin_ASEF cd01224
Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; ...
412-514 6.69e-08

Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain; Collybistin (also called PEM2) is homologous to the Dbl proteins ASEF (also called ARHGEF4/RhoGEF4) and SPATA13 (Spermatogenesis-associated protein 13; also called ASEF2). It activates CDC42 specifically and not any other Rho-family GTPases. Collybistin consists of an SH3 domain, followed by a RhoGEF/DH and PH domain. In Dbl proteins, the DH and PH domains catalyze the exchange of GDP for GTP in Rho GTPases, allowing them to signal to downstream effectors. It induces submembrane clustering of the receptor-associated peripheral membrane protein gephyrin, which is thought to form a scaffold underneath the postsynaptic membrane linking receptors to the cytoskeleton. It also acts as a tumor suppressor that links adenomatous polyposis coli (APC) protein, a negative regulator of the Wnt signaling pathway and promotes the phosphorylation and degradation of beta-catenin, to Cdc42. Autoinhibition of collybistin is accomplished by the binding of its SH3 domain with both the RhoGEF and PH domains to block access of Cdc42 to the GTPase-binding site. Inactivation promotes cancer progression. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269931  Cd Length: 138  Bit Score: 52.26  E-value: 6.69e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 412 EDIVSPTKELIKEGHILKLSAknGTTQDRYLILFNDRLLYCVPRLRLLgQKFSVRARIDVDGMELkessnLNMP----RT 487
Cdd:cd01224   20 EDLSDRSSELIHSGELTKISA--GRAQERTFFLFDHQLVYCKKDLLRR-KNYIYKGRIDTDNMEI-----EDLPdgkdDE 91
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 569011688 488 FLVS----------GKQRSLELQARTEEEKKDWVQAI 514
Cdd:cd01224   92 SGVTvknawkiynaSKNKWYVLCAKSAEEKQRWLEAF 128
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
654-746 1.08e-07

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 50.23  E-value: 1.08e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 654 ICSFLHYMEKGG-KGWHKAWFVVPENeplVLYIYGAPQDV--KAQRSLPLIGFEVgpPEAGERPDRRHVFKI-TQSHLSW 729
Cdd:cd00821    1 KEGYLLKRGGGGlKSWKKRWFVLFEG---VLLYYKSKKDSsyKPKGSIPLSGILE--VEEVSPKERPHCFELvTPDGRTY 75
                         90
                 ....*....|....*..
gi 569011688 730 YFSPETEELQRRWMAVL 746
Cdd:cd00821   76 YLQADSEEERQEWLKAL 92
FYVE_RUFY3 cd15744
FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar ...
566-616 2.87e-07

FYVE-related domain found in RUN and FYVE domain-containing protein 3 (RUFY3) and similar proteins; RUFY3, also termed Rap2-interacting protein x (RIPx or RPIPx), or single axon-regulated protein (singar), is an N-terminal RUN domain and a C-terminal FYVE domain containing protein predominantly expressed in the brain. It suppresses formation of surplus axons for neuronal polarity. Unlike other RUFY proteins, RUFY3 can associate with the GTP-bound active form of Rab5. Moreover, the FYVE domain of RUFY3 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue).


Pssm-ID: 277283 [Multi-domain]  Cd Length: 52  Bit Score: 47.80  E-value: 2.87e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 569011688 566 CMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15744    2 CSLCQEDFASLALPKHNCYNCGGTFCDACSSNELPLPSSIYEPARVCDVCY 52
FYVE_RUFY4 cd15745
FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar ...
566-616 3.14e-07

FYVE-related domain found in RUN and FYVE domain-containing protein 4 (RUFY4) and similar proteins; RUFY4 belongs to the FUFY protein family which is characterized by the presence of an N-terminal RUN domain and a C-terminal FYVE domain. The FYVE domain of RUFY4 resembles the FYVE-related domain as it lacks the WxxD motif (x for any residue). The biological function of RUFY4 still remains unclear.


Pssm-ID: 277284 [Multi-domain]  Cd Length: 52  Bit Score: 47.50  E-value: 3.14e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569011688 566 CMRCQEPFnSITKRRHHCKACGHVVCGKCS-EFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15745    2 CAICAKAF-SLFRRKYVCRLCGGVVCHSCSsEDLVLSVPDTCIYLRVCKTCY 52
FYVE_protrudin cd15723
FYVE-related domain found in protrudin and similar proteins; Protrudin, also termed zinc ...
566-619 4.94e-07

FYVE-related domain found in protrudin and similar proteins; Protrudin, also termed zinc finger FYVE domain-containing protein 27 (ZFY27 or ZFYVE27), is a FYVE domain-containing protein involved in transport of neuronal cargoes and implicated in the onset of hereditary spastic paraplegia (HSP). It is involved in neurite outgrowth through binding to spastin. Moreover, it functions as a key regulator of the Rab11-dependent membrane trafficking during neurite extension. It serves as an adaptor molecule that links its associated proteins, such as Rab11-GDP, VAP-A and -B, Surf4, and RTN3, to KIF5, a motor protein that mediates anterograde vesicular transport in neurons, and thus plays a key role in the maintenance of neuronal function. The FYVE domain of protrudin resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. In addition, unlike canonical FYVE domains that is located to early endosomes and specifically binds to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), the FYVE domain of protrudin is located to plasma membrane and preferentially binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). In addition to FYVE-related domain, protrudin also contains a Rab11-binding domain (RBD11), two hydrophobic domains, HP-1 and HP-2, an FFAT motif, and a coiled-coil domain.


Pssm-ID: 277262 [Multi-domain]  Cd Length: 62  Bit Score: 47.49  E-value: 4.94e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569011688 566 CMRCQEPFNSITKRRHHCKACGHVVCGKC-------SEFRARLIYDNNRSNRVCTDCYVAL 619
Cdd:cd15723    2 CTGCGASFSVLLKKRRSCNNCGNAFCSRCcskkvprSVMGATAPAAQRETVFVCSGCNDKL 62
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
654-746 5.66e-07

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 48.47  E-value: 5.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 654 ICSFLHYMEKGG---KGWHKAWFVVPENEPLvLYIYGAPQDVKAQRSLPLIG--FEVgPPEAGErpdrrHVFKITQSHLS 728
Cdd:cd01265    2 LCGYLNKLETRGlglKGWKRRWFVLDESKCQ-LYYYRSPQDATPLGSIDLSGaaFSY-DPEAEP-----GQFEIHTPGRV 74
                         90
                 ....*....|....*...
gi 569011688 729 WYFSPETEELQRRWMAVL 746
Cdd:cd01265   75 HILKASTRQAMLYWLQAL 92
FYVE_PIKfyve_Fab1 cd15725
FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, ...
566-616 1.03e-06

FYVE domain found in metazoan PIKfyve, fungal and plant Fab1, and similar proteins; PIKfyve, also termed FYVE finger-containing phosphoinositide kinase, or 1-phosphatidylinositol 3-phosphate 5-kinase, or phosphatidylinositol 3-phosphate 5-kinase (PIP5K3), or phosphatidylinositol 3-phosphate 5-kinase type III (PIPkin-III or type III PIP kinase), is a phosphoinositide 5-kinase that forms a complex with its regulators, the scaffolding protein Vac14 and the lipid phosphatase Fig4. The complex is responsible for synthesizing phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] from phosphatidylinositol 3-phosphate (PtdIns3P or PI3P). Then phosphatidylinositol-5-phosphate (PtdIns5P) is generated directly from PtdIns(3,5)P2. PtdIns(3,5)P2 and PtdIns5P regulate endosomal trafficking and responses to extracellular stimuli. At this point, PIKfyve is vital in early embryonic development. Moreover, PIKfyve forms a complex with ArPIKfyve (associated regulator of PIKfyve) and SAC3 at the endomembranes, which plays a role in receptor tyrosine kinase (RTK) degradation. The phosphorylation of PIKfyve by AKT can facilitate Epidermal growth factor receptor (EGFR) degradation. In addition, PIKfyve may participate in the regulation of the glutamate transporters EAAT2, EAAT3 and EAAT4, and the cystic fibrosis transmembrane conductance regulator (CFTR). It is also essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle. It can be activated by protein kinase B (PKB/Akt) and further up-regulates human ether-a-go-go (hERG) channels. This family also includes the yeast and plant orthologs of human PIKfyve, Fab1. PIKfyve and its orthologs share a similar architecture. They contain an N-terminal FYVE domain, a middle region related to the CCT/TCP-1/Cpn60 chaperonins that are involved in productive folding of actin and tubulin, a second middle domain that contains a number of conserved cysteine residues (CCR) unique to this family, and a C-terminal lipid kinase domain related to PtdInsP kinases.


Pssm-ID: 277264 [Multi-domain]  Cd Length: 62  Bit Score: 46.55  E-value: 1.03e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 569011688 566 CMRCQEPFNSItKRRHHCKACGHVVCGKCSEFR---ARLIYDNNRsnRVCTDCY 616
Cdd:cd15725   11 CYECSEKFTTF-RRRHHCRLCGQIFCSRCCNQEipgKFIGYPGDL--RVCTYCC 61
FYVE_RUFY2 cd15759
FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; ...
558-619 3.16e-06

FYVE domain found in RUN and FYVE domain-containing protein 2 (RUFY2) and similar proteins; RUFY2, also termed Rab4-interacting protein related, is a novel embryonic factor that contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. It is present in the nucleus at early stages of embryonic development. It may have both endosomal functions in the cytoplasm and nuclear functions.


Pssm-ID: 277298 [Multi-domain]  Cd Length: 71  Bit Score: 45.40  E-value: 3.16e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569011688 558 IREKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIyDNNRSNRVCTDCYVAL 619
Cdd:cd15759    5 LKDKEATHCKLCEKEF-SLSKRKHHCRNCGEIFCNACSDNELPLP-SSPKPVRVCDSCHAML 64
FYVE_ZFY19 cd15749
FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ...
566-616 3.28e-06

FYVE-related domain found in FYVE domain-containing protein 19 (ZFY19) and similar proteins; ZFY19, also termed mixed lineage leukemia (MLL) partner containing FYVE domain, is encoded by a novel gene, MLL partner containing FYVE domain (MPFYVE). The FYVE domain of ZFY19 resembles FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. The biological function of ZFY19 remains unclear.


Pssm-ID: 277288 [Multi-domain]  Cd Length: 51  Bit Score: 44.80  E-value: 3.28e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 569011688 566 CMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIYDNNRSNRVCTDCY 616
Cdd:cd15749    2 CFGCAAKF-SLFKKECGCKNCGRSFCKGCLTFSAVVPRKGNQKQKVCKQCH 51
FYVE_SlaC2-c cd15753
FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; ...
566-615 4.33e-06

FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; SlaC2-c, also termed Rab effector MyRIP, or exophilin-8, or myosin-VIIa- and Rab-interacting protein, or synaptotagmin-like protein lacking C2 domains c, is a GTP-bound form of Rab27A-, myosin Va/VIIa-, and actin-binding protein mainly present on retinal melanosomes and secretory granules. It may play a role in insulin granule exocytosis. It is also involved in the control of isoproterenol (IPR)-induced amylase release from parotid acinar cells. SlaC2-c belongs to the Slp homolog lacking C2 domains (Slac2) family. It contains an N-terminal Slp homology domain (SHD), but lacks tandem C2 domains. The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of SlaC2-c are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. Moreover, Slac2-c has a middle myosin-binding domain and a C-terminal actin-binding domain.


Pssm-ID: 277292  Cd Length: 49  Bit Score: 44.32  E-value: 4.33e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 569011688 566 CMRCQEPFNSITKRRHHCKACGHVVCGKCSEfrarliYDNNRSNRVCTDC 615
Cdd:cd15753    2 CMRCCSPFTFLFNRKRQCRDCKFNVCKSCAS------YDKKEKGWTCNVC 45
FYVE_MTMR_unchar cd15738
FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from ...
561-616 4.74e-06

FYVE-related domain found in uncharacterized myotubularin-related proteins mainly from eumetazoa; This family includes a group of uncharacterized myotubularin-related proteins mainly found in eumetazoa. Although their biological functions remain unclear, they share similar domain architecture that consists of an N-terminal pleckstrin homology (PH) domain, a highly conserved region related to myotubularin proteins, a C-terminal FYVE domain. The model corresponds to the FYVE domain, which resembles the FYVE-related domain as it has an altered sequence in the basic ligand binding patch.


Pssm-ID: 277277 [Multi-domain]  Cd Length: 61  Bit Score: 44.63  E-value: 4.74e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569011688 561 KEVTMCmRCQEPFNSITkRRHHCKACGHVVCGKCSEFRARL-IYDNNRSNRVCTDCY 616
Cdd:cd15738    7 RNVTEC-SCSTPFDHFS-KKHHCWRCGNVFCTRCIDKQRALpGHLSQRPVPVCRACY 61
FYVE_WDFY2 cd15757
FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also ...
566-616 7.44e-06

FYVE domain found in WD40 repeat and FYVE domain-containing protein 2 (WDFY2); WDFY2, also termed zinc finger FYVE domain-containing protein 22, or ProF (propeller-FYVE protein), is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) binding protein that is localized to a distinct subset of early endosomes close to the plasma membrane. It interacts preferentially with endogenous serine/threonine kinase Akt2, but not Akt1, and plays a specific role in modulating signaling through Akt downstream of the interaction of this kinase with the endosomal proteins APPL (adaptor protein containing PH domain, PTB domain, and leucine zipper motif). In addition to Akt, WDFY2 serves as a binding partner for protein kinase C, zeta (PRKCZ), and its substrate vesicle-associated membrane protein 2 (VAMP2), and is involved in vesicle cycling in various secretory pathways. Moreover, Silencing of WDFY2 by siRNA produces a strong inhibition of endocytosis. WDFY2 contains WD40 motifs and a FYVE domain.


Pssm-ID: 277296 [Multi-domain]  Cd Length: 70  Bit Score: 44.29  E-value: 7.44e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569011688 566 CMRCQEPF----------NSITKRRHHCKACGHVVCGKCSEFRARL-IYDNNRSNRVCTDCY 616
Cdd:cd15757    9 CQKCDQPFfwnfkqmwdsKKIGLRQHHCRKCGKAVCGKCSSKRSTIpLMGFEFEVRVCDSCH 70
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
423-517 1.33e-05

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 44.52  E-value: 1.33e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 423 KEGHILKLSAKNGTT-QDRYLILFNDRLLYC-----------VPRLRLLgqkfSVRARIDVDgmelkessnlnmpRTF-- 488
Cdd:cd13250    1 KEGYLFKRSSNAFKTwKRRWFSLQNGQLYYQkrdkkdeptvmVEDLRLC----TVKPTEDSD-------------RRFcf 63
                         90       100       110
                 ....*....|....*....|....*....|
gi 569011688 489 -LVSgKQRSLELQARTEEEKKDWVQAINST 517
Cdd:cd13250   64 eVIS-PTKSYMLQAESEEDRQAWIQAIQSA 92
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
210-455 1.49e-05

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 48.73  E-value: 1.49e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  210 ELLQTEKAYVSRLHLLDQVFcARLLEE-----ARNRSSFpadvVHGIFSNICSIYCFHQQFLlPELEKRMEEWDRYPRIG 284
Cdd:COG5422   491 EVIYTERDFVKDLEYLRDTW-IKPLEEsniipENARRNF----IKHVFANINEIYAVNSKLL-KALTNRQCLSPIVNGIA 564
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  285 DILQKLAPFLKMYGEYVKNFDRAVELVNTwtERST--QFKVIIHEVQKEEACGNLTLQHHMLEPVQRIPRYELLLKDYLL 362
Cdd:COG5422   565 DIFLDYVPKFEPFIKYGASQPYAKYEFER--EKSVnpNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLK 642
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688  363 KLPHGSPDSKDAQKSLELIATAAEHSNAAIRKMERMHKLLKVYELLGGEEDIVS-----PTKELIKEGhILKLSAKNGT- 436
Cdd:COG5422   643 FTDPDNPDTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKPEYVNlglndEYRKIIFKG-VLKRKAKSKTd 721
                         250       260
                  ....*....|....*....|..
gi 569011688  437 ---TQDRYLILFNDRLLYCVPR 455
Cdd:COG5422   722 gslRGDIQFFLLDNMLLFCKAK 743
PH_ephexin cd01221
Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine ...
414-513 1.77e-05

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269929  Cd Length: 131  Bit Score: 44.94  E-value: 1.77e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 414 IVSPTKELIKEGHILKLSAKNG--------TTQDRYLILFNDRLLYCVPRlrlLGQKFSV-----RARIDVDGMELKESS 480
Cdd:cd01221    7 LISSSRWLVKRGELTELVEDGGsltfrkkfSKTPVYLFLFNDLLLITKKK---SEERYLVldyapRNLVQVEEVEDPLQL 83
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 569011688 481 NL-NMPRTFLV------SGKQRSLELQARTEEEKKDWVQA 513
Cdd:cd01221   84 PQpLGKNLFLLtllenhEGKTVELLLSAESESDRERWLSA 123
PH_Phafin2-like cd01218
Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; ...
400-515 4.70e-05

Phafin2 (also called EAPF, FLJ13187, ZFYVE18 or PLEKHF2) Pleckstrin Homology (PH) domain; Phafin2 is differentially expressed in the liver cancer cell and regulates the structure and function of the endosomes through Rab5-dependent processes. Phafin2 modulates the cell's response to extracellular stimulation by modulating the receptor density on the cell surface. Phafin2 contains a PH domain and a FYVE domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269927 [Multi-domain]  Cd Length: 123  Bit Score: 43.40  E-value: 4.70e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 400 KLLKVYELLGG-EEDIVSPTKELIKEGHILKLSAKngTTQDRYLILFNDRLLY---CVPRLRLLGQKF----SVRARIDV 471
Cdd:cd01218    8 RIAAVESCFGGsGQPLVKPGRVLVGEGVLTKVCRK--KPKPRQFFLFNDILVYgsiVINKKKYNKQRIipleDVKIEDLE 85
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 569011688 472 DGMELKESsnlnmprtFLVSGKQRSLELQARTEEEKKDWVQAIN 515
Cdd:cd01218   86 DTGELKNG--------WQIISPKKSFVVYAATATEKSEWMDHIN 121
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
466-519 4.87e-05

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 42.97  E-value: 4.87e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 466 RARIDVDG-MELkessNLNMPRTFLVSGKQRSLELQARTEEEKKDWVQAINSTLL 519
Cdd:cd01233   53 TARVEYSPdQEA----LLGRPNVFAVYTPTNSYLLQARSEKEMQDWLYAIDPLLA 103
FYVE_MTMR3 cd15732
FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also ...
560-616 9.13e-05

FYVE domain found in myotubularin-related protein 3 (MTMR3) and similar proteins; MTMR3, also termed Myotubularin-related phosphatase 3, or FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1), or zinc finger FYVE domain-containing protein 10, is a ubiquitously expressed phosphoinositide 3-phosphatase specific for phosphatidylinositol 3-phosphate (PtdIns3P or PI3P) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and PIKfyve, which produces PtdIns(3,5)P2 from PtdIns3P. It regulates cell migration through modulating phosphatidylinositol 5-phosphate (PtdIns5P) levels. MTMR3 contains an N-terminal PH-GRAM (PH-G) domain, a MTM phosphatase domain, a coiled-coil region, and a C-terminal FYVE domain. Unlike conventional FYVE domains, the FYVE domain of MTMR3 neither confers endosomal localization nor binds to PtdIns3P. It is also not required for the enzyme activity of MTMR3. In contrast, the PH-G domain binds phosphoinositides.


Pssm-ID: 277271 [Multi-domain]  Cd Length: 61  Bit Score: 41.04  E-value: 9.13e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569011688 560 EKEVTMCMRCQEPFnSITKRRHHCKACGHVVCGKCSEFRARLIYDNN-RSNRVCTDCY 616
Cdd:cd15732    5 DHLAASCYGCEREF-WLASRKHHCRNCGNVFCGSCCNQKLPVPSQQLfEPSRVCKSCF 61
PH_SOS cd01261
Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide ...
420-514 1.03e-04

Son of Sevenless (SOS) Pleckstrin homology (PH) domain; SOS is a Ras guanine nucleotide exchange factor. SOS is thought to transmit signals from activated receptor tyrosine kinases to the Ras signaling pathway. SOS contains a histone domain, Dbl-homology (DH), a PH domain, Rem domain, Cdc25 domain, and a Grb2 binding domain. The SOS PH domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidic acid (PA). SOS is dependent on Ras binding to the allosteric site via its histone domain for both a lower level of activity (Ras GDP) and maximal activity (Ras GTP). The DH domain blocks the allosteric Ras binding site in SOS. The PH domain is closely associated with the DH domain and the action of the DH-PH unit gates a reciprocal interaction between Ras and SOS. The C-terminal proline-rich domain of SOS binds to the adapter protein Grb2 which localizes the Sos protein to the plasma membrane and diminishes the negative effect of the C-terminal domain on the guanine nucleotide exchange activity of the CDC25-homology domain of SOS. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269963  Cd Length: 109  Bit Score: 42.35  E-value: 1.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 420 ELIKEGHILKLSAKNGTTqDRYLILFNDRLLYCVPRLRL-----------LGQKFSVRaRIDV----DGMELKESsnlnm 484
Cdd:cd01261    5 EFIMEGTLGKVGSGKRKT-ERHAFLFDGLLLLCKSNRRRtstggpkpeyrLKEKFFIR-KVEIndleDTEELKNA----- 77
                         90       100       110
                 ....*....|....*....|....*....|.
gi 569011688 485 prtF-LVSGKQRSLELQARTEEEKKDWVQAI 514
Cdd:cd01261   78 ---FeIVPRDQPSVILFAKSAEEKNNWMAAL 105
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
423-518 1.51e-04

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 41.51  E-value: 1.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 423 KEGHILKLSAKNGTTQDRYLILFNDRLLYC-----VPRlRLLGQkfsvrarIDVDGmeLKESSNLNMPRTFLVSGKQRSL 497
Cdd:cd13282    1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYkspndVIR-KPQGQ-------IALDG--SCEIARAEGAQTFEIVTEKRTY 70
                         90       100
                 ....*....|....*....|.
gi 569011688 498 ELQARTEEEKKDWVQAINSTL 518
Cdd:cd13282   71 YLTADSENDLDEWIRVIQNVL 91
FYVE_Slp3_4_5 cd15747
FYVE-related domain found in the synaptotagmin-like proteins 3, 4, 5; The synaptotagmin-like ...
565-616 1.94e-04

FYVE-related domain found in the synaptotagmin-like proteins 3, 4, 5; The synaptotagmin-like proteins 1-5 (Slp1-5) family belongs to the carboxyl-terminal-type (C-type) tandem C2 proteins superfamily, which also contains the synaptotagmin and the Doc2 families. Slp proteins are putative membrane trafficking proteins that are characterized by the presence of a unique N-terminal Slp homology domain (SHD), and C-terminal tandem C2 domains (known as the C2A domain and C2B domain). The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2. The SHD1 and SHD2 of Slp3, Slp4 and Slp5 are separated by a putative FYVE zinc finger. By contrast, Slp1 and Slp2 lack such zinc finger and their SHD1 and SHD2 are linked together. This model corresponds to the FYVE zinc finger. At this point, Slp1 and Slp2 are not included in this model. Moreover, the FYVE domains of Slp3, Slp4 and Slp5 resemble a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.


Pssm-ID: 277286  Cd Length: 48  Bit Score: 39.59  E-value: 1.94e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569011688 565 MCMRCQEPFNSITKRRHHCKACGHVVCGKCSEFrarliyDNNRSNRVCTDCY 616
Cdd:cd15747    2 ICARCREKLGFIFNRGARCPKCSHKVCKKCRVL------TSNTGKWLCTVCH 47
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
422-517 2.23e-04

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270093  Cd Length: 97  Bit Score: 40.84  E-value: 2.23e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 422 IKEGHILKLSAKNGTTQDRYLILFNDRLLYCVPrlrllgQKFSVRARIDVDGMELKESSNLNMPRTFLVSGKQRSLELQA 501
Cdd:cd13274    1 IKEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKD------SKSLIFEEIDLSDASVAECSTKNVNNSFTVITPFRKLILCA 74
                         90
                 ....*....|....*.
gi 569011688 502 RTEEEKKDWVQAINST 517
Cdd:cd13274   75 ESRKEMEEWISALKTV 90
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
660-746 6.02e-04

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 39.59  E-value: 6.02e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 660 YMEK-GG--KGWHKAWFVVPENEplvLYIYGAPQDV--KAQRSLPLIGF-EVGPPEAGerpdrrHVFKITQSHLSWYFSP 733
Cdd:cd13282    4 YLTKlGGkvKTWKRRWFVLKNGE---LFYYKSPNDVirKPQGQIALDGScEIARAEGA------QTFEIVTEKRTYYLTA 74
                         90
                 ....*....|...
gi 569011688 734 ETEELQRRWMAVL 746
Cdd:cd13282   75 DSENDLDEWIRVI 87
FYVE_Slp4 cd15764
FYVE-related domain found in synaptotagmin-like protein 4 (Slp4) and similar proteins; Slp4, ...
566-599 7.59e-04

FYVE-related domain found in synaptotagmin-like protein 4 (Slp4) and similar proteins; Slp4, also termed exophilin-2, or granuphilin, has been characterized as a regulator of the release of insulin granules from pancreatic beta-cells and dense core granules from PC12 neuronal cells by binding to Rab27A , and amylase granules from parotid gland acinar cells through interaction with syntaxin-2/3 in a Munc18-2-dependent manner on the apical plasma membrane. It can binds to syntaxin 2 in parotid acinar cells. It is also involved in granule transport by recruitment of the motor protein myosin Va. Moreover, it requires Rab8 to increase granule release in platelets. Slp4 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp4 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.


Pssm-ID: 277303  Cd Length: 50  Bit Score: 37.84  E-value: 7.59e-04
                         10        20        30
                 ....*....|....*....|....*....|....
gi 569011688 566 CMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRA 599
Cdd:cd15764    6 CGRCQESLGRLSPKANQCRGCNHLVCRDCRAVRP 39
PH2_AFAP cd13307
Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are ...
668-758 1.72e-03

Actin filament associated protein family Pleckstrin homology (PH) domain, repeat 2; There are 3 members of the AFAP family of adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. AFAP1 is a cSrc binding partner and actin cross-linking protein. AFAP1L1 is thought to play a similar role to AFAP1 in terms of being an actin cross-linking protein, but it preferentially binds to cortactin and not cSrc, thereby playing a role in invadosome formation. AFAP1L2 is a cSrc binding protein, but does not bind to actin filaments. AFAP1L2 acts as an intermediary between the RET/PTC kinase and PI-3kinase pathway in the thyroid. The AFAPs share a similar structure of a SH3 binding motif, 3 SH2 binding motifs, 2 PH domains, a coiled-coil region corresponding to the AFAP1 leucine zipper, and an actin binding domain. This cd is the second PH domain of AFAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270117  Cd Length: 101  Bit Score: 38.51  E-value: 1.72e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 668 WHKAWFVVPENEplvLYIYGAPQDVK-AQRSLPLIGFEVGPpeaGERPDRRHVFKITQSH--LSWYFSPETEELQrRWMA 744
Cdd:cd13307   16 WRSRWCCVKDGQ---LHFYQDRNKTKsPQQSLPLHGCEVVP---GPDPKHPYSFRILRNGeeVAALEASSSEDMG-RWLG 88
                         90
                 ....*....|....
gi 569011688 745 VLgRAGRGDTFCPG 758
Cdd:cd13307   89 VL-LAETGSATDPE 101
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
666-749 2.08e-03

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 38.52  E-value: 2.08e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 666 KGWHKAWFVVPENEplvLYIYGAPQDVKAQRSLPLIG-----------------FEVGPPEAGERPDRRHvfkitQSHLS 728
Cdd:cd13263   17 KNWQQRWFVLRGDQ---LYYYKDEDDTKPQGTIPLPGnkvkevpfnpeepgkflFEIIPGGGGDRMTSNH-----DSYLL 88
                         90       100
                 ....*....|....*....|..
gi 569011688 729 WYFSP-ETEElqrrWMAVLGRA 749
Cdd:cd13263   89 MANSQaEMEE----WVKVIRRV 106
PH_Vav cd01223
Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) ...
421-518 2.83e-03

Vav pleckstrin homology (PH) domain; Vav acts as a guanosine nucleotide exchange factor (GEF) for Rho/Rac proteins. They control processes including T cell activation, phagocytosis, and migration of cells. The Vav subgroup of Dbl GEFs consists of three family members (Vav1, Vav2, and Vav3) in mammals. Vav1 is preferentially expressed in the hematopoietic system, while Vav2 and Vav3 are described by broader expression patterns. Mammalian Vav proteins consist of a calponin homology (CH) domain, an acidic region, a catalytic Dbl homology (DH) domain, a PH domain, a zinc finger cysteine rich domain (C1/CRD), and an SH2 domain, flanked by two SH3 domains. In invertebrates such as Drosophila and C. elegans, Vav is missing the N-terminal SH3 domain. The DH domain is involved in RhoGTPase recognition and selectivity and stimulates the reorganization of the switch regions for GDP/GTP exchange. The PH domain is implicated in directing membrane localization, allosteric regulation of guanine nucleotide exchange activity, and as a phospholipid- dependent regulator of GEF activity. Vavs bind RhoGTPases including Rac1, RhoA, RhoG, and Cdc42, while other members of the GEF family are specific for a single RhoGTPase. This promiscuity is thought to be a result of its CRD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269930  Cd Length: 127  Bit Score: 38.38  E-value: 2.83e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 421 LIKEGHiLKLSA-KNGTTQDRYLILFNDRLLYCVprlRLLGQKFSVRA-------RIDVDGMELKESSNLNMPRTFLVSG 492
Cdd:cd01223   19 LQIDGE-LKIKShEDQKKKDRYAFLFDKVLLICK---SLRGDQYEYKEiinlseyRIEDDPSRRTLKRDKRWSYQFLLVH 94
                         90       100
                 ....*....|....*....|....*...
gi 569011688 493 KQR--SLELQARTEEEKKDWVQAINSTL 518
Cdd:cd01223   95 KQGktAYTLYAKTEELKKKWMEAIEMAL 122
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
653-746 3.26e-03

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 37.69  E-value: 3.26e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011688 653 VICSFLHYMEKGG---KGWHKAWFVVPENEplvLYIYGAPQDVKAQRSLPLI-GFEVgppEAGERPDRRHVFKITQSHLS 728
Cdd:cd10573    1 SLGSKEGYLTKLGgivKNWKTRWFVLRRNE---LKYFKTRGDTKPIRVLDLReCSSV---QRDYSQGKVNCFCLVFPERT 74
                         90
                 ....*....|....*...
gi 569011688 729 WYFSPETEELQRRWMAVL 746
Cdd:cd10573   75 FYMYANTEEEADEWVKLL 92
FYVE_Slp3 cd15765
FYVE-related domain found in synaptotagmin-like protein 3 (Slp3) and similar proteins; Slp3, ...
566-616 3.44e-03

FYVE-related domain found in synaptotagmin-like protein 3 (Slp3) and similar proteins; Slp3, also termed exophilin-6, functions as a Rab27A-specific effector in cytotoxic T lymphocytes. It binds to kinesin-1 motor through interaction with the tetratricopeptide repeat of the kinesin-1 light chain (KLC1). The kinesin-1/Slp3/Rab27a complex plays a role in mediating the terminal transport of lytic granules to the immune synapse. Slp3 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp3 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. In addition, the Slp3 C2A domain showed Ca2+-dependent phospholipid binding activity. At this point, Slp3 is a Ca2+-dependent isoform in Slp proteins family.


Pssm-ID: 277304  Cd Length: 48  Bit Score: 35.94  E-value: 3.44e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 569011688 566 CMRCQEPFNSITKRRHHCKACGHVVCGKCSEFRARLIYDnnrsnrvCTDCY 616
Cdd:cd15765    4 CARCQKPLGKLLNRGAVCNGCSHRVCSECRVFLGREIWK-------CTVCH 47
FYVE_SlaC2-a cd15752
FYVE-related domain found in Slp homolog lacking C2 domains a (SlaC2-a) and similar proteins; ...
564-618 7.48e-03

FYVE-related domain found in Slp homolog lacking C2 domains a (SlaC2-a) and similar proteins; SlaC2-a, also termed melanophilin, or exophilin-3, is a GTP-bound form of Rab27A-, myosin Va-, and actin-binding protein present on melanosomes. It is involved in the control of transferring of melanosomes from microtubules to actin filaments. It also functions as a melanocyte type myosin Va (McM5) binding partner and directly activates the actin-activated ATPase activity of McM5 through forming a tripartite protein complex with Rab27A and an actin-based motor myosin Va. SlaC2-a belongs to the Slp homolog lacking C2 domains (Slac2) family. It contains an N-terminal Slp homology domain (SHD), but lacks tandem C2 domains. The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of SlaC2-a are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. Moreover, Slac2-a has a middle myosin-binding domain and a C-terminal actin-binding domain.


Pssm-ID: 277291  Cd Length: 76  Bit Score: 35.93  E-value: 7.48e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 569011688 564 TMCMRCQEPFNSITKRRHHCKACGHVVCGKCSEfrarliYDNNRSNRVCTDCYVA 618
Cdd:cd15752    1 THCARCLQPFQFLLNSGRQCLDCGLRTCKSCSR------YHPEEQGWVCDPCHLA 49
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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