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Conserved domains on  [gi|1061899719|ref|NP_001317700|]
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connector enhancer of kinase suppressor of ras 2 isoform 6 [Homo sapiens]

Protein Classification

connector enhancer of kinase suppressor of ras 2( domain architecture ID 10175707)

connector enhancer of kinase suppressor of ras 2 (CNKSR2) may function as an adapter protein or regulator of Ras signaling pathways

Gene Symbol:  CNKSR2
Gene Ontology:  GO:0019901|GO:0005515
SCOP:  4002395|4001790

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
480-593 8.80e-78

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, with the exception of CNK3, 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 mammals, chickens, amphibians, fish, and crustacea. 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: 269962  Cd Length: 114  Bit Score: 246.55  E-value: 8.80e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 480 SKRRISCKDLGRGDCEGWLWKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKKYAFK 559
Cdd:cd01260     1 SRRRVSCKDLGRGDCQGWLWKKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERASECKKKYAFK 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1061899719 560 ACHPKIKSFYFAAEHLDDMNRWLNRINMLTAGYA 593
Cdd:cd01260    81 ACHPKIKTFYFAAENLDDMNKWLSKLNMAINKYA 114
CRIC_ras_sig pfam10534
Connector enhancer of kinase suppressor of ras; The CRIC - Connector enhancer of kinase ...
84-176 1.07e-44

Connector enhancer of kinase suppressor of ras; The CRIC - Connector enhancer of kinase suppressor of ras - domain functions as a scaffold in several signal cascades and acts on proliferation, differentiation and apoptosis.


:

Pssm-ID: 431342  Cd Length: 93  Bit Score: 155.51  E-value: 1.07e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719  84 NLKTLSHKLNASAKNLQNFITGRRRSGHYDGRTSRKLPNDFLTSVVDLIGAAKSLLAWLDRSPFAAVTDYSVTRNNVIQL 163
Cdd:pfam10534   1 NLQSLTEKLRASANSLQNIIQSRRRSNSYDGRSSVKPPNDVLSAVVELIAAAKGLLSWLDRYPFSQLNDYSATRNNIIQL 80
                          90
                  ....*....|...
gi 1061899719 164 CLELTTIVQQDCT 176
Cdd:pfam10534  81 CLELTTIVQKDLT 93
SAM_CNK1,2,3-suppressor cd09511
SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK ...
8-76 8.59e-40

SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK (connector enhancer of kinase suppressor of ras (Ksr)) subfamily is a protein-protein interaction domain. CNK proteins are multidomain scaffold proteins containing a few protein-protein interaction domains and are required for connecting Rho and Ras signaling pathways. In Drosophila, the SAM domain of CNK is known to interact with the SAM domain of the aveugle protein, forming a heterodimer. Mutation of the SAM domain in human CNK1 abolishes the ability to cooperate with the Ras effector, supporting the idea that this interaction is necessary for proper Ras signal transduction.


:

Pssm-ID: 188910  Cd Length: 69  Bit Score: 140.89  E-value: 8.59e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719   8 VSKWSPSQVVDWMKGLDDCLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLLCAL 76
Cdd:cd09511     1 VAKWSPKQVTDWLKGLDDCLQQYIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELLCAL 69
DUF1170 super family cl05942
Protein of unknown function (DUF1170); This family represents a conserved region of unknown ...
290-408 7.37e-35

Protein of unknown function (DUF1170); This family represents a conserved region of unknown function within MAGUIN, a neuronal membrane-associated guanylate kinase-interacting protein. This region is situated between the pfam00595 and pfam00169 domains. All family members also contain an N-terminal pfam00536 domain.


The actual alignment was detected with superfamily member pfam06663:

Pssm-ID: 429057  Cd Length: 214  Bit Score: 132.22  E-value: 7.37e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 290 TPTKRDSSALQDLYIPPPPAEPYIPRDEKGNLPCEDLRGHMVGKPVHKGSESPNSFLDQEYRKRFNIVEEDTVLYCYEYE 369
Cdd:pfam06663   1 SSKKKEKPAILDLYIPPPPAVPYTPRDEKGSLYSGGSKRSHPGLPGKKGSESPNSFLDQESRRRFTIADYDQLGYGYPYE 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899719 370 kGRSSSQGRRESTPTY-------------------------------ENSLLRYMSNEK---IAQEEYMFQRN 408
Cdd:pfam06663  81 -ARVPPARRREKTPSYgkprplsmpvdyswvgavdppakprrggrkgEDLLRRYLSNERippIEEESPSTQPP 152
PDZ_signaling cd00992
PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. ...
222-270 3.03e-05

PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of PDZ domains an N-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in proteases.


:

Pssm-ID: 238492 [Multi-domain]  Cd Length: 82  Bit Score: 42.94  E-value: 3.03e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1061899719 222 KPSEGLGMYIKS--TYDGLHVITGTTENSPADRCKkIHAGDEVIQVNHQTV 270
Cdd:cd00992     9 DPGGGLGFSLRGgkDSGGGIFVSRVEPGGPAERGG-LRVGDRILEVNGVSV 58
 
Name Accession Description Interval E-value
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
480-593 8.80e-78

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, with the exception of CNK3, 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 mammals, chickens, amphibians, fish, and crustacea. 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: 269962  Cd Length: 114  Bit Score: 246.55  E-value: 8.80e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 480 SKRRISCKDLGRGDCEGWLWKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKKYAFK 559
Cdd:cd01260     1 SRRRVSCKDLGRGDCQGWLWKKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERASECKKKYAFK 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1061899719 560 ACHPKIKSFYFAAEHLDDMNRWLNRINMLTAGYA 593
Cdd:cd01260    81 ACHPKIKTFYFAAENLDDMNKWLSKLNMAINKYA 114
CRIC_ras_sig pfam10534
Connector enhancer of kinase suppressor of ras; The CRIC - Connector enhancer of kinase ...
84-176 1.07e-44

Connector enhancer of kinase suppressor of ras; The CRIC - Connector enhancer of kinase suppressor of ras - domain functions as a scaffold in several signal cascades and acts on proliferation, differentiation and apoptosis.


Pssm-ID: 431342  Cd Length: 93  Bit Score: 155.51  E-value: 1.07e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719  84 NLKTLSHKLNASAKNLQNFITGRRRSGHYDGRTSRKLPNDFLTSVVDLIGAAKSLLAWLDRSPFAAVTDYSVTRNNVIQL 163
Cdd:pfam10534   1 NLQSLTEKLRASANSLQNIIQSRRRSNSYDGRSSVKPPNDVLSAVVELIAAAKGLLSWLDRYPFSQLNDYSATRNNIIQL 80
                          90
                  ....*....|...
gi 1061899719 164 CLELTTIVQQDCT 176
Cdd:pfam10534  81 CLELTTIVQKDLT 93
SAM_CNK1,2,3-suppressor cd09511
SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK ...
8-76 8.59e-40

SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK (connector enhancer of kinase suppressor of ras (Ksr)) subfamily is a protein-protein interaction domain. CNK proteins are multidomain scaffold proteins containing a few protein-protein interaction domains and are required for connecting Rho and Ras signaling pathways. In Drosophila, the SAM domain of CNK is known to interact with the SAM domain of the aveugle protein, forming a heterodimer. Mutation of the SAM domain in human CNK1 abolishes the ability to cooperate with the Ras effector, supporting the idea that this interaction is necessary for proper Ras signal transduction.


Pssm-ID: 188910  Cd Length: 69  Bit Score: 140.89  E-value: 8.59e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719   8 VSKWSPSQVVDWMKGLDDCLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLLCAL 76
Cdd:cd09511     1 VAKWSPKQVTDWLKGLDDCLQQYIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELLCAL 69
DUF1170 pfam06663
Protein of unknown function (DUF1170); This family represents a conserved region of unknown ...
290-408 7.37e-35

Protein of unknown function (DUF1170); This family represents a conserved region of unknown function within MAGUIN, a neuronal membrane-associated guanylate kinase-interacting protein. This region is situated between the pfam00595 and pfam00169 domains. All family members also contain an N-terminal pfam00536 domain.


Pssm-ID: 429057  Cd Length: 214  Bit Score: 132.22  E-value: 7.37e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 290 TPTKRDSSALQDLYIPPPPAEPYIPRDEKGNLPCEDLRGHMVGKPVHKGSESPNSFLDQEYRKRFNIVEEDTVLYCYEYE 369
Cdd:pfam06663   1 SSKKKEKPAILDLYIPPPPAVPYTPRDEKGSLYSGGSKRSHPGLPGKKGSESPNSFLDQESRRRFTIADYDQLGYGYPYE 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899719 370 kGRSSSQGRRESTPTY-------------------------------ENSLLRYMSNEK---IAQEEYMFQRN 408
Cdd:pfam06663  81 -ARVPPARRREKTPSYgkprplsmpvdyswvgavdppakprrggrkgEDLLRRYLSNERippIEEESPSTQPP 152
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
494-590 4.98e-19

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  Cd Length: 102  Bit Score: 82.98  E-value: 4.98e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719  494 CEGWLWKKKDAKSyfsQKWKKYWFVLKDASLYWYINEEDEKA---EGFISLPEFKIDRA---SECRKKYAFKACHPKIKS 567
Cdd:smart00233   3 KEGWLYKKSGGGK---KSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTVREApdpDSSKKPHCFEIKTSDRKT 79
                           90       100
                   ....*....|....*....|...
gi 1061899719  568 FYFAAEHLDDMNRWLNRINMLTA 590
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAIA 102
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
9-73 1.47e-18

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerize with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 80.01  E-value: 1.47e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899719   9 SKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:pfam00536   1 DGWSVEDVGEWLESIG--LGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
8-73 2.11e-17

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 76.95  E-value: 2.11e-17
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899719    8 VSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQE-LEDLGVSRIGHQELILEAVDLL 73
Cdd:smart00454   1 VSQWSPESVADWLESIG--LEQYADNFRKNGIDGALLLLLTSEEdLKELGITKLGHRKKILKAIQKL 65
PH pfam00169
PH domain; PH stands for pleckstrin homology.
494-590 3.72e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 66.05  E-value: 3.72e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKdakSYFSQKWKKYWFVLKDASLYWY---INEEDEKAEGFISLPEFKIDRASECR---KKYAFKACHPKI-- 565
Cdd:pfam00169   3 KEGWLLKKG---GGKKKSWKKRYFVLFDGSLLYYkddKSKKSKEPKGSISLSGCEVVEVVASDspkRKFCFELRTGERtg 79
                          90       100
                  ....*....|....*....|....*.
gi 1061899719 566 -KSFYFAAEHLDDMNRWLNRINMLTA 590
Cdd:pfam00169  80 kRTYLLQAESEEERKDWIKAIQSAIR 105
PDZ_signaling cd00992
PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. ...
222-270 3.03e-05

PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of PDZ domains an N-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in proteases.


Pssm-ID: 238492 [Multi-domain]  Cd Length: 82  Bit Score: 42.94  E-value: 3.03e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1061899719 222 KPSEGLGMYIKS--TYDGLHVITGTTENSPADRCKkIHAGDEVIQVNHQTV 270
Cdd:cd00992     9 DPGGGLGFSLRGgkDSGGGIFVSRVEPGGPAERGG-LRVGDRILEVNGVSV 58
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
214-270 5.32e-04

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 39.67  E-value: 5.32e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719  214 EVIQLANIKPSEGLGMYIKSTYDGLH--VITGTTENSPADRCKkIHAGDEVIQVNHQTV 270
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDEGGgvVVSSVVPGSPAAKAG-LRVGDVILEVNGTSV 58
 
Name Accession Description Interval E-value
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
480-593 8.80e-78

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, with the exception of CNK3, 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 mammals, chickens, amphibians, fish, and crustacea. 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: 269962  Cd Length: 114  Bit Score: 246.55  E-value: 8.80e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 480 SKRRISCKDLGRGDCEGWLWKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKKYAFK 559
Cdd:cd01260     1 SRRRVSCKDLGRGDCQGWLWKKKEAKSFFGQKWKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERASECKKKYAFK 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1061899719 560 ACHPKIKSFYFAAEHLDDMNRWLNRINMLTAGYA 593
Cdd:cd01260    81 ACHPKIKTFYFAAENLDDMNKWLSKLNMAINKYA 114
CRIC_ras_sig pfam10534
Connector enhancer of kinase suppressor of ras; The CRIC - Connector enhancer of kinase ...
84-176 1.07e-44

Connector enhancer of kinase suppressor of ras; The CRIC - Connector enhancer of kinase suppressor of ras - domain functions as a scaffold in several signal cascades and acts on proliferation, differentiation and apoptosis.


Pssm-ID: 431342  Cd Length: 93  Bit Score: 155.51  E-value: 1.07e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719  84 NLKTLSHKLNASAKNLQNFITGRRRSGHYDGRTSRKLPNDFLTSVVDLIGAAKSLLAWLDRSPFAAVTDYSVTRNNVIQL 163
Cdd:pfam10534   1 NLQSLTEKLRASANSLQNIIQSRRRSNSYDGRSSVKPPNDVLSAVVELIAAAKGLLSWLDRYPFSQLNDYSATRNNIIQL 80
                          90
                  ....*....|...
gi 1061899719 164 CLELTTIVQQDCT 176
Cdd:pfam10534  81 CLELTTIVQKDLT 93
SAM_CNK1,2,3-suppressor cd09511
SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK ...
8-76 8.59e-40

SAM domain of CNK1,2,3-suppressor subfamily; SAM (sterile alpha motif) domain of CNK (connector enhancer of kinase suppressor of ras (Ksr)) subfamily is a protein-protein interaction domain. CNK proteins are multidomain scaffold proteins containing a few protein-protein interaction domains and are required for connecting Rho and Ras signaling pathways. In Drosophila, the SAM domain of CNK is known to interact with the SAM domain of the aveugle protein, forming a heterodimer. Mutation of the SAM domain in human CNK1 abolishes the ability to cooperate with the Ras effector, supporting the idea that this interaction is necessary for proper Ras signal transduction.


Pssm-ID: 188910  Cd Length: 69  Bit Score: 140.89  E-value: 8.59e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719   8 VSKWSPSQVVDWMKGLDDCLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLLCAL 76
Cdd:cd09511     1 VAKWSPKQVTDWLKGLDDCLQQYIYTFEREKVTGEQLLNLSPQDLENLGVTKIGHQELILEAVELLCAL 69
DUF1170 pfam06663
Protein of unknown function (DUF1170); This family represents a conserved region of unknown ...
290-408 7.37e-35

Protein of unknown function (DUF1170); This family represents a conserved region of unknown function within MAGUIN, a neuronal membrane-associated guanylate kinase-interacting protein. This region is situated between the pfam00595 and pfam00169 domains. All family members also contain an N-terminal pfam00536 domain.


Pssm-ID: 429057  Cd Length: 214  Bit Score: 132.22  E-value: 7.37e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 290 TPTKRDSSALQDLYIPPPPAEPYIPRDEKGNLPCEDLRGHMVGKPVHKGSESPNSFLDQEYRKRFNIVEEDTVLYCYEYE 369
Cdd:pfam06663   1 SSKKKEKPAILDLYIPPPPAVPYTPRDEKGSLYSGGSKRSHPGLPGKKGSESPNSFLDQESRRRFTIADYDQLGYGYPYE 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899719 370 kGRSSSQGRRESTPTY-------------------------------ENSLLRYMSNEK---IAQEEYMFQRN 408
Cdd:pfam06663  81 -ARVPPARRREKTPSYgkprplsmpvdyswvgavdppakprrggrkgEDLLRRYLSNERippIEEESPSTQPP 152
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
494-585 2.20e-25

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: 100.50  E-value: 2.20e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKDAKSYFSqKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECR-KKYAFKACHPKiKSFYFAA 572
Cdd:cd13326     1 YQGWLYQRRRKGKGGG-KWAKRWFVLKGSNLYGFRSQESTKADCVIFLPGFTVSPAPEVKsRKYAFKVYHTG-TVFYFAA 78
                          90
                  ....*....|...
gi 1061899719 573 EHLDDMNRWLNRI 585
Cdd:cd13326    79 ESQEDMKKWLDLL 91
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
493-586 3.13e-24

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: 97.73  E-value: 3.13e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 493 DCEGWLWKKkdAKSYFSQkWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRAS---ECRKKYAFKACHPKIKSFY 569
Cdd:cd13248     8 VMSGWLHKQ--GGSGLKN-WRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPpsdEISRKFAFKAEHANMRTYY 84
                          90
                  ....*....|....*..
gi 1061899719 570 FAAEHLDDMNRWLNRIN 586
Cdd:cd13248    85 FAADTAEEMEQWMNAMS 101
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
494-590 4.98e-19

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  Cd Length: 102  Bit Score: 82.98  E-value: 4.98e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719  494 CEGWLWKKKDAKSyfsQKWKKYWFVLKDASLYWYINEEDEKA---EGFISLPEFKIDRA---SECRKKYAFKACHPKIKS 567
Cdd:smart00233   3 KEGWLYKKSGGGK---KSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTVREApdpDSSKKPHCFEIKTSDRKT 79
                           90       100
                   ....*....|....*....|...
gi 1061899719  568 FYFAAEHLDDMNRWLNRINMLTA 590
Cdd:smart00233  80 LLLQAESEEEREKWVEALRKAIA 102
SAM_1 pfam00536
SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily ...
9-73 1.47e-18

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerize with other SAM domains.


Pssm-ID: 425739  Cd Length: 64  Bit Score: 80.01  E-value: 1.47e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899719   9 SKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:pfam00536   1 DGWSVEDVGEWLESIG--LGQYIDSFRAGYIDGDALLQLTEDDLLKLGVTLLGHRKKILYAIQRL 63
SAM smart00454
Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related ...
8-73 2.11e-17

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.


Pssm-ID: 197735  Cd Length: 68  Bit Score: 76.95  E-value: 2.11e-17
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899719    8 VSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQE-LEDLGVSRIGHQELILEAVDLL 73
Cdd:smart00454   1 VSQWSPESVADWLESIG--LEQYADNFRKNGIDGALLLLLTSEEdLKELGITKLGHRKKILKAIQKL 65
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
493-583 7.13e-16

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. 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: 270126  Cd Length: 97  Bit Score: 73.56  E-value: 7.13e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 493 DCEGWLWKKKDAKSyfsqKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRK---KYAFKACHPKI-KSF 568
Cdd:cd13316     1 DHSGWMKKRGERYG----TWKTRYFVLKGTRLYYLKSENDDKEKGLIDLTGHRVVPDDSNSPfrgSYGFKLVPPAVpKVH 76
                          90
                  ....*....|....*
gi 1061899719 569 YFAAEHLDDMNRWLN 583
Cdd:cd13316    77 YFAVDEKEELREWMK 91
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
494-585 2.01e-15

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: 72.19  E-value: 2.01e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKDaksYFSQKWKKYWFVLKDASLYWYINEED--EKAEGFISLPE-FKIDRASECRKKYAFKACHPKIKSFYF 570
Cdd:cd00821     1 KEGYLLKRGG---GGLKSWKKRWFVLFEGVLLYYKSKKDssYKPKGSIPLSGiLEVEEVSPKERPHCFELVTPDGRTYYL 77
                          90
                  ....*....|....*
gi 1061899719 571 AAEHLDDMNRWLNRI 585
Cdd:cd00821    78 QADSEEERQEWLKAL 92
SAM_superfamily cd09487
SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of ...
15-71 6.23e-14

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.


Pssm-ID: 188886 [Multi-domain]  Cd Length: 56  Bit Score: 66.88  E-value: 6.23e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899719  15 QVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVD 71
Cdd:cd09487     1 DVAEWLESLG--LEQYADLFRKNEIDGDALLLLTDEDLKELGITSPGHRKKILRAIQ 55
PH pfam00169
PH domain; PH stands for pleckstrin homology.
494-590 3.72e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 395117 [Multi-domain]  Cd Length: 105  Bit Score: 66.05  E-value: 3.72e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKdakSYFSQKWKKYWFVLKDASLYWY---INEEDEKAEGFISLPEFKIDRASECR---KKYAFKACHPKI-- 565
Cdd:pfam00169   3 KEGWLLKKG---GGKKKSWKKRYFVLFDGSLLYYkddKSKKSKEPKGSISLSGCEVVEVVASDspkRKFCFELRTGERtg 79
                          90       100
                  ....*....|....*....|....*.
gi 1061899719 566 -KSFYFAAEHLDDMNRWLNRINMLTA 590
Cdd:pfam00169  80 kRTYLLQAESEEERKDWIKAIQSAIR 105
SAM_2 pfam07647
SAM domain (Sterile alpha motif);
11-73 3.79e-12

SAM domain (Sterile alpha motif);


Pssm-ID: 429573  Cd Length: 66  Bit Score: 61.90  E-value: 3.79e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899719  11 WSPSQVVDWMKGLDdcLQQYIKNFEREKISG-DQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:pfam07647   4 WSLESVADWLRSIG--LEQYTDNFRDQGITGaELLLRLTLEDLKRLGITSVGHRRKILKKIQEL 65
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
488-586 1.66e-11

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: 61.65  E-value: 1.66e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 488 DLGRGDC--EGWLwKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECR--KKYAFKACH- 562
Cdd:cd13308     3 LTLPRDVihSGTL-TKKGGSQKTLQNWQLRYVIIHQGCVYYYKNDQSAKPKGVFSLNGYNRRAAEERTskLKFVFKIIHl 81
                          90       100
                  ....*....|....*....|....*
gi 1061899719 563 -PKIKSFYFAAEHLDDMNRWLNRIN 586
Cdd:cd13308    82 sPDHRTWYFAAKSEDEMSEWMEYIR 106
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
496-586 2.63e-10

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd 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: 270108  Cd Length: 103  Bit Score: 57.86  E-value: 2.63e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDAKSYFSQK-WKKYWFVLKDASLYWYIN-EEDEKAEGFISLPEFK--IDRASecrKKYAFKACHPKiKSFYFA 571
Cdd:cd13296     3 GWLTKKGGGSSTLSRRnWKSRWFVLRDTVLKYYENdQEGEKLLGTIDIRSAKeiVDNDP---KENRLSITTEE-RTYHLV 78
                          90
                  ....*....|....*
gi 1061899719 572 AEHLDDMNRWLNRIN 586
Cdd:cd13296    79 AESPEDASQWVNVLT 93
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
495-588 3.20e-10

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 270086  Cd Length: 106  Bit Score: 57.92  E-value: 3.20e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKK----YAFKACHPKIKSFYF 570
Cdd:cd13266     4 AGYLEKRRKDHSFFGSEWQKRWCAISKNVFYYYGSDKDKQQKGEFAINGYDVRMNPTLRKDgkkdCCFELVCPDKRTYQF 83
                          90
                  ....*....|....*...
gi 1061899719 571 AAEHLDDMNRWLNRINML 588
Cdd:cd13266    84 TAASPEDAEDWVDQISFI 101
SAM_Ste50-like_fungal cd09533
SAM domain of Ste50_like (ubc2) subfamily; SAM (sterile alpha motif) domain of Ste50-like (or ...
15-70 3.51e-10

SAM domain of Ste50_like (ubc2) subfamily; SAM (sterile alpha motif) domain of Ste50-like (or Ubc2 for Ustilago bypass of cyclase) subfamily is a putative protein-protein interaction domain. This group includes only fungal proteins. Basidiomycetes have an N-terminal SAM domain, central UBQ domain, and C-terminal SH3 domain, while Ascomycetes lack the SH3 domain. Ubc2 of Ustilago maydis is a major virulence and maize pathogenicity factor. It is required for filamentous growth (the budding haploid form of Ustilago maydis is a saprophyte, while filamentous dikaryotic form is a pathogen). Also the Ubc2 protein is involved in the pheromone-responsive morphogenesis via the MAP kinase cascade. The SAM domain is necessary for ubc2 function; deletion of SAM eliminates this function. A Lys-to-Glu mutation in the SAM domain of ubc2 gene induces temperature sensitivity.


Pssm-ID: 188932  Cd Length: 58  Bit Score: 56.17  E-value: 3.51e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899719  15 QVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAV 70
Cdd:cd09533     1 DVADWLSSLG--LPQYEDQFIENGITGDVLVALDHEDLKEMGITSVGHRLTILKAV 54
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
492-586 6.66e-10

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 57.32  E-value: 6.66e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 492 GDCEGWLWKK-KDAKSyfsqkWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKKYAF-----------K 559
Cdd:cd01252     3 PDREGWLLKLgGRVKS-----WKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFelyspsngqviK 77
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1061899719 560 AChpKIKS----------FYF-AAEHLDDMNRWLNRIN 586
Cdd:cd01252    78 AC--KTDSdgkvvegnhtVYRiSAASEEERDEWIKSIK 113
SAM_Shank1,2,3 cd09506
SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 ...
7-69 1.63e-09

SAM domain of Shank1,2,3 family proteins; SAM (sterile alpha motif) domain of Shank1,2,3 family proteins is a protein-protein interaction domain. Shank1,2,3 proteins are scaffold proteins that are known to interact with a variety of cytoplasmic and membrane proteins. SAM domains of the Shank1,2,3 family are prone to homooligomerization. They are highly enriched in the postsynaptic density, acting as scaffolds to organize assembly of postsynaptic proteins. SAM domains of Shank3 proteins can form large sheets of helical fibers. Shank genes show distinct patterns of expression, in rat Shank1 mRNA is found almost exclusively in brain, Shank2 in brain, kidney and liver, and Shank3 in heart, brain and spleen.


Pssm-ID: 188905  Cd Length: 66  Bit Score: 54.63  E-value: 1.63e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899719   7 PVSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEA 69
Cdd:cd09506     1 PVHEWTVDDVGDWLESLN--LGEHRERFMDNEIDGSHLPNLDKEDLTELGVTRVGHRMNIERA 61
SAM_DGK-delta-eta cd09507
SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain ...
7-70 1.78e-09

SAM domain of diacylglycerol kinase delta and eta subunits; SAM (sterile alpha motif) domain of DGK-eta-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DGK proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers between the SAM domains of DGK delta and eta proteins. The oligomerization plays a role in the regulation of DGK intracellular localization.


Pssm-ID: 188906  Cd Length: 65  Bit Score: 54.34  E-value: 1.78e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899719   7 PVSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAV 70
Cdd:cd09507     1 PVTNWTTEEVGAWLESLQ--LGEYRDIFARNDIRGSELLHLERRDLKDLGITKVGHVKRILQAI 62
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
494-585 7.49e-09

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. 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: 270133  Cd Length: 112  Bit Score: 53.95  E-value: 7.49e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKDAKSYFSQKWKKYWFVLKDAS-------LYWYINEEDEKAEGFISLPEFKIDRAS------ECRKKYAFKA 560
Cdd:cd13324     3 YEGWLTKSPPEKKIWRAAWRRRWFVLRSGRlsggqdvLEYYTDDHCKKLKGIIDLDQCEQVDAGltfekkKFKNQFIFDI 82
                          90       100
                  ....*....|....*....|....*
gi 1061899719 561 CHPKiKSFYFAAEHLDDMNRWLNRI 585
Cdd:cd13324    83 RTPK-RTYYLVAETEEEMNKWVRCI 106
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
496-588 1.14e-08

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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: 270181  Cd Length: 106  Bit Score: 53.42  E-value: 1.14e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKKY----AFKACHPKIKSFYFA 571
Cdd:cd13381     5 GYLEKRRKDHSFFGFEWQKRWCALSNSVFYYYGSDKDKQQKGEFAIDGYDVKMNNTLRKDAkkdcCFEICAPDKRVYQFT 84
                          90
                  ....*....|....*..
gi 1061899719 572 AEHLDDMNRWLNRINML 588
Cdd:cd13381    85 AASPKEAEEWVQQIKFI 101
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
495-585 1.72e-08

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. 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: 241535  Cd Length: 115  Bit Score: 53.22  E-value: 1.72e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDAKSYFSQKWKKYWFVLKDAS------LYWYINEEDEKAEGFISLPE-------FKIDRASECRKKYAFKAC 561
Cdd:cd13384     6 EGWLTKSPPEKRIWRAKWRRRYFVLRQSEipgqyfLEYYTDRTCRKLKGSIDLDQceqvdagLTFETKNKLKDQHIFDIR 85
                          90       100
                  ....*....|....*....|....
gi 1061899719 562 HPKiKSFYFAAEHLDDMNRWLNRI 585
Cdd:cd13384    86 TPK-RTYYLVADTEDEMNKWVNCI 108
SAM_DGK-delta cd09575
SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-delta ...
7-70 2.42e-08

SAM domain of diacylglycerol kinase delta; SAM (sterile alpha motif) domain of DGK-delta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases with a SAM domain located at the C-terminus. DGK-delta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. In particular DGK-delta is involved in the regulation of clathrin-dependent endocytosis. The SAM domain of DGK-delta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-eta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it inhibits the translocation of the protein to the plasma membrane from the cytoplasm. The SAM domain also can bind Zn at multiple (not conserved) sites driving the formation of highly ordered large sheets of polymers, thus suggesting that Zn may play important role in the function of DCK-delta.


Pssm-ID: 188974  Cd Length: 65  Bit Score: 51.10  E-value: 2.42e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061899719   7 PVSKWSPSQVVDWMKGLddCLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAV 70
Cdd:cd09575     1 PVHLWGTEEVAAWLEHL--SLCEYKDIFTRHDVRGSELLHLERRDLKDLGVTKVGHMKRILCGI 62
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
496-585 4.30e-08

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: 51.26  E-value: 4.30e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDAKsyfsQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFK---IDRASECRKKYAFKACHPKIKSFYFAA 572
Cdd:cd13237     3 GYLQRRKKSK----KSWKRLWFVLKDKVLYTYKASEDVVALESVPLLGFTvvtIDESFEEDESLVFQLLHKGQLPIIFRA 78
                          90
                  ....*....|...
gi 1061899719 573 EHLDDMNRWLNRI 585
Cdd:cd13237    79 DDAETAQRWIEAL 91
SAM_DGK-eta cd09576
SAM domain of diacylglycerol kinase eta; SAM (sterile alpha motif) domain of DGK-eta subfamily ...
7-73 4.33e-08

SAM domain of diacylglycerol kinase eta; SAM (sterile alpha motif) domain of DGK-eta subfamily proteins is a protein-protein interaction domain. Proteins of this subfamily are multidomain diacylglycerol kinases. The SAM domain is located at the C-terminus of two out of three isoforms of DGK-eta protein. DGK-eta proteins participate in signal transduction. They regulate the level of second messengers such as diacylglycerol and phosphatidic acid. The SAM domain of DCK-eta proteins can form high molecular weight homooligomers through head-to-tail interactions as well as heterooligomers with the SAM domain of DGK-delta proteins. The oligomerization plays a role in the regulation of the DGK-delta intracellular localization: it is responsible for sustained endosomal localization of the protein and resulted in negative regulation of DCK-eta catalytic activity.


Pssm-ID: 188975  Cd Length: 65  Bit Score: 50.35  E-value: 4.33e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899719   7 PVSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:cd09576     1 PVQKWGTDEVAAWLDLLS--LGEYKEIFIRHDIRGSELLHLERRDLKDLGIPKVGHMKRILQGIKEL 65
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
493-582 4.93e-08

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single 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: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 51.85  E-value: 4.93e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 493 DCEGWLWKKKDA-KSYfsqkwKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDrASECRKKYAFKACH--PKIKSFY 569
Cdd:cd13288     9 DKEGYLWKKGERnTSY-----QKRWFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE-LAEDAEPYAFAIRFdgPGARSYV 82
                          90
                  ....*....|...
gi 1061899719 570 FAAEHLDDMNRWL 582
Cdd:cd13288    83 LAAENQEDMESWM 95
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
495-588 2.00e-07

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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: 270180  Cd Length: 106  Bit Score: 49.86  E-value: 2.00e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDAKSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRA----SECRKKYAFKACHPKIKSFYF 570
Cdd:cd13380     4 QGYLEKRSKDHSFFGSEWQKRWCVLTNRAFYYYASEKSKQPKGGFLIKGYSAQMAphlrKDSRRDSCFELTTPGRRTYQF 83
                          90
                  ....*....|....*...
gi 1061899719 571 AAEHLDDMNRWLNRINML 588
Cdd:cd13380    84 TAASPSEARDWVDQIQFL 101
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
496-600 2.70e-07

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. 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: 270075  Cd Length: 110  Bit Score: 49.72  E-value: 2.70e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDAKsyfsQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEfkIDRASEC---RKKYAFKACHPKiKSFYFAA 572
Cdd:cd13255    10 GYLEKKGERR----KTWKKRWFVLRPTKLAYYKNDKEYRLLRLIDLTD--IHTCTEVqlkKHDNTFGIVTPA-RTFYVQA 82
                          90       100
                  ....*....|....*....|....*...
gi 1061899719 573 EHLDDMNRWLNRINMLTAGYAERERIKQ 600
Cdd:cd13255    83 DSKAEMESWISAINLARQALRATITPNT 110
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
494-588 3.84e-07

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents 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: 270111  Cd Length: 102  Bit Score: 48.78  E-value: 3.84e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKdAKSYfsQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEF----KIDRASEcRKKYAFKACHPKiKSFY 569
Cdd:cd13299     8 EQGYLQVLK-KKGV--NQWKKYWLVLRNRSLSFYKDQSEYSPVKIIPIDDIidvvELDPLSK-SKKWCLQIITPE-KRIR 82
                          90
                  ....*....|....*....
gi 1061899719 570 FAAEHLDDMNRWLNRINML 588
Cdd:cd13299    83 FCADDEESLIKWLGALKSL 101
SAM_Neurabin-like cd09512
SAM domain of SAM_Neurabin-like subfamily; SAM (sterile alpha motif) domain of Neurabin-like ...
7-58 4.52e-07

SAM domain of SAM_Neurabin-like subfamily; SAM (sterile alpha motif) domain of Neurabin-like (Neural actin-binding) subfamily is a putative protein-protein interaction domain. This group currently includes the SAM domains of neurobin-I, SAMD14 and neurobin-I/SAMD14-like proteins. Most are multidomain proteins and in addition to SAM domain they contain other protein-binding domains such as PDZ and actin-binding domains. Members of this subfamily participate in signal transduction. Neurabin-I is involved in the regulation of Ca signaling intensity in alpha-adrenergic receptors; it forms a functional pair of opposing regulators with neurabin-II. Neurabins are expressed almost exclusively in neuronal cells. They are known to interact with protein phosphatase 1 and inhibit its activity; they also can bind actin filaments; however, the exact role of the SAM domain is unclear, since SAM doesn't participate in these interactions.


Pssm-ID: 188911  Cd Length: 70  Bit Score: 47.65  E-value: 4.52e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1061899719   7 PVSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVS 58
Cdd:cd09512     3 PVSEWSVQQVCQWLMGLG--LEQYIPEFTANNIDGQQLLQLDSSKLKALGIT 52
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
496-542 7.04e-07

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: 48.53  E-value: 7.04e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1061899719 496 GWLWKKKDaksyFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLP 542
Cdd:cd13263     7 GWLKKQGS----IVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLP 49
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
496-585 1.35e-06

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. 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: 241529  Cd Length: 116  Bit Score: 47.63  E-value: 1.35e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDaksyFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISL-----------PE------FKIDRASEcRKKYAF 558
Cdd:cd13378     7 GWLKKQRS----IMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLqgsqvnelppnPEepgkhlFEILPGGA-GDREKV 81
                          90       100
                  ....*....|....*....|....*..
gi 1061899719 559 KACHpkiKSFYFAAEHLDDMNRWLNRI 585
Cdd:cd13378    82 PMNH---EAFLLMANSQSDMEDWVKAI 105
SAM_TAL cd09523
SAM domain of TAL subfamily; SAM (sterile alpha motif) domain of TAL (Tsg101-associated ligase) ...
15-73 1.93e-06

SAM domain of TAL subfamily; SAM (sterile alpha motif) domain of TAL (Tsg101-associated ligase) proteins, also known as LRSAM1 (Leucine-rich repeat and sterile alpha motif-containing) proteins, is a putative protein-protein interaction domain. Proteins of this subfamily participate in the regulation of retrovirus budding and receptor endocytosis. They show E3 ubiquitin ligase activity. Human TAL protein interacts with Tsg101 and TAL's C-terminal ring finger domain is essential for the multiple monoubiquitylation of Tsg101.


Pssm-ID: 188922  Cd Length: 65  Bit Score: 45.74  E-value: 1.93e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719  15 QVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:cd09523     7 QLVNLLNELS--AEHYLPVFARHRITMETLSTMTDEDLKKIGIHEIGLRKEILRAAQEL 63
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
495-591 3.43e-06

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.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: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 47.22  E-value: 3.43e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDAKSYFSQK-WKKYWFVLKDASLYWYINEEDEKAE--GFISLPEFKI----DRASECRKKYAFKACHPKIKS 567
Cdd:cd01238     2 EGLLVKRSQGKKRFGPVnYKERWFVLTKSSLSYYEGDGEKRGKekGSIDLSKVRCveevKDEAFFERKYPFQVVYDDYTL 81
                          90       100
                  ....*....|....*....|....
gi 1061899719 568 FYFAAEHLDDmNRWLNRINMLTAG 591
Cdd:cd01238    82 YVFAPSEEDR-DEWIAALRKVCRN 104
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
495-585 3.51e-06

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. 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: 270095  Cd Length: 106  Bit Score: 46.16  E-value: 3.51e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDaksyFSQKWKKYWFVLKDASLYWYINEE---DEKAEGFISLPEFKIDRASE--CRKKYAFKACHPKiKSFY 569
Cdd:cd13276     2 AGWLEKQGE----FIKTWRRRWFVLKQGKLFWFKEPDvtpYSKPRGVIDLSKCLTVKSAEdaTNKENAFELSTPE-ETFY 76
                          90
                  ....*....|....*.
gi 1061899719 570 FAAEHLDDMNRWLNRI 585
Cdd:cd13276    77 FIADNEKEKEEWIGAI 92
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
511-582 4.02e-06

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: 45.75  E-value: 4.02e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061899719 511 KWKKYWFVLKDASLYWYINEED--EKAEGFISLPEF-KIDRASECRkkyAFKACHPKiKSFYFAAEHLDDMNRWL 582
Cdd:cd13282    14 TWKRRWFVLKNGELFYYKSPNDviRKPQGQIALDGScEIARAEGAQ---TFEIVTEK-RTYYLTADSENDLDEWI 84
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
496-590 5.86e-06

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: 45.66  E-value: 5.86e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDAksyfSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASE----CRKKYAFKACHPKiKSFYFA 571
Cdd:cd01233    10 GYLLFLEDA----TDGWVRRWVVLRRPYLHIYSSEKDGDERGVINLSTARVEYSPDqealLGRPNVFAVYTPT-NSYLLQ 84
                          90
                  ....*....|....*....
gi 1061899719 572 AEHLDDMNRWLNRINMLTA 590
Cdd:cd01233    85 ARSEKEMQDWLYAIDPLLA 103
SAM_tankyrase1,2 cd09524
SAM domain of tankyrase1,2 subfamily; SAM (sterile alpha motif) domain of Tankyrase1,2 ...
26-73 6.84e-06

SAM domain of tankyrase1,2 subfamily; SAM (sterile alpha motif) domain of Tankyrase1,2 subfamily is a protein-protein interaction domain. In addition to the SAM domain, proteins of this group have ankyrin repeats and a ADP- ribosyltransferase (poly-(ADP-ribose) synthase) domain. Tankyrases can polymerize through their SAM domains forming homoligomers and these complexes are disrupted by autoribosylation. Tankyrases apparently act as master scaffolding proteins and thus may interact simultaneously with multiple proteins, in particular with TRF1, NuMA, IRAP and Grb14 (ankyrin repeats are involved in these interactions). Tankyrases participate in a variety of cell signaling pathways as effector molecules. Their functions are different depending on the intracellular location: at telomeres they play a role in the regulation of telomere length via control of telomerase access to telomeres, at centrosomes they promote spindle assembly/disassembly, in Golgi vesicles they participate in the regulation of vesicle trafficking and Golgi dynamics. Tankyrase 1 may be of interest as new potential target for telomerase-directed cancer therapy.


Pssm-ID: 188923  Cd Length: 66  Bit Score: 44.24  E-value: 6.84e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1061899719  26 CLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:cd09524    16 GLEHLREIFEREQITLDVLAEMGHEELKEIGINAYGHRHKLIKGVERL 63
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
494-589 9.16e-06

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents 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: 270110  Cd Length: 106  Bit Score: 44.92  E-value: 9.16e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKDAKSyfsqKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEF-KIDRASECRKKYAFKACHPKiKSFYFAA 572
Cdd:cd13298     8 KSGYLLKRSRKTK----NWKKRWVVLRPCQLSYYKDEKEYKLRRVINLSELlAVAPLKDKKRKNVFGIYTPS-KNLHFRA 82
                          90
                  ....*....|....*..
gi 1061899719 573 EHLDDMNRWLNRINMLT 589
Cdd:cd13298    83 TSEKDANEWVEALREEF 99
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
495-586 9.44e-06

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: 44.90  E-value: 9.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKdakSYFSQKWKKYWFVLKDASLYWYI---NEEDEKAEGFISLPEFKIDRASECRkkYAFKACHPKiKSFYFA 571
Cdd:cd13250     2 EGYLFKRS---SNAFKTWKRRWFSLQNGQLYYQKrdkKDEPTVMVEDLRLCTVKPTEDSDRR--FCFEVISPT-KSYMLQ 75
                          90
                  ....*....|....*
gi 1061899719 572 AEHLDDMNRWLNRIN 586
Cdd:cd13250    76 AESEEDRQAWIQAIQ 90
PH_APBB1IP cd01259
Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin ...
495-591 1.06e-05

Amyloid beta (A4) Precursor protein-Binding, family B, member 1 Interacting Protein pleckstrin homology (PH) domain; APBB1IP consists of a Ras-associated (RA) domain, a PH domain, a family-specific BPS region, and a C-terminal SH2 domain. Grb7, Grb10 and Grb14 are paralogs that are also present in this hierarchy. These adapter proteins bind a variety of receptor tyrosine kinases, including the insulin and insulin-like growth factor-1 (IGF1) receptors. Grb10 and Grb14 are important tissue-specific negative regulators of insulin and IGF1 signaling based and may contribute to type 2 (non-insulin-dependent) diabetes in humans. RA-PH function as a single structural unit and is dimerized via a helical extension of the PH domain. The PH domain here are proposed to bind phosphoinositides non-cannonically ahd are unlikely to bind an activated GTPase. The tandem RA-PH domains are present in a second adapter-protein family, MRL proteins, Caenorhabditis elegans protein MIG-1012, the mammalian proteins RIAM and lamellipodin and the Drosophila melanogaster protein Pico12, all of which are Ena/VASP-binding proteins involved in actin-cytoskeleton rearrangement. 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: 269961  Cd Length: 124  Bit Score: 45.31  E-value: 1.06e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDAKsyfsQKWKKYWFVLKDASLYWYINEEDEKAEG---FISLPEFKIDRASECRKKY--------AFKacHP 563
Cdd:cd01259     9 EGFLYLKEDGK----KSWKKRYFVLRASGLYYSPKGKSKESRDlqcLAQFDDYNVYTGLNGKKKYkaptdfgfCLK--PN 82
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1061899719 564 KIKSF------YFAAEHLDDMNRWLNRINMLTAG 591
Cdd:cd01259    83 KQQEKgskdikYLCAEDEQSRTCWLTAIRLAKYG 116
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
494-582 1.45e-05

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. 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: 270099  Cd Length: 139  Bit Score: 45.39  E-value: 1.45e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKkdAKSYFSQKWKKYWFVLKDASLYWYinEEDEKAE------------GFISLPEFKIDRASECRKKYAFKAC 561
Cdd:cd13281    14 LHGILWKK--PFGHQSAKWSKRFFIIKEGFLLYY--SESEKKDfektrhfnihpkGVIPLGGCSIEAVEDPGKPYAISIS 89
                          90       100
                  ....*....|....*....|..
gi 1061899719 562 HPKIKSFYF-AAEHLDDMNRWL 582
Cdd:cd13281    90 HSDFKGNIIlAADSEFEQEKWL 111
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
496-553 1.48e-05

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. 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: 270085  Cd Length: 108  Bit Score: 44.60  E-value: 1.48e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1061899719 496 GWLWKKkdakSYFSQKWKKYWFVLK-DASLYWYINEEDEKAEGFISLPE--FKIDRASECR 553
Cdd:cd13265     7 GWLLRQ----STILKRWKKNWFVLYgDGNLVYYEDETRREVEGRINMPRecRNIRVGLECR 63
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
495-586 1.56e-05

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: 44.24  E-value: 1.56e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKkdakSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPE-FKIDRASECRKKYAFKACHPKiKSFYFAAE 573
Cdd:cd10573     6 EGYLTKL----GGIVKNWKTRWFVLRRNELKYFKTRGDTKPIRVLDLREcSSVQRDYSQGKVNCFCLVFPE-RTFYMYAN 80
                          90
                  ....*....|...
gi 1061899719 574 HLDDMNRWLNRIN 586
Cdd:cd10573    81 TEEEADEWVKLLK 93
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
495-586 1.76e-05

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain 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: 270113  Cd Length: 108  Bit Score: 44.29  E-value: 1.76e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKkdakSYFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIdrASEC----RKKYAFKACHPKIKSFYF 570
Cdd:cd13301     6 EGYLVKK----GHVVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTI--TSPCleygKRPLVFKLTTAKGQEHFF 79
                          90
                  ....*....|....*.
gi 1061899719 571 AAEHLDDMNRWLNRIN 586
Cdd:cd13301    80 QACSREERDAWAKDIT 95
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
495-586 2.17e-05

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. 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: 269941  Cd Length: 106  Bit Score: 44.24  E-value: 2.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKkdakSYFSQKWKKYWFVLkDAS---LYWYINEEDEKAEGFISLPEfkIDRASECR----------KKYAFKAC 561
Cdd:cd01235     6 EGYLYKR----GALLKGWKQRWFVL-DSTkhqLRYYESREDTKCKGFIDLAE--VESVTPATpiigapkradEGAFFDLK 78
                          90       100
                  ....*....|....*....|....*
gi 1061899719 562 HPKiKSFYFAAEHLDDMNRWLNRIN 586
Cdd:cd01235    79 TNK-RVYNFCAFDAESAQQWIEKIQ 102
SAM_BOI-like_fungal cd09535
SAM domain of BOI-like fungal subfamily; SAM (sterile alpha motif) domain of BOI-like fungal ...
11-61 2.23e-05

SAM domain of BOI-like fungal subfamily; SAM (sterile alpha motif) domain of BOI-like fungal subfamily is a potential protein-protein interaction domain. Proteins of this subfamily are apparently scaffold proteins, since most contain SH3 and PH domains, which are also protein-protein interaction domains, in addition to SAM domain. BOI-like proteins participate in cell cycle regulation. In particular BOI1 and BOI2 proteins of budding yeast S.cerevisiae are involved in bud formation, and POB1 protein of fission yeast S.pombe plays a role in cell elongation and separation. Among binding partners of BOI-like fungal subfamily members are such proteins as Bem1 and Cdc42 (they are known to be involved in cell polarization and bud formation).


Pssm-ID: 188934  Cd Length: 65  Bit Score: 42.93  E-value: 2.23e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1061899719  11 WSPSQVVDWM--KGLDDclqQYIKNFEREKISGDQLLRITHQELEDLGVSRIG 61
Cdd:cd09535     3 WSPEQVAEWLlsAGFDD---SVCEKFRENEITGDILLELDLEDLKELDIGSFG 52
SAM_caskin1,2_repeat2 cd09498
SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 ...
13-70 2.93e-05

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.


Pssm-ID: 188897  Cd Length: 71  Bit Score: 42.67  E-value: 2.93e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719  13 PSQVVDWMKGLDdcLQQYIKNFEREKI-SGDQLLRITHQELEDLGVSRIGHQELILEAV 70
Cdd:cd09498     7 PNDLLEWLSLLG--LPQYHKVLVENGYdSIDFVTDLTWEDLQDIGITKLGHQKKLMLAI 63
PDZ_signaling cd00992
PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. ...
222-270 3.03e-05

PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of PDZ domains an N-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in proteases.


Pssm-ID: 238492 [Multi-domain]  Cd Length: 82  Bit Score: 42.94  E-value: 3.03e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1061899719 222 KPSEGLGMYIKS--TYDGLHVITGTTENSPADRCKkIHAGDEVIQVNHQTV 270
Cdd:cd00992     9 DPGGGLGFSLRGgkDSGGGIFVSRVEPGGPAERGG-LRVGDRILEVNGVSV 58
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
494-585 3.73e-05

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. 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: 241297  Cd Length: 123  Bit Score: 43.78  E-value: 3.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 494 CEGWLWKKKDAKSYFSQKWKKYWFVLKDAS-------LYWYINEEDEKAEGFISLPEF-KIDRASECRKKYAFKACHPKI 565
Cdd:cd01266     6 CSGWLRKSPPEKKLRRYAWKKRWFVLRSGRlsgdpdvLEYYKNDHAKKPIRVIDLNLCeQVDAGLTFNKKELENSYIFDI 85
                          90       100
                  ....*....|....*....|....
gi 1061899719 566 KS----FYFAAEHLDDMNRWLNRI 585
Cdd:cd01266    86 KTidriFYLVAETEEDMNKWVRNI 109
PH2_FARP1-like cd13235
FERM, RhoGEF and pleckstrin domain-containing protein 1 and related proteins Pleckstrin ...
509-589 4.32e-05

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: 43.08  E-value: 4.32e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 509 SQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASE---CRKKYAFKaCHPKIKSFYFAAEHLDDMNRWLNRI 585
Cdd:cd13235    16 SNGWQKLWVVFTNFCLFFYKSHQDEFPLASLPLLGYSVGLPSEadnIDKDYVFK-LQFKSHVYFFRAESEYTFERWMEVI 94

                  ....
gi 1061899719 586 NMLT 589
Cdd:cd13235    95 RSAT 98
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
496-585 4.51e-05

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) 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. 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: 241530  Cd Length: 114  Bit Score: 43.42  E-value: 4.51e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 496 GWLWKKKDaksyFSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDR---ASECRKKYAFK-----------AC 561
Cdd:cd13379     7 GWLRKQGG----FVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEhpcNEEEPGKFLFEvvpggdrermtAN 82
                          90       100
                  ....*....|....*....|....
gi 1061899719 562 HpkiKSFYFAAEHLDDMNRWLNRI 585
Cdd:cd13379    83 H---ETYLLMASTQNDMEDWVKSI 103
PH_ARHGAP21-like cd01253
ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho ...
495-585 4.72e-05

ARHGAP21 and related proteins pleckstrin homology (PH) domain; ARHGAP family genes encode Rho/Rac/Cdc42-like GTPase activating proteins with a RhoGAP domain. These proteins functions as a GTPase-activating protein (GAP) for RHOA and CDC42. ARHGAP21 controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. It is recruited to the Golgi by to GTPase, ARF1, through its PH domain and its helical motif. It is also required for CTNNA1 recruitment to adherens junctions. ARHGAP21 and it related proteins all contains a PH domain and a RhoGAP domain. Some of the members have additional N-terminal domains including PDZ, SH3, and SPEC. The ARHGAP21 PH domain interacts with the GTPbound forms of both ARF1 and ARF6 ARF-binding domain/ArfBD. The members here include: ARHGAP15, ARHGAP21, and ARHGAP23. 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: 269955  Cd Length: 113  Bit Score: 43.13  E-value: 4.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDA----KSYFSQKWKKYWFVLKDASLYWYiNEEDE---------KAEGFISLPEFKIDRA-SECRKKYAFKA 560
Cdd:cd01253     3 EGWLHYKQIVtdkgKRVSDRSWKQAWAVLRGHSLYLY-KDKREqtpalsielGSEQRISIRGCIVDIAySYTKRKHVFRL 81
                          90       100
                  ....*....|....*....|....*
gi 1061899719 561 CHPKIKSFYFAAEHLDDMNRWLNRI 585
Cdd:cd01253    82 TTSDFSEYLFQAEDRDDMLGWIKAI 106
SAM_Ste11_fungal cd09534
SAM domain of Ste11_fungal subfamily; SAM (sterile alpha motif) domain of Ste11 subfamily is a ...
11-73 6.53e-05

SAM domain of Ste11_fungal subfamily; SAM (sterile alpha motif) domain of Ste11 subfamily is a protein-protein interaction domain. Proteins of this subfamily have SAM domain at the N-terminus and protein kinase domain at the C-terminus. They participate in regulation of mating pheromone response, invasive growth and high osmolarity growth response. MAP triple kinase Ste11 from S.cerevisia is known to interact with Ste20 kinase and Ste50 regulator. These kinases are able to form homodimers interacting through their SAM domains as well as heterodimers or heterogenous complexes when either SAM domain of monomeric or homodimeric form of Ste11 interacts with Ste50 regulator.


Pssm-ID: 188933  Cd Length: 62  Bit Score: 41.43  E-value: 6.53e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899719  11 WSPSQVVDWMKGLDdClQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:cd09534     1 WDEEFVEEWLNELN-C-GQYLDIFEKNLITGDLLLELDKEALKELGITKVGDRIRLLRAIKSL 61
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
512-583 7.69e-05

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: 42.31  E-value: 7.69e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899719 512 WKKYWFVLKDAS--LYWYINEEDEKAEGFISLPE--FKIDrasECRKKYAFKaCHPKIKSFYFAAEHLDDMNRWLN 583
Cdd:cd01265    19 WKRRWFVLDESKcqLYYYRSPQDATPLGSIDLSGaaFSYD---PEAEPGQFE-IHTPGRVHILKASTRQAMLYWLQ 90
SAM_HD cd09508
SAM domain of HD-phosphohydrolase; SAM (sterile alpha motif) domain of SAM_HD subfamily ...
11-74 7.75e-05

SAM domain of HD-phosphohydrolase; SAM (sterile alpha motif) domain of SAM_HD subfamily proteins is a putative protein-protein interaction domain. Proteins of this group, additionally to the SAM domain, contain a HD hydrolase domain. Human SAM-HD1 is a nuclear protein involved in innate immune response and may act as a negative regulator of the cell-intrinsic antiviral response. Mutations in this gene lead to Aicardi-Goutieres syndrome (symptoms include cerebral atrophy, leukoencephalopathy, hepatosplenomegaly, and increased production of alpha-interferon).


Pssm-ID: 188907  Cd Length: 70  Bit Score: 41.53  E-value: 7.75e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061899719  11 WSPSQVVDWM--KGLDDclQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELILEAVDLLC 74
Cdd:cd09508     5 WDPEDVCQFLrgNGFGE--PELLEIFRENEITGAHLPDLTESRLEKLGVSSLGERLKLLKCLQKLS 68
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
495-581 8.58e-05

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. 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: 270073  Cd Length: 94  Bit Score: 41.99  E-value: 8.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWKKKDAKSyfSQKWKKYWFVLKDASLYWYINEEDEKAEGFISLPEFKIDRASECRKkyaFKAcHPKIKSFYFAAEH 574
Cdd:cd13253     3 SGYLDKQGGQGN--NKGFQKRWVVFDGLSLRYFDSEKDAYSKRIIPLSAISTVRAVGDNK---FEL-VTTNRTFVFRAES 76

                  ....*..
gi 1061899719 575 LDDMNRW 581
Cdd:cd13253    77 DDERNLW 83
SAM_EPH-R cd09488
SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH ...
12-73 1.38e-04

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.


Pssm-ID: 188887  Cd Length: 61  Bit Score: 40.29  E-value: 1.38e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061899719  12 SPSQVVDWMKGLDdcLQQYIKNFEREKISG-DQLLRITHQELEDLGVSRIGHQELILEAVDLL 73
Cdd:cd09488     1 AFRSVGEWLESIK--MGRYKENFTAAGYTSlDAVAQMTAEDLTRLGVTLVGHQKKILNSIQAL 61
SAM_aveugle-like cd09510
SAM domain of aveugle-like subfamily; SAM (sterile alpha motif) domain of SAM_aveugle-like ...
7-67 1.51e-04

SAM domain of aveugle-like subfamily; SAM (sterile alpha motif) domain of SAM_aveugle-like subfamily is a protein-protein interaction domain. In Drosophila, the aveugle (AVE) protein (also known as HYP (Hyphen)) is involved in normal photoreceptor differentiation, and required for epidermal growth factor receptor (EGFR) signaling between ras and raf genes during eye development and wing vein formation. SAM domain of the HYP(AVE) protein interacts with SAM domain of CNK, the multidomain scaffold protein connector enhancer of kinase suppressor of ras. CNK/HYP(AVE) complex interacts with KSR (kinase suppressor of Ras) protein. This interaction leads to stimulation of Ras-dependent Raf activation. This subfamily also includes vertebrate AVE homologs - Samd10 and Samd12 proteins. Their exact function is unknown, but they may play a role in signal transduction during embryogenesis.


Pssm-ID: 188909  Cd Length: 75  Bit Score: 40.75  E-value: 1.51e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899719   7 PVSKWSPSQVVDWMK-GLDDCLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGHQELIL 67
Cdd:cd09510     2 PVYLWSVQDVCKWLKrHCPDYYLLYAELFLQHDITGRALLRLNDNKLERMGITDEDHRQDIL 63
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
496-536 1.86e-04

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. 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: 270094  Cd Length: 104  Bit Score: 41.16  E-value: 1.86e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1061899719 496 GWLWKKkdakSYFSQKWKKYWFVLKDASLYWYineEDEKAE 536
Cdd:cd13275     3 GWLMKQ----GSRQGEWSKHWFVLRGAALKYY---RDPSAE 36
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
512-582 2.83e-04

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: 40.80  E-value: 2.83e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061899719 512 WKKYWFVLKDAS---LYWYINEEDEKAEGFISLPEFKI---DRASECRKKYAFKACHPKiKSFYFAAEHLDDMNRWL 582
Cdd:cd13236    23 WQKVWCVIPRTEplvLYLYGAPQDVRAQRTIPLPGCEVtvpPPEERLDGRHVFKLSQSK-QSHYFSAESEELQQRWL 98
PDZ_CTP_protease cd00988
PDZ domain of C-terminal processing-, tail-specific-, and tricorn proteases, which function in ...
225-270 3.26e-04

PDZ domain of C-terminal processing-, tail-specific-, and tricorn proteases, which function in posttranslational protein processing, maturation, and disassembly or degradation, in Bacteria, Archaea, and plant chloroplasts. May be responsible for substrate recognition and/or binding, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. In this subfamily of protease-associated PDZ domains a C-terminal beta-strand forms the peptide-binding groove base, a circular permutation with respect to PDZ domains found in Eumetazoan signaling proteins.


Pssm-ID: 238488 [Multi-domain]  Cd Length: 85  Bit Score: 39.90  E-value: 3.26e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1061899719 225 EGLGMYIKSTYDGLhVITGTTENSPADRcKKIHAGDEVIQVNHQTV 270
Cdd:cd00988     2 GGIGLELKYDDGGL-VITSVLPGSPAAK-AGIKAGDIIVAIDGEPV 45
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
495-527 3.34e-04

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but 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: 275402  Cd Length: 116  Bit Score: 41.07  E-value: 3.34e-04
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1061899719 495 EGWLWKKkdakSYFSQKWKKYWFVLKDASLYWY 527
Cdd:cd13215    24 SGYLSKR----SKRTLRYTRYWFVLKGDTLSWY 52
PDZ smart00228
Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF ...
214-270 5.32e-04

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.


Pssm-ID: 214570 [Multi-domain]  Cd Length: 85  Bit Score: 39.67  E-value: 5.32e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1061899719  214 EVIQLANIKPSEGLGMYIKSTYDGLH--VITGTTENSPADRCKkIHAGDEVIQVNHQTV 270
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDEGGgvVVSSVVPGSPAAKAG-LRVGDVILEVNGTSV 58
SAM_SARM1-like_repeat1 cd09501
SAM domain ot SARM1-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of ...
8-58 6.18e-04

SAM domain ot SARM1-like proteins, repeat 1; SAM (sterile alpha motif) domain repeat 1 of SARM1-like adaptor proteins is a protein-protein interaction domain. SARM1-like proteins contain two tandem SAM domains. SARM1-like proteins are involved in TLR (Toll-like receptor) signaling. They are responsible for targeted localization of the whole protein to post-synaptic regions of axons. In humans SARM1 expression is detected in kidney and liver.


Pssm-ID: 188900  Cd Length: 69  Bit Score: 38.82  E-value: 6.18e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1061899719   8 VSKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELE-DLGVS 58
Cdd:cd09501     1 VPLWSVADVQTWLKQIG--FEDYAEKFSESQVDGDLLLQLTEDELKqDLGMS 50
SAM_liprin-beta1,2_repeat1 cd09563
SAM domain of liprin-beta1,2 proteins repeat 1; SAM (sterile alpha motif) domain repeat 1 of ...
9-56 7.77e-04

SAM domain of liprin-beta1,2 proteins repeat 1; SAM (sterile alpha motif) domain repeat 1 of liprin-beta1,2 proteins is a protein-protein interaction domain. Liprin-beta protein contain three copies (repeats) of SAM domain. They may form heterodimers with liprins-alpha through their SAM domains. It was suggested based on bioinformatic approaches that the second SAM domain of liprin-beta is potentially able to form polymers. Liprins were originally identified as LAR (leukocyte common antigen-related) transmembrane protein-tyrosine phosphatase-interacting proteins. They participate in mammary gland development, in axon guidance, and in the maintenance of lymphatic vessel integrity.


Pssm-ID: 188962  Cd Length: 64  Bit Score: 38.36  E-value: 7.77e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1061899719   9 SKWSPSQVVDWMKGLDdcLQQYIKNFEREKISGDQLLRITHQELE-DLG 56
Cdd:cd09563     2 AEWSTEQVCDWLAELG--LGQYVDECRRWVKSGQTLLKASPQELEkELG 48
SAM_AIDA1AB-like_repeat2 cd09500
SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of ...
12-71 8.18e-04

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.


Pssm-ID: 188899  Cd Length: 65  Bit Score: 38.44  E-value: 8.18e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899719  12 SPSQVVDWMKGLddCLQQYIKNFEREKI-SGDQLLRITHQELED-LGVSRIGHQELILEAVD 71
Cdd:cd09500     4 SPASVSEWLDSI--GLGDYIETFLKHGYtSMERVKRIWEVELTNvLEINKLGHRKRILASLA 63
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
495-586 9.21e-04

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain 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: 241282  Cd Length: 105  Bit Score: 39.49  E-value: 9.21e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWK----KKDAksyfsqkWKKYWFVLKDASLYWYINEED--EKAEGFISLPE--FKID----RASECRKKYAFKACH 562
Cdd:cd01251     5 EGYLEKtgpkQTDG-------FRKRWFTLDDRRLMYFKDPLDafPKGEIFIGSKEegYSVReglpPGIKGHWGFGFTLVT 77
                          90       100
                  ....*....|....*....|....
gi 1061899719 563 PKiKSFYFAAEHLDDMNRWLNRIN 586
Cdd:cd01251    78 PD-RTFLLSAETEEERREWITAIQ 100
SAM_STIM-1,2-like cd09504
SAM domain of STIM-1,2-like proteins; SAM (sterile alpha motif) domain of STIM-1,2-like ...
7-71 9.75e-04

SAM domain of STIM-1,2-like proteins; SAM (sterile alpha motif) domain of STIM-1,2-like (Stromal interaction molecule) proteins is a putative protein-protein interaction domain. STIM1 and STIM2 human proteins are type I transmembrane proteins. The N-terminal part of them includes "hidden" EF-hand and SAM domains. This region is responsible for sensing changes in store-operated and basal cytoplasmic Ca2+ levels and initiates oligomerization. "Hidden" EF hand and SAM domains have a stable intramolecular association, and the SAM domain is a component that regulates stability within STIM proteins. Destabilization of the EF-SAM association during Ca2+ depletion leads to partial unfolding and aggregation (homooligomerization), thus activating the store-operated Ca2+ entry. Immunoprecipitation analysis indicates that STIM1 and STIM2 can form co-precipitable oligomeric associations in vivo. It was suggested that STIM1 and STIM2 are involved in opposite regulation of store operated channels in plasma membrane.


Pssm-ID: 188903  Cd Length: 74  Bit Score: 38.47  E-value: 9.75e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1061899719   7 PVSKWSPSQVVDWmkgLDDC--LQQYIKNFEREKISGDQLLRITHQELE----DLGV-SRIGHQELILEAVD 71
Cdd:cd09504     1 EVHNWTVEDTVEW---LVNSveLPQYVEAFKENGVDGSALPRLAVNNPSfltsVLGIkDPIHRQKLSLKAMD 69
SAM_Polycomb cd09509
SAM domain of Polycomb group; SAM (sterile alpha motif) domain of Polycomb group is a ...
8-55 9.98e-04

SAM domain of Polycomb group; SAM (sterile alpha motif) domain of Polycomb group is a protein-protein interaction domain. The Polycomb group includes transcriptional repressors which are involved in the regulation of some key regulatory genes during development in many organisms. They are best known for silencing Hox (Homeobox) genes. Polycomb proteins work together in large multimeric and chromatin-associated complexes. They organize chromatin of the target genes and maintain repressed states during many cell divisions. Polycomb proteins are classified based on their common function, but not on conserved domains and/or motifs; however many Polycomb proteins (members of PRC1 class complex) contain SAM domains which are more similar to each other inside of the Polycomb group than to SAM domains outside of it. Most information about structure and function of Polycomb SAM domains comes from studies of Ph (Polyhomeotic) and Scm (Sex comb on midleg) proteins. Polycomb SAM domains usually can be found at the C-terminus of the proteins. Some members of this group contain, in addition to the SAM domain, MTB repeats, Zn finger, and/or DUF3588 domains. Polycomb SAM domains can form homo- and/or heterooligomers through ML and EH surfaces. SAM/SAM oligomers apparently play a role in transcriptional repression through polymerization along the chromosome. Polycomb proteins are known to be highly expressed in some cells years before their cancer pathology; thus they are attractive markers for early cancer therapy.


Pssm-ID: 188908  Cd Length: 64  Bit Score: 38.23  E-value: 9.98e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1061899719   8 VSKWSPSQVVDWMKGLDDClQQYIKNFEREKISGDQLLRIThqeLEDL 55
Cdd:cd09509     1 PSKWSVDDVAQFIKSLDGC-AEYAEVFREQEIDGQALLLLT---EDDL 44
SAM_BAR cd09513
SAM domain of BAR subfamily; SAM (sterile alpha motif) domain of BAR (Bifunctional Apoptosis ...
8-53 1.11e-03

SAM domain of BAR subfamily; SAM (sterile alpha motif) domain of BAR (Bifunctional Apoptosis Regulator) subfamily is a protein-protein interaction domain. In addition to the SAM domain, this type of regulator has a RING finger domain. Proteins of this subfamily are involved in the apoptosis signal network. Their overexpression in human neuronal cells significantly protects cells from a broad range of cell death stimuli. SAM domain can interact with Caspase8, Bcl-2 and Bcl-X resulting in suppression of Bax-induced cell death.


Pssm-ID: 188912  Cd Length: 71  Bit Score: 38.24  E-value: 1.11e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1061899719   8 VSKWSPSQVVDWMKGLDDCLQQYIKNFEREKISGDQLLRITHQELE 53
Cdd:cd09513     1 VSKWTPEEVVLWLEQLGPWASLYRERFLSENVNGRLLLTLTEEELS 46
PDZ cd00136
PDZ domain, also called DHR (Dlg homologous region) or GLGF (after a conserved sequence motif). ...
226-270 1.26e-03

PDZ domain, also called DHR (Dlg homologous region) or GLGF (after a conserved sequence motif). Many PDZ domains bind C-terminal polypeptides, though binding to internal (non-C-terminal) polypeptides and even to lipids has been demonstrated. Heterodimerization through PDZ-PDZ domain interactions adds to the domain's versatility, and PDZ domain-mediated interactions may be modulated dynamically through target phosphorylation. Some PDZ domains play a role in scaffolding supramolecular complexes. PDZ domains are found in diverse signaling proteins in bacteria, archebacteria, and eurkayotes. This CD contains two distinct structural subgroups with either a N- or C-terminal beta-strand forming the peptide-binding groove base. The circular permutation placing the strand on the N-terminus appears to be found in Eumetazoa only, while the C-terminal variant is found in all three kingdoms of life, and seems to co-occur with protease domains. PDZ domains have been named after PSD95(post synaptic density protein), DlgA (Drosophila disc large tumor suppressor), and ZO1, a mammalian tight junction protein.


Pssm-ID: 238080 [Multi-domain]  Cd Length: 70  Bit Score: 38.06  E-value: 1.26e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1061899719 226 GLGMYIKSTYDGLHVITGTTENSPADRCKkIHAGDEVIQVNHQTV 270
Cdd:cd00136     2 GLGFSIRGGTEGGVVVLSVEPGSPAERAG-LQAGDVILAVNGTDV 45
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
495-612 1.69e-03

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. 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: 270087  Cd Length: 126  Bit Score: 39.23  E-value: 1.69e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 495 EGWLWK-----KKDAKSYFSQKWKKYWFVLK---DAS--LYWYINEEDEKAEGFISLPEFKIDRASECRKKYAFKACHPK 564
Cdd:cd13267     9 EGYLYKgpensSDSFISLAMKSFKRRFFHLKqlvDGSyiLEFYKDEKKKEAKGTIFLDSCTGVVQNSKRRKFCFELRMQD 88
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1061899719 565 IKSFYFAAEHLDDMNRWLNRINMLtagyaererIKQEQDyWSESDKEE 612
Cdd:cd13267    89 KKSYVLAAESEAEMDEWISKLNKI---------LQSSKE-QSIQKKRS 126
SAM_MLTK cd09529
SAM domain of MLTK subfamily; SAM (sterile alpha motif) domain of MLTK subfamily is a ...
11-62 1.85e-03

SAM domain of MLTK subfamily; SAM (sterile alpha motif) domain of MLTK subfamily is a protein-protein interaction domain. Besides SAM domain, these proteins have N-terminal protein tyrosine kinase domain and leucine-zipper motif. Proteins of this group act as mitogen-activated protein triple kinase in a number of MAPK cascades. They can be activated by autophosphorylation in response to stress signals. MLTK-alpha is known to phosphorylate histone H3. In mammals, MLTKs participate in the activation of the JNK/SAPK, p38, ERK5 pathways, the transcriptional factor NF-kB, in the regulation of the cell cycle checkpoint, and in the induction of apoptosis in a hepatoma cell line. Some members of this subfamily are proto-oncogenes, thus MLTK-alpha is involved in neoplasmic cell transformation and/or skin cancer development in athymic nude mice. Based on in vivo coprecipitation experiments in mammalian cells, it has been demonstrated that MLTK proteins might form homodimers/oligomers via their SAM domains.


Pssm-ID: 188928  Cd Length: 71  Bit Score: 37.49  E-value: 1.85e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1061899719  11 WSPSQVVDWMK------GLDDCLQQYIKNFEREKISGDQLLRITHQELEDLGVSRIGH 62
Cdd:cd09529     2 WTEEDVHFWMQqlvrkgGHPSELSQYADLFKENHITGKRLLLLTEEDLRDMGIGSKGH 59
PH_dynamin cd01256
Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle ...
513-595 2.69e-03

Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle formation. It has an N-terminal GTPase domain, followed by a PH domain, a GTPase effector domain and a C-terminal proline arginine rich domain. Dynamin-like proteins, which are found in metazoa, plants and yeast have the same domain architecture as dynamin, but lack the 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: 269958  Cd Length: 112  Bit Score: 38.07  E-value: 2.69e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 513 KKYWFVLKDASLYWYINEEDEKAEGFISLPEFKI-DRASECR-KKYAFKACHPKIKSFY-------FAAEHLDDMNRWln 583
Cdd:cd01256    22 KEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLrDVEKGFMsRKHIFALFNTDQRNVYkdykqleLSCETQEEVDSW-- 99
                          90
                  ....*....|...
gi 1061899719 584 RINMLTAG-YAER 595
Cdd:cd01256   100 KASFLRAGvYPEK 112
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
505-582 4.57e-03

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: 37.24  E-value: 4.57e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 505 KSYFSQKWKKYWFVLK-DASLYWYINEEDEKAEGFISLPEFKI---------DRASECRKKYAFKACHPKiKSFYFAAEH 574
Cdd:cd13238     8 KTNGRKTWSRRWFALQpDFVLYSYKSQEDKLPLTATPVPGFLVtllekgsavDPLNDPKRPRTFKMFHVK-KSYYFQAND 86

                  ....*...
gi 1061899719 575 LDDMNRWL 582
Cdd:cd13238    87 GDEQKKWV 94
PH_beta_spectrin cd10571
Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a ...
512-586 5.31e-03

Beta-spectrin pleckstrin homology (PH) domain; Beta spectrin binds actin and functions as a major component of the cytoskeleton underlying cellular membranes. Beta spectrin consists of multiple spectrin repeats followed by a PH domain, which binds to inositol-1,4,5-trisphosphate. The PH domain of beta-spectrin is thought to play a role in the association of spectrin with the plasma membrane of cells. 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: 269975  Cd Length: 106  Bit Score: 37.21  E-value: 5.31e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 512 WKKYWFVLKDASLYWYINEEDEK------AEGFISLPEFKIDRASECRK-KYAFKACHPKIKSFYFAAEHLDDMNRWLNR 584
Cdd:cd10571    23 WKNVYTVLRGQELSFYKDQKAAKsgityaAEPPLNLYNAVCEVASDYTKkKHVFRLKLSDGAEFLFQAKDEEEMNQWVKK 102

                  ..
gi 1061899719 585 IN 586
Cdd:cd10571   103 IS 104
SAM_kazrin_repeat2 cd09567
SAM domain of kazrin proteins repeat 2; SAM (sterile alpha motif) domain repeat 2 of kazrin ...
27-73 5.83e-03

SAM domain of kazrin proteins repeat 2; SAM (sterile alpha motif) domain repeat 2 of kazrin proteins is a protein-protein interaction domain. The long isoform of kazrins contains three copies (repeats) of SAM domain. Kazrin can interact with periplakin. It is involved in interplay between desmosomes and in adheren junctions. Additionally kazrins play a role in regulation of intercellular differentiation, junction assembly, and cytoskeletal organization.


Pssm-ID: 188966  Cd Length: 65  Bit Score: 35.85  E-value: 5.83e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1061899719  27 LQQYIKNFEREKISGDQLLRITHQELED-LGVSRIGHQELILEAVDLL 73
Cdd:cd09567    17 LPQYSEAFREHLVDGRVLDTLSRKDLEKhLGVSKKFHQASLLRGIELL 64
PH_Gab3 cd13385
Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes ...
490-588 7.34e-03

Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1, Gab2, and Gab3 proteins. 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: 270184  Cd Length: 125  Bit Score: 37.26  E-value: 7.34e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061899719 490 GRGDCEGWLWKKKDAKSYFSQKWKKYWFVLKDAS-------LYWYINEEDEKAEGFISLPEFKIDRAS-------ECRKK 555
Cdd:cd13385     4 GDVVCTGWLIKSPPERKLKRYAWRKRWFVLRRGRmsgnpdvLEYYRNNHSKKPIRVIDLSECEVLKHSgpnfirkEFQNN 83
                          90       100       110
                  ....*....|....*....|....*....|...
gi 1061899719 556 YAFkACHPKIKSFYFAAEHLDDMNRWLNRINML 588
Cdd:cd13385    84 FVF-IVKTTYRTFYLVAKTEEEMQVWVHNISQI 115
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
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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