Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306 408 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 486
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 694948306 487 LLVHCPSPTDRAQWLEKTQQ 506
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306 408 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 486
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 694948306 487 LLVHCPSPTDRAQWLEKTQQ 506
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306   165 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 243
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306   244 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 323
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                          170       180
                   ....*....|....*....|....*....
gi 694948306   324 LKRSPEA-RAQEALNAMIEAVESFLRHIN 351
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  120 RLPPEDRRHWEIG---EGGDSGLTIE-----KSWRELVPghKEMSRELCHQ----QEALWELLTTELIYVRKLKIMTDLL 187
Cdd:COG5422   433 RLEQQARLHLKLMgglKRNSSLALDKfdeekNLWTLSVP--KEVWESLPKQeikrQEAIYEVIYTERDFVKDLEYLRDTW 510

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  188 aagllnlqrVGLLMEVSAetlfgnVPS-----LIRTHRSFWDEVLGPT--LEETRASGQPLDPI--GLQSGFLTFGQRFH 258
Cdd:COG5422   511 ---------IKPLEESNI------IPEnarrnFIKHVFANINEIYAVNskLLKALTNRQCLSPIvnGIADIFLDYVPKFE 575

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  259 PYVQYclrVKQTMAYARE---QQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAVLKRS-PEARAQE 334
Cdd:COG5422   576 PFIKY---GASQPYAKYEferEKSVNPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTdPDNPDTE 652

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  335 ALNAMIEAVESFLRHINgqvrqgeeQESLAAAAQrigpYEVLEPPSDEVEKNLRPFSTLDltspmlgvasEHTRQLLLEG 414
Cdd:COG5422   653 DIPKVIDMLREFLSRLN--------FESGKAENR----GDLFHLNQQLLFKPEYVNLGLN----------DEYRKIIFKG 710

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  415 PVRVKEGR----EGKLDVYLFLFSDVLLVTKP--QRKADKAKVIRPPLMLEKLVCQP----------LRDPNSFLLI--- 475
Cdd:COG5422   711 VLKRKAKSktdgSLRGDIQFFLLDNMLLFCKAkaVNKWRQHKVFQRPIPLELLFISPdedspdraeyLKPAPSADVLdpa 790

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*....
gi 694948306  476 ---------HLTEFQCVSSALLV--HCPSPTDRAQWLEKTQQAQAALQK 513
Cdd:COG5422   791 yntkppknaYGFELYGNGQRYQItlYAETHAGRDTWLEHIKNQQDILRT 839

PH domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  385 KNLRPFSTLDLTspmlgvasehTRQLLLEGPVRVKEGREGKLDVYLFLFSD--VLLVTKPQRKA----------DKAKVI 452
Cdd:pfam17838   2 PLGEEFKKLDLT----------TRKLIHEGPLTWRNSKGKLVEVHALLLEDilVLLQEKDQKLVlaclstgsenVDQKTQ 71

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 694948306  453 RPPLMLEKL-VCQPLRDPNSFLLIHLTEFQcvSSALLVHCPSPTDRAQWLEKTQQA 507
Cdd:pfam17838  72 SPIISLKKLiVREVATDKKAFFLISTSPSD--PQMYELHASTKSERNTWTKLIQDA 125

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306 408 RQLLLEGPVRVKEGREGKLDVYLFLFSDVLLVTKP-QRKADKAKVIRPPLMLEKLVCQPLRDPNSFLLIHLTEFQCVSSA 486
Cdd:cd13244    1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                         90       100
                 ....*....|....*....|
gi 694948306 487 LLVHCPSPTDRAQWLEKTQQ 506
Cdd:cd13244   81 YTFQTSSQEDTRRWLDAIRK 100

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306   165 ALWELLTTELIYVRKLKIMTDLLAAGLLnlQRVGLLMEVSAETLFGNVPSLIRTHRSFWDEvlgptLEETRA-SGQPLDP 243
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLK--KELKLLSPNELETLFGNIEEIYEFHRDFLDE-----LEERIEeWDDSVER 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306   244 IGlqSGFLTFGQRFHPYVQYCLRVKQTMAYaREQQETNPLFHAFVQWCEKHKRSGRQMLCDLLIKPHQRITKYPLLLHAV 323
Cdd:smart00325  74 IG--DVFLKLEEFFKIYSEYCSNHPDALEL-LKKLKKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLLLKEL 150

                          170       180
                   ....*....|....*....|....*....
gi 694948306   324 LKRSPEA-RAQEALNAMIEAVESFLRHIN 351
Cdd:smart00325 151 LKHTPEDhEDREDLKKALKAIKELANQVN 179

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306 409 QLLLEGPVRVKEGreGK-LDVYLFLFSDVLLVTKPQRKADKAK------------------------VIRPPLMLEKLV- 462
Cdd:cd13245    1 QLLHEGPLTLIES--GKtLDVYLFLFDDMLLITKMKKNLKKKKssdsensmpsleltplikeggsytVYKQPIPLDRLCl 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 694948306 463 -------CQPLRDPNSFLLIHLTEFQCVSSALLVHCPSPTDRAQWLEKTQ 505
Cdd:cd13245   79 hdvdpneATANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306 406 HTRQLLLEGPVRVKEGREGKL---------DVYLFLFSDVLLVTKP------------QRKADKAKVIRPPLMLEKLVCq 464
Cdd:cd01221   10 SSRWLVKRGELTELVEDGGSLtfrkkfsktPVYLFLFNDLLLITKKkseerylvldyaPRNLVQVEEVEDPLQLPQPLG- 88

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 694948306 465 plrdPNSFLLIHLTEFQCVSSALLVHCPSPTDRAQWLE 502
Cdd:cd01221   89 ----KNLFLLTLLENHEGKTVELLLSAESESDRERWLS 122

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306   410 LLLEGPVRVKE--GREGKLDVYLFLFSDVLLVTKpQRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTEFQ 481
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYK-SKKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDRKT 79

                           90       100
                   ....*....|....*....|....*...
gi 694948306   482 cvssaLLVHCPSPTDRAQWLEKTQQAQA 509
Cdd:smart00233  80 -----LLLQAESEEEREKWVEALRKAIA 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306 412 LEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRDPNSFLLIHLTEfqcvsSAL 487
Cdd:cd00821    1 KEGYLLKRGGGGLKSwkKRWFVLFEGVLLYYKSKKDSSYKpkGSIPLSGILEVEEVSPKERPHCFELVTPDG-----RTY 75

                         90
                 ....*....|....*
gi 694948306 488 LVHCPSPTDRAQWLE 502
Cdd:cd00821   76 YLQADSEEERQEWLK 90

Neuroepithelial cell transforming 1 Pleckstrin homology (PH) domain; Net1 (also called ArhGEF8) is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation. Net1 contains a RhoGEF domain N-terminal to 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 694948306 405 EHTRQLLLEGPVRVKEGREgkldVYLFLFSDVLLVTKPQRKADKA--KVIRPPLMLEKLVCQPLRD 468
Cdd:cd13224   15 ENSKALLCHGELRNKSGHK----LYVFLFQDILVLTRPVTRNERQsfQVYRQPIPVQELVLEDLQD 76

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 694948306  410 LLLEGPVRVKEGREGKL--DVYLFLFSDVLLVTKPqRKADKAKVIRPPLMLEKLVCQPLRD------PNSFLLIHLTefQ 481
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwkKRYFVLFDGSLLYYKD-DKSGKSKEPKGSISLSGCEVVEVVAsdspkrKFCFELRTGE--R 77

                          90       100
                  ....*....|....*....|....*.
gi 694948306  482 CVSSALLVHCPSPTDRAQWLEKTQQA 507
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIKAIQSA 103