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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 261 FNPDREGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQKVDDPKKPFCLELYNPSCRGQkIKAC 340
Cdd:cd01252     1 FNPDREGWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVEDKKKPFCFELYSPSNGQV-IKAC 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958791058 341 KTDGDGKVVEGKHESYRISAANAEERDQWIEAIRASITR 379
Cdd:cd01252    80 KTDSDGKVVEGNHTVYRISAASEEERDEWIKSIKASISR 118

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the central domain of the guanine-nucleotide-exchange factors (GEFs) of the ADP-ribosylation factor family of small GTPases (ARFs) . It carries the exchange factor activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058  61 KEKEMCIGRKKFNMDPAKGIQYLTEHKLLTSDV-QDIAQFLYKGEGLNKTAIGTYLGEKDPINLQVLQAFVDCHEFANLN 139
Cdd:cd00171     1 RKTLLSEGRQLFNRKPKKGISFLIEKGFLEDDSpKEIAKFLYETEGLNKKAIGEYLGENNEFNSLVLHEFVDLFDFSGLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 140 LVQALRQFLWSFRLPGEAQKIDRMMEAFAARYCLCNPGVFRStgSTDTCYVLSFSVIMLNTGLHNPNVRDRPHFEHFVSM 219
Cdd:cd00171    81 LDEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIFSS--SADAAYTLAYSIIMLNTDLHNPNVKKKMTLEDFIKN 158

                         170       180
                  ....*....|....*....|....*..
gi 1958791058 220 NRGINSGSDLPEEQLRNLFDSIKSEPF 246
Cdd:cd00171   159 LRGINDGEDFPREFLKELYDSIKNNEI 185

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058   60 QKEKEMCIGRKKFNMDPAKGIQYLTEHKLL-TSDVQDIAQFLYKGEGLNKTAIGTYLGEKDPINLQVLQAFVDCHEFANL 138
Cdd:smart00222   3 GRKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSAK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058  139 NLVQALRQFLWSFRLPGEAQKIDRMMEAFAARYCLCNPGVFrSTGSTDTCYVLSFSVIMLNTGLHNPNVRDRPHFEHFVS 218
Cdd:smart00222  83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVF-SKANADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIK 161

                          170       180
                   ....*....|....*....|....*...
gi 1958791058  219 MNRGINSGSDLPEEQLRNLFDSIKSEPF 246
Cdd:smart00222 162 NVRGSNDGEDLPREFLEELYDSIKNNEI 189

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 1958791058  263 PDREGWLLKLG-GRVKTWKRRWFILTDNCLYYFE---FTTDKEPRGIIPLENLSVQKVDDP---KKPFCLELYNPScrgq 335
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKskkDKKSYKPKGSIDLSGCTVREAPDPdssKKPHCFEIKTSD---- 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958791058  336 kikacktdgdgkvvegkHESYRISAANAEERDQWIEAIRASI 377
Cdd:smart00233  77 -----------------RKTLLLQAESEEEREKWVEALRKAI 101

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product. The Sec7 domain is the central domain of the guanine-nucleotide-exchange factors (GEFs) of the ADP-ribosylation factor family of small GTPases (ARFs) . It carries the exchange factor activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058  61 KEKEMCIGRKKFNMDPAKGIQYLTEHKLLTSDV-QDIAQFLYKGEGLNKTAIGTYLGEKDPINLQVLQAFVDCHEFANLN 139
Cdd:cd00171     1 RKTLLSEGRQLFNRKPKKGISFLIEKGFLEDDSpKEIAKFLYETEGLNKKAIGEYLGENNEFNSLVLHEFVDLFDFSGLR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 140 LVQALRQFLWSFRLPGEAQKIDRMMEAFAARYCLCNPGVFRStgSTDTCYVLSFSVIMLNTGLHNPNVRDRPHFEHFVSM 219
Cdd:cd00171    81 LDEALRKFLQSFRLPGEAQKIDRLLEKFSERYCECNPGIFSS--SADAAYTLAYSIIMLNTDLHNPNVKKKMTLEDFIKN 158

                         170       180
                  ....*....|....*....|....*..
gi 1958791058 220 NRGINSGSDLPEEQLRNLFDSIKSEPF 246
Cdd:cd00171   159 LRGINDGEDFPREFLKELYDSIKNNEI 185

Sec7 domain; Domain named after the S. cerevisiae SEC7 gene product, which is required for proper protein transport through the Golgi. The domain facilitates guanine nucleotide exchange on the small GTPases, ARFs (ADP ribosylation factors).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058   60 QKEKEMCIGRKKFNMDPAKGIQYLTEHKLL-TSDVQDIAQFLYKGEGLNKTAIGTYLGEKDPINLQVLQAFVDCHEFANL 138
Cdd:smart00222   3 GRKKLLSEGIVKFNDKPKKGIQSLQEKGFLaNEDPQDVADFLSKNEGLNKKAIGDYLGEHDEFNRLVLHAFVDLFDFSAK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058  139 NLVQALRQFLWSFRLPGEAQKIDRMMEAFAARYCLCNPGVFrSTGSTDTCYVLSFSVIMLNTGLHNPNVRDRPHFEHFVS 218
Cdd:smart00222  83 DLDQALREFLESFRLPGEAQKIDRLLEAFSSRYCECNPGVF-SKANADAAYTLAYSLIMLNTDLHNPNVKKKMTLEDFIK 161

                          170       180
                   ....*....|....*....|....*...
gi 1958791058  219 MNRGINSGSDLPEEQLRNLFDSIKSEPF 246
Cdd:smart00222 162 NVRGSNDGEDLPREFLEELYDSIKNNEI 189

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 262 NPDREGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQKVDDpKKPFCLELynpscrgqkikacK 341
Cdd:cd13288     7 PVDKEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGDREPLGVIVLEGCTVELAED-AEPYAFAI-------------R 72

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958791058 342 TDGDGkvvegkHESYRISAANAEERDQWIEAI-RASITR 379
Cdd:cd13288    73 FDGPG------ARSYVLAAENQEDMESWMKALsRASYDY 105

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 262 NPDREGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQKV----DDPKKpFCLELynpscrgqki 337
Cdd:cd13263     2 RPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVpfnpEEPGK-FLFEI---------- 70

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958791058 338 kacKTDGDGKVVEGKHESYRISAANAEERDQWIEAIR 374
Cdd:cd13263    71 ---IPGGGGDRMTSNHDSYLLMANSQAEMEEWVKVIR 104

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 1958791058 265 REGWLLKLGGRV-KTWKRRWFILTDNCLYYFEFTTD--KEPRGIIPLEN-LSVQKVDDPKKPFCLELYNPscrgqkikac 340
Cdd:cd00821     1 KEGYLLKRGGGGlKSWKKRWFVLFEGVLLYYKSKKDssYKPKGSIPLSGiLEVEEVSPKERPHCFELVTP---------- 70

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958791058 341 ktdgdgkvvegKHESYRISAANAEERDQWIEAI 373
Cdd:cd00821    71 -----------DGRTYYLQADSEEERQEWLKAL 92

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 262 NPDREGWLLKLGG-RVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQKV---DDPKKPFCLELYNPSCRgqki 337
Cdd:cd13248     6 PVVMSGWLHKQGGsGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAppsDEISRKFAFKAEHANMR---- 81

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958791058 338 kacktdgdgkvvegkheSYRISAANAEERDQWIEAIR 374
Cdd:cd13248    82 -----------------TYYFAADTAEEMEQWMNAMS 101

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 265 REGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTD--KEPRGIIPLenlsvqkvddpkkpfclelyNPSCRGQKIKACKT 342
Cdd:cd13282     1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDviRKPQGQIAL--------------------DGSCEIARAEGAQT 60

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1958791058 343 dgdgKVVEGKHESYRISAANAEERDQWIEAI 373
Cdd:cd13282    61 ----FEIVTEKRTYYLTADSENDLDEWIRVI 87

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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 1958791058 262 NPDREGWLLKLGGRVKT----WKRRWFILTDNCLYYF---EFTTDKEPRGIIPLENLSVQKVDDPKKPFCLELY---NPS 331
Cdd:cd13258    15 PAEKEGKIAERQMGGPKksevFKERWFKLKGNLLFYFrtnEFGDCSEPIGAIVLENCRVQMEEITEKPFAFSIVfndEPE 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1958791058 332 CRgqkikacktdgdgkvvegkhesYRISAANAEERDQWIEAIR-ASI 377
Cdd:cd13258    95 KK----------------------YIFSCRSEEQCEQWIEALRqASY 119

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 265 REGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPL-ENLSVQKVDDPKKPFCLELYNPScrgqkikacktd 343
Cdd:cd10573     5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDTKPIRVLDLrECSSVQRDYSQGKVNCFCLVFPE------------ 72

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1958791058 344 gdgkvvegkhESYRISAANAEERDQWIEAIRASI 377
Cdd:cd10573    73 ----------RTFYMYANTEEEADEWVKLLKWKL 96

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 266 EGWLLKLGGRVKTWKRRWFIL--TDNCLYYFEFTTDKEPRGIIPLENL-SVQkvddPKKPFclelynpscrgqkIKACKT 342
Cdd:cd01235     6 EGYLYKRGALLKGWKQRWFVLdsTKHQLRYYESREDTKCKGFIDLAEVeSVT----PATPI-------------IGAPKR 68

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958791058 343 DGDGKVVEGKHE--SYRISAANAEERDQWIEAIRASI 377
Cdd:cd01235    69 ADEGAFFDLKTNkrVYNFCAFDAESAQQWIEKIQSCL 105

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 265 REGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQKV----DDPKKpfclELYNPSCRGQkikac 340
Cdd:cd13378     5 KAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELppnpEEPGK----HLFEILPGGA----- 75

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958791058 341 ktdGDGKVVEGKHESYRISAANAEERDQWIEAIRASI 377
Cdd:cd13378    76 ---GDREKVPMNHEAFLLMANSQSDMEDWVKAIRRVI 109

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and 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). TAPP1 and TAPP2 contain 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. 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 1958791058 262 NPDREGWLLKLGGRVKTWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLsvqkvddpkkpfclelynpscrgQKIKACK 341
Cdd:cd13271     7 NVIKSGYCVKQGAVRKNWKRRFFILDDNTISYYKSETDKEPLRTIPLREV-----------------------LKVHECL 63

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1958791058 342 T------DGDGKVVEGKHESYrISAANAEERDQWIEAIRASITR 379
Cdd:cd13271    64 VksllmrDNLFEIITTSRTFY-IQADSPEEMHSWIKAISGAIVA 106

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; 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 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 265 REGWLLKLGGRVKTWKRRWFILTDN--CLYYFEFTTDKEPRGIIPLENLSVQKVDDpkkpfclelyNPSCRGQKIkackt 342
Cdd:cd13302     9 KQGCLLKQGHRRKNWKVRKFVLRDDpaYLHYYDPAKGEDPLGAIHLRGCVVTAVED----------NSNPRKGSV----- 73

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958791058 343 DGD-GKVVEGKHESYRISAANAEERDQWIEAIR 374
Cdd:cd13302    74 EGNlFEIITADEVHYYLQAATPAERTEWIKAIQ 106

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 267 GWLLKLGGRV-----KTWKRRWFILTDNCLYYFEFTTDKE-PRGIIPLENLSVqKVDDPKKPFCLELYNPScrgqkikac 340
Cdd:cd13296     3 GWLTKKGGGSstlsrRNWKSRWFVLRDTVLKYYENDQEGEkLLGTIDIRSAKE-IVDNDPKENRLSITTEE--------- 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958791058 341 ktdgdgkvvegkhESYRISAANAEERDQWIeairASITRV 380
Cdd:cd13296    73 -------------RTYHLVAESPEDASQWV----NVLTRV 95

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 265 REGWLLK------LGGRVkTWKRRWFILTDNCLYYFE--FTTDKEPRGIIPLENLS-VQKVDDP-----KKPFclelynp 330
Cdd:cd01238     1 LEGLLVKrsqgkkRFGPV-NYKERWFVLTKSSLSYYEgdGEKRGKEKGSIDLSKVRcVEEVKDEafferKYPF------- 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958791058 331 scrgqkikacktdgdgKVVegkHESY--RISAANAEERDQWIEAIRASITRVPF 382
Cdd:cd01238    73 ----------------QVV---YDDYtlYVFAPSEEDRDEWIAALRKVCRNNSN 107

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958791058 262 NPDREGWLLK-------LGGRvktWKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQKVDDPKKPFCLELYNPS 331
Cdd:cd01260    12 RGDCQGWLWKkkeaksfFGQK---WKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERASECKKKYAFKACHPK 85

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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 1958791058 261 FNPDREGWLLKLGGRVKTWKRRWFIL--TDNCLYYFEFTTDKEPRGIIPLENLSVQKVDDP--KKPFCLELynpscrgqk 336
Cdd:cd13260     1 KGIDKKGYLLKKGGKNKKWKNLYFVLegKEQHLYFFDNEKRTKPKGLIDLSYCSLYPVHDSlfGRPNCFQI--------- 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958791058 337 ikacktdgdgkVVE--GKHESYRISAANAEERDQWIEAIRA 375
Cdd:cd13260    72 -----------VVRalNESTITYLCADTAELAQEWMRALRA 101

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958791058 279 WKRRWFILTDNCLYYFEFTTDKEPRGIIPLENLSVQ---KVD-DPKKPFCLELYNPSCRgqkikacktdgdgkvvegkhe 354
Cdd:cd13266    21 WQKRWCAISKNVFYYYGSDKDKQQKGEFAINGYDVRmnpTLRkDGKKDCCFELVCPDKR--------------------- 79

                          90       100
                  ....*....|....*....|....*..
gi 1958791058 355 SYRISAANAEERDQWIEAIRASITRVP 381
Cdd:cd13266    80 TYQFTAASPEDAEDWVDQISFILQDLS 106

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; 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 third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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 1958791058 267 GWLLKLGGRVK-----TWKRRWFILTDNCL-YYFEFTTDKEPRGIIPLENL-SVQKVDDpkkpfclelynpscrgqkiKA 339
Cdd:cd13297    17 GWLYKEGGKGGargnlTKKKRWFVLTGNSLdYYKSSEKNSLKLGTLVLNSLcSVVPPDE-------------------KM 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958791058 340 CKTDGDGKV-VEGKHESYRISAANAEERDQWIEAIRASI 377
Cdd:cd13297    78 AKETGYWTFtVHGRKHSFRLYTKLQEEAMRWVNAIQDVI 116

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. 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 1958791058 266 EGWLLKLGGRVKTWKRRWFILTDNCLY-YFEFTtdKEPRGIIpleNLS-VQKVDDPKKpfclelynPSCRGQKIKACKTD 343
Cdd:cd13278    22 EGYLLQEGGDCEYWRRRFFKLQGTKLVaYHEVT--RKPRATI---NLLkVVDVVDDDD--------ARERTSSFKRNFTD 88