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 1039774687 376 RQLLLEGPVRVKEGREGKMDVYLFLFSDVLLVTKP-QRKADRAKVIRPPLMLEKLVCRPLRDPNSFLLIHLTEFQCVSSA 454
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90
                  ....*....|....*....
gi 1039774687 455 LTVHCPSSTERARWLEKTQ 473
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIR 99

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 1039774687 376 RQLLLEGPVRVKEGREGKMDVYLFLFSDVLLVTKP-QRKADRAKVIRPPLMLEKLVCRPLRDPNSFLLIHLTEFQCVSSA 454
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90
                  ....*....|....*....
gi 1039774687 455 LTVHCPSSTERARWLEKTQ 473
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIR 99

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 162 QQEALWELLTTELIYLRKLKIMTDLLAAGLlnLQRVGLLTEVSAETLFGNVPNLIRAHRRFWEEVLQPILEDtrtsgqPL 241
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPL--DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEW------DK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 242 DPVSLQNGFLTFGQRFQPYVQYCLRVKQTMAYAREQQDTNPLFHTFVQAVRKRS-------------------------- 295
Cdd:cd00160    73 SGPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECgrlkleslllkpvqrltkyplllkel 152

                         170       180
                  ....*....|....*....|....*....
gi 1039774687 296 -----PEPRAQEALNAMIEAVESFLRHIN 319
Cdd:cd00160   153 lkhtpDGHEDREDLKKALEAIKEVASQVN 181

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 1039774687  378 LLLEGPVRVKE--GREGKMDVYLFLFSDVLLVTKpQRKADRAKVIRPPLMLEKLVCRPLRD------PNSFLLIHLTEFQ 449
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYK-SKKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDRKT 79

                           90       100
                   ....*....|....*....|.
gi 1039774687  450 cvssaLTVHCPSSTERARWLE 470
Cdd:smart00233  80 -----LLLQAESEEEREKWVE 95

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 1039774687 376 RQLLLEGPVRVKEGREGKMDVYLFLFSDVLLVTKP-QRKADRAKVIRPPLMLEKLVCRPLRDPNSFLLIHLTEFQCVSSA 454
Cdd:cd13244     1 RRLLLEGDLRLKEGKGSKVDVHCFLFTDMLLICKPvKRKKDRLKVIRPPYLVDKLVVQELKDPGGFLLVYLNEFHTAVAA 80

                          90
                  ....*....|....*....
gi 1039774687 455 LTVHCPSSTERARWLEKTQ 473
Cdd:cd13244    81 YTFQTSSQEDTRRWLDAIR 99

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 162 QQEALWELLTTELIYLRKLKIMTDLLAAGLlnLQRVGLLTEVSAETLFGNVPNLIRAHRRFWEEVLQPILEDtrtsgqPL 241
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPL--DKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEW------DK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 242 DPVSLQNGFLTFGQRFQPYVQYCLRVKQTMAYAREQQDTNPLFHTFVQAVRKRS-------------------------- 295
Cdd:cd00160    73 SGPRIGDVFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESECgrlkleslllkpvqrltkyplllkel 152

                         170       180
                  ....*....|....*....|....*....
gi 1039774687 296 -----PEPRAQEALNAMIEAVESFLRHIN 319
Cdd:cd00160   153 lkhtpDGHEDREDLKKALEAIKEVASQVN 181

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 165 ALWELLTTELIYLRKLKIMTDLLAagllnLQRVGLLTEVSAE--TLFGNVPNLIRAHRRFWeevlqpiLEDTRTSGQPLD 242
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFL-----PPNSKPLSESEEEikTIFSNIEEIYELHRQLL-------LEELLKEWISIQ 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 243 PVSlqNGFLTFGQRFQPYVQYCLRVKQTMAYAREQQDTNPLFHTFVQAVRKR---------------------------- 294
Cdd:pfam00621  69 RIG--DIFLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANpecrgldlnsflikpvqripryplllke 146

                         170       180       190
                  ....*....|....*....|....*....|
gi 1039774687 295 -----SPEPRAQEALNAMIEAVESFLRHIN 319
Cdd:pfam00621 147 llkhtPPDHPDYEDLKKALEAIKEVAKQIN 176

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 1039774687  378 LLLEGPVRVKE--GREGKMDVYLFLFSDVLLVTKpQRKADRAKVIRPPLMLEKLVCRPLRD------PNSFLLIHLTEFQ 449
Cdd:smart00233   1 VIKEGWLYKKSggGKKSWKKRYFVLFNSTLLYYK-SKKDKKSYKPKGSIDLSGCTVREAPDpdsskkPHCFEIKTSDRKT 79

                           90       100
                   ....*....|....*....|.
gi 1039774687  450 cvssaLTVHCPSSTERARWLE 470
Cdd:smart00233  80 -----LLLQAESEEEREKWVE 95

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 376 RQLLLEGPVrVKEGREGKMDVYLFLFSDVLLVTKPQRKADRAKVIRP-PLMLEKlVCRPLRDPNSFllihltEFQCVSSA 454
Cdd:cd13389    12 RKLIKEGEL-MKVSRKEMQPRYFFLFNDCLLYTTPVQSSGMLKLNNElPLSGMK-VKLPEDEEYSN------EFQIISTK 83

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039774687 455 --LTVHCPSSTERARWLEKTQHAQTTLQKLK 483
Cdd:cd13389    84 rsFTLIASSEEERDEWVKALSRAIEEHTKKQ 114

Intersectin Pleckstrin homology (PH) domain; ITSNs, an adaptor protein family, play a role in endo- and exocytosis, actin cytoskeleton rearrangement and signal transduction. There are two human ITSN genes: ITSN1 and ITSN2. They share significant sequence identity and a similar domain structure having both short and long isoforms produced by alternative splicing. The short isoform (ITSN-S) consists of two Eps15 homology domains (EH1 and EH2), a coiled-coil region (CCR) and five Src homology 3 domains (SH3A-E). The EH domains bind to Asn-Pro-Phe motifs and are implicated in endocytosis and vesicle transport. The SH3 domains bind to proline-rich sequences and are commonly found in proteins implicated in cell signalling pathways, cytoskeletal organization and membrane traffic. The long isoform (ITSN-L) contains three additional C-terminal domains, a Dbl homology domain (DH), a Pleckstrin homology domain (PH) and a C2 domain. The tandem DH-PH domains are present in all Dbl family of GEFs. ITSN acts specifically on Cdc42 through its DH domain with no portion of the PH domain making contact with Cdc42. This is in contrast to Dbs which requires the PH domain for full catalytic activity. The ITSN PH domain binds phosphoinositides. C2 domains are usually involved in Ca2+-dependent and Ca2+-independent phospholipid binding. There are more than 30 proteins that interact with ITSNs. ITSN-S is present in mammals, frogs, flies and nematodes, while ITSN-L is present only in vertebrates. 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 1039774687 365 TPVLGvapeyTRQLLLEGP-VRVKEGREgkmdVYLFLFSDVLLVTKPQR---------KADRAKVI-----RPPLMLEKL 429
Cdd:cd13264     8 TNCLG-----PRKFLHSGKlYKAKSNKE----LYGFLFNDFLLLTQPIKplgssgndfVFDNKANIqykmyKTPIFLNEV 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1039774687 430 VCRPLRDPNS----FLLIHltefqcVSSALTVHCPSSTERARWLEKTQHAqttlqklkGEQYIQQKR 492
Cdd:cd13264    79 LVKLPTDPSGdepiFHISH------IDRVYTLRAESINERTAWVQKIKAA--------SELYIETEK 131

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 373 EYTRqLLLEGPVRVKE-GREGKMDVYLFLFSDVLLVTKPQRkaDRAKVIRPPLMLEK------LVCRPLRDPNS----FL 441
Cdd:cd01223    15 DYGR-LQIDGELKIKShEDQKKKDRYAFLFDKVLLICKSLR--GDQYEYKEIINLSEyrieddPSRRTLKRDKRwsyqFL 91

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1039774687 442 LIHLTEfqcvSSALTVHCPSSTERARWLEKTQHAQTTL 479
Cdd:cd01223    92 LVHKQG----KTAYTLYAKTEELKKKWMEAIEMALSNI 125

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039774687 378 LLLEGPVRVKEGREGKM--DVYLFLFSDVLLVTKPqRKADRAKVIRPPLMLEKLVCRPLRD------PNSFLLIHLTefQ 449
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKSwkKRYFVLFDGSLLYYKD-DKSGKSKEPKGSISLSGCEVVEVVAsdspkrKFCFELRTGE--R 77

                          90       100
                  ....*....|....*....|.
gi 1039774687 450 CVSSALTVHCPSSTERARWLE 470
Cdd:pfam00169  78 TGKRTYLLQAESEEERKDWIK 98

Exocyst complex 84-kDa subunit Ral-binding domain/Pleckstrin Homology (PH) domain; The Sec6/8 complex, also called the exocyst complex, forms an octameric protein (Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84) involved in the tethering of secretory vesicles to specific regions on the plasma membrane. The regulation of Sec6/8 complex differs between mammals and yeast. Mamalian Exo84 and Sec5 are effector targets for active Ral GTPases which are not present in yeast. Ral GTPases are members of the Ras superfamily, and as such cycle between an active GTP-bound state and an inactive GDP-bound state. The Exo84 Ral-binding domain adopts a PH domain fold. Mammalian Exo84 and Sec5 competitively bind to active RalA. 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 1039774687 375 TRQLLLEGPVRVKEGREGK--MDVYLFLFSDVLLVTKPqrKADRakviRPPLMLEKLVCRPLRD------------PNSF 440
Cdd:cd01226     5 GRYLLHEGDLLELDPDDYKpiQKVHLFLLNDVLLIASW--LPNR----RGPVRYKFQALYPLEDlavvnvkdlgpvKNAF 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039774687 441 LLIHLTE---FQCVSSAltvhcpsstERARWLEK 471
Cdd:cd01226    79 KLLTFPEtrvFQCENAK---------IKKEWLEK 103