Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829   11 SDVRKVGYLRKPKSMHKRFFVLRAASEaGGPARLEYYENEKKWRHKSsAPKRSIPLESCFNINKRADSKNKHLVALYTRD 90
Cdd:cd01257    1 TDVRKSGYLKKLKTMRKRYFVLRAESH-GGPARLEYYENEKKFRRNA-EPKRVIPLSSCFNINKRADAKHKHLIALYTKD 78

                         90       100
                 ....*....|....*....|....*...
gi 29825829   91 EHFAIAADSEAEQDSWYQALLQLHNRAK 118
Cdd:cd01257   79 ECFGLVAESEEEQDEWYQALLELQRPAR 106

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829   11 SDVRKVGYLRKPKSMHKRFFVLRAASEaGGPARLEYYENEKKWRHKSsAPKRSIPLESCFNINKRADSKNKHLVALYTRD 90
Cdd:cd01257    1 TDVRKSGYLKKLKTMRKRYFVLRAESH-GGPARLEYYENEKKFRRNA-EPKRVIPLSSCFNINKRADAKHKHLIALYTKD 78

                         90       100
                 ....*....|....*....|....*...
gi 29825829   91 EHFAIAADSEAEQDSWYQALLQLHNRAK 118
Cdd:cd01257   79 ECFGLVAESEEEQDEWYQALLELQRPAR 106

PTB domain (IRS-1 type);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829    156 KEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQV 235
Cdd:pfam02174    1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                           90       100
                   ....*....|....*....|..
gi 29825829    236 DDsvvAQNMHETILEAMRAMSD 257
Cdd:pfam02174   81 DD---AEEIFETVLAAMKAQKE 99

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829     17 GYLRK-----PKSMHKRFFVLRaaseaggPARLEYYENEKkwRHKSSAPKRSIPLESCFN--INKRADSKNKHLVALYT- 88
Cdd:pfam00169    5 GWLLKkgggkKKSWKKRYFVLF-------DGSLLYYKDDK--SGKSKEPKGSISLSGCEVveVVASDSPKRKFCFELRTg 75

                           90       100
                   ....*....|....*....|....*
gi 29825829     89 ---RDEHFAIAADSEAEQDSWYQAL 110
Cdd:pfam00169   76 ertGKRTYLLQAESEEERKDWIKAI 100

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829   11 SDVRKVGYLRKPKSMHKRFFVLRAASEaGGPARLEYYENEKKWRHKSsAPKRSIPLESCFNINKRADSKNKHLVALYTRD 90
Cdd:cd01257    1 TDVRKSGYLKKLKTMRKRYFVLRAESH-GGPARLEYYENEKKFRRNA-EPKRVIPLSSCFNINKRADAKHKHLIALYTKD 78

                         90       100
                 ....*....|....*....|....*...
gi 29825829   91 EHFAIAADSEAEQDSWYQALLQLHNRAK 118
Cdd:cd01257   79 ECFGLVAESEEEQDEWYQALLELQRPAR 106

PTB domain (IRS-1 type);

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829    156 KEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQV 235
Cdd:pfam02174    1 VEVFPVTVRRTGASERCGLSGSYRLCLTAEALTLDKLNTRVPLVSWPLTSLRRYGRDKNFFSFEAGRRCVTGEGEFWFQT 80

                           90       100
                   ....*....|....*....|..
gi 29825829    236 DDsvvAQNMHETILEAMRAMSD 257
Cdd:pfam02174   81 DD---AEEIFETVLAAMKAQKE 99

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 29825829      13 VRKVGYLRKP-----KSMHKRFFVLRaaseaggPARLEYYENEKKwrHKSSAPKRSIPLESCfNINKRADS---KNKHLV 84
Cdd:smart00233    1 VIKEGWLYKKsgggkKSWKKRYFVLF-------NSTLLYYKSKKD--KKSYKPKGSIDLSGC-TVREAPDPdssKKPHCF 70

                            90       100       110
                    ....*....|....*....|....*....|..
gi 29825829      85 ALYTRDEH-FAIAADSEAEQDSWYQALLQLHN 115
Cdd:smart00233   71 EIKTSDRKtLLLQAESEEEREKWVEALRKAIA 102

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829   17 GYLRKPKSMHK--------RFFVLRAASEAGGPARLEYYENEKKWRhkssaPKRSIPLESC------FNINKRaDSKNKH 82
Cdd:cd13324    5 GWLTKSPPEKKiwraawrrRWFVLRSGRLSGGQDVLEYYTDDHCKK-----LKGIIDLDQCeqvdagLTFEKK-KFKNQF 78

                         90       100
                 ....*....|....*....|....
gi 29825829   83 LVALYTRDEHFAIAADSEAEQDSW 106
Cdd:cd13324   79 IFDIRTPKRTYYLVAETEEEMNKW 102

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829   11 SDVRKVGYLRK-------------PKSMHKRFFVLRaaSEAGGPARLEYYENEKKwrhksSAPKRSIPLESCFNI--NKR 75
Cdd:cd13267    4 SGITKEGYLYKgpenssdsfislaMKSFKRRFFHLK--QLVDGSYILEFYKDEKK-----KEAKGTIFLDSCTGVvqNSK 76

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 29825829   76 adsKNKHLVALYTRD-EHFAIAADSEAEQDSWYQAL 110
Cdd:cd13267   77 ---RRKFCFELRMQDkKSYVLAAESEAEMDEWISKL 109

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829   13 VRKVGYLRKP----KSMHKRFFVLRaaseaggPARLEYYENEKKWRhkssaPKRSIPL---ESCFNIN-KRADsknkHLV 84
Cdd:cd13255    6 VLKAGYLEKKgerrKTWKKRWFVLR-------PTKLAYYKNDKEYR-----LLRLIDLtdiHTCTEVQlKKHD----NTF 69

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 29825829   85 ALYTRDEHFAIAADSEAEQDSWYQALlqlhNRAKA 119
Cdd:cd13255   70 GIVTPARTFYVQADSKAEMESWISAI----NLARQ 100

Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins; The Dok family adapters are phosphorylated by different protein tyrosine kinases. Dok proteins are involved in processes such as modulation of cell differentiation and proliferation, as well as in control of the cell spreading and migration The Dok protein contains an N-terminal pleckstrin homology (PH) domain followed by a central phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a proline- and tyrosine-rich C-terminal tail. The PH domain binds to acidic phospholids and localizes proteins to the plasma membrane, while the PTB domain mediates protein-protein interactions by binding to phosphotyrosine-containing motifs. The C-terminal part of Dok contains multiple tyrosine phosphorylation sites that serve as potential docking sites for Src homology 2-containing proteins such as ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. There are 7 mammalian Dok members: Dok-1 to Dok-7. Dok-1 and Dok-2 act as negative regulators of the Ras-Erk pathway downstream of many immunoreceptor-mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok-1 and Dok-2 is critical to their negative regulation. Dok-3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B-cell receptor-mediated signaling, interacting with SHIP-1 and Grb2. Dok-4- 6 play roles in protein tyrosine kinase(PTK)-mediated signaling in neural cells and Dok-7 is the key cytoplasmic activator of MuSK (Muscle-Specific Protein Tyrosine Kinase). In general, PH domains have diverse functions, but are generally 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. 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 29825829   15 KVGYL----RKPKSMHKRFFVLRAASeAGGPARLEYYENEKKWRHKSSaPKrSIPLESCFNINKRADSKNKHLVALYTRD 90
Cdd:cd14678    2 KQGYVrirsRKLGIYRRCWLVFRKAS-SKGPKRLEKYPDERAAYLRAC-HK-VTELSNVKNITRLPKETKRHAVAIIFTD 78

                         90       100
                 ....*....|....*....|...
gi 29825829   91 EHF-AIAADSEAEQDSWYQALLQ 112
Cdd:cd14678   79 DSSkTFACDSELEAEEWCKVLSM 101

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829     15 KVGYLRK--PKSMHKRFFVLRaaseagGPARLEYYENEKK--WRHKSSAPK-------RSIPLESCFNI-NKRADSKNKH 82
Cdd:pfam15413    1 IEGYLKKkgPKTWKHRWFAVL------RNGVLFYYKSEKMkvVKHVIVLSNyivgklgTDIISGALFKIdNIRSETSDDL 74

                           90       100       110
                   ....*....|....*....|....*....|.
gi 29825829     83 LVALYTRDEHFAIAADSEAEQDSWYQALLQL 113
Cdd:pfam15413   75 LLEISTETKIFFLYGDNNEETYEWVEALQEA 105

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29825829    6 DTDGFSDVRKVGYL-RKPK-----SMHKRFFVLRAASeaggparLEYY-ENEKKW----RHKSSAPKRSIPLESCFnINK 74
Cdd:cd13281    5 DLDITTKVQLHGILwKKPFghqsaKWSKRFFIIKEGF-------LLYYsESEKKDfektRHFNIHPKGVIPLGGCS-IEA 76

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 29825829   75 RADSKNKHLVALYTRDEHFAI--AADSEAEQDSWYQAL 110
Cdd:cd13281   77 VEDPGKPYAISISHSDFKGNIilAADSEFEQEKWLDML 114

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 29825829   15 KVGYLRKP---------KSMHKRFFVLRAAseaggpaRLEYYENEkkwrHKSSAPKRSIPLESCFNINKRADSKNKhlVA 85
Cdd:cd13296    1 KSGWLTKKgggsstlsrRNWKSRWFVLRDT-------VLKYYEND----QEGEKLLGTIDIRSAKEIVDNDPKENR--LS 67

                         90       100       110
                 ....*....|....*....|....*....|..
gi 29825829   86 LYTRDEHFAIAADSEAEQDSWYQALLQLHNRA 117
Cdd:cd13296   68 ITTEERTYHLVAESPEDASQWVNVLTRVISAT 99

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 29825829   11 SDVRKVGYLRKPKSM----HKRFFVLRAASeaggparLEYYENEKKwrhksSAPKRSIPLESCfNINK---RADSKNKHL 83
Cdd:cd13263    1 ERPIKSGWLKKQGSIvknwQQRWFVLRGDQ-------LYYYKDEDD-----TKPQGTIPLPGN-KVKEvpfNPEEPGKFL 67

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 29825829   84 VAL-------YTRDEH--FAIAADSEAEQDSWYQAL 110
Cdd:cd13263   68 FEIipggggdRMTSNHdsYLLMANSQAEMEEWVKVI 103