Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  38 GHVLYSGWLRKSPPEKKLRLFAWRKRWFILRRGQTSSDPDVLEYYKNDGSKKPLRTINLNLCEQldVDVTLNFNKKEIQK 117
Cdd:cd01266    2 GEVVCSGWLRKSPPEKKLRRYAWKKRWFVLRSGRLSGDPDVLEYYKNDHAKKPIRVIDLNLCEQ--VDAGLTFNKKELEN 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768022724 118 GYMFDIKTSERTFYLVAETREDMNEWVQSICQICGFRQEES 158
Cdd:cd01266   80 SYIFDIKTIDRIFYLVAETEEDMNKWVRNICDICGFNPTEE 120

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  38 GHVLYSGWLRKSPPEKKLRLFAWRKRWFILRRGQTSSDPDVLEYYKNDGSKKPLRTINLNLCEQldVDVTLNFNKKEIQK 117
Cdd:cd01266    2 GEVVCSGWLRKSPPEKKLRRYAWKKRWFVLRSGRLSGDPDVLEYYKNDHAKKPIRVIDLNLCEQ--VDAGLTFNKKELEN 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768022724 118 GYMFDIKTSERTFYLVAETREDMNEWVQSICQICGFRQEES 158
Cdd:cd01266   80 SYIFDIKTIDRIFYLVAETEEDMNKWVRNICDICGFNPTEE 120

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 768022724    40 VLYSGWLRKSPPEKKLRlfaWRKRWFILRRgqtssdpDVLEYYKNDGSK---KPLRTINLNLCEqldvdVTLNFNKKEIQ 116
Cdd:smart00233   1 VIKEGWLYKKSGGGKKS---WKKRYFVLFN-------STLLYYKSKKDKksyKPKGSIDLSGCT-----VREAPDPDSSK 65

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 768022724   117 KGYMFDIKTSER-TFYLVAETREDMNEWVQSICQIC 151
Cdd:smart00233  66 KPHCFEIKTSDRkTLLLQAESEEEREKWVEALRKAI 101

Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1 and Gab2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  38 GHVLYSGWLRKSPPEKKLRLFAWRKRWFILRRGQTSSDPDVLEYYKNDGSKKPLRTINLNLCEQldVDVTLNFNKKEIQK 117
Cdd:cd01266    2 GEVVCSGWLRKSPPEKKLRRYAWKKRWFVLRSGRLSGDPDVLEYYKNDHAKKPIRVIDLNLCEQ--VDAGLTFNKKELEN 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768022724 118 GYMFDIKTSERTFYLVAETREDMNEWVQSICQICGFRQEES 158
Cdd:cd01266   80 SYIFDIKTIDRIFYLVAETEEDMNKWVRNICDICGFNPTEE 120

Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1, Gab2, and Gab3 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  37 SGHVLYSGWLRKSPPEKKLRLFAWRKRWFILRRGQTSSDPDVLEYYKNDGSKKPLRTINLNLCEQLDvDVTLNFNKKEIQ 116
Cdd:cd13385    3 AGDVVCTGWLIKSPPERKLKRYAWRKRWFVLRRGRMSGNPDVLEYYRNNHSKKPIRVIDLSECEVLK-HSGPNFIRKEFQ 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 768022724 117 KGYMFDIKTSERTFYLVAETREDMNEWVQSICQICGFRQEESTA 160
Cdd:cd13385   82 NNFVFIVKTTYRTFYLVAKTEEEMQVWVHNISQICNFGHLEDGT 125

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724   40 VLYSGWLRKSPPEKKLRlfaWRKRWFILRRgqtssdpDVLEYYKNDG---SKKPLRTINLNLCEQLDVDVTLNFNKKeiq 116
Cdd:pfam00169   1 VVKEGWLLKKGGGKKKS---WKKRYFVLFD-------GSLLYYKDDKsgkSKEPKGSISLSGCEVVEVVASDSPKRK--- 67

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 768022724  117 kgYMFDIKTSE----RTFYLVAETREDMNEWVQSICQIC 151
Cdd:pfam00169  68 --FCFELRTGErtgkRTYLLQAESEEERKDWIKAIQSAI 104

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 768022724  34 STRSGHVLYSGWLRKSppekklrlfaWRKRWFILRRGQtssdpdvLEYYKNDGSKKPLRTINLNLCEQLDVDvtlnfNKK 113
Cdd:cd10573    3 GSKEGYLTKLGGIVKN----------WKTRWFVLRRNE-------LKYFKTRGDTKPIRVLDLRECSSVQRD-----YSQ 60

                         90       100       110
                 ....*....|....*....|....*....|.
gi 768022724 114 EiqKGYMFDIKTSERTFYLVAETREDMNEWV 144
Cdd:cd10573   61 G--KVNCFCLVFPERTFYMYANTEEEADEWV 89

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 768022724  40 VLYSGWLRKSPPEKKlrlfAWRKRWFILRRGQtssdpdvLEYYKNDGSKKPLRTINLNlceqlDVD--VTLNFNKKEiqk 117
Cdd:cd13255    6 VLKAGYLEKKGERRK----TWKKRWFVLRPTK-------LAYYKNDKEYRLLRLIDLT-----DIHtcTEVQLKKHD--- 66

                         90       100       110
                 ....*....|....*....|....*....|...
gi 768022724 118 gYMFDIKTSERTFYLVAETREDMNEWVQSICQI 150
Cdd:cd13255   67 -NTFGIVTPARTFYVQADSKAEMESWISAINLA 98

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 768022724  43 SGWLrksppeKKL--RLFAWRKRWFILRRGQtssdpdvLEYYK--NDGSKKPLRTINLN-LCEqldvdvtlnfnkkeIQK 117
Cdd:cd13282    2 AGYL------TKLggKVKTWKRRWFVLKNGE-------LFYYKspNDVIRKPQGQIALDgSCE--------------IAR 54

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 768022724 118 ---GYMFDIKTSERTFYLVAETREDMNEWVQSICQICGFRQ 155
Cdd:cd13282   55 aegAQTFEIVTEKRTYYLTADSENDLDEWIRVIQNVLRRQA 95

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 768022724  36 RSGHVLYSGWLRKSppekklrlfaWRKRWFILrrgqtssDPDVLEYYKNDGSKKPLRTINLNlcEQLDVDVTLNfnKKEI 115
Cdd:cd13271   10 KSGYCVKQGAVRKN----------WKRRFFIL-------DDNTISYYKSETDKEPLRTIPLR--EVLKVHECLV--KSLL 68

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768022724 116 QKGYMFDIKTSERTFYLVAETREDMNEWVQSICQIC 151
Cdd:cd13271   69 MRDNLFEIITTSRTFYIQADSPEEMHSWIKAISGAI 104

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  43 SGWLRKSPPEKKLRLfaWRKRWFILrrgqtssDPDVLEYYKNDGSKKPLRTINLNlceQLDVDVTLNFNKkeiqkgymFD 122
Cdd:cd13253    3 SGYLDKQGGQGNNKG--FQKRWVVF-------DGLSLRYFDSEKDAYSKRIIPLS---AISTVRAVGDNK--------FE 62

                         90       100
                 ....*....|....*....|....
gi 768022724 123 IKTSERTFYLVAETREDMNEWVQS 146
Cdd:cd13253   63 LVTTNRTFVFRAESDDERNLWCST 86

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 768022724  40 VLYSGWLrksppeKKLRLFA--WRKRWFILRRGQtssdpdvLEYYKNDGSKKPLRTINLNLCEqldVDVtLNFNKKEIQK 117
Cdd:cd13263    3 PIKSGWL------KKQGSIVknWQQRWFVLRGDQ-------LYYYKDEDDTKPQGTIPLPGNK---VKE-VPFNPEEPGK 65

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 768022724 118 gYMFDI---------KTSERTFYLVAETREDMNEWVQSICQICGFR 154
Cdd:cd13263   66 -FLFEIipggggdrmTSNHDSYLLMANSQAEMEEWVKVIRRVIGSP 110

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  43 SGWLRKSPPEKKlrlfAWRKRWFILRRGQ--TSSDPDVLEYykndgsKKPLRTINLNLCeqldvdVTLNFNKKEIQKGYM 120
Cdd:cd13276    2 AGWLEKQGEFIK----TWRRRWFVLKQGKlfWFKEPDVTPY------SKPRGVIDLSKC------LTVKSAEDATNKENA 65

                         90       100
                 ....*....|....*....|....*..
gi 768022724 121 FDIKTSERTFYLVAETREDMNEWVQSI 147
Cdd:cd13276   66 FELSTPEETFYFIADNEKEKEEWIGAI 92

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  43 SGWLRKSPpEKKLRLFAWRKRWFILrrgqtssDPD--VLEYYKNDGSKKPLRTINL-NLCEQLDVDVtlnfnkkeiQKGy 119
Cdd:cd01265    3 CGYLNKLE-TRGLGLKGWKRRWFVL-------DESkcQLYYYRSPQDATPLGSIDLsGAAFSYDPEA---------EPG- 64

                         90       100
                 ....*....|....*....|....*.
gi 768022724 120 MFDIKTSERTFYLVAETREDMNEWVQ 145
Cdd:cd01265   65 QFEIHTPGRVHILKASTRQAMLYWLQ 90

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 768022724  40 VLYSGWLRKSPPEKKLRLFAW-RKRWFILRRgqtssdpDVLEYYKN-DGSKKPLRTINLN-LCEQLDVDvtlnfNKKEIQ 116
Cdd:cd13297   13 VIERGWLYKEGGKGGARGNLTkKKRWFVLTG-------NSLDYYKSsEKNSLKLGTLVLNsLCSVVPPD-----EKMAKE 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 768022724 117 KGY-MFDIKTSERTFYLVAETREDMNEWVQSI 147
Cdd:cd13297   81 TGYwTFTVHGRKHSFRLYTKLQEEAMRWVNAI 112

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  35 TRSGHVLYSGWLRKsppeKKLRLFAWRKRWFILRRgqtssdpDVLEYYKNdgSKK---PLRTINLNLCeqldVDVTLNFN 111
Cdd:cd13215   16 KRSGAVIKSGYLSK----RSKRTLRYTRYWFVLKG-------DTLSWYNS--STDlyfPAGTIDLRYA----TSIELSKS 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768022724 112 KKEIQKGymFDIKTSERTFYLVAETREDMNEWVQSI 147
Cdd:cd13215   79 NGEATTS--FKIVTNSRTYKFKADSETSADEWVKAL 112

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  40 VLYSGWLRKSPPEKKLrLFAWRKRWFILRRGqtssdpdVLEYYKNDGSKKPLRTINLNlceqldvdvtlNFN---KKEIQ 116
Cdd:cd13308    9 VIHSGTLTKKGGSQKT-LQNWQLRYVIIHQG-------CVYYYKNDQSAKPKGVFSLN-----------GYNrraAEERT 69

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 768022724 117 KGYMFDIK-----TSERTFYLVAETREDMNEWVQSI 147
Cdd:cd13308   70 SKLKFVFKiihlsPDHRTWYFAAKSEDEMSEWMEYI 105

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 768022724  43 SGWLRK-SPPEKKLRLFAWRKRWFILRrgqtssdPDVLEYYKNDGSKKPLR--TINLN---LCEQLDVDVtlnfnkkEIQ 116
Cdd:cd01238    2 EGLLVKrSQGKKRFGPVNYKERWFVLT-------KSSLSYYEGDGEKRGKEkgSIDLSkvrCVEEVKDEA-------FFE 67

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 768022724 117 KGYMFDIKTSERTFYLVAETREDMNEWVQSICQIC 151
Cdd:cd01238   68 RKYPFQVVYDDYTLYVFAPSEEDRDEWIAALRKVC 102

Pleckstrin homology (PH) domain; Budding yeast contain two main p21-activated kinases (PAKs), Cla4 and Ste20. The yeast Ste20 protein kinase is involved in pheromone response, though the function of Ste20 mammalian homologs is unknown. Cla4 is involved in budding and cytokinesis and interacts with Cdc42, a GTPase required for polarized cell growth as is Pak. Cla4 and Ste20 kinases share a function in localizing cell growth with respect to the septin ring. They both contain a PH domain, a Cdc42/Rac interactive binding (CRIB) domain, and a C-terminal Protein Kinase catalytic (PKc) 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 768022724  40 VLYSGWLrkSPPEKKLRLFAWRKRWFILRRGQtssdpdvLEYYKNDGSKKPLRTINLNlceqldvDVTlNFNKKEIqKGY 119
Cdd:cd13279    1 VVKSGWV--SVKEDGLLSFRWSKRYLVLREQS-------LDFYKNESSSSASLSIPLK-------DIS-NVSRTDL-KPY 62

                         90       100       110
                 ....*....|....*....|....*....|
gi 768022724 120 MFDI--KTSERTFYLVAETREDMNEWVQSI 147
Cdd:cd13279   63 CFEIvrKSSTKSIYISVKSDDELYDWMDDI 92

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal 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 768022724  38 GHVLYSGWLRKsppeKKLRLFAWRKRWFILRrgqtssdPDVLEYYKNDGSKKPLRTINLNlcEQLDVDVTLNFNKKEiqk 117
Cdd:cd13273    6 LDVIKKGYLWK----KGHLLPTWTERWFVLK-------PNSLSYYKSEDLKEKKGEIALD--SNCCVESLPDREGKK--- 69

                         90       100       110
                 ....*....|....*....|....*....|
gi 768022724 118 gYMFDIKTSERTFYLVAETREDMNEWVQSI 147
Cdd:cd13273   70 -CRFLVKTPDKTYELSASDHKTRQEWIAAI 98

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 3; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the third PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  40 VLYSGWLRKSP------PEKKLRLfAWRKRWFILRRGqtssdpdVLEYYKNDGSKKPLRTINLNlceqlDVdVTLNFNKK 113
Cdd:cd13256    2 VFHSGFLYKSPsaakptLERRARE-EFSRRWCVLEDG-------FLSYYESERSPEPNGEIDVS-----EI-VCLAVSPP 67

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 768022724 114 EIQKG----YMFDIKT-SERTFYLVAETREDMNEWVQSI 147
Cdd:cd13256   68 DTHPGdgfpFTFELYLeSERLYLFGLETAEALHEWVKAI 106

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  38 GHVLYSGWLRKSPPEKKLRLFAWRKRWFILRRgqtssdpDVLEYYKNDGSKKPLRTINLNlceqldvDVTLNfNKKEIQK 117
Cdd:cd01260   11 GRGDCQGWLWKKKEAKSFFGQKWKKYWFVLKG-------SSLYWYSNQQDEKAEGFINLP-------DFKIE-RASECKK 75

                         90       100       110
                 ....*....|....*....|....*....|.
gi 768022724 118 GYMFDI-KTSERTFYLVAETREDMNEWVQSI 147
Cdd:cd01260   76 KYAFKAcHPKIKTFYFAAENLDDMNKWLSKL 106

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724   44 GWLRKSPPEkklrlfAWRKRWFILRRgqtssdPDVLEYYKNDGSKKPLRTINLNLCEQ--LDVDVTLN--------FNKK 113
Cdd:pfam15413   3 GYLKKKGPK------TWKHRWFAVLR------NGVLFYYKSEKMKVVKHVIVLSNYIVgkLGTDIISGalfkidniRSET 70

                          90       100       110
                  ....*....|....*....|....*....|....
gi 768022724  114 EIQKgyMFDIKTSERTFYLVAETREDMNEWVQSI 147
Cdd:pfam15413  71 SDDL--LLEISTETKIFFLYGDNNEETYEWVEAL 102

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 768022724  44 GWLRKSPPEKKlrlfAWRKRWFILRrGqtssdpDVLEYYKNDGSKKPLRTINLNLCE-QLDVDVTLnfnkkeiqkgYMFD 122
Cdd:cd13288   12 GYLWKKGERNT----SYQKRWFVLK-G------NLLFYFEKKGDREPLGVIVLEGCTvELAEDAEP----------YAFA 70

                         90       100
                 ....*....|....*....|....*...
gi 768022724 123 IKTS---ERTFYLVAETREDMNEWVQSI 147
Cdd:cd13288   71 IRFDgpgARSYVLAAENQEDMESWMKAL 98

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF 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 768022724  60 WRKRWFILRRGqtssdpdVLEYYKNDGSK--KPLRTINLNLCeqldvdvTLNFNKKEIQKGYMFdikTSERTFYLVAETR 137
Cdd:cd13294   15 WRSRWFVLQDG-------VLSYYKVHGPDkvKPSGEVHLKVS-------SIRESRSDDKKFYIF---TGTKTLHLRAESR 77

                         90
                 ....*....|
gi 768022724 138 EDMNEWVQSI 147
Cdd:cd13294   78 EDRAAWLEAL 87

GTPase activating protein 1 m pleckstrin homology (PH) domain; GAP1(m) (also called RASA2/RAS p21 protein activator (GTPase activating protein) 2) is a member of the GAP1 family of GTPase-activating proteins, along with RASAL1, GAP1(IP4BP), and CAPRI. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. GAP1(m) contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its C2 domains, like those of GAP1IP4BP, do not contain the C2 motif that is known to be required for calcium-dependent phospholipid binding. GAP1(m) is regulated by the binding of its PH domains to phophoinositides, PIP3 (phosphatidylinositol 3,4,5-trisphosphate). It suppresses RAS, 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. GAP1(m) binds inositol tetrakisphosphate (IP4). 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  60 WRKRWFILrrgqTSSDpdvLEYYKNDGsKKPLRTI---NLNLCEQLDVDvtlNFNKKEiqkgyMFDIKTSERTFYLVAET 136
Cdd:cd13370   37 FKKRWFCL----TSRE---LTYHKQKG-KEAIFTIpvkNILAVEKLEES---AFNKKN-----MFQVIHSEKPLYVQANN 100

                         90
                 ....*....|....
gi 768022724 137 REDMNEWVQSICQI 150
Cdd:cd13370  101 CVEANEWIEVLSRV 114

Phospholipase D pleckstrin homology (PH) domain; PLD hydrolyzes phosphatidylcholine to phosphatidic acid (PtdOH), which can bind target proteins. PLD contains a PH domain, a PX domain and four conserved PLD signature domains. The PLD PH domain is specific for bisphosphorylated inositides. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  60 WRKRWFILRrgqtssdPDVLEYYKNDGSKKPLrtinlnlceqlDV-------DVTLNFNKKEIQKGYMFDIKTSERTFYL 132
Cdd:cd01254   57 WSKRWFIVK-------DSFLAYVKDPDSGAIL-----------DVflfdqefKVSRGGKETKYGSRHGLKITNLSRKLKL 118

                         90
                 ....*....|....*
gi 768022724 133 VAETREDMNEWVQSI 147
Cdd:cd01254  119 KCKSERKAKQWVESI 133

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768022724  59 AWRKRWFILRRGqtssdpdVLEYYK---NDGSKKPLRTINLNLC-----EQLDVDVTLNFNKKEIQ------KGYMFDIK 124
Cdd:cd01263   19 AWHRRWCVLRGG-------YLSFWKypdDEEKKKPIGSIDLTKCitekvEPAPRELCARPNTFLLEtlrpaeDDDRDDTN 91