Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633   1 MAFVKSGWLLRQSTILKRWKKNWFDLWSDGHLIYYDDQTRQNIEDKVHMPMDCINIRTGQECRDTQPPDGKSKDCMLQIV 80
Cdd:cd13265    1 MALVKSGWLLRQSTILKRWKKNWFVLYGDGNLVYYEDETRREVEGRINMPRECRNIRVGLECRDVQPPEGRSRDCLLQIV 80

                         90       100
                 ....*....|....*....|....*...
gi 767918633  81 CRDGKTISLCAESTDDCLAWKFTLQDSR 108
Cdd:cd13265   81 LRDGSTLFLCAESADDALAWKLALQDAR 108

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633   1 MAFVKSGWLLRQSTILKRWKKNWFDLWSDGHLIYYDDQTRQNIEDKVHMPMDCINIRTGQECRDTQPPDGKSKDCMLQIV 80
Cdd:cd13265    1 MALVKSGWLLRQSTILKRWKKNWFVLYGDGNLVYYEDETRREVEGRINMPRECRNIRVGLECRDVQPPEGRSRDCLLQIV 80

                         90       100
                 ....*....|....*....|....*...
gi 767918633  81 CRDGKTISLCAESTDDCLAWKFTLQDSR 108
Cdd:cd13265   81 LRDGSTLFLCAESADDALAWKLALQDAR 108

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633    4 VKSGWLLRQSTILK-RWKKNWFDLwSDGHLIYYDDQTRQNIEDKVHMpmdcINIRTGQeCRDTQPPDGKSKDCMLQIVCR 82
Cdd:pfam00169   2 VKEGWLLKKGGGKKkSWKKRYFVL-FDGSLLYYKDDKSGKSKEPKGS----ISLSGCE-VVEVVASDSPKRKFCFELRTG 75

                          90       100
                  ....*....|....*....|.
gi 767918633   83 D---GKTISLCAESTDDCLAW 100
Cdd:pfam00169  76 ErtgKRTYLLQAESEEERKDW 96

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633   1 MAFVKSGWLLRQSTILKRWKKNWFDLWSDGHLIYYDDQTRQNIEDKVHMPMDCINIRTGQECRDTQPPDGKSKDCMLQIV 80
Cdd:cd13265    1 MALVKSGWLLRQSTILKRWKKNWFVLYGDGNLVYYEDETRREVEGRINMPRECRNIRVGLECRDVQPPEGRSRDCLLQIV 80

                         90       100
                 ....*....|....*....|....*...
gi 767918633  81 CRDGKTISLCAESTDDCLAWKFTLQDSR 108
Cdd:cd13265   81 LRDGSTLFLCAESADDALAWKLALQDAR 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633   5 KSGWLLRQS-TILKRWKKNWFDLwSDGHLIYYDDQTrqnieDKVHMPMDCINIRTGQECRDTQPpdgKSKDCMLQIVCRD 83
Cdd:cd00821    1 KEGYLLKRGgGGLKSWKKRWFVL-FEGVLLYYKSKK-----DSSYKPKGSIPLSGILEVEEVSP---KERPHCFELVTPD 71

                         90
                 ....*....|....*..
gi 767918633  84 GKTISLCAESTDDCLAW 100
Cdd:cd00821   72 GRTYYLQADSEEERQEW 88

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 767918633   5 KSGWLLRQ----STILKR-WKKNWFDLwSDGHLIYYDDQTrqnIEDKvhmPMDCINIRTGQECRDTQPpdgksKDCMLQI 79
Cdd:cd13296    1 KSGWLTKKgggsSTLSRRnWKSRWFVL-RDTVLKYYENDQ---EGEK---LLGTIDIRSAKEIVDNDP-----KENRLSI 68

                         90       100
                 ....*....|....*....|.
gi 767918633  80 VCrDGKTISLCAESTDDCLAW 100
Cdd:cd13296   69 TT-EERTYHLVAESPEDASQW 88

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633   4 VKSGWLLRQSTILKRWKKNWFDLWSDgHLIYYDDQTrqniEDKvhmPMDCINIRTGQECRDTQPPDGKSK 73
Cdd:cd13378    4 LKAGWLKKQRSIMKNWQQRWFVLRGD-QLFYYKDEE----ETK---PQGCISLQGSQVNELPPNPEEPGK 65

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767918633   7 GWLLRQSTILKRWKKNWFDLWSDGH-LIYYDdqtrqNIEDKVhmPMDCIN---IRTGQECRDTQPPDGKSKDCMLQIVCR 82
Cdd:cd01235    7 GYLYKRGALLKGWKQRWFVLDSTKHqLRYYE-----SREDTK--CKGFIDlaeVESVTPATPIIGAPKRADEGAFFDLKT 79

                         90       100
                 ....*....|....*....|....*
gi 767918633  83 DGKTISLCAESTDDCLAWKFTLQDS 107
Cdd:cd01235   80 NKRVYNFCAFDAESAQQWIEKIQSC 104

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 767918633   5 KSGWLLRQSTILKRWKKNWFDLwSDGHLIYYDDQTRQNIEDKVHMPMDcinirtgQECRdTQPPDGkskDCMLQIVCrDG 84
Cdd:cd13282    1 KAGYLTKLGGKVKTWKRRWFVL-KNGELFYYKSPNDVIRKPQGQIALD-------GSCE-IARAEG---AQTFEIVT-EK 67

                         90       100
                 ....*....|....*....|..
gi 767918633  85 KTISLCAESTDDCLAWKFTLQD 106
Cdd:cd13282   68 RTYYLTADSENDLDEWIRVIQN 89

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 767918633   4 VKSGWLLRQSTILKRWKKNWFDLWSDgHLIYYDDqtrqniEDKVHmPMDCINIRTGQECRDTQPPDGKSKdCMLQIVCRD 83
Cdd:cd13263    4 IKSGWLKKQGSIVKNWQQRWFVLRGD-QLYYYKD------EDDTK-PQGTIPLPGNKVKEVPFNPEEPGK-FLFEIIPGG 74

                         90       100
                 ....*....|....*....|....*
gi 767918633  84 GKTIS--------LCAESTDDCLAW 100
Cdd:cd13263   75 GGDRMtsnhdsylLMANSQAEMEEW 99

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 767918633   5 KSGWLLRQSTILKRWKKNWFDLwSDGHLIYYDDQtrqniEDKVhmPMDCINIRTGQEC-RDTQPpdGKSkDCMlqIVCRD 83
Cdd:cd10573    5 KEGYLTKLGGIVKNWKTRWFVL-RRNELKYFKTR-----GDTK--PIRVLDLRECSSVqRDYSQ--GKV-NCF--CLVFP 71

                         90       100
                 ....*....|....*....|..
gi 767918633  84 GKTISLCAESTDDCLAWKFTLQ 105
Cdd:cd10573   72 ERTFYMYANTEEEADEWVKLLK 93

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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 767918633   5 KSGWLL-RQSTILKRWKKNWFDLwSDGHLIYYDDQTrqniedKVHMPMDCINIRTgqeC--RDTQPPDGK--------SK 73
Cdd:cd13250    1 KEGYLFkRSSNAFKTWKRRWFSL-QNGQLYYQKRDK------KDEPTVMVEDLRL---CtvKPTEDSDRRfcfevispTK 70

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767918633  74 DCMLQivcrdgktislcAESTDDCLAWKFTLQDS 107
Cdd:cd13250   71 SYMLQ------------AESEEDRQAWIQAIQSA 92

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

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gi 767918633   4 VKSGWLLRQSTILKRWKKNWFDL-WSDGHLIYYDDQTR 40
Cdd:cd13260    4 DKKGYLLKKGGKNKKWKNLYFVLeGKEQHLYFFDNEKR 41

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first 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.

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gi 767918633   4 VKSGWLLRQSTILKRWKKNWFDLWSDGhLIYYDDQ 38
Cdd:cd13298    7 LKSGYLLKRSRKTKNWKKRWVVLRPCQ-LSYYKDE 40