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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNIL 785
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 2462570088  786 EEWIKVLQNVLRVQAA 801
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088   20 LESQLMKFRVQASKIRELLAE---KMQQLERQVidaeRQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQ 96
Cdd:TIGR02168  759 LEAEIEELEERLEEAEEELAEaeaEIEELEAQI----EQLKEELKALREALDELRAELTLLNEEAANLRERLESLERRIA 834

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088   97 EKDDVIQNLELQLEEQKQIRIQEAKIIEE---KAAKIKEWVTVKLNELELENQNLRLIN---QNQTEEIRTMQSKLQEVQ 170
Cdd:TIGR02168  835 ATERRLEDLEEQIEELSEDIESLAAEIEEleeLIEELESELEALLNERASLEEALALLRselEELSEELRELESKRSELR 914

                   ..
gi 2462570088  171 GK 172
Cdd:TIGR02168  915 RE 916

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088    3 ELSEPEGPVDWKERCVALESQLMKFRvQASKIREllAEKMQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESET 82
Cdd:PTZ00121  1556 ELKKAEEKKKAEEAKKAEEDKNMALR-KAEEAKK--AEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEK 1632

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088   83 RlynKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAKIIEEKAAKIKEWVTVKLNELELENQNLRLINQ-NQTEEIRT 161
Cdd:PTZ00121  1633 K---KVEQLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEaKKAEELKK 1709

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088  162 MQS--KLQEVQGKKSSTVSTLKLSEGQRLSSltfgcfLSRARSPPQVVKSEEMSKISSKEPEftEGKDMEEMEIPEKSVD 239
Cdd:PTZ00121  1710 KEAeeKKKAEELKKAEEENKIKAEEAKKEAE------EDKKKAEEAKKDEEEKKKIAHLKKE--EEKKAEEIRKEKEAVI 1781

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088  240 NQVLENNRGQRTLhqtpcgsEQNRKTRTSFATDGGISQ--NSGAPVSDWSSDEEDGSkgrSKSRCTSTLSSHTSEEGVQC 317
Cdd:PTZ00121  1782 EEELDEEDEKRRM-------EVDKKIKDIFDNFANIIEggKEGNLVINDSKEMEDSA---IKEVADSKNMQLEEADAFEK 1851

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462570088  318 SRMGSEMYLTASDDSSSIFEEETFGIKRPEHKKLYSWQQEaQWKALNSPLGKGNSELSKKEQDSSSDELNKKFQSQR 394
Cdd:PTZ00121  1852 HKFNKNNENGEDGNKEADFNKEKDLKEDDEEEIEEADEIE-KIDKDDIEREIPNNNMAGKNNDIIDDKLDKDEYIKR 1927

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNIL 785
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 2462570088  786 EEWIKVLQNVLRVQAA 801
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96

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 2462570088   704 LEKSGYLLKMS-GKVKSWKRRWFVLKGGELLYYKSPSDV-IRKPQGHIELSaSCSILRGDNKQTVQ-------LTTEKHT 774
Cdd:smart00233    1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLS-GCTVREAPDPDSSKkphcfeiKTSDRKT 79

                            90       100
                    ....*....|....*....|...
gi 2462570088   775 YYLTADSPNILEEWIKVLQNVLR 797
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 2462570088 1003 AQSALQICLTHPELQNEICCQLIKQTRRrqpqNQPGPLQDRIWkicHLLpALC 1055
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTN----NPKPESLLRGW---QLL-ALC 45

phosphodiesterase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088   40 EKMQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNL-ELQLEEQKQIRIQ 118
Cdd:PRK12704    82 NELQKLEKRLLQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERIsGLTAEEAKEILLE 161

                           90
                   ....*....|....*..
gi 2462570088  119 --EAKIIEEKAAKIKEW 133
Cdd:PRK12704   162 kvEEEARHEAAVLIKEI 178

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 2462570088   812 PTMKGLLTKVKHGYS---KRVWCTLIGKTLYYFRS---QEDKFPLGQIKLWEAKVEEVDRSCDSDEDyeasgrsllsthY 885
Cdd:smart00233    1 VIKEGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------H 68

                            90       100
                    ....*....|....*....|....*....
gi 2462570088   886 TIVIHPKDQGPTYLLIGSKHEKDTWLYHL 914
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEAL 97

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462570088  811 KPTMKGLLTK---VKHGYSKRvWCTLIGKTLYYFRSQEDKFPLGQIKLWEAKVEevdrSCDSDEDY 873
Cdd:cd13288      7 PVDKEGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY 67

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088    3 ELSEPEGPVDWKERCVALESQLMKFRvQASKIREllAEKMQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESET 82
Cdd:PTZ00121  1556 ELKKAEEKKKAEEAKKAEEDKNMALR-KAEEAKK--AEEARIEEVMKLYEEEKKMKAEEAKKAEEAKIKAEELKKAEEEK 1632

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088   83 RlynKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAKIIEEKAAKIKEWVTVKLNELELENQNLRLINQ-NQTEEIRT 161
Cdd:PTZ00121  1633 K---KVEQLKKKEAEEKKKAEELKKAEEENKIKAAEEAKKAEEDKKKAEEAKKAEEDEKKAAEALKKEAEEaKKAEELKK 1709

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088  162 MQS--KLQEVQGKKSSTVSTLKLSEGQRLSSltfgcfLSRARSPPQVVKSEEMSKISSKEPEftEGKDMEEMEIPEKSVD 239
Cdd:PTZ00121  1710 KEAeeKKKAEELKKAEEENKIKAEEAKKEAE------EDKKKAEEAKKDEEEKKKIAHLKKE--EEKKAEEIRKEKEAVI 1781

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088  240 NQVLENNRGQRTLhqtpcgsEQNRKTRTSFATDGGISQ--NSGAPVSDWSSDEEDGSkgrSKSRCTSTLSSHTSEEGVQC 317
Cdd:PTZ00121  1782 EEELDEEDEKRRM-------EVDKKIKDIFDNFANIIEggKEGNLVINDSKEMEDSA---IKEVADSKNMQLEEADAFEK 1851

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462570088  318 SRMGSEMYLTASDDSSSIFEEETFGIKRPEHKKLYSWQQEaQWKALNSPLGKGNSELSKKEQDSSSDELNKKFQSQR 394
Cdd:PTZ00121  1852 HKFNKNNENGEDGNKEADFNKEKDLKEDDEEEIEEADEIE-KIDKDDIEREIPNNNMAGKNNDIIDDKLDKDEYIKR 1927

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNIL 785
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 2462570088  786 EEWIKVLQNVLRVQAA 801
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088   955 HSKEGIISPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQICLTHPELQNEICCQLIKQTRRRQPQ 1034
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDNPSR 79

                            90
                    ....*....|....*..
gi 2462570088  1035 NqpgpLQDRIWKICHLL 1051
Cdd:smart00139   80 Q----SEERGWQLLYLC 92

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 2462570088  706 KSGYLLKMSGKV-----KSWKRRWFVLKGGELLYYKSPSDViRKPQGHIELSASCSILRGDNKQT-VQLTTEKHTYYLTA 779
Cdd:cd13296      1 KSGWLTKKGGGSstlsrRNWKSRWFVLRDTVLKYYENDQEG-EKLLGTIDIRSAKEIVDNDPKENrLSITTEERTYHLVA 79

                           90
                   ....*....|....*...
gi 2462570088  780 DSPNILEEWIKVLQNVLR 797
Cdd:cd13296     80 ESPEDASQWVNVLTRVIS 97

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASC----------------SILRGDNKQtvQLT 769
Cdd:cd13263      5 KSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDT--KPQGTIPLPGNKvkevpfnpeepgkflfEIIPGGGGD--RMT 80

                           90       100
                   ....*....|....*....|....*..
gi 2462570088  770 TEKHTYYLTADSPNILEEWIKVLQNVL 796
Cdd:cd13263     81 SNHDSYLLMANSQAEMEEWVKVIRRVI 107

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASCSILRGDNKQTV---QLTTEKHTYYLTADSP 782
Cdd:cd10573      5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDT--KPIRVLDLRECSSVQRDYSQGKVncfCLVFPERTFYMYANTE 82

                           90
                   ....*....|.
gi 2462570088  783 NILEEWIKVLQ 793
Cdd:cd10573     83 EEADEWVKLLK 93

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 2462570088  701 NEPLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELsASCSI--LRGDNKQTVQLTT---EKHTY 775
Cdd:cd13288      5 NSPVDKEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGD--REPLGVIVL-EGCTVelAEDAEPYAFAIRFdgpGARSY 81

                           90
                   ....*....|....*....
gi 2462570088  776 YLTADSPNILEEWIKVLQN 794
Cdd:cd13288     82 VLAAENQEDMESWMKALSR 100

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPsDVIR--KPQGHIELSaSCSILRGD----NKQ-TVQLTTEKHTYYLT 778
Cdd:cd13276      1 KAGWLEKQGEFIKTWRRRWFVLKQGKLFWFKEP-DVTPysKPRGVIDLS-KCLTVKSAedatNKEnAFELSTPEETFYFI 78

                           90
                   ....*....|.
gi 2462570088  779 ADSPNILEEWI 789
Cdd:cd13276     79 ADNEKEKEEWI 89

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELSASCSI----LRGDNKQTVQLTTEKHTYYLTADS 781
Cdd:cd13273     10 KKGYLWKKGHLLPTWTERWFVLKPNSLSYYKSEDL--KEKKGEIALDSNCCVeslpDREGKKCRFLVKTPDKTYELSASD 87

                           90
                   ....*....|....*...
gi 2462570088  782 PNILEEWIKVLQNVLRVQ 799
Cdd:cd13273     88 HKTRQEWIAAIQTAIRLS 105

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 2462570088  706 KSGYLLKMSGKV-KSWKRRWFVLKGGELLYYKspsdvirKPQGHIELSASCSILRGdnkqTVQLTTEKH----------- 773
Cdd:cd13250      1 KEGYLFKRSSNAfKTWKRRWFSLQNGQLYYQK-------RDKKDEPTVMVEDLRLC----TVKPTEDSDrrfcfevispt 69

                           90       100
                   ....*....|....*....|...
gi 2462570088  774 -TYYLTADSPNILEEWIKVLQNV 795
Cdd:cd13250     70 kSYMLQAESEEDRQAWIQAIQSA 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 2462570088  707 SGYLLKMSGK---VKSWKRRWFVLKGG--ELLYYKSPSDVirKPQGHIELS-ASCSILRGDNKQTVQLTTEKHTYYLTAD 780
Cdd:cd01265      3 CGYLNKLETRglgLKGWKRRWFVLDESkcQLYYYRSPQDA--TPLGSIDLSgAAFSYDPEAEPGQFEIHTPGRVHILKAS 80

                           90
                   ....*....|...
gi 2462570088  781 SPNILEEWIKVLQ 793
Cdd:cd01265     81 TRQAMLYWLQALQ 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088  702 EPLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSAS----------------CSILRGDNKQT 765
Cdd:cd13378      1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEET--KPQGCISLQGSqvnelppnpeepgkhlFEILPGGAGDR 78

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2462570088  766 VQLTTEKHTYYLTADSPNILEEWIKVLQNVL 796
Cdd:cd13378     79 EKVPMNHEAFLLMANSQSDMEDWVKAIRRVI 109

Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; Human ORP3 is proposed to function in regulating the cell-matrix and cell-cell adhesion. A proposed specific function for Human ORP6 was not found at present. Human ORP7is proposed to function in negatively regulating the Golgi soluble NSF attachment protein receptor (SNARE) of 28kDa (GS28) protein stability via sequestration of Golgi-associated ATPase enhancer of 16 kDa (GATE-16). ORP3 has 2 isoforms: the longer ORP3(1) and the shorter ORP3(2). ORP3(1), ORP6, and ORP7 all contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. The shorter ORP3(2) is missing the C-terminal portion of its OSBP-related domain. 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 2462570088  700 KNEPLEKSGYLLKM-SGKVKSWKRRWFVLKGGELLYYKSPSDVIR-KPQGHIELSASC-SILRgdNKQTVQLTTEKHTYY 776
Cdd:cd13287     18 VQEPGKQEGYLLKKrKWPLKGWHKRFFVLEKGILKYAKSPLDIAKgKLHGSIDVGLSVmSIKK--KARRIDLDTEEFIYH 95

                           90
                   ....*....|....*..
gi 2462570088  777 LTADSPNILEEWIKVLQ 793
Cdd:cd13287     96 LKVKSQDLFDSWVAKLR 112

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL---SASCSILRGDNKQTV-QLTTEK-HTYYLTAD 780
Cdd:cd13301      5 KEGYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTD--SSPKGMIPLkgcTITSPCLEYGKRPLVfKLTTAKgQEHFFQAC 82

                           90
                   ....*....|....*..
gi 2462570088  781 SPNILEEWIKVLQNVLR 797
Cdd:cd13301     83 SREERDAWAKDITKAIT 99

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 2462570088  706 KSGYLLKMSGKVKS---WKRRWFVLKGGELLYYKSPSDVirKPQGHIELS-ASCSI---LRGDNK---QTVQLTTEKHTY 775
Cdd:cd13308     11 HSGTLTKKGGSQKTlqnWQLRYVIIHQGCVYYYKNDQSA--KPKGVFSLNgYNRRAaeeRTSKLKfvfKIIHLSPDHRTW 88

                           90       100
                   ....*....|....*....|
gi 2462570088  776 YLTADSPNILEEWIKVLQNV 795
Cdd:cd13308     89 YFAAKSEDEMSEWMEYIRRE 108

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. 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 2462570088  703 PLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSAscSILRGDNKQTVQL-----TTEKHTYYL 777
Cdd:cd13292      1 PPTMKGYLKKWTNYAKGYKTRWFVLEDGVLSYYRHQDDEGSACRGSINMKN--ARLVSDPSEKLRFevsskTSGSPKWYL 78

                           90       100
                   ....*....|....*....|
gi 2462570088  778 TADSPNILEEWIKVLQNVLR 797
Cdd:cd13292     79 KANHPVEAARWIQALQKAIE 98

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 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL-----SASC---SILRGDNkqTVQLTTEKHTYYL 777
Cdd:cd13271     10 KSGYCVKQGAVRKNWKRRFFILDDNTISYYKSETD--KEPLRTIPLrevlkVHEClvkSLLMRDN--LFEIITTSRTFYI 85

                           90
                   ....*....|...
gi 2462570088  778 TADSPNILEEWIK 790
Cdd:cd13271     86 QADSPEEMHSWIK 98

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. 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.

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gi 2462570088  706 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCsILRGDNKQTVQLTTEKHTYYLTADSPNIL 785
Cdd:cd13284      1 MKGWLLKWTNYIKGYQRRWFVLSNGLLSYYRNQAEMAHTCRGTINLAGAE-IHTEDSCNFVISNGGTQTFHLKASSEVER 79

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gi 2462570088  786 EEWIKVLQN 794
Cdd:cd13284     80 QRWVTALEL 88