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 285811007  289 PPTYKGFLKKWTNFAHGYKLRWFILSgDGNLSYYKDQ-SHVDRPRGTLKVSTCRLHIDSSEKLNFELLGGITGTTRWRLK 367
Cdd:cd13292     1 PPTMKGYLKKWTNYAKGYKTRWFVLE-DGVLSYYRHQdDEGSACRGSINMKNARLVSDPSEKLRFEVSSKTSGSPKWYLK 79

                          90       100
                  ....*....|....*....|....
gi 285811007  368 GNHPIETTRWVNAIQSAIRFAKDK 391
Cdd:cd13292    80 ANHPVEAARWIQALQKAIEWAKDE 103

Ankyrin repeats (many copies);

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285811007    59 ILHYAVQVAPILLIKEIVAHWVDqvgdeksssksddgihldLNYQDENGNTPLHLAAAQSRSDVISFLL 127
Cdd:pfam13637    4 ALHAAAASGHLELLRLLLEKGAD------------------INAVDGNGETALHFAASNGNVEVLKLLL 54

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 285811007  289 PPTYKGFLKKWTNFAHGYKLRWFILSgDGNLSYYKDQ-SHVDRPRGTLKVSTCRLHIDSSEKLNFELLGGITGTTRWRLK 367
Cdd:cd13292     1 PPTMKGYLKKWTNYAKGYKTRWFVLE-DGVLSYYRHQdDEGSACRGSINMKNARLVSDPSEKLRFEVSSKTSGSPKWYLK 79

                          90       100
                  ....*....|....*....|....
gi 285811007  368 GNHPIETTRWVNAIQSAIRFAKDK 391
Cdd:cd13292    80 ANHPVEAARWIQALQKAIEWAKDE 103

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007   99 DLNYQDENGNTPLHLAAAQSRSDVISFLLSQK-SINdcVKNKAHQQPLdmckdlnvaqmiqlkrddyfletvhsLRAAMN 177
Cdd:COG0666   112 DVNARDKDGETPLHLAAYNGNLEIVKLLLEAGaDVN--AQDNDGNTPL--------------------------HLAAAN 163

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 285811007  178 KrdfskldsiwkNPRNLNLL-----DINGIDPEtGTTLLYEYSQKKDIEMCQWLLKHGAEATVKDGKGRSPLDL 246
Cdd:COG0666   164 G-----------NLEIVKLLleagaDVNARDND-GETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDL 225

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007   99 DLNYQDENGNTPLHLAAAQSRSDVISFLLSQKSINDcVKNKAHQQPLDmckdlNVAQMIQLKRDDYFLETVHSLraaMNK 178
Cdd:PHA02874  149 DVNIEDDNGCYPIHIAIKHNFFDIIKLLLEKGAYAN-VKDNNGESPLH-----NAAEYGDYACIKLLIDHGNHI---MNK 219

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285811007  179 --RDFSKLDS----------IWKNPRNLNLLDINGIDPetgttLLYEYSQKKDIEMCQWLLKHGAEATVKDGKGRSPLD 245
Cdd:PHA02874  220 ckNGFTPLHNaiihnrsaieLLINNASINDQDIDGSTP-----LHHAINPPCDIDIIDILLYHKADISIKDNKGENPID 293

Ankyrin repeats (many copies);

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285811007    59 ILHYAVQVAPILLIKEIVAHWVDqvgdeksssksddgihldLNYQDENGNTPLHLAAAQSRSDVISFLL 127
Cdd:pfam13637    4 ALHAAAASGHLELLRLLLEKGAD------------------INAVDGNGETALHFAASNGNVEVLKLLL 54

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 285811007  289 PPTYKGFLKKWTNFAHGYKLRWFILSgDGNLSYYKDQ-SHVDRPRGTLKVSTCRLHIDSSEKLNFELLGGITGTTRWRLK 367
Cdd:cd13292     1 PPTMKGYLKKWTNYAKGYKTRWFVLE-DGVLSYYRHQdDEGSACRGSINMKNARLVSDPSEKLRFEVSSKTSGSPKWYLK 79

                          90       100
                  ....*....|....*....|....
gi 285811007  368 GNHPIETTRWVNAIQSAIRFAKDK 391
Cdd:cd13292    80 ANHPVEAARWIQALQKAIEWAKDE 103

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007  292 YKGFLKKWTNFAHGYKLRWFILSgDGNLSYYKDQSHVDRP-RGTLKVSTCrlHIDSSEKLNFELLGGitGTTRWRLKGNH 370
Cdd:cd13284     1 MKGWLLKWTNYIKGYQRRWFVLS-NGLLSYYRNQAEMAHTcRGTINLAGA--EIHTEDSCNFVISNG--GTQTFHLKASS 75

                          90
                  ....*....|....
gi 285811007  371 PIETTRWVNAIQSA 384
Cdd:cd13284    76 EVERQRWVTALELA 89

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007   290 PTYKGFLKKWTN-FAHGYKLRWFILSgDGNLSYYKDQS--HVDRPRGTLKVSTCRL-----HIDSSEKLNFELLGGI-TG 360
Cdd:pfam00169    1 VVKEGWLLKKGGgKKKSWKKRYFVLF-DGSLLYYKDDKsgKSKEPKGSISLSGCEVvevvaSDSPKRKFCFELRTGErTG 79

                           90       100
                   ....*....|....*....|....*.
gi 285811007   361 TTRWRLKGNHPIETTRWVNAIQSAIR 386
Cdd:pfam00169   80 KRTYLLQAESEEERKDWIKAIQSAIR 105

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 285811007    290 PTYKGFLKKWT-NFAHGYKLRWFILSgDGNLSYYKDQSHVD--RPRGTLKVSTCRLHIDSSEKLN-----FELLGGitGT 361
Cdd:smart00233    1 VIKEGWLYKKSgGGKKSWKKRYFVLF-NSTLLYYKSKKDKKsyKPKGSIDLSGCTVREAPDPDSSkkphcFEIKTS--DR 77

                            90       100
                    ....*....|....*....|....*
gi 285811007    362 TRWRLKGNHPIETTRWVNAIQSAIR 386
Cdd:smart00233   78 KTLLLQAESEEEREKWVEALRKAIA 102

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 285811007  294 GFLKKWtnfahgyKLRWFILSgDGNLSYYKDQSHVDR-PRGTLKV-STCRLhIDSSEKLNFELlggITGTTRWRLKGNHP 371
Cdd:cd13282    10 GKVKTW-------KRRWFVLK-NGELFYYKSPNDVIRkPQGQIALdGSCEI-ARAEGAQTFEI---VTEKRTYYLTADSE 77

                          90
                  ....*....|....*.
gi 285811007  372 IETTRWVNAIQSAIRF 387
Cdd:cd13282    78 NDLDEWIRVIQNVLRR 93

Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin homology (PH) domain; Human ORP10 is involvedt in intracellular transport or organelle positioning and is proposed to function as a regulator of cellular lipid metabolism. Human ORP11 localizes at the Golgi-late endosome interface and is thought to form a dimer with ORP9 functioning as an intracellular lipid sensor or transporter. Both ORP10 and ORP11 contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal 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
                  ....*....|....*....|....*....|....*....|....*.
gi 285811007  292 YKGFLKKWTNFAHGYKLRWFILSGD-GNLSYY-KDQSHVDRPRGTL 335
Cdd:cd13291     1 LEGQLLKYTNVVKGWQNRWFVLDPDtGILEYFlSEESKNQKPRGSL 46

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 285811007  290 PTYKGFLKKWTNFAHGYKLRWFILSGDgNLSYYKDQSHVdRPRGTLKVSTCRLHI-----DSSEKLNFELLGGITGTtrw 364
Cdd:cd13263     3 PIKSGWLKKQGSIVKNWQQRWFVLRGD-QLYYYKDEDDT-KPQGTIPLPGNKVKEvpfnpEEPGKFLFEIIPGGGGD--- 77

                          90       100       110
                  ....*....|....*....|....*....|
gi 285811007  365 RLKGNH---------PIETTRWVNAIQSAI 385
Cdd:cd13263    78 RMTSNHdsyllmansQAEMEEWVKVIRRVI 107

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007   99 DLNYQDENGNTPLHLAAAQSRSDVISFLLSQKSINDcVKNKAHQQPLDmckdlNVAQMIQLKRDDYFLETVHSLraaMNK 178
Cdd:PHA02874  149 DVNIEDDNGCYPIHIAIKHNFFDIIKLLLEKGAYAN-VKDNNGESPLH-----NAAEYGDYACIKLLIDHGNHI---MNK 219

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285811007  179 --RDFSKLDS----------IWKNPRNLNLLDINGIDPetgttLLYEYSQKKDIEMCQWLLKHGAEATVKDGKGRSPLD 245
Cdd:PHA02874  220 ckNGFTPLHNaiihnrsaieLLINNASINDQDIDGSTP-----LHHAINPPCDIDIIDILLYHKADISIKDNKGENPID 293

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 285811007  293 KGFL-KKWTNFAHGYKLRWFILSgDGNLSYYKDQSHVDRPRGTLKVSTCRLHIDSSEKLN--FELlggITGTTRWRLKGN 369
Cdd:cd13250     2 EGYLfKRSSNAFKTWKRRWFSLQ-NGQLYYQKRDKKDEPTVMVEDLRLCTVKPTEDSDRRfcFEV---ISPTKSYMLQAE 77

                          90
                  ....*....|....*.
gi 285811007  370 HPIETTRWVNAIQSAI 385
Cdd:cd13250    78 SEEDRQAWIQAIQSAI 93

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 285811007  294 GFLKKWTNFAHGYKLRWFILSgDGNLSYYKDQSHVD--RPRGTLKVSTCrLHIDSSE-KLN----FELlggITGTTRWRL 366
Cdd:cd13276     3 GWLEKQGEFIKTWRRRWFVLK-QGKLFWFKEPDVTPysKPRGVIDLSKC-LTVKSAEdATNkenaFEL---STPEETFYF 77

                          90
                  ....*....|....*....
gi 285811007  367 KGNHPIETTRWVNAIQSAI 385
Cdd:cd13276    78 IADNEKEKEEWIGAIGRAI 96

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007  101 NYQDENGNTPLHLAAAQSRSDVISFLLSQKSINDcVKNKAHQQPLDM----CKDLNVAQMIqlkrddyfLETVHSLRAAM 176
Cdd:PHA02878  195 NIPDKTNNSPLHHAVKHYNKPIVHILLENGASTD-ARDKCGNTPLHIsvgyCKDYDILKLL--------LEHGVDVNAKS 265

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007  177 NKRDFSKLDSIWKNPRNLNLL-----DINGIDPETGTTLLYEYSQKKDIEMCQWLLKHGAEATVKDGKGRSPLDLVKNIK 251
Cdd:PHA02878  266 YILGLTALHSSIKSERKLKLLleygaDINSLNSYKLTPLSSAVKQYLCINIGRILISNICLLKRIKPDIKNSEGFIDNMD 345

                         170       180
                  ....*....|....*....|..
gi 285811007  252 lpAKPSNNVTPEIKLKNLLEKN 273
Cdd:PHA02878  346 --CITSNKRLNQIKDKCEDELN 365

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
                  ....*....|....*....|....*....|...
gi 285811007  294 GFLKKWtnfahgyKLRWFILSGDGNLSYYKDQS 326
Cdd:cd13265    14 TILKRW-------KKNWFVLYGDGNLVYYEDET 39

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 285811007  294 GFLKKWTNFAHGYKLRWFILSGDgNLSYYKDQSHVdRPRGTL-----KVSTCRLHIDSSEKLNFELLGGITGtTRWRLKG 368
Cdd:cd13378     7 GWLKKQRSIMKNWQQRWFVLRGD-QLFYYKDEEET-KPQGCIslqgsQVNELPPNPEEPGKHLFEILPGGAG-DREKVPM 83

                          90       100
                  ....*....|....*....|....*.
gi 285811007  369 NHPI---------ETTRWVNAIQSAI 385
Cdd:cd13378    84 NHEAfllmansqsDMEDWVKAIRRVI 109

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007   60 LHYAVQVAPILLIKEIVAHWVDqvgdeksssksddgihldLNYQDENGNTPLHLAAAQSRSDVISFLLSqkSINDCVKNK 139
Cdd:PHA02878   41 LHQAVEARNLDVVKSLLTRGHN------------------VNQPDHRDLTPLHIICKEPNKLGMKEMIR--SINKCSVFY 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007  140 AHQQPLDMC--KDLNVAQMIQLKRDD--YFLETVHSlraamnkRDFSKLDSIWKNPRNLNL---LDINGIDPETGTTLLY 212
Cdd:PHA02878  101 TLVAIKDAFnnRNVEIFKIILTNRYKniQTIDLVYI-------DKKSKDDIIEAEITKLLLsygADINMKDRHKGNTALH 173

                         170       180       190
                  ....*....|....*....|....*....|..
gi 285811007  213 EYSQKKDIEMCQWLLKHGAEATVKDGKGRSPL 244
Cdd:PHA02878  174 YATENKDQRLTELLLSYGANVNIPDKTNNSPL 205

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. 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 285811007  293 KGFLKKWTNFAHGYKLRWFILSGDGnLSYYKDQSHVDR--PRGTLKVSTCR--LHIDSSEKLNFEL---------LGGIT 359
Cdd:cd13275     2 KGWLMKQGSRQGEWSKHWFVLRGAA-LKYYRDPSAEEAgeLDGVIDLSSCTevTELPVSRNYGFQVktwdgkvyvLSAMT 80

                          90       100
                  ....*....|....*....|....*..
gi 285811007  360 GTTRwrlkgnhpietTRWVNAIQSAIR 386
Cdd:cd13275    81 SGIR-----------TNWIQALRKAAG 96

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 285811007  285 ASSKPPTYK-GFLKKWTNFAHGYKLRWFILSgdGNLSYYKDQSHVDRPRGTLKVSTCRLHI-DSSEKLNFELLGGITGTT 362
Cdd:cd13288     2 ATCNSPVDKeGYLWKKGERNTSYQKRWFVLK--GNLLFYFEKKGDREPLGVIVLEGCTVELaEDAEPYAFAIRFDGPGAR 79

                          90       100
                  ....*....|....*....|..
gi 285811007  363 RWRLKGNHPIETTRWVNAIQSA 384
Cdd:cd13288    80 SYVLAAENQEDMESWMKALSRA 101

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 285811007   98 LDLNYQDENGNTPLHLAAAQSRSDVISFLLSQKSINDCVKnkahqqpLDmckDLNVaqmIQLKRDDYFLETVHSL---RA 174
Cdd:PHA02876  169 ADVNAKDIYCITPIHYAAERGNAKMVNLLLSYGADVNIIA-------LD---DLSV---LECAVDSKNIDTIKAIidnRS 235

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 285811007  175 AMNKRDFSKLDSIWKNPRNLNLL------DINGIDPETGTTLLYEYSQKKDIEMCQWLLKHGAEATVKDGKGRSPLDLV 247
Cdd:PHA02876  236 NINKNDLSLLKAIRNEDLETSLLlydagfSVNSIDDCKNTPLHHASQAPSLSRLVPKLLERGADVNAKNIKGETPLYLM 314

Viral ankyrin protein; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 285811007   99 DLNYQDE-NGNTPLHLAAAQSRSDVISFLLSQKSINDCVKNKAHQQPLDMCKDLNVAQMIQLKR 161
Cdd:PHA02736   83 DINGKERvFGNTPLHIAVYTQNYELATWLCNQPGVNMEILNYAFKTPYYVACERHDAKMMNILR 146