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Conserved domains on  [gi|2079037536|ref|XP_042797183|]
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ceramide transfer protein isoform X2 [Panthera leo]

Protein Classification

ceramide transfer protein( domain architecture ID 10192988)

ceramide transfer protein (CERT) shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
START_STARD11-like cd08872
Ceramide-binding START domain of mammalian STARD11 and related domains; This subfamily ...
495-729 4.55e-157

Ceramide-binding START domain of mammalian STARD11 and related domains; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD11 and related domains. The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD11 can mediate transfer of the natural ceramide isomers, dihydroceramide and phytoceramide, as well as ceramides having C14, C16, C18, and C20 chains. They can also transfer diacylglycerol, but with a lower efficiency. STARD11 is synthesized from two major transcripts: a larger one encoding Goodpasture antigen-binding protein (GPBP)/ceramide transporter long form (CERTL); and a smaller one encoding GPBPdelta26/CERT, which is deleted for 26 amino acids. Both splicing variants mediate ceramide transfer from the ER to the Golgi, in a non-vesicular manner. It is likely that these two carry out different functions in specific sub-cellular locations. These proteins have roles in brain homeostasis and disease processes. GPBP/CERTL exists in multiple isoforms originating from alternative translation initiation sites and post-translational modifications. Goodpasture syndrome is a human disorder caused by antibodies directed against the a3-chain of collagen type IV. GPBP/CERTL binds and phosphorylates this antigen. The human gene encoding STARD11 is referred to as COL4A3BP referring to its collagen binding function. It is unknown whether the ceramide-transfer function of GPBP/CERTL is related to this collagen interaction. The expression of GPBP/CERTL is elevated in these and other spontaneous autoimmune disorders including cutaneous lupus erythematosus, pemphigoid, and lichen planus. GPBL/CERTL contains an N-terminal pleckstrin homology domain (PH), which targets the protein to the Golgi, a middle region containing two serine-rich domains (SR1, SR2), a FFAT (two phenylalanine amino acids in an acidic tract) motif which is involved in endoplasmic reticulum targeting, and this C-terminal SMART domain. The shorter splicing variant, CERT, lacks the SR2 domain.


:

Pssm-ID: 176881  Cd Length: 235  Bit Score: 454.11  E-value: 4.55e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 495 THRFVQKVEEMVQNHMTYSLQDVGGDaNWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWNVDVRN 574
Cdd:cd08872     1 THRLSPEVDEKVQEQLTYALEDVGAD-GWQLFAEEGEMKVYRREVEEDGVVLDPLKATHAVKGVTGHEVCHYFFDPDVRM 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 575 DWETTIENFHVVETLADNAIIIYQTHKRVWPASQRDVLYLSAIRKIPALTE-NDPETWIVCNFSVDHDSAPLNNRCVRAK 653
Cdd:cd08872    80 DWETTLENFHVVETLSQDTLIFHQTHKRVWPAAQRDALFVSHIRKIPALEEpNAHDTWIVCNFSVDHDSAPLNNKCVRAK 159
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2079037536 654 INIAMICQTLVSPPEGNQEISRDNILCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAGKPILF 729
Cdd:cd08872   160 LTVAMICQTFVSPPDGNQEITRDNILCKITYVANVNPGGWAPASVLRAVYKREYPKFLKRFTSYVQEKTKGKPILF 235
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
157-256 3.03e-71

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. 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.


:

Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 226.78  E-value: 3.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDHR 236
Cdd:cd13283     1 LRGVLSKWTNYIHGWQDRYFVLKDGTLSYYKSESEKEYGCRGSISLSKAVIKPHEFDECRFDVSVNDSVWYLRAESPEER 80
                          90       100
                  ....*....|....*....|
gi 2079037536 237 QQWIDAIEQHKTESGYGSES 256
Cdd:cd13283    81 QRWIDALESHKAASGYGSSS 100
 
Name Accession Description Interval E-value
START_STARD11-like cd08872
Ceramide-binding START domain of mammalian STARD11 and related domains; This subfamily ...
495-729 4.55e-157

Ceramide-binding START domain of mammalian STARD11 and related domains; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD11 and related domains. The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD11 can mediate transfer of the natural ceramide isomers, dihydroceramide and phytoceramide, as well as ceramides having C14, C16, C18, and C20 chains. They can also transfer diacylglycerol, but with a lower efficiency. STARD11 is synthesized from two major transcripts: a larger one encoding Goodpasture antigen-binding protein (GPBP)/ceramide transporter long form (CERTL); and a smaller one encoding GPBPdelta26/CERT, which is deleted for 26 amino acids. Both splicing variants mediate ceramide transfer from the ER to the Golgi, in a non-vesicular manner. It is likely that these two carry out different functions in specific sub-cellular locations. These proteins have roles in brain homeostasis and disease processes. GPBP/CERTL exists in multiple isoforms originating from alternative translation initiation sites and post-translational modifications. Goodpasture syndrome is a human disorder caused by antibodies directed against the a3-chain of collagen type IV. GPBP/CERTL binds and phosphorylates this antigen. The human gene encoding STARD11 is referred to as COL4A3BP referring to its collagen binding function. It is unknown whether the ceramide-transfer function of GPBP/CERTL is related to this collagen interaction. The expression of GPBP/CERTL is elevated in these and other spontaneous autoimmune disorders including cutaneous lupus erythematosus, pemphigoid, and lichen planus. GPBL/CERTL contains an N-terminal pleckstrin homology domain (PH), which targets the protein to the Golgi, a middle region containing two serine-rich domains (SR1, SR2), a FFAT (two phenylalanine amino acids in an acidic tract) motif which is involved in endoplasmic reticulum targeting, and this C-terminal SMART domain. The shorter splicing variant, CERT, lacks the SR2 domain.


Pssm-ID: 176881  Cd Length: 235  Bit Score: 454.11  E-value: 4.55e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 495 THRFVQKVEEMVQNHMTYSLQDVGGDaNWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWNVDVRN 574
Cdd:cd08872     1 THRLSPEVDEKVQEQLTYALEDVGAD-GWQLFAEEGEMKVYRREVEEDGVVLDPLKATHAVKGVTGHEVCHYFFDPDVRM 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 575 DWETTIENFHVVETLADNAIIIYQTHKRVWPASQRDVLYLSAIRKIPALTE-NDPETWIVCNFSVDHDSAPLNNRCVRAK 653
Cdd:cd08872    80 DWETTLENFHVVETLSQDTLIFHQTHKRVWPAAQRDALFVSHIRKIPALEEpNAHDTWIVCNFSVDHDSAPLNNKCVRAK 159
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2079037536 654 INIAMICQTLVSPPEGNQEISRDNILCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAGKPILF 729
Cdd:cd08872   160 LTVAMICQTFVSPPDGNQEITRDNILCKITYVANVNPGGWAPASVLRAVYKREYPKFLKRFTSYVQEKTKGKPILF 235
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
157-256 3.03e-71

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. 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.


Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 226.78  E-value: 3.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDHR 236
Cdd:cd13283     1 LRGVLSKWTNYIHGWQDRYFVLKDGTLSYYKSESEKEYGCRGSISLSKAVIKPHEFDECRFDVSVNDSVWYLRAESPEER 80
                          90       100
                  ....*....|....*....|
gi 2079037536 237 QQWIDAIEQHKTESGYGSES 256
Cdd:cd13283    81 QRWIDALESHKAASGYGSSS 100
START pfam01852
START domain;
518-724 1.67e-22

START domain;


Pssm-ID: 426476  Cd Length: 205  Bit Score: 95.93  E-value: 1.67e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 518 GGDANW-QLVVEEGEMKVYRREVEENGIvldPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHVVETLADNAIII 596
Cdd:pfam01852  16 SDEPGWvLLSSNENGDVVLQIVEPDHGE---ASRASGVVPMVAALLVAELLKDMEYRAQWDKDVRSAETLEVISSGGDLQ 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 597 YQTHKRVW--PASQRDVLYLSAIRKIPAltendpETWIVCNFSVDHDSAPLNNRCVRAKINIAMICQTlvspPEGNQeis 674
Cdd:pfam01852  93 YYVAALVApsPLSPRDFVFLRYWRRLGG------GVYVIVDRSVTHPQFPPSSGYVRAERLPSGYLIQ----PCGNG--- 159
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2079037536 675 rdniLCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAG 724
Cdd:pfam01852 160 ----PSKVTWVSHADLKGWLPSWLLRSLYKSGMPEGAKTWVATLQRLCEK 205
START smart00234
in StAR and phosphatidylcholine transfer protein; putative lipid-binding domain in StAR and ...
519-720 2.11e-22

in StAR and phosphatidylcholine transfer protein; putative lipid-binding domain in StAR and phosphatidylcholine transfer protein


Pssm-ID: 214575  Cd Length: 205  Bit Score: 95.96  E-value: 2.11e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536  519 GDANWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHVVETLADNAIIIYQ 598
Cdd:smart00234  16 SEEGWVLSSENENGDEVRSIFSPGRKPGEAFRLVGVVPMVCADLVEELMDDLEYRPEWDKNVAKAETLEVIDNGTVIYHY 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536  599 THKRVW-PASQRDVLYLSAIRkipaltENDPETWIVCNFSVDHDSAPLNNRCVRAKINIAMIC-QTLVSPPegnqeisrd 676
Cdd:smart00234  96 VSKFAAgPVSPRDFVFVRYWR------EDEDGSYAVVDVSVTHPTSPPESGYVRAENLPSGLLiEPLGNGP--------- 160
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 2079037536  677 nilCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQE 720
Cdd:smart00234 161 ---SKVTWVSHADLKGWLPHWLVRSLIKSGLAEFAKTLVATLQK 201
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
155-246 1.14e-16

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.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 76.05  E-value: 1.14e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536  155 VERCGVLSKWT-NYIHGWQDRWVVLKNNTLSYYKSE-DETEYGCRGSICLSKAVITP-----HDFDECRFDISVND-SVW 226
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKkDKKSYKPKGSIDLSGCTVREapdpdSSKKPHCFEIKTSDrKTL 80
                           90       100
                   ....*....|....*....|
gi 2079037536  227 YLRAQDPDHRQQWIDAIEQH 246
Cdd:smart00233  81 LLQAESEEEREKWVEALRKA 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
155-245 1.01e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 67.59  E-value: 1.01e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 155 VERCGVLSKWTNYIH-GWQDRWVVLKNNTLSYYKSED-ETEYGCRGSICLSKAVITPHDFDE-----CRFDISVNDS--- 224
Cdd:pfam00169   1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDKsGKSKEPKGSISLSGCEVVEVVASDspkrkFCFELRTGERtgk 80
                          90       100
                  ....*....|....*....|..
gi 2079037536 225 -VWYLRAQDPDHRQQWIDAIEQ 245
Cdd:pfam00169  81 rTYLLQAESEEERKDWIKAIQS 102
 
Name Accession Description Interval E-value
START_STARD11-like cd08872
Ceramide-binding START domain of mammalian STARD11 and related domains; This subfamily ...
495-729 4.55e-157

Ceramide-binding START domain of mammalian STARD11 and related domains; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD11 and related domains. The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD11 can mediate transfer of the natural ceramide isomers, dihydroceramide and phytoceramide, as well as ceramides having C14, C16, C18, and C20 chains. They can also transfer diacylglycerol, but with a lower efficiency. STARD11 is synthesized from two major transcripts: a larger one encoding Goodpasture antigen-binding protein (GPBP)/ceramide transporter long form (CERTL); and a smaller one encoding GPBPdelta26/CERT, which is deleted for 26 amino acids. Both splicing variants mediate ceramide transfer from the ER to the Golgi, in a non-vesicular manner. It is likely that these two carry out different functions in specific sub-cellular locations. These proteins have roles in brain homeostasis and disease processes. GPBP/CERTL exists in multiple isoforms originating from alternative translation initiation sites and post-translational modifications. Goodpasture syndrome is a human disorder caused by antibodies directed against the a3-chain of collagen type IV. GPBP/CERTL binds and phosphorylates this antigen. The human gene encoding STARD11 is referred to as COL4A3BP referring to its collagen binding function. It is unknown whether the ceramide-transfer function of GPBP/CERTL is related to this collagen interaction. The expression of GPBP/CERTL is elevated in these and other spontaneous autoimmune disorders including cutaneous lupus erythematosus, pemphigoid, and lichen planus. GPBL/CERTL contains an N-terminal pleckstrin homology domain (PH), which targets the protein to the Golgi, a middle region containing two serine-rich domains (SR1, SR2), a FFAT (two phenylalanine amino acids in an acidic tract) motif which is involved in endoplasmic reticulum targeting, and this C-terminal SMART domain. The shorter splicing variant, CERT, lacks the SR2 domain.


Pssm-ID: 176881  Cd Length: 235  Bit Score: 454.11  E-value: 4.55e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 495 THRFVQKVEEMVQNHMTYSLQDVGGDaNWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWNVDVRN 574
Cdd:cd08872     1 THRLSPEVDEKVQEQLTYALEDVGAD-GWQLFAEEGEMKVYRREVEEDGVVLDPLKATHAVKGVTGHEVCHYFFDPDVRM 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 575 DWETTIENFHVVETLADNAIIIYQTHKRVWPASQRDVLYLSAIRKIPALTE-NDPETWIVCNFSVDHDSAPLNNRCVRAK 653
Cdd:cd08872    80 DWETTLENFHVVETLSQDTLIFHQTHKRVWPAAQRDALFVSHIRKIPALEEpNAHDTWIVCNFSVDHDSAPLNNKCVRAK 159
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2079037536 654 INIAMICQTLVSPPEGNQEISRDNILCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAGKPILF 729
Cdd:cd08872   160 LTVAMICQTFVSPPDGNQEITRDNILCKITYVANVNPGGWAPASVLRAVYKREYPKFLKRFTSYVQEKTKGKPILF 235
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
157-256 3.03e-71

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. 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.


Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 226.78  E-value: 3.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDHR 236
Cdd:cd13283     1 LRGVLSKWTNYIHGWQDRYFVLKDGTLSYYKSESEKEYGCRGSISLSKAVIKPHEFDECRFDVSVNDSVWYLRAESPEER 80
                          90       100
                  ....*....|....*....|
gi 2079037536 237 QQWIDAIEQHKTESGYGSES 256
Cdd:cd13283    81 QRWIDALESHKAASGYGSSS 100
START cd00177
Lipid-binding START domain of mammalian STARD1-STARD15 and related proteins; This family ...
512-719 7.10e-43

Lipid-binding START domain of mammalian STARD1-STARD15 and related proteins; This family includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD1-STARD15, and related domains, such as the START domain of the Arabidopsis homeobox protein GLABRA 2. The mammalian STARDs are grouped into 8 subfamilies. This family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. For some members of this family, specific lipids that bind in this pocket are known; these include cholesterol (STARD1/STARD3/ STARD4/STARD5), 25-hydroxycholesterol (STARD5), phosphatidylcholine (STARD2/ STARD7/STARD10), phosphatidylethanolamine (STARD10) and ceramides (STARD11). The START domain is found either alone or in association with other domains. Mammalian STARDs participate in the control of various cellular processes including lipid trafficking between intracellular compartments, lipid metabolism, and modulation of signaling events. Mutation or altered expression of STARDs is linked to diseases such as cancer, genetic disorders, and autoimmune disease. The Arabidopsis homeobox protein GLABRA 2 suppresses root hair formation in hairless epidermal root cells.


Pssm-ID: 176851 [Multi-domain]  Cd Length: 193  Bit Score: 153.65  E-value: 7.10e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 512 YSLQDVGGDANWQLVVEEGEMKVYRREVEENGIVLdpLKATHAVKGvTGHEVCNYFWNVDVRNDWETTIENFHVVETLAD 591
Cdd:cd00177     6 ELLELLEEPEGWKLVKEKDGVKIYTKPYEDSGLKL--LKAEGVIPA-SPEQVFELLMDIDLRKKWDKNFEEFEVIEEIDE 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 592 NAIIIYQTHKRVWPASQRDVLYLSAIRKIpaltenDPETWIVCNFSVDHDSAPLNNRCVRAKINIAMICqtlVSPPEGNQ 671
Cdd:cd00177    83 HTDIIYYKTKPPWPVSPRDFVYLRRRRKL------DDGTYVIVSKSVDHDSHPKEKGYVRAEIKLSGWI---IEPLDPGK 153
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 2079037536 672 eisrdnilCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQ 719
Cdd:cd00177   154 --------TKVTYVLQVDPKGSIPKSLVNSAAKKQLASFLKDLRKAKK 193
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
159-243 5.04e-29

Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also called PLEKHA3/Pleckstrin homology domain-containing, family A member 3) regulates secretory transport from the trans-Golgi network to the plasma membrane. It is recruited through binding of PH domain to phosphatidylinositol 4-phosphate (PtdIns(4)P) and a small GTPase ADP-ribosylation factor 1 (ARF1). These two binding sites have little overlap the FAPP1 PH domain to associate with both ligands simultaneously and independently. FAPP1 has a N-terminal PH domain followed by a short proline-rich region. FAPP1 is a member of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), and Goodpasture antigen binding protein (GPBP). 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. FAPP2 (also called PLEKHA8/Pleckstrin homology domain-containing, family A member 8), a member of the Glycolipid lipid transfer protein(GLTP) family has an N-terminal PH domain that targets the TGN and C-terminal GLTP domain. FAPP2 functions to traffic glucosylceramide (GlcCer) which is made in the Golgi. It's interaction with vesicle-associated membrane protein-associated protein (VAP) could be a means of regulation. Some FAPP2s share the FFAT-like motifs found in GLTP. 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.


Pssm-ID: 269951  Cd Length: 100  Bit Score: 110.96  E-value: 5.04e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDISV-NDSVWYLRAQDPDHRQ 237
Cdd:cd01247     3 GVLWKWTNYLSGWQPRWFVLDDGVLSYYKSQEEVNQGCKGSVKMSVCEIIVHPTDPTRMDLIIpGEQHFYLKASSAAERQ 82

                  ....*.
gi 2079037536 238 QWIDAI 243
Cdd:cd01247    83 RWLVAL 88
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
159-252 4.36e-24

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an 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.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 97.13  E-value: 4.36e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNT--LSYYKSEDETEYGC-RGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDH 235
Cdd:cd13290     3 GPLSKWTNVMKGWQYRWFVLDDNAglLSYYTSKEKMMRGSrRGCVRLKGAVVGIDDEDDSTFTITVDQKTFHFQARDAEE 82
                          90
                  ....*....|....*..
gi 2079037536 236 RQQWIDAIEQHKTESGY 252
Cdd:cd13290    83 RERWIRALEDTILRHSQ 99
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
154-246 1.01e-23

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.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 96.22  E-value: 1.01e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 154 PVERCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDISVNDSV---WYLRA 230
Cdd:cd13292     1 PPTMKGYLKKWTNYAKGYKTRWFVLEDGVLSYYRHQDDEGSACRGSINMKNARLVSDPSEKLRFEVSSKTSGspkWYLKA 80
                          90
                  ....*....|....*.
gi 2079037536 231 QDPDHRQQWIDAIEQH 246
Cdd:cd13292    81 NHPVEAARWIQALQKA 96
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
159-256 1.89e-23

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.


Pssm-ID: 270101  Cd Length: 99  Bit Score: 95.14  E-value: 1.89e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVItpHDFDECRFDISvNDS--VWYLRAQDPDHR 236
Cdd:cd13284     3 GWLLKWTNYIKGYQRRWFVLSNGLLSYYRNQAEMAHTCRGTINLAGAEI--HTEDSCNFVIS-NGGtqTFHLKASSEVER 79
                          90       100
                  ....*....|....*....|
gi 2079037536 237 QQWIDAIEQHKTESGYGSES 256
Cdd:cd13284    80 QRWVTALELAKAKAIRLLES 99
START pfam01852
START domain;
518-724 1.67e-22

START domain;


Pssm-ID: 426476  Cd Length: 205  Bit Score: 95.93  E-value: 1.67e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 518 GGDANW-QLVVEEGEMKVYRREVEENGIvldPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHVVETLADNAIII 596
Cdd:pfam01852  16 SDEPGWvLLSSNENGDVVLQIVEPDHGE---ASRASGVVPMVAALLVAELLKDMEYRAQWDKDVRSAETLEVISSGGDLQ 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 597 YQTHKRVW--PASQRDVLYLSAIRKIPAltendpETWIVCNFSVDHDSAPLNNRCVRAKINIAMICQTlvspPEGNQeis 674
Cdd:pfam01852  93 YYVAALVApsPLSPRDFVFLRYWRRLGG------GVYVIVDRSVTHPQFPPSSGYVRAERLPSGYLIQ----PCGNG--- 159
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2079037536 675 rdniLCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAG 724
Cdd:pfam01852 160 ----PSKVTWVSHADLKGWLPSWLLRSLYKSGMPEGAKTWVATLQRLCEK 205
START smart00234
in StAR and phosphatidylcholine transfer protein; putative lipid-binding domain in StAR and ...
519-720 2.11e-22

in StAR and phosphatidylcholine transfer protein; putative lipid-binding domain in StAR and phosphatidylcholine transfer protein


Pssm-ID: 214575  Cd Length: 205  Bit Score: 95.96  E-value: 2.11e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536  519 GDANWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHVVETLADNAIIIYQ 598
Cdd:smart00234  16 SEEGWVLSSENENGDEVRSIFSPGRKPGEAFRLVGVVPMVCADLVEELMDDLEYRPEWDKNVAKAETLEVIDNGTVIYHY 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536  599 THKRVW-PASQRDVLYLSAIRkipaltENDPETWIVCNFSVDHDSAPLNNRCVRAKINIAMIC-QTLVSPPegnqeisrd 676
Cdd:smart00234  96 VSKFAAgPVSPRDFVFVRYWR------EDEDGSYAVVDVSVTHPTSPPESGYVRAENLPSGLLiEPLGNGP--------- 160
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 2079037536  677 nilCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQE 720
Cdd:smart00234 161 ---SKVTWVSHADLKGWLPHWLVRSLIKSGLAEFAKTLVATLQK 201
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
158-257 2.34e-19

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.


Pssm-ID: 270106  Cd Length: 107  Bit Score: 83.88  E-value: 2.34e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 158 CGVLSKWTNYIHGWQDRWVVLKNNT--LSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDI-SVNDSVWYLRAQDPD 234
Cdd:cd13291     2 EGQLLKYTNVVKGWQNRWFVLDPDTgiLEYFLSEESKNQKPRGSLSLAGAVISPSDEDSHTFTVnAANGEMYKLRAADAK 81
                          90       100
                  ....*....|....*....|....*.
gi 2079037536 235 HRQQWID---AIEQHKTESGYGSESS 257
Cdd:cd13291    82 ERQEWVNrlrAVAEHHTEAIAKSNSS 107
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
157-243 1.37e-18

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


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 81.05  E-value: 1.37e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNY-IHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAV---ITPHDFDECRFDISVNDS-VWYLRAQ 231
Cdd:cd00821     1 KEGYLLKRGGGgLKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILeveEVSPKERPHCFELVTPDGrTYYLQAD 80
                          90
                  ....*....|..
gi 2079037536 232 DPDHRQQWIDAI 243
Cdd:cd00821    81 SEEERQEWLKAL 92
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
155-246 1.14e-16

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.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 76.05  E-value: 1.14e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536  155 VERCGVLSKWT-NYIHGWQDRWVVLKNNTLSYYKSE-DETEYGCRGSICLSKAVITP-----HDFDECRFDISVND-SVW 226
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKkDKKSYKPKGSIDLSGCTVREapdpdSSKKPHCFEIKTSDrKTL 80
                           90       100
                   ....*....|....*....|
gi 2079037536  227 YLRAQDPDHRQQWIDAIEQH 246
Cdd:smart00233  81 LLQAESEEEREKWVEALRKA 100
START_STARD10-like cd08871
Lipid-binding START domain of mammalian STARD10 and related proteins; This subfamily includes ...
520-713 5.96e-16

Lipid-binding START domain of mammalian STARD10 and related proteins; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD10 (also known as CGI-52, PTCP-like, and SDCCAG28). The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD10 binds phophatidylcholine and phosphatidylethanolamine. This protein is widely expressed and is synthesized constitutively in many organs. It may function in the liver in the export of phospholipids into bile. It is concentrated in the sperm flagellum, and may play a role in energy metabolism. In the mammary gland it may participate in the enrichment of lipids in milk, and be a potential marker of differentiation. Its expression is induced in this gland during gestation and lactation. It is overexpressed in mammary tumors from Neu/ErbB2 transgenic mice, in several breast carcinoma cell lines, and in 35% of primary human breast cancers, and may cooperate with c-erbB receptor signaling in breast oncogenesis. It is a potential marker of disease outcome in breast cancer; loss of STARD10 expression in breast cancer strongly predicts an aggressive disease course. The lipid transfer activity of STRAD10 is downregulated by phosphorylation of its Ser284 by CK2 (casein kinase 2).


Pssm-ID: 176880  Cd Length: 222  Bit Score: 77.68  E-value: 5.96e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 520 DANWQLVVEEGEMKVYRREVEENGIVLdpLKATHAVKGVTGHEVCNYFWNVDVRNDWETT-IENFHVvETLADNAIIIYQ 598
Cdd:cd08871    22 TDGWKLKYNKNNVKVWTKNPENSSIKM--IKVSAIFPDVPAETLYDVLHDPEYRKTWDSNmIESFDI-CQLNPNNDIGYY 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 599 THKRVWPASQRDVLYLSAIRKipalTENDpetWIVCNFSVDHDSAPLNNRCVRAkinIAMICQTLVSP--PEGnqeisrd 676
Cdd:cd08871    99 SAKCPKPLKNRDFVNLRSWLE----FGGE---YIIFNHSVKHKKYPPRKGFVRA---ISLLTGYLIRPtgPKG------- 161
                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 2079037536 677 nilCKITYVANVNPGGWAPASVLRAVAKREYPKFLKR 713
Cdd:cd08871   162 ---CTLTYVTQNDPKGSLPKWVVNKATTKLAPKVMKK 195
PH pfam00169
PH domain; PH stands for pleckstrin homology.
155-245 1.01e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 67.59  E-value: 1.01e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 155 VERCGVLSKWTNYIH-GWQDRWVVLKNNTLSYYKSED-ETEYGCRGSICLSKAVITPHDFDE-----CRFDISVNDS--- 224
Cdd:pfam00169   1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDKsGKSKEPKGSISLSGCEVVEVVASDspkrkFCFELRTGERtgk 80
                          90       100
                  ....*....|....*....|..
gi 2079037536 225 -VWYLRAQDPDHRQQWIDAIEQ 245
Cdd:pfam00169  81 rTYLLQAESEEERKDWIKAIQS 102
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
171-245 1.57e-12

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.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 64.24  E-value: 1.57e-12
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2079037536 171 WQDRWVVLKNNTLSYYKSEDETEYgcRGSICLSK----AVITPHDFDECRFDISVNDSVWYLRAQDPDHRQQWIDAIEQ 245
Cdd:cd13273    24 WTERWFVLKPNSLSYYKSEDLKEK--KGEIALDSnccvESLPDREGKKCRFLVKTPDKTYELSASDHKTRQEWIAAIQT 100
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
159-247 2.24e-12

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241448  Cd Length: 100  Bit Score: 63.67  E-value: 2.24e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDHRQQ 238
Cdd:cd13294     3 GILYKWVNYGKGWRSRWFVLQDGVLSYYKVHGPDKVKPSGEVHLKVSSIRESRSDDKKFYIFTGTKTLHLRAESREDRAA 82

                  ....*....
gi 2079037536 239 WIDAIEQHK 247
Cdd:cd13294    83 WLEALQAAK 91
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
159-245 2.96e-12

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 63.41  E-value: 2.96e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKseDETEYGCRGSICLSK----AVITPHDFDEcRFDISVNDSVWYLRAQDPD 234
Cdd:cd13298    10 GYLLKRSRKTKNWKKRWVVLRPCQLSYYK--DEKEYKLRRVINLSEllavAPLKDKKRKN-VFGIYTPSKNLHFRATSEK 86
                          90
                  ....*....|.
gi 2079037536 235 HRQQWIDAIEQ 245
Cdd:cd13298    87 DANEWVEALRE 97
PH_CpORP2-like cd13293
Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) ...
159-245 7.20e-11

Cryptosporidium-like Oxysterol binding protein related protein 2 Pleckstrin homology (PH) domain; There are 2 types of ORPs found in Cryptosporidium: CpORP1 and CpORP2. Cryptosporium differs from other apicomplexans like Plasmodium, Toxoplasma, and Eimeria which possess only a single long-type ORP consisting of an N-terminal PH domain followed by a C-terminal ligand binding (LB) domain. CpORP2 is like this, but CpORP1 differs and has a truncated N-terminus resulting in only having a LB domain present. The exact functions of these proteins are largely unknown though CpORP1 is thought to be involved in lipid transport across the parasitophorous vacuole membrane. 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.


Pssm-ID: 241447  Cd Length: 88  Bit Score: 58.88  E-value: 7.20e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEygcRGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDHRQQ 238
Cdd:cd13293     3 GYLKKWTNIFNSWKPRYFILYPGILCYSKQKGGPK---KGTIHLKICDIRLVPDDPLRIIINTGTNQLHLRASSVEEKLK 79

                  ....*..
gi 2079037536 239 WIDAIEQ 245
Cdd:cd13293    80 WYNALKY 86
START_1 cd08876
Uncharacterized subgroup of the steroidogenic acute regulatory protein (StAR)-related lipid ...
518-705 1.41e-09

Uncharacterized subgroup of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain family; Functionally uncharacterized subgroup of the START domain family. The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. For some mammalian members of the START family (STARDs), it is known which lipids bind in this pocket; these include cholesterol (STARD1, -3, -4, and -5), 25-hydroxycholesterol (STARD5), phosphatidylcholine (STARD2, -7, and -10), phosphatidylethanolamine (STARD10) and ceramides (STARD11). Mammalian STARDs participate in the control of various cellular processes, including lipid trafficking between intracellular compartments, lipid metabolism, and modulation of signaling events. Mutation or altered expression of STARDs is linked to diseases such as cancer, genetic disorders, and autoimmune disease.


Pssm-ID: 176885  Cd Length: 195  Bit Score: 58.44  E-value: 1.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 518 GGDANWQLVVEEGEMKVYRREVEENGIvldplkatHAVKGVTghEVCNYFWNV-----DVRN--DWettIEN---FHVVE 587
Cdd:cd08876    14 APDGDWQLVKDKDGIKVYTRDVEGSPL--------KEFKAVA--EVDASIEAFlallrDTESypQW---MPNckeSRVLK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 588 TLADNAIIIYQTHKRVWPASQRDVLYLSairkipaLTENDPETWIVC-NFSVDHDSAPLNNRCVRAKINIAMIcqTLVsp 666
Cdd:cd08876    81 RTDDNERSVYTVIDLPWPVKDRDMVLRS-------TTEQDADDGSVTiTLEAAPEALPEQKGYVRIKTVEGQW--TFT-- 149
                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 2079037536 667 PEGNQEIsrdnilcKITYVANVNPGGWAPASVLRAVAKR 705
Cdd:cd08876   150 PLGNGKT-------RVTYQAYADPGGSIPGWLANAFAKD 181
PH_ORP1 cd13285
Human Oxysterol binding protein related protein 1 Pleckstrin homology (PH) domain; Human ORP1 ...
170-246 1.57e-09

Human Oxysterol binding protein related protein 1 Pleckstrin homology (PH) domain; Human ORP1 has 2 forms, a long (ORP1L) and a short (ORP1S). ORP1L contains 3 N-terminal ankyrin repeats, followed by a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains only an OSBP-related domain. ORP1L is proposed to function in motility and distribution of late endosomes, autophagy, and macrophage lipid metabolism. ORP1S is proposed to function in vesicle transport from Golgi. 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.


Pssm-ID: 270102  Cd Length: 125  Bit Score: 56.25  E-value: 1.57e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 170 GWQDRWVVLKNNTLSYYKSEDETEYGCRGSIC--LSKAVITPHDFDECRFDISV-NDSVWYLRA---QDPDH-RQQWIDA 242
Cdd:cd13285    22 GWRSYWVVLEDGVLSWYHKQADAAAGIKRQGCksLTQAKCTVKSTDSCFFTIRCfDDTVHRFKVppkNNPVVtRKKWLEA 101

                  ....
gi 2079037536 243 IEQH 246
Cdd:cd13285   102 LEEH 105
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
159-243 3.40e-09

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


Pssm-ID: 269941  Cd Length: 106  Bit Score: 54.64  E-value: 3.40e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNT--LSYYKSEDETEygCRGSICLSK---------AVITPHDFDECR-FDISVNDSVW 226
Cdd:cd01235     7 GYLYKRGALLKGWKQRWFVLDSTKhqLRYYESREDTK--CKGFIDLAEvesvtpatpIIGAPKRADEGAfFDLKTNKRVY 84
                          90
                  ....*....|....*..
gi 2079037536 227 YLRAQDPDHRQQWIDAI 243
Cdd:cd01235    85 NFCAFDAESAQQWIEKI 101
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
157-243 8.05e-09

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.


Pssm-ID: 270083  Cd Length: 114  Bit Score: 53.93  E-value: 8.05e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYgcRGSICLSKAVI-----TPHDFDECRFDI---------SVN 222
Cdd:cd13263     5 KSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKP--QGTIPLPGNKVkevpfNPEEPGKFLFEIipggggdrmTSN 82
                          90       100
                  ....*....|....*....|.
gi 2079037536 223 DSVWYLRAQDPDHRQQWIDAI 243
Cdd:cd13263    83 HDSYLLMANSQAEMEEWVKVI 103
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
158-249 8.27e-09

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.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 53.48  E-value: 8.27e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 158 CGVLSKWTN---YIHGWQDRWVVL--KNNTLSYYKSEDETEygCRGSICLSKAVITpHDFD--ECRFDISVNDSVWYLRA 230
Cdd:cd01265     3 CGYLNKLETrglGLKGWKRRWFVLdeSKCQLYYYRSPQDAT--PLGSIDLSGAAFS-YDPEaePGQFEIHTPGRVHILKA 79
                          90
                  ....*....|....*....
gi 2079037536 231 QDPDHRQQWIDAIEQHKTE 249
Cdd:cd01265    80 STRQAMLYWLQALQSKRRE 98
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
157-244 3.76e-08

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.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 51.93  E-value: 3.76e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYG-CRGSICLSKaVITPHDFDEC-----RFDISVNDSVWYLRA 230
Cdd:cd13276     1 KAGWLEKQGEFIKTWRRRWFVLKQGKLFWFKEPDVTPYSkPRGVIDLSK-CLTVKSAEDAtnkenAFELSTPEETFYFIA 79
                          90
                  ....*....|....
gi 2079037536 231 QDPDHRQQWIDAIE 244
Cdd:cd13276    80 DNEKEKEEWIGAIG 93
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
171-245 8.42e-08

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.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 50.93  E-value: 8.42e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2079037536 171 WQDRWVVLKNNTLSYYKSEDETEyGCRGSICLSKA-VITPHDFDECRFDISVNDSVWYLRAQDPDHRQQWIDAIEQ 245
Cdd:cd13296    20 WKSRWFVLRDTVLKYYENDQEGE-KLLGTIDIRSAkEIVDNDPKENRLSITTEERTYHLVAESPEDASQWVNVLTR 94
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
171-245 1.25e-07

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 51.46  E-value: 1.25e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 171 WQDRWVVLKNNTLSYYKSEDETEYGCRGSICLS--KAVITPHDFDECR----FDISVNDSVWYLRAQDPDHRQQWIDAIE 244
Cdd:cd01238    20 YKERWFVLTKSSLSYYEGDGEKRGKEKGSIDLSkvRCVEEVKDEAFFErkypFQVVYDDYTLYVFAPSEEDRDEWIAALR 99

                  .
gi 2079037536 245 Q 245
Cdd:cd01238   100 K 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
159-245 1.57e-07

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.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 49.60  E-value: 1.57e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYGCRGSICL-SKAVITPHDfDECRFDISVNDSVWYLRAQDPDHRQ 237
Cdd:cd13282     3 GYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALdGSCEIARAE-GAQTFEIVTEKRTYYLTADSENDLD 81

                  ....*...
gi 2079037536 238 QWIDAIEQ 245
Cdd:cd13282    82 EWIRVIQN 89
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
154-245 2.44e-07

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.


Pssm-ID: 241529  Cd Length: 116  Bit Score: 49.94  E-value: 2.44e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 154 PVERCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEygCRGSICLSKAVIT-----PHDFDECRFDIS-------- 220
Cdd:cd13378     2 GVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETK--PQGCISLQGSQVNelppnPEEPGKHLFEILpggagdre 79
                          90       100
                  ....*....|....*....|....*...
gi 2079037536 221 ---VNDSVWYLRAQDPDHRQQWIDAIEQ 245
Cdd:cd13378    80 kvpMNHEAFLLMANSQSDMEDWVKAIRR 107
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
157-245 3.38e-07

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) 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. 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.


Pssm-ID: 241530  Cd Length: 114  Bit Score: 49.20  E-value: 3.38e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEygCRGSICLSKAVITPHDFDE--------------CRFDISVN 222
Cdd:cd13379     5 KCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETK--PLGTIFLPGNRVTEHPCNEeepgkflfevvpggDRERMTAN 82
                          90       100
                  ....*....|....*....|...
gi 2079037536 223 DSVWYLRAQDPDHRQQWIDAIEQ 245
Cdd:cd13379    83 HETYLLMASTQNDMEDWVKSIRR 105
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
156-245 4.07e-07

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


Pssm-ID: 270073  Cd Length: 94  Bit Score: 48.54  E-value: 4.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 156 ERCGVLSKW----TNYihGWQDRWVVLKNNTLSYYKSEDETEygCRGSICLSkAVITPHDFDECRFDISVNDSVWYLRAQ 231
Cdd:cd13253     1 IKSGYLDKQggqgNNK--GFQKRWVVFDGLSLRYFDSEKDAY--SKRIIPLS-AISTVRAVGDNKFELVTTNRTFVFRAE 75
                          90
                  ....*....|....
gi 2079037536 232 DPDHRQQWIDAIEQ 245
Cdd:cd13253    76 SDDERNLWCSTLQA 89
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
151-243 3.03e-06

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.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 46.58  E-value: 3.03e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 151 SGPPVERCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEyGCRgSICLsKAVitpHDFDECR----------FDIS 220
Cdd:cd13271     4 AGRNVIKSGYCVKQGAVRKNWKRRFFILDDNTISYYKSETDKE-PLR-TIPL-REV---LKVHECLvksllmrdnlFEII 77
                          90       100
                  ....*....|....*....|...
gi 2079037536 221 VNDSVWYLRAQDPDHRQQWIDAI 243
Cdd:cd13271    78 TTSRTFYIQADSPEEMHSWIKAI 100
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
155-246 3.28e-06

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


Pssm-ID: 275402  Cd Length: 116  Bit Score: 46.46  E-value: 3.28e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 155 VERCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETeYGCRGSICLSKAV---ITPHDFDECR-FDISVNDSVWYLRA 230
Cdd:cd13215    21 VIKSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTDL-YFPAGTIDLRYATsieLSKSNGEATTsFKIVTNSRTYKFKA 99
                          90
                  ....*....|....*.
gi 2079037536 231 QDPDHRQQWIDAIEQH 246
Cdd:cd13215   100 DSETSADEWVKALKKQ 115
PH_ORP3_ORP6_ORP7 cd13287
Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; ...
170-247 4.18e-06

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.


Pssm-ID: 270104  Cd Length: 123  Bit Score: 46.55  E-value: 4.18e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2079037536 170 GWQDRWVVLKNNTLSYYKSEDETEYG-CRGSICLSKAVITPHDfDECRFDISVNDSVWYLRAQDPDHRQQWIDAIEQHK 247
Cdd:cd13287    38 GWHKRFFVLEKGILKYAKSPLDIAKGkLHGSIDVGLSVMSIKK-KARRIDLDTEEFIYHLKVKSQDLFDSWVAKLRAHR 115
PH_11 pfam15413
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
158-246 5.33e-06

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


Pssm-ID: 405988  Cd Length: 105  Bit Score: 45.66  E-value: 5.33e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 158 CGVLskWTNYIHGWQDRW-VVLKNNTLSYYKSedETEYGCRGSICLSKAVITPHDF------------------DECRFD 218
Cdd:pfam15413   2 EGYL--KKKGPKTWKHRWfAVLRNGVLFYYKS--EKMKVVKHVIVLSNYIVGKLGTdiisgalfkidnirsetsDDLLLE 77
                          90       100
                  ....*....|....*....|....*...
gi 2079037536 219 ISVNDSVWYLRAQDPDHRQQWIDAIEQH 246
Cdd:pfam15413  78 ISTETKIFFLYGDNNEETYEWVEALQEA 105
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
171-244 8.45e-06

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.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 44.90  E-value: 8.45e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2079037536 171 WQDRWVVLKNNTLSYYKSEDETEYG---CRGSICLSKaVITPHDFDECrFD-ISVNDSvWYLRAQDPDHRQQWIDAIE 244
Cdd:cd13250    16 WKRRWFSLQNGQLYYQKRDKKDEPTvmvEDLRLCTVK-PTEDSDRRFC-FEvISPTKS-YMLQAESEEDRQAWIQAIQ 90
START_STARD1_3_like cd08868
Cholesterol-binding START domain of mammalian STARD1, -3 and related proteins; This subfamily ...
498-699 1.69e-05

Cholesterol-binding START domain of mammalian STARD1, -3 and related proteins; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of STARD1 (also known as StAR) and STARD3 (also known as metastatic lymph node 64/MLN64). The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. This STARD1-like subfamily has a high affinity for cholesterol. STARD1/StAR can reduce macrophage lipid content and inflammatory status. It plays an essential role in steroidogenic tissues: transferring the steroid precursor, cholesterol, from the outer to the inner mitochondrial membrane, across the aqueous space. Mutations in the gene encoding STARD1/StAR can cause lipid congenital adrenal hyperplasia (CAH), an autosomal recessive disorder characterized by a steroid synthesis deficiency and an accumulation of cholesterol in the adrenal glands and the gonads. STARD3 may function in trafficking endosomal cholesterol to a cytosolic acceptor or membrane. In addition to having a cytoplasmic START cholesterol-binding domain, STARD3 also contains an N-terminal MENTAL cholesterol-binding and protein-protein interaction domain. The MENTAL domain contains transmembrane helices and anchors MLN64 to endosome membranes. The gene encoding STARD3 is overexpressed in about 25% of breast cancers.


Pssm-ID: 176877  Cd Length: 208  Bit Score: 46.58  E-value: 1.69e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 498 FVQKVEEMVQNhmTYSLQDvggDANWQLVVEEGE-MKVYRREVEENGIVLdplKATHAVKGVTGHEVCNYFWNVDVRNDW 576
Cdd:cd08868     6 YLKQGAEALAR--AWSILT---DPGWKLEKNTTWgDVVYSRNVPGVGKVF---RLTGVLDCPAEFLYNELVLNVESLPSW 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 577 ETTIENFHVVETLADNAIIIYQTHKrvwPA-----SQRDVLYLSAIrkipALTENdpeTWIVCNFSVDHDSAPLNNRCVR 651
Cdd:cd08868    78 NPTVLECKIIQVIDDNTDISYQVAA---EAggglvSPRDFVSLRHW----GIREN---CYLSSGVSVEHPAMPPTKNYVR 147
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 2079037536 652 AKINI-AMICQTLVSPPegNQeisrdnilCKITYVANVNPGGWAPASVL 699
Cdd:cd08868   148 GENGPgCWILRPLPNNP--NK--------CNFTWLLNTDLKGWLPQYLV 186
START_STARD2-like cd08910
Lipid-binding START domain of mammalian STARD2 and related proteins; This subgroup includes ...
519-712 3.10e-05

Lipid-binding START domain of mammalian STARD2 and related proteins; This subgroup includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of STARD2 (also known as phosphatidylcholine transfer protein/PC-TP) and related proteins. It belongs to the START domain family, and in turn to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD2 is a cytosolic phosphatidycholine (PtdCho) transfer protein, which traffics PtdCho, the most common class of phospholipids in eukaryotes, between membranes. It represents a minimal START domain structure. STARD2 plays roles in hepatic cholesterol metabolism, in the development of atherosclerosis, and may have a mitochondrial function.


Pssm-ID: 176919  Cd Length: 207  Bit Score: 45.56  E-value: 3.10e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 519 GDANWQLVVEEGEMKVYRREVEENGivLDPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHvvETLADNAIIIYQ 598
Cdd:cd08910    23 DGAAWELLVESSGISIYRLLDEQSG--LYEYKVFGVLEDCSPSLLADVYMDLEYRKQWDQYVKELY--EKECDGETVIYW 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 599 THKRVWPASQRDVLYlsaIRKIPALTENDPETWIVCNFSVDHDSAPlnNRCvrAKINIAMICQTLVSPPEGNQEisrdni 678
Cdd:cd08910    99 EVKYPFPLSNRDYVY---IRQRRDLDVEGRKIWVILARSTSLPQLP--EKP--GVIRVKQYKQSLAIESDGKKG------ 165
                         170       180       190
                  ....*....|....*....|....*....|....
gi 2079037536 679 lCKITYVANVNPGGWAPASVLRAVAKREYPKFLK 712
Cdd:cd08910   166 -SKVFMYYFDNPGGMIPSWLINWAAKNGVPNFLK 198
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
153-243 3.63e-05

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.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 43.52  E-value: 3.63e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 153 PPVERCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETEYgcRGSICLSKAVITPH--DFDECRFDISVNDSV---WY 227
Cdd:cd13301     1 PGIIKEGYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTDSSP--KGMIPLKGCTITSPclEYGKRPLVFKLTTAKgqeHF 78
                          90
                  ....*....|....*.
gi 2079037536 228 LRAQDPDHRQQWIDAI 243
Cdd:cd13301    79 FQACSREERDAWAKDI 94
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
171-245 1.11e-04

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 41.87  E-value: 1.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 171 WQDRWVVLKNNTLSYYKSEDETEygCRGSICLSKAVITP----------HDFDECRFDIsvndSVWYLRAQDPDHRQQWI 240
Cdd:cd13248    24 WRKRWFVLKDNCLYYYKDPEEEK--ALGSILLPSYTISPappsdeisrkFAFKAEHANM----RTYYFAADTAEEMEQWM 97

                  ....*
gi 2079037536 241 DAIEQ 245
Cdd:cd13248    98 NAMSL 102
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
151-243 1.23e-04

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.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 42.22  E-value: 1.23e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 151 SGPPVERCGVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETE-------YGCRGSICLSKaviTPHDFdECRFDiSVND 223
Cdd:cd13288     4 CNSPVDKEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGDREplgvivlEGCTVELAEDA---EPYAF-AIRFD-GPGA 78
                          90       100
                  ....*....|....*....|
gi 2079037536 224 SVWYLRAQDPDHRQQWIDAI 243
Cdd:cd13288    79 RSYVLAAENQEDMESWMKAL 98
PH_Osh3p_yeast cd13289
Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is ...
170-245 1.62e-04

Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is proposed to function in sterol transport and regulation of nuclear fusion during mating and of pseudohyphal growth as well as sphingolipid metabolism. Osh3 contains a N-GOLD (Golgi dynamics) domain, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. GOLD domains are thought to mediate protein-protein interactions, but their role in ORPs are unknown. 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.


Pssm-ID: 241443  Cd Length: 90  Bit Score: 41.09  E-value: 1.62e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 170 GWQDRWVVL--KNNTLSYYKSEDETeygCRGSICLSKAVITPhdfDECRFDISVND--SVWYLRAQDPDHRQQWIDAIEQ 245
Cdd:cd13289    16 GFARRYFVLnfKYGTLSYYFNPNSP---VRGQIPLRLASISA---SPRRRTIHIDSgsEVWHLKALNDEDFQAWMKALRK 89
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
171-249 3.34e-04

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


Pssm-ID: 270075  Cd Length: 110  Bit Score: 40.86  E-value: 3.34e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 171 WQDRWVVLKNNTLSYYKSedETEYGCRGSICLSK-AVITP-----HDFdecRFDISVNDSVWYLRAQDPDHRQQWIDAIE 244
Cdd:cd13255    22 WKKRWFVLRPTKLAYYKN--DKEYRLLRLIDLTDiHTCTEvqlkkHDN---TFGIVTPARTFYVQADSKAEMESWISAIN 96

                  ....*
gi 2079037536 245 QHKTE 249
Cdd:cd13255    97 LARQA 101
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
163-193 3.36e-04

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. 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.


Pssm-ID: 270126  Cd Length: 97  Bit Score: 40.43  E-value: 3.36e-04
                          10        20        30
                  ....*....|....*....|....*....|.
gi 2079037536 163 KWTNYiHGWQDRWVVLKNNTLSYYKSEDETE 193
Cdd:cd13316     9 RGERY-GTWKTRYFVLKGTRLYYLKSENDDK 38
PH_CNK_insect-like cd13326
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
171-243 3.56e-04

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from insects, spiders, mollusks, and nematodes. 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.


Pssm-ID: 270135  Cd Length: 91  Bit Score: 40.02  E-value: 3.56e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2079037536 171 WQDRWVVLKNNTLSYYKSEDETEYGCrgSICLSKAVITPHdfDECR-----FDISVNDSVWYLRAQDPDHRQQWIDAI 243
Cdd:cd13326    18 WAKRWFVLKGSNLYGFRSQESTKADC--VIFLPGFTVSPA--PEVKsrkyaFKVYHTGTVFYFAAESQEDMKKWLDLL 91
START_STARD2_7-like cd08870
Lipid-binding START domain of mammalian STARD2, -7, and related proteins; This subfamily ...
495-713 3.63e-04

Lipid-binding START domain of mammalian STARD2, -7, and related proteins; This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of STARD2 (also known as phosphatidylcholine transfer protein/PC-TP), and STARD7 (also known as gestational trophoblastic tumor 1/GTT1). The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD2 is a cytosolic phosphatidycholine (PtdCho) transfer protein, which traffics PtdCho, the most common class of phospholipids in eukaryotes, between membranes. It represents a minimal START domain structure. STARD2 plays roles in hepatic cholesterol metabolism, in the development of atherosclerosis, and may also have a mitochondrial function. The gene encoding STARD7 is overexpressed in choriocarcinoma. STARD7 appears to be involved in the intracellular trafficking of PtdCho to mitochondria. STARD7 was shown to be surface active and to interact differentially with phospholipid monolayers. It showed a preference for phosphatidylserine, cholesterol, and phosphatidylglycerol.


Pssm-ID: 176879  Cd Length: 209  Bit Score: 42.37  E-value: 3.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 495 THRFVQKVEEMVQNhmtysLQDVGGDANWQLVVEEGE----MKVYRREVEENGivLDPLKATHAVKGVTGHEVCNYFWNV 570
Cdd:cd08870     1 GHVSEEDLRDLVQE-----LQEGAEGQAWQQVMDKSTpdmsYQAWRRKPKGTG--LYEYLVRGVFEDCTPELLRDFYWDD 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 571 DVRNDWETTIENFHVVETLADNAIIIYQTHKRV-WPASQRDVLYLSAIRkipaltENDPETWIVCNFSVDHDSAPLNNRC 649
Cdd:cd08870    74 EYRKKWDETVIEHETLEEDEKSGTEIVRWVKKFpFPLSDREYVIARRLW------ESDDRSYVCVTKGVPYPSVPRSGRK 147
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2079037536 650 -VRAKINIAMICqtlvsPPEGNQEISRdnilCKITYVAnvNPGGWAPASVLRAVAKREYPKFLKR 713
Cdd:cd08870   148 rVDDYESSLVIR-----AVKGDGQGSA----CEVTYFH--NPDGGIPRELAKLAVKRGMPGFLKK 201
PH_8 pfam15409
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
170-247 7.43e-04

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


Pssm-ID: 405984  Cd Length: 89  Bit Score: 39.27  E-value: 7.43e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 170 GWQDRWVVL--KNNTLSYYKSEDETEYgcRGSICLSKAVITPhdfDECRFDISVnDS---VWYLRAQDPDHRQQWIDAIE 244
Cdd:pfam15409  13 GYAKRFFVLnfKSGTLSYYRDDNSSAL--RGKIPLSLAAISA---NAKTREIII-DSgmeVWHLKALNEKDFQAWVDALE 86

                  ...
gi 2079037536 245 QHK 247
Cdd:pfam15409  87 KAK 89
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
155-246 8.63e-04

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.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 39.70  E-value: 8.63e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 155 VERCGVLSKWTNY---IHGWQDRWVVLKNNTLSYYKseDETEYGCRGSICLSKAVITPHdfDECRFD---------ISVN 222
Cdd:cd13308     9 VIHSGTLTKKGGSqktLQNWQLRYVIIHQGCVYYYK--NDQSAKPKGVFSLNGYNRRAA--EERTSKlkfvfkiihLSPD 84
                          90       100
                  ....*....|....*....|....*...
gi 2079037536 223 DSVWYLRAQDPDHRQQWI----DAIEQH 246
Cdd:cd13308    85 HRTWYFAAKSEDEMSEWMeyirREIDHY 112
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
170-250 9.07e-04

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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.


Pssm-ID: 270078  Cd Length: 123  Bit Score: 39.61  E-value: 9.07e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 170 GWQDRWVVLKNNTLSYYKSeDETEYGCR--GSICLSKAVITPHDFDECR--FDISVNDSV---WYLRAQDPDHRQQWIDA 242
Cdd:cd13258    35 VFKERWFKLKGNLLFYFRT-NEFGDCSEpiGAIVLENCRVQMEEITEKPfaFSIVFNDEPekkYIFSCRSEEQCEQWIEA 113

                  ....*...
gi 2079037536 243 IEQHKTES 250
Cdd:cd13258   114 LRQASYEY 121
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
155-248 9.11e-04

Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain that may be involved in binding to specific ligands. Phosphatidylinositol (3)-phosphate (PI3P) was recognized as the innate ligand of the PH domain of MINERVA (melanoma invasion by ERK, also known as FAM129B) PH. Niban family proteins have been found to regulate phosphorylation of a number of proteins involved in the regularion of translation, such as EIF2A, EIF4EBP1 and RPS6KB1. They may also be involved in the endoplasmic reticulum stress response (FAM129A, Niban-like protein 1), suggested to play a role in apoptosis suppression in cancer cells, while Niban-like protein 2 (FAM129C) is a B-cell membrane protein that is overexpressed in chronic lymphocytic leukemia.


Pssm-ID: 469558 [Multi-domain]  Cd Length: 550  Bit Score: 42.67  E-value: 9.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 155 VERCGVLSKWTNYIHGWQDRWVVLKNN-TLSYYKSEDETEYG--CRGSICLS--KAVITPHDFDE---CRFDISVNDSV- 225
Cdd:cd23949    62 VIFSGKLSKYGEDSKKWKERFCVVRGDyNLEYYESKEAYERGkkPKGSINLAgyKVLTSPEEYLElvdRKFPDLAGKSEk 141
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2079037536 226 -----------------------WYLRAQDPDHRQQWI----DAIEQHKT 248
Cdd:cd23949   142 asvpfperpppftlelyhpyrrhYYFCFETEKEQEEWVavlqDCIRHVNW 191
PH_anillin cd01263
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
171-246 9.66e-04

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269964  Cd Length: 121  Bit Score: 39.57  E-value: 9.66e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 171 WQDRWVVLKNNTLSYYK-SEDETEYGCRGSICLSKAV---ITPHDFDECRF-------------DISVNDSV----WYLR 229
Cdd:cd01263    20 WHRRWCVLRGGYLSFWKyPDDEEKKKPIGSIDLTKCItekVEPAPRELCARpntflletlrpaeDDDRDDTNekirVLLS 99
                          90
                  ....*....|....*..
gi 2079037536 230 AQDPDHRQQWIDAIEQH 246
Cdd:cd01263   100 ADTKEERIEWLSALNQT 116
PH_RasGRF1_2 cd13261
Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; ...
159-245 1.16e-03

Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain; RasGRF1 (also called GRF1; CDC25Mm/Ras-specific nucleotide exchange factor CDC25; GNRP/Guanine nucleotide-releasing protein) and RasGRF2 (also called GRF2; Ras guanine nucleotide exchange factor 2) are a family of guanine nucleotide exchange factors (GEFs). They both promote the exchange of Ras-bound GDP by GTP, thereby regulating the RAS signaling pathway. RasGRF1 and RasGRF2 form homooligomers and heterooligomers. GRF1 has 3 isoforms and GRF2 has 2 isoforms. The longest isoforms of RasGRF1 and RasGRF2 contain the following domains: a Rho-GEF domain sandwiched between 2 PH domains, IQ domains, a REM (Ras exchanger motif) domain, and a Ras-GEF domainwhich gives them the capacity to activate both Ras and Rac GTPases in response to signals from a variety of neurotransmitter receptors. Their IQ domains allow them to act as calcium sensors to mediate the actions of NMDA-type and calcium-permeable AMPA-type glutamate receptors. GRF1 also mediates the action of dopamine receptors that signal through cAMP. GRF1 and GRF2 play strikingly different roles in regulating MAP kinase family members, neuronal synaptic plasticity, specific forms of learning and memory, and behavioral responses to psychoactive drugs. 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.


Pssm-ID: 270081  Cd Length: 136  Bit Score: 39.72  E-value: 1.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETE----YGCRGSIClsKAVITP--------HDFDECRFDISV---ND 223
Cdd:cd13261     9 GYLSKKTSDSGKWHERWFALYQNLLFYFENESSSRpsglYLLEGCYC--ERLPTPkgalkgkdHLEKQHYFTISFrheNQ 86
                          90       100
                  ....*....|....*....|..
gi 2079037536 224 SVWYLRAQDPDHRQQWIDAIEQ 245
Cdd:cd13261    87 RQYELRAETESDCDEWVEAIKQ 108
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
170-246 2.13e-03

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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.


Pssm-ID: 270096  Cd Length: 111  Bit Score: 38.42  E-value: 2.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 170 GWQDRWVVLKNNTLSYYKSEDETEYgcrGSICLSKAVI------------TPHDF--DECRFDISVNDSVWYLRAQDPDH 235
Cdd:cd13277    22 GWKLRYGVLDGNILELYESRGGQLL---ESIKLRNAQIerqpnlpddkygTRHGFliNEHKKSGLSSTTKYYLCAETDKE 98
                          90
                  ....*....|.
gi 2079037536 236 RQQWIDAIEQH 246
Cdd:cd13277    99 RDEWVSALSEY 109
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
157-243 2.27e-03

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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.


Pssm-ID: 270086  Cd Length: 106  Bit Score: 38.27  E-value: 2.27e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RCGVLSKWTN----YIHGWQDRWVVLKNNTLSYYKSEDETEYgcRGSICLSKAVITPH-DFD-----ECRFDISVNDSVW 226
Cdd:cd13266     3 KAGYLEKRRKdhsfFGSEWQKRWCAISKNVFYYYGSDKDKQQ--KGEFAINGYDVRMNpTLRkdgkkDCCFELVCPDKRT 80
                          90
                  ....*....|....*...
gi 2079037536 227 Y-LRAQDPDHRQQWIDAI 243
Cdd:cd13266    81 YqFTAASPEDAEDWVDQI 98
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
159-193 3.05e-03

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.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 37.69  E-value: 3.05e-03
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 2079037536 159 GVLSKWTNYIHGWQDRWVVLKNNTLSYYKSEDETE 193
Cdd:cd10573     7 GYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDTK 41
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
157-243 3.26e-03

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (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.


Pssm-ID: 270192  Cd Length: 105  Bit Score: 37.94  E-value: 3.26e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 157 RC-GVLSKWTNYIHGWQDRWVVLKNN--TLSYYKSEDETEygCRGSIC-----------LSKAVITPHdfDECRFDISVN 222
Cdd:cd14673     4 RCrGFLTKMGGKIKTWKKRWFVFDRNkrTLSYYVDKHEKK--LKGVIYfqaieevyydhLRSAAKSPN--PALTFCVKTH 79
                          90       100
                  ....*....|....*....|.
gi 2079037536 223 DSVWYLRAQDPDHRQQWIDAI 243
Cdd:cd14673    80 DRLYYMVAPSPEAMRIWMDVI 100
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
171-245 3.87e-03

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.


Pssm-ID: 270085  Cd Length: 108  Bit Score: 37.67  E-value: 3.87e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 171 WQDRWVVLK-NNTLSYYKSEDETE--------YGCR----GSICLSKAVITPHDFDeCRFDI-SVNDSVWYLRAQDPDHR 236
Cdd:cd13265    19 WKKNWFVLYgDGNLVYYEDETRREvegrinmpRECRnirvGLECRDVQPPEGRSRD-CLLQIvLRDGSTLFLCAESADDA 97

                  ....*....
gi 2079037536 237 QQWIDAIEQ 245
Cdd:cd13265    98 LAWKLALQD 106
START_STARD7-like cd08911
Lipid-binding START domain of mammalian STARD7 and related proteins; This subgroup includes ...
520-653 4.77e-03

Lipid-binding START domain of mammalian STARD7 and related proteins; This subgroup includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of STARD7 (also known as gestational trophoblastic tumor 1/GTT1). It belongs to the START domain family, and in turn to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. The gene encoding STARD7 is overexpressed in choriocarcinoma. STARD7 appears to be involved in the intracellular trafficking of phosphatidycholine (PtdCho) to mitochondria. STARD7 was shown to be surface active and to interact differentially with phospholipid monolayers, it showed a preference for phosphatidylserine, cholesterol, and phosphatidylglycerol.


Pssm-ID: 176920  Cd Length: 207  Bit Score: 39.20  E-value: 4.77e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079037536 520 DANWQLVVEEGEMKVYRREVEENGivLDPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHVVET--LADNAIIIY 597
Cdd:cd08911    20 PDGWEPFIEKKDMLVWRREHPGTG--LYEYKVYGSFDDVTARDFLNVQLDLEYRKKWDATAVELEVVDEdpETGSEIIYW 97
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2079037536 598 QTHkrvWP---ASqRDVLYLSAIRKipaltenDPET--WIVCNFSVDHDSAPLNNRCVRAK 653
Cdd:cd08911    98 EMQ---WPkpfAN-RDYVYVRRYII-------DEENklIVIVSKAVQHPSYPESPKKVRVE 147
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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