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Conserved domains on  [gi|29788755|ref|NP_112224|]
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myotubularin-related protein 13 isoform 2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1138-1485 0e+00

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 13; Myotubularin related phosphoinositide phosphatase 13 (MTMR13), also known as SET binding factor 2 (SBF2), is enzymatically inactive and contains a variety of other domains, including a DENN and a PH-like domain. Mutations in MTMR13 causes Charcot-Marie-Tooth type 4B2, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR2. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR13 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It is believed to interact with MTMR2 and stimulate its phosphatase activity. It is also a guanine nucleotide exchange factor (GEF) which may activate RAB28, promoting the exchange of GDP to GTP and converting inactive GDP-bound Rab proteins into their active GTP-bound form.


:

Pssm-ID: 350437  Cd Length: 297  Bit Score: 593.82  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 APTSSLESSSsIEQEKYLQALLNAVSVHQKLRGNSTLtvrpafalspgvwaslrsstrlissptsfidvgarlagkdhsa 1297
Cdd:cd14589   81 APASSESSSS-IEQEKYLQALLNAISVHQKMNGNSTL------------------------------------------- 116

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1298 sfsnssyLQNQLLKRQAALYIFGEKSQLRNFKVEFALNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKAL 1377
Cdd:cd14589  117 -------LQSQLLKRQAALYIFGEKSQLRGFKLDFALNCEFVPVEFHDIRQVKASFKKLMRACVPSTIPTDSEVTFLKAL 189

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1378 GDSEWFPQLHRIMQLAVVVSEVLENGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 1457
Cdd:cd14589  190 GESEWFLQLHRIMQLAVVISELLESGSSVMVCLEDGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 269

                        330       340
                 ....*....|....*....|....*...
gi 29788755 1458 SLTLNCQGSGFAPVFLQFLDCVHQVHNQ 1485
Cdd:cd14589  270 NLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 530-754 1.55e-143

Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 amino acids in length. The family is found in association with pfam02141, pfam03456, pfam03455. This family is the middle region of SBF2, a member of the myotubularin family. Myotubularin-related proteins have been suggested to work in phosphoinositide-mediated signalling events that may also convey control of myelination. Mutations of SBF2 are implicated in Charcot-Marie-Tooth disease.


:

Pssm-ID: 463536  Cd Length: 227  Bit Score: 442.91  E-value: 1.55e-143
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    530 GPPVVSIMDKVTTVF-NSAQRLEVVRNCISFIFENKILETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 608
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    609 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 688
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755    689 KEDNHAPHLKQK-DKLPDDHYQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 754
Cdd:pfam12335  161 DEKNPHISAQGKnTASLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 116-298 2.27e-67

DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a domain which occurs in several proteins involved in Rab- mediated processes or regulation of MAPK signalling pathways.


:

Pssm-ID: 460461  Cd Length: 186  Bit Score: 225.53  E-value: 2.27e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    116 FAPKSLVLVSRLYYPEIFRACLGLIYTVYVDSLN-VSLESLIANLCAC-LVPAAGGSQKLFSLGAGDRQLIQTPLHDSLP 193
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQKLKPLGGTEPILLQRPEDSELP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    194 ITGTSVALLFQQLGIQNVLSLFCAVLTENKVLFHSASFQRLSDACRALESLMFPLKYSYPYIPILPAQLLEVLSSPTPFI 273
Cdd:pfam02141   81 LEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDVLSAPTPFI 160

                          170       180
                   ....*....|....*....|....*.
gi 29788755    274 IGVHS-VFKTDVHELLDVIIADLDGG 298
Cdd:pfam02141  161 IGVHSrYFDLLEDPLDDVVLVDLDTG 186
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1742-1847 4.27e-64

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: 212.58  E-value: 4.27e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1742 ENRSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTSDKAFFDLKTS 1821
Cdd:cd01235    1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                         90       100
                 ....*....|....*....|....*.
gi 29788755 1822 KRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd01235   81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 882-1000 4.41e-58

Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR13 (also called SBF2/SET binding factor 2) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Leu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR13 has high sequence similarity to MTMR5 and has recently been shown to be a second gene mutated in type 4B Charcot-Marie-Tooth syndrome. Both MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


:

Pssm-ID: 275416  Cd Length: 119  Bit Score: 195.96  E-value: 4.41e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13339    1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 29788755  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13339   81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 1-86 1.84e-30

Domain always found upstream of DENN domain, found in a variety of signalling proteins; The uDENN domain is part of the tripartite DENN domain. It is always found upstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


:

Pssm-ID: 214824  Cd Length: 89  Bit Score: 115.89  E-value: 1.84e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755       1 MARLADYFIVVGYDHEKPGSGEG-LGKIIQRFPQKDWDDTPFPQGIELFCQPGGWQL--SRERKQPTFFVVVLTDIDSDR 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSyKPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFvtQTSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 29788755      78 HYCSCLTFY 86
Cdd:smart00800   81 RYGFCLRFY 89
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 352-420 1.11e-18

Domain always found downstream of DENN domain, found in a variety of signalling proteins; The dDENN domain is part of the tripartite DENN domain. It is always found downstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


:

Pssm-ID: 129037  Cd Length: 69  Bit Score: 81.57  E-value: 1.11e-18
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29788755     352 DKEVRAVFLRLFAQLFQGYRSCLQLIRIHAEPVIHFHKTAFLGQRGLVENDFLTKVLSGMAFAGFVSER 420
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
 
Name Accession Description Interval E-value
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1138-1485 0e+00

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 13; Myotubularin related phosphoinositide phosphatase 13 (MTMR13), also known as SET binding factor 2 (SBF2), is enzymatically inactive and contains a variety of other domains, including a DENN and a PH-like domain. Mutations in MTMR13 causes Charcot-Marie-Tooth type 4B2, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR2. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR13 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It is believed to interact with MTMR2 and stimulate its phosphatase activity. It is also a guanine nucleotide exchange factor (GEF) which may activate RAB28, promoting the exchange of GDP to GTP and converting inactive GDP-bound Rab proteins into their active GTP-bound form.


Pssm-ID: 350437  Cd Length: 297  Bit Score: 593.82  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 APTSSLESSSsIEQEKYLQALLNAVSVHQKLRGNSTLtvrpafalspgvwaslrsstrlissptsfidvgarlagkdhsa 1297
Cdd:cd14589   81 APASSESSSS-IEQEKYLQALLNAISVHQKMNGNSTL------------------------------------------- 116

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1298 sfsnssyLQNQLLKRQAALYIFGEKSQLRNFKVEFALNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKAL 1377
Cdd:cd14589  117 -------LQSQLLKRQAALYIFGEKSQLRGFKLDFALNCEFVPVEFHDIRQVKASFKKLMRACVPSTIPTDSEVTFLKAL 189

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1378 GDSEWFPQLHRIMQLAVVVSEVLENGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 1457
Cdd:cd14589  190 GESEWFLQLHRIMQLAVVISELLESGSSVMVCLEDGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 269

                        330       340
                 ....*....|....*....|....*...
gi 29788755 1458 SLTLNCQGSGFAPVFLQFLDCVHQVHNQ 1485
Cdd:cd14589  270 NLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 530-754 1.55e-143

Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 amino acids in length. The family is found in association with pfam02141, pfam03456, pfam03455. This family is the middle region of SBF2, a member of the myotubularin family. Myotubularin-related proteins have been suggested to work in phosphoinositide-mediated signalling events that may also convey control of myelination. Mutations of SBF2 are implicated in Charcot-Marie-Tooth disease.


Pssm-ID: 463536  Cd Length: 227  Bit Score: 442.91  E-value: 1.55e-143
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    530 GPPVVSIMDKVTTVF-NSAQRLEVVRNCISFIFENKILETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 608
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    609 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 688
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755    689 KEDNHAPHLKQK-DKLPDDHYQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 754
Cdd:pfam12335  161 DEKNPHISAQGKnTASLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 1116-1520 6.03e-93

Myotubularin-like phosphatase domain; This family represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate. Mutations in gene encoding myotubularin-related proteins have been associated with disease.


Pssm-ID: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 304.79  E-value: 6.03e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1116 RDYQRLGLGTisgsssrsrPEYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 1195
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1196 RSGgfhgKGVVGLFKSQNspqaaptsslessssIEQEKYLQALLNAVSVHQKLRGnstltvrpafalspgvwaslrsstr 1275
Cdd:pfam06602   83 RSS----QPLVGLNGKRS---------------IEDEKLLQAIFKSSNPYSAKKL------------------------- 118

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1276 LIssptsfID-------VGARLAGKdhsaSFSNSSYLQNqllkrqaalyifgeksqlrnfkvefalnCEFVPVEFHEIRQ 1348
Cdd:pfam06602  119 YI------VDarpklnaMANRAKGG----GYENEDNYPN----------------------------CKKIFLGIENIHV 160

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1349 VKASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWDITAQVTSLVQLL 1427
Cdd:pfam06602  161 MRDSLNKLVEACNDRSPSMDK---WLSRLESSGWLKHIKAILDGACLIAQAVDlEGSSVLVHCSDGWDRTAQLTSLAQLL 237

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1428 SDPFYRTLEGFQMLVEKEWLSFGHKFSQRSS-LTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEFNLYYLKFLAFHYVS 1506
Cdd:pfam06602  238 LDPYYRTIEGFQVLIEKEWLSFGHKFADRCGhLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYS 317

                          410
                   ....*....|....
gi 29788755   1507 NRFKTFLLDSDYER 1520
Cdd:pfam06602  318 CQFGTFLCNSEKER 331
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 116-298 2.27e-67

DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a domain which occurs in several proteins involved in Rab- mediated processes or regulation of MAPK signalling pathways.


Pssm-ID: 460461  Cd Length: 186  Bit Score: 225.53  E-value: 2.27e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    116 FAPKSLVLVSRLYYPEIFRACLGLIYTVYVDSLN-VSLESLIANLCAC-LVPAAGGSQKLFSLGAGDRQLIQTPLHDSLP 193
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQKLKPLGGTEPILLQRPEDSELP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    194 ITGTSVALLFQQLGIQNVLSLFCAVLTENKVLFHSASFQRLSDACRALESLMFPLKYSYPYIPILPAQLLEVLSSPTPFI 273
Cdd:pfam02141   81 LEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDVLSAPTPFI 160

                          170       180
                   ....*....|....*....|....*.
gi 29788755    274 IGVHS-VFKTDVHELLDVIIADLDGG 298
Cdd:pfam02141  161 IGVHSrYFDLLEDPLDDVVLVDLDTG 186
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 117-298 2.11e-64

Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The DENN domain is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


Pssm-ID: 214823  Cd Length: 183  Bit Score: 216.68  E-value: 2.11e-64
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755     117 APKSLVLVSRLYYPEIFRACLGLIYTVYVDSLNVSLEsLIANLCACLVPAAGGSQKLFSLGAGDRQLIQTPLHDSLPITG 196
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLE-LLISLLLYPVPPPGGSLVLVSLGPGDLIELQRPLDSSLPLID 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755     197 TSVALLFQQLGIQNVLSLFCAVLTENKVLFHSASFQRLSDACRALESLMFPLKYSYPYIPILPAQLLEVLSSPTPFIIGV 276
Cdd:smart00799   80 FSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSAPTPFIIGV 159

                           170       180
                    ....*....|....*....|....
gi 29788755     277 HSVFKTDVHELL--DVIIADLDGG 298
Cdd:smart00799  160 HSSYFEEVKELPdeDVVVVDLDTG 183
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1742-1847 4.27e-64

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: 212.58  E-value: 4.27e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1742 ENRSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTSDKAFFDLKTS 1821
Cdd:cd01235    1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                         90       100
                 ....*....|....*....|....*.
gi 29788755 1822 KRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd01235   81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 882-1000 4.41e-58

Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR13 (also called SBF2/SET binding factor 2) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Leu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR13 has high sequence similarity to MTMR5 and has recently been shown to be a second gene mutated in type 4B Charcot-Marie-Tooth syndrome. Both MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 275416  Cd Length: 119  Bit Score: 195.96  E-value: 4.41e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13339    1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 29788755  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13339   81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 1-86 1.84e-30

Domain always found upstream of DENN domain, found in a variety of signalling proteins; The uDENN domain is part of the tripartite DENN domain. It is always found upstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


Pssm-ID: 214824  Cd Length: 89  Bit Score: 115.89  E-value: 1.84e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755       1 MARLADYFIVVGYDHEKPGSGEG-LGKIIQRFPQKDWDDTPFPQGIELFCQPGGWQL--SRERKQPTFFVVVLTDIDSDR 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSyKPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFvtQTSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 29788755      78 HYCSCLTFY 86
Cdd:smart00800   81 RYGFCLRFY 89
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 25-84 3.61e-23

uDENN domain; This region is always found associated with pfam02141. It is predicted to form an all beta domain.


Pssm-ID: 460926  Cd Length: 59  Bit Score: 94.21  E-value: 3.61e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755     25 GKIIQRFPQKDWDDTPFPQGIELFCQPGGWQLSRERKqPTFFVVVLTDIDSDRHYCSCLT 84
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSRE-PTFFSFVLTDEDGSRLYGACLT 59
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 352-420 1.11e-18

Domain always found downstream of DENN domain, found in a variety of signalling proteins; The dDENN domain is part of the tripartite DENN domain. It is always found downstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


Pssm-ID: 129037  Cd Length: 69  Bit Score: 81.57  E-value: 1.11e-18
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29788755     352 DKEVRAVFLRLFAQLFQGYRSCLQLIRIHAEPVIHFHKTAFLGQRGLVENDFLTKVLSGMAFAGFVSER 420
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1747-1847 4.35e-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: 75.66  E-value: 4.35e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    1747 EGTLYKRGA-LLKGWKPRWFVLdvTKHQLRYYDS---GEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTsdkafFDLKTSK 1822
Cdd:smart00233    4 EGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKPHC-----FEIKTSD 76

                            90       100
                    ....*....|....*....|....*.
gi 29788755    1823 R-VYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:smart00233   77 RkTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1747-1847 7.62e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.43  E-value: 7.62e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1747 EGTLYKRG-ALLKGWKPRWFVLdvTKHQLRYYD---SGEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTsdkafFDLKTS- 1821
Cdd:pfam00169    4 EGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFC-----FELRTGe 76

                           90       100
                   ....*....|....*....|....*....
gi 29788755   1822 ---KRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:pfam00169   77 rtgKRTYLLQAESEEERKDWIKAIQSAIR 105
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
879-957 5.87e-05

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 42.58  E-value: 5.87e-05
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29788755     879 LPGEEIVCEGLRVLLDPDGReeatggllggpqllpAEGALFLTTYRILFRGTPHDQLvgeqtVVRSFPIASITKEKKIT 957
Cdd:smart00568    2 LPEEEKLIADYSCYLSRTGP---------------VQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 387-433 9.38e-05

dDENN domain; This region is always found associated with pfam02141. It is predicted to form a globular domain. Although not statistically supported it has been suggested that this domain may be similar to members of the Rho/Rac/Cdc42 GEF family. This N-terminal region of DENN folds into a longin module, consisting of a central antiparallel beta-sheet layered between helix H1 and helices H2 and H3 (strands S1-S5). Rab35 interacts with dDENN via residues in helix 1 and in the loop S3-S4.


Pssm-ID: 460925  Cd Length: 48  Bit Score: 41.41  E-value: 9.38e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 29788755    387 FHKTAFLGQRGLVENDFLTKVLSGMAFAGFVSERG-PPYRSCDLFDEL 433
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 914-1006 7.52e-04

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.


Pssm-ID: 397160  Cd Length: 112  Bit Score: 40.81  E-value: 7.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    914 AEGALFLTTYRILFRGTPHDQLvgeQTVVrsFPIASITKEKKITmqnQLQQNMQEGLQITSASFQliKVAFDEEVSPEVV 993
Cdd:pfam02893   30 VQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDIEEIEKLK---GGANLFPNGIQVETGSND--KFSFAGFVTRDEA 99

                           90
                   ....*....|...
gi 29788755    994 EIFKKQLMKFRYP 1006
Cdd:pfam02893  100 IEFILALLKNAHP 112
 
Name Accession Description Interval E-value
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1138-1485 0e+00

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 13; Myotubularin related phosphoinositide phosphatase 13 (MTMR13), also known as SET binding factor 2 (SBF2), is enzymatically inactive and contains a variety of other domains, including a DENN and a PH-like domain. Mutations in MTMR13 causes Charcot-Marie-Tooth type 4B2, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR2. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR13 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It is believed to interact with MTMR2 and stimulate its phosphatase activity. It is also a guanine nucleotide exchange factor (GEF) which may activate RAB28, promoting the exchange of GDP to GTP and converting inactive GDP-bound Rab proteins into their active GTP-bound form.


Pssm-ID: 350437  Cd Length: 297  Bit Score: 593.82  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 APTSSLESSSsIEQEKYLQALLNAVSVHQKLRGNSTLtvrpafalspgvwaslrsstrlissptsfidvgarlagkdhsa 1297
Cdd:cd14589   81 APASSESSSS-IEQEKYLQALLNAISVHQKMNGNSTL------------------------------------------- 116

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1298 sfsnssyLQNQLLKRQAALYIFGEKSQLRNFKVEFALNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKAL 1377
Cdd:cd14589  117 -------LQSQLLKRQAALYIFGEKSQLRGFKLDFALNCEFVPVEFHDIRQVKASFKKLMRACVPSTIPTDSEVTFLKAL 189

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1378 GDSEWFPQLHRIMQLAVVVSEVLENGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 1457
Cdd:cd14589  190 GESEWFLQLHRIMQLAVVISELLESGSSVMVCLEDGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 269

                        330       340
                 ....*....|....*....|....*...
gi 29788755 1458 SLTLNCQGSGFAPVFLQFLDCVHQVHNQ 1485
Cdd:cd14589  270 NLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1138-1485 1.83e-148

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatases 5 and 13; This subgroup of enzymatically inactive phosphatase domains of myotubularins consists of MTMR5, also known as SET binding factor 1 (SBF1) and MTMR13, also known as SET binding factor 2 (SBF2), and similar domains. Beside the pseudophosphatase domain, they contain a variety of other domains, including a DENN and a PH-like domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR5 and MTMR13 are pseudophosphatases that lack the catalytic cysteine in their catalytic pocket. Mutations in MTMR13 causes Charcot-Marie-Tooth type 4B2, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR2. Mutations in the MTMR5 gene cause Charcot-Marie-tooth disease type 4B3. MTMR5 and MTMR13 interact with MTMR2 and stimulate its phosphatase activity.


Pssm-ID: 350382 [Multi-domain]  Cd Length: 274  Bit Score: 458.37  E-value: 1.83e-148
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14534    1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFHGKGVMGMLKSANTSTS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 APTSSLE-SSSSIEQEKYLQALlnavsvhqklrgnstltvrpafalspgvwaslrsstrlissptsfidvgarlagkdhs 1296
Cdd:cd14534   81 SPTVSSSeTSSSLEQEKYLSAL---------------------------------------------------------- 102

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1297 asfsnssylqnqllkrqaALYIFGEKSQLRNFKVEFALNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKA 1376
Cdd:cd14534  103 ------------------VLYVLGEKSQMKGVKAESDPKCEFIPVEYPEVRQVKASFKKLLRACVPSSAPTEPEQSFLKA 164

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1377 LGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQ 1455
Cdd:cd14534  165 VEDSEWLQQLQCLMQLSGAVVDLLDvQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVEKEWLAFGHRFSH 244

                        330       340       350
                 ....*....|....*....|....*....|
gi 29788755 1456 RSSLTLNCQGSGFAPVFLQFLDCVHQVHNQ 1485
Cdd:cd14534  245 RSNLTAASQSSGFAPVFLQFLDAVHQIHRQ 274
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 530-754 1.55e-143

Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 amino acids in length. The family is found in association with pfam02141, pfam03456, pfam03455. This family is the middle region of SBF2, a member of the myotubularin family. Myotubularin-related proteins have been suggested to work in phosphoinositide-mediated signalling events that may also convey control of myelination. Mutations of SBF2 are implicated in Charcot-Marie-Tooth disease.


Pssm-ID: 463536  Cd Length: 227  Bit Score: 442.91  E-value: 1.55e-143
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    530 GPPVVSIMDKVTTVF-NSAQRLEVVRNCISFIFENKILETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 608
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    609 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 688
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755    689 KEDNHAPHLKQK-DKLPDDHYQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 754
Cdd:pfam12335  161 DEKNPHISAQGKnTASLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1138-1485 6.76e-129

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 5; Myotubularin related phosphoinositide phosphatase 5 (MTMR5), also known as SET binding factor 1 (SBF1), is enzymatically inactive and contains a variety of other domains, including a DENN and a PH-like domain. Mutations in the MTMR5 gene cause Charcot-Marie-tooth disease type 4B3. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR5 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It interacts with MTMR2, an active myotubularin related phosphatidylinositol phosphatase, regulates its enzymatic activity and subcellular location.


Pssm-ID: 350436 [Multi-domain]  Cd Length: 291  Bit Score: 405.12  E-value: 6.76e-129
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14588    1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 APTSSLESSssIEQEKYLQALLNAVSVHQKLRGNSTLTvrpAFalspgvwaslrsstrlissptsfidvgarlagkdhsa 1297
Cdd:cd14588   81 GQSQTDSTS--LEQEKYLQAVINSMPRYADASGRNTLS---GF------------------------------------- 118

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1298 sfsnssylqnqllkrQAALYIFGEKSQLRNFKVEFALNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKAL 1377
Cdd:cd14588  119 ---------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASFKKLMKACVPSCPSTDPSQTYLRTL 183

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1378 GDSEWFPQLHRIMQLAVVVSEVLENGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRS 1457
Cdd:cd14588  184 EESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYYRTIEGFRLLVEKEWLSFGHRFSHRG 263

                        330       340
                 ....*....|....*....|....*...
gi 29788755 1458 SLTLNCQGSGFAPVFLQFLDCVHQVHNQ 1485
Cdd:cd14588  264 AQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 1116-1520 6.03e-93

Myotubularin-like phosphatase domain; This family represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate. Mutations in gene encoding myotubularin-related proteins have been associated with disease.


Pssm-ID: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 304.79  E-value: 6.03e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1116 RDYQRLGLGTisgsssrsrPEYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 1195
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1196 RSGgfhgKGVVGLFKSQNspqaaptsslessssIEQEKYLQALLNAVSVHQKLRGnstltvrpafalspgvwaslrsstr 1275
Cdd:pfam06602   83 RSS----QPLVGLNGKRS---------------IEDEKLLQAIFKSSNPYSAKKL------------------------- 118

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1276 LIssptsfID-------VGARLAGKdhsaSFSNSSYLQNqllkrqaalyifgeksqlrnfkvefalnCEFVPVEFHEIRQ 1348
Cdd:pfam06602  119 YI------VDarpklnaMANRAKGG----GYENEDNYPN----------------------------CKKIFLGIENIHV 160

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1349 VKASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWDITAQVTSLVQLL 1427
Cdd:pfam06602  161 MRDSLNKLVEACNDRSPSMDK---WLSRLESSGWLKHIKAILDGACLIAQAVDlEGSSVLVHCSDGWDRTAQLTSLAQLL 237

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1428 SDPFYRTLEGFQMLVEKEWLSFGHKFSQRSS-LTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEFNLYYLKFLAFHYVS 1506
Cdd:pfam06602  238 LDPYYRTIEGFQVLIEKEWLSFGHKFADRCGhLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYS 317

                          410
                   ....*....|....
gi 29788755   1507 NRFKTFLLDSDYER 1520
Cdd:pfam06602  318 CQFGTFLCNSEKER 331
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 1178-1481 2.65e-70

protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. Not all members are catalytically active proteins, some function as adaptors for the active members.


Pssm-ID: 350357  Cd Length: 226  Bit Score: 235.52  E-value: 2.65e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1178 NRLPVVCWKNSRSGTLLLRSGGFHgkgvVGLFKSQNSpqaaptsslessssiEQEKYLQALLNAVsvhqklrgnstltvr 1257
Cdd:cd14507    1 GRIPVLSWRHPRNGAVICRSSQPL----VGLTGSRSK---------------EDEKLLNAIRKAS--------------- 46

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1258 pafalspgvwaslrsstrlissptsfidvgarlagkdhsasfsnssylqnqllKRQAALYIFGEKSQLrNFKVEFALNC- 1336
Cdd:cd14507   47 -----------------------------------------------------PSSKKLYIVDARPKL-NAVANRAKGGg 72

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1337 -------EFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLEN-GSSVLV 1408
Cdd:cd14507   73 yenteyyPNCELEFLNIENIHAMRDSLNKLRDACLSPNDEESNWLSALESSGWLEHIRLILKGAVRVADLLEKeGTSVLV 152

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 29788755 1409 CLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSLTL-NCQGSGFAPVFLQFLDCVHQ 1481
Cdd:cd14507  153 HCSDGWDRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDkNSSDEERSPIFLQFLDCVWQ 226
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 116-298 2.27e-67

DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a domain which occurs in several proteins involved in Rab- mediated processes or regulation of MAPK signalling pathways.


Pssm-ID: 460461  Cd Length: 186  Bit Score: 225.53  E-value: 2.27e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    116 FAPKSLVLVSRLYYPEIFRACLGLIYTVYVDSLN-VSLESLIANLCAC-LVPAAGGSQKLFSLGAGDRQLIQTPLHDSLP 193
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQKLKPLGGTEPILLQRPEDSELP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    194 ITGTSVALLFQQLGIQNVLSLFCAVLTENKVLFHSASFQRLSDACRALESLMFPLKYSYPYIPILPAQLLEVLSSPTPFI 273
Cdd:pfam02141   81 LEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDVLSAPTPFI 160

                          170       180
                   ....*....|....*....|....*.
gi 29788755    274 IGVHS-VFKTDVHELLDVIIADLDGG 298
Cdd:pfam02141  161 IGVHSrYFDLLEDPLDDVVLVDLDTG 186
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 117-298 2.11e-64

Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The DENN domain is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


Pssm-ID: 214823  Cd Length: 183  Bit Score: 216.68  E-value: 2.11e-64
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755     117 APKSLVLVSRLYYPEIFRACLGLIYTVYVDSLNVSLEsLIANLCACLVPAAGGSQKLFSLGAGDRQLIQTPLHDSLPITG 196
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLE-LLISLLLYPVPPPGGSLVLVSLGPGDLIELQRPLDSSLPLID 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755     197 TSVALLFQQLGIQNVLSLFCAVLTENKVLFHSASFQRLSDACRALESLMFPLKYSYPYIPILPAQLLEVLSSPTPFIIGV 276
Cdd:smart00799   80 FSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSAPTPFIIGV 159

                           170       180
                    ....*....|....*....|....
gi 29788755     277 HSVFKTDVHELL--DVIIADLDGG 298
Cdd:smart00799  160 HSSYFEEVKELPdeDVVVVDLDTG 183
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1742-1847 4.27e-64

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: 212.58  E-value: 4.27e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1742 ENRSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTSDKAFFDLKTS 1821
Cdd:cd01235    1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                         90       100
                 ....*....|....*....|....*.
gi 29788755 1822 KRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd01235   81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 882-1000 4.41e-58

Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR13 (also called SBF2/SET binding factor 2) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Leu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR13 has high sequence similarity to MTMR5 and has recently been shown to be a second gene mutated in type 4B Charcot-Marie-Tooth syndrome. Both MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 275416  Cd Length: 119  Bit Score: 195.96  E-value: 4.41e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13339    1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 29788755  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13339   81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
PH-GRAM_MTMR5_MTMR13 cd13208
Myotubularian (MTM) related 5 and 13 proteins (MTMR5 and MTMR13) Pleckstrin ...
 882-1000 3.23e-49

Myotubularian (MTM) related 5 and 13 proteins (MTMR5 and MTMR13) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR5 is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It lacks several amino acids in the dsPTPase catalytic pocket which renders it catalytically inactive as a phosphatase. MTMR5 is the most well-studied inactive member of this family and has been implicated in cellular growth control and oncogenic transformation. MTMR13 is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Leu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR13 has high sequence similarity to MTMR5 and has recently been shown to be a second gene mutated in type 4B Charcot-Marie-Tooth syndrome. Both MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date. Although the majority of the sequences are MTMR 5 and 13, this cd also contains MTM5 nematode sequences.


Pssm-ID: 275396  Cd Length: 120  Bit Score: 170.61  E-value: 3.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLpAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13208    1 EELVMEGLRVYLLPDGREEGTGGNGGPNLLP-AEGALFLTNYRVIFKGTPCDPLACEQTVVRSFPIASLTKEKKIAVQKL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 29788755  962 L--QQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13208   80 AhlDQKLQEGLQLRSATFQLIKVAFDEEVSSEKIEKFRKQL 120
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1117-1497 3.98e-49

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases 6, 7, and 8; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTMR6, MTMR7 and MTMR8, and related domains. Beside the phosphatase domain, they contain a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR6, MTMR7 and MTMR8 form complexes with catalytically inactive MTMR9, and display differential substrate preferences. In cells, the MTMR6/R9 complex significantly increases the cellular levels of PtdIns(5)P, the product of PI(3,5)P(2) dephosphorylation, whereas the MTMR8/R9 complex reduces cellular PtdIns(3)P levels. The MTMR6/R9 complex serves to inhibit stress-induced apoptosis while the MTMR8/R9 complex inhibits autophagy.


Pssm-ID: 350380 [Multi-domain]  Cd Length: 301  Bit Score: 177.53  E-value: 3.98e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1117 DYQRLGLgtisgsssrsrP-EYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 1195
Cdd:cd14532    4 EYTRMGV-----------PnDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAIC 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1196 RS----GGFHGKGVvglfksqnspqaaptsslessssiEQEKYLQALLNAVSVHQKLRGNSTltvRP---AFAlspgvwa 1268
Cdd:cd14532   73 RCsqplSGFSARCV------------------------EDEQLLQAIRKANPNSKFMYVVDT---RPkinAMA------- 118

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1269 slrsstrlissptsfidvgARLAGKdhsaSFSNssylqnqllkrqaalyifgeksqLRNFKvefalNCEFVPVEFHEIRQ 1348
Cdd:cd14532  119 -------------------NKAAGK----GYEN-----------------------EDNYS-----NIKFQFFGIENIHV 147

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1349 VKASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSEVLENGSSVLVCLEEGWDITAQVTSLVQLLS 1428
Cdd:cd14532  148 MRSSLQKLLEVCELKNPSMSA---FLSGLESSGWLKHIKAVMDTSVFIAKAVSEGASVLVHCSDGWDRTAQTCSLASLLL 224

                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 29788755 1429 DPFYRTLEGFQMLVEKEWLSFGHKFSQRSSLTlncQGSG--FAPVFLQFLDCVHQVHNQYPTEFEFNLYYL 1497
Cdd:cd14532  225 DPYYRTIKGFQVLIEKEWLSFGHKFTDRCGHL---QGDAkeVSPVFTQFLDCVWQLMQQFPRAFEFNERFL 292
PH-GRAM_MTMR5 cd13340
Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, ...
 882-1000 8.83e-43

Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR5 (also called SBF1/SET binding factor 1) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It lacks several amino acids in the dsPTPase catalytic pocket which renders it catalytically inactive as a phosphatase. MTMR5 is the most well-studied inactive member of this family and has been implicated in cellular growth control and oncogenic transformation. MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 275417  Cd Length: 119  Bit Score: 152.32  E-value: 8.83e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13340    1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 29788755  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13340   81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 1335-1497 9.90e-42

protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related phosphoinositide phosphatases 1 and 2; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTM1, MTMR1 and MTMR2. All contain an additional N-terminal PH-GRAM domain and C-terminal coiled-coiled domain and PDZ binding site. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350383  Cd Length: 249  Bit Score: 154.53  E-value: 9.90e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1335 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVLVCLEEG 1413
Cdd:cd14535   81 NAELVFLDIHNIHVMRESLRKLKDICFPNI----DDSHWLSNLESTHWLEHIKLILAGAVRIADKVESGkTSVVVHCSDG 156

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1414 WDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQR-SSLTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEF 1492
Cdd:cd14535  157 WDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRiGHGDKNHSDADRSPVFLQFIDCVWQMTRQFPNAFEF 236


                 ....*
gi 29788755 1493 NLYYL 1497
Cdd:cd14535  237 NEHFL 241
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1138-1481 4.09e-40

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 4; Myotubularin related phosphoinositide phosphatase 4 (MTMR4), also known as FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2) or zinc finger FYVE domain-containing protein 11 (ZFYVE11), is enzymatically active and contains a C-terminal FYVE domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway. It plays a role in bacterial pathogenesis by stabilizing the integrity of bacteria-containing vacuoles.


Pssm-ID: 350435 [Multi-domain]  Cd Length: 308  Bit Score: 151.72  E-value: 4.09e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGgfhgKGVVGLFKSQNSpqa 1217
Cdd:cd14587    3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCS----QPEISWWGWRNA--- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 aptsslessssieQEKYLqallnavsvhqklrgnsTLTVRPAFALSPGVWASLRSSTRLIS--SPTSFIDVGARLAGkdh 1295
Cdd:cd14587   76 -------------DDEYL-----------------VTSIAKACALDPGTRAPGGSPSKGNSdgSDASDTDFDSSLTA--- 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1296 sASFSNSSYLQNQLLKRQAALYIFGEKSQLRNFKVE---FALNCEFVPVEFHEIRQVKASFKKLMRACipSTIPTDSevT 1372
Cdd:cd14587  123 -CSAVESGAAPQKLLILDARSYTAAVANRAKGGGCEceeYYPNCEVMFMGMANIHSIRNSFQYLRAVC--SQMPDPG--N 197

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1373 FLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGH 1451
Cdd:cd14587  198 WLSALESTKWLQHLSVMLKAAVLVASAVDrEGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGH 277

                        330       340       350
                 ....*....|....*....|....*....|.
gi 29788755 1452 KFSQRSSLTLNCQG-SGFAPVFLQFLDCVHQ 1481
Cdd:cd14587  278 KFGDRCGHQENVEDqNEQCPVFLQWLDCVHQ 308
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1138-1481 7.75e-40

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 3; Myotubularin related phosphoinositide phosphatase 3 (MTMR3), also known as FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1) or Zinc finger FYVE domain-containing protein 10 (ZFYVE10), is enzymatically active and contains a C-terminal FYVE domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. Together with phosphoinositide 5-kinase PIKfyve, phosphoinositide 3-phosphatase MTMR3 constitutes a phosphoinositide loop that produces PI(5)P via PI(3,5)P2 and regulates cell migration.


Pssm-ID: 350434  Cd Length: 317  Bit Score: 151.33  E-value: 7.75e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGgfhgKGVVGLFKSQNSpqa 1217
Cdd:cd14586    8 WRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCG----QPEVSWWGWRNA--- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1218 aptsslessssiEQEKYLQALLNAVSVHQklrgnstltvrpafalspgvwASLRSSTRLISSPTSFIDvGARLAGKDHSA 1297
Cdd:cd14586   81 ------------DDEHLVQSVAKACASDS---------------------SSCKSVLMTGNCSRDFPN-GGDLSDVEFDS 126

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1298 SFSNSSYLQN------QLLKRQAALYIFGEKSQLRNFKVE---FALNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTD 1368
Cdd:cd14586  127 SMSNASGVESlaiqpqKLLILDARSYAAAVANRAKGGGCEcpeYYPNCEVVFMGMANIHSIRKSFQSLRLLCTQMPDPAN 206

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1369 sevtFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWL 1447
Cdd:cd14586  207 ----WLSALESTKWLQHLSMLLKSALLVVHAVDrDQRPVLVHCSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWL 282

                        330       340       350
                 ....*....|....*....|....*....|....*
gi 29788755 1448 SFGHKFSQRSSLTLNCQG-SGFAPVFLQFLDCVHQ 1481
Cdd:cd14586  283 DFGHKFADRCGHGENSDDlNERCPVFLQWLDCVHQ 317
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1177-1481 4.88e-37

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases 3 and 4; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTMR3, also known as ZFYVE10, and MTMR4, also known as ZFYVE11, and related domains. Beside the phosphatase domain, they contain a C-terminal FYVE domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350381  Cd Length: 229  Bit Score: 140.23  E-value: 4.88e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1177 HNRLPVVCWKNSRSGTLLLRSGgfhgKGVVGLFKSQNSpqaaptsslessssiEQEKYLQALLNAVSVhqklrgnstltv 1256
Cdd:cd14533    1 SKRIPSVVWRHQRNGAVIARCS----QPEVGWLGWRNA---------------EDENLLQAIAEACAS------------ 49

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1257 rpafalspgvwaSLRSSTRLIssptsfidVGARlagkDHSASFSNSsylqnqlLKRQAALYIfgeksqlrnfkvEFALNC 1336
Cdd:cd14533   50 ------------NASPKKLLI--------VDAR----SYAAAVANR-------AKGGGCECP------------EYYPNC 86

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1337 EFVPVEFHEIRQVKASFKKLMRACIPSTIPTdsevTFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWD 1415
Cdd:cd14533   87 EVVFMNLANIHAIRKSFHSLRALCSSAPDQP----NWLSNLESTKWLHHLSGLLKAALLVVNAVDeEGRPVLVHCSDGWD 162

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755 1416 ITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSLTLNCQGSG-FAPVFLQFLDCVHQ 1481
Cdd:cd14533  163 RTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVNSEDINeRCPVFLQWLDCVHQ 229
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 1335-1497 6.23e-37

protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; Myotubularin phosphoinositide phosphatase 1 (MTM1), also called myotubularin, is enzymatically active and contains an N-terminal PH-GRAM domain and C-terminal coiled-coiled domain and PDZ binding site. Mutations in MTM1 cause X-linked myotubular myopathy. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350439  Cd Length: 249  Bit Score: 140.55  E-value: 6.23e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1335 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVLVCLEEG 1413
Cdd:cd14591   81 NAELVFLDIHNIHVMRESLKKLKDIVYPNV----EESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLVHCSDG 156

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1414 WDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQR-SSLTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEF 1492
Cdd:cd14591  157 WDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRiGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEF 236


                 ....*
gi 29788755 1493 NLYYL 1497
Cdd:cd14591  237 NEQFL 241
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1335-1497 1.30e-36

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 2; Myotubularin related phosphoinositide phosphatase 2 (MTMR2) is enzymatically active and contains an additional N-terminal PH-GRAM domain and C-terminal coiled-coiled domain and PDZ binding site. Mutations in MTMR2 causes Charcot-Marie-Tooth type 4B1, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR13. MTMR13, an inactive phosphatase, is believed to interact with MTMR2 and stimulate its phosphatase activity. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350438  Cd Length: 262  Bit Score: 140.17  E-value: 1.30e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1335 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVLVCLEEG 1413
Cdd:cd14590   94 NAELVFLDIHNIHVMRESLRKLKEIVYPNI----EESHWLSNLESTHWLEHIKLILAGALRIADKVESGkTSVVVHCSDG 169

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1414 WDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSL-TLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEF 1492
Cdd:cd14590  170 WDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHgDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEF 249


                 ....*
gi 29788755 1493 NLYYL 1497
Cdd:cd14590  250 NEYFL 254
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1117-1497 2.98e-36

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 8; Myotubularin related phosphoinositide phosphatase 8 (MTMR8) is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR8 forms a complex with catalytically inactive MTMR9 and preferentially dephosphorylates PtdIns(3)P; the MTMR8/R9 complex inhibits autophagy. In zebrafish, it cooperates with PI3K to regulate actin filament modeling and muscle development.


Pssm-ID: 350432 [Multi-domain]  Cd Length: 308  Bit Score: 140.39  E-value: 2.98e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1117 DYQRLGLGTisgsssrsrpEYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLR 1196
Cdd:cd14584   10 DFQRMGIPN----------DYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1197 SG----GFHGKGVvglfksqnspqaaptsslessssiEQEKYLQALLNAvsvhqklrgnstltvrpafalSPGvwaslrs 1272
Cdd:cd14584   80 CSqplsGFSARCV------------------------EDEQMLQAISKA---------------------NPG------- 107

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1273 strlisSPTSFI-DVGARLagkdhsasfsnssylqNQLLKRQAALyifGEKSQLRNFKVEFalncEFVPVEfhEIRQVKA 1351
Cdd:cd14584  108 ------SPFMYVvDTRPKL----------------NAMANRAAGK---GYENEDNYSNIRF----QFIGIE--NIHVMRS 156

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1352 SFKKLMRACIPSTiPTDSEvtFLKALGDSEWFPQLHRIMQLAVVVSE-VLENGSSVLVCLEEGWDITAQVTSLVQLLSDP 1430
Cdd:cd14584  157 SLQKLLEVCEMKS-PSMSD--FLTGLENSGWLRHIKAVMDAGVFLAKaVKEEKASVLVHCSDGWDRTAQVCSLASLLLDP 233

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755 1431 FYRTLEGFQMLVEKEWLSFGHKFSQRSSlTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEFNLYYL 1497
Cdd:cd14584  234 FYRTIKGLMVLIEKEWISMGHKFSQRCG-HLDGDPKEVSPVFTQFLECVWQLMEQFPCAFEFNEHFL 299
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1335-1506 1.35e-34

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 7; Myotubularin related phosphoinositide phosphatase 7 (MTMR7) is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. In neuronal cells, MTMR7 forms a complex with catalytically inactive MTMR9 and dephosphorylates phosphatidylinositol 3-phosphate and Ins(1,3)P2.


Pssm-ID: 350431 [Multi-domain]  Cd Length: 302  Bit Score: 135.47  E-value: 1.35e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1335 NCEFVPVEFHEIRQVKASFKKLMRACipsTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSE-VLENGSSVLVCLEEG 1413
Cdd:cd14583  134 NIKFQFIGIENIHVMRNSLQKMLEVC---ELRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKaVAEEGASVLVHCSDG 210

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1414 WDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSlTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEFN 1493
Cdd:cd14583  211 WDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVSFGHKFNHRYG-HLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFN 289

                        170
                 ....*....|...
gi 29788755 1494 LYYLKFLAFHYVS 1506
Cdd:cd14583  290 ERFLIHIHHHIYS 302
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1335-1497 3.75e-34

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 1; Myotubularin-related phosphoinositide phosphatase 1 (MTMR1) is enzymatically active and contains an N-terminal PH-GRAM domain, a C-terminal coiled-coiled domain and a PDZ binding site. MTMR1 is associated with myotonic dystrophy. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350440  Cd Length: 249  Bit Score: 132.41  E-value: 3.75e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1335 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVLVCLEEG 1413
Cdd:cd14592   81 NAELVFLEIHNIHVMRESLRKLKEIVYPSI----DEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGkTSVVVHCSDG 156

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1414 WDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQR-SSLTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEF 1492
Cdd:cd14592  157 WDRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRvGHGDDNHADADRSPIFLQFIDCVWQMTRQFPSAFEF 236


                 ....*
gi 29788755 1493 NLYYL 1497
Cdd:cd14592  237 NELFL 241
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1337-1497 3.27e-33

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 6; Myotubularin related phosphoinositide phosphatase 6 is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR6 forms a complex with catalytically inactive MTMR9 and preferentially dephosphorylates PtdIns(3,5)P(2); the MTMR6/R9 complex serves to inhibit stress-induced apoptosis.


Pssm-ID: 350433 [Multi-domain]  Cd Length: 302  Bit Score: 131.59  E-value: 3.27e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1337 EFVPVEfhEIRQVKASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSE-VLENGSSVLVCLEEGWD 1415
Cdd:cd14585  138 QFVGIE--NIHVMRSSLQKLLEVCGTKALSVND---FLSGLESSGWLRHIKAVLDAAVFLAKaVAVEGASVLVHCSDGWD 212

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1416 ITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSlTLNCQGSGFAPVFLQFLDCVHQVHNQYPTEFEFNLY 1495
Cdd:cd14585  213 RTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGHKFSDRCG-QLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEA 291


                 ..
gi 29788755 1496 YL 1497
Cdd:cd14585  292 FL 293
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 1346-1481 3.64e-31

protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. Not all members are catalytically active proteins, some function as adaptors for the active members.


Pssm-ID: 350504  Cd Length: 229  Bit Score: 123.32  E-value: 3.64e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1346 IRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAV-VVSEVLENGSSVLVCLEEGWDITAQVTSLV 1424
Cdd:cd17666   99 IHVMRDSLNKVTEALKDGDDSNPSYPPLINALKKSNWLKYLAIILQGADlIAKSIHFNHSHVLIHCSDGWDRTSQLSALA 178

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755 1425 QLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSLTLNcqgsgfAPVFLQFLDCVHQ 1481
Cdd:cd17666  179 QLCLDPYYRTLEGFMVLVEKDWLSFGHRFAERSGHKET------SPVFHQFLDCVYQ 229
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 1-86 1.84e-30

Domain always found upstream of DENN domain, found in a variety of signalling proteins; The uDENN domain is part of the tripartite DENN domain. It is always found upstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


Pssm-ID: 214824  Cd Length: 89  Bit Score: 115.89  E-value: 1.84e-30
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755       1 MARLADYFIVVGYDHEKPGSGEG-LGKIIQRFPQKDWDDTPFPQGIELFCQPGGWQL--SRERKQPTFFVVVLTDIDSDR 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSyKPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFvtQTSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 29788755      78 HYCSCLTFY 86
Cdd:smart00800   81 RYGFCLRFY 89
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1340-1481 5.54e-28

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 9; Myotubularin related phosphoinositide phosphatase 9 (MTMR9) is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. Mutations have been associated with obesity and metabolic syndrome. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR9 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It forms complexes with catalytically active MTMR6, MTMR7 and MTMR8, and regulates their activities; the complexes display differential substrate preferences. The MTMR6/R9 complex serves to inhibit stress-induced apoptosis while the MTMR8/R9 complex inhibits autophagy.


Pssm-ID: 350384  Cd Length: 224  Bit Score: 113.97  E-value: 5.54e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1340 PVEFHEIRQvkASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSEVLEN-GSSVLVCLEEGWDITA 1418
Cdd:cd14536   85 PIERYNVLQ--ESLIKLVEACNDQGHSMDK---WLSKLESSNWLSHVKEILTTACLVAQCIDReGASVLVHGSEGMDSTL 159

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 29788755 1419 QVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRssltlnCQGSGF--------APVFLQFLDCVHQ 1481
Cdd:cd14536  160 QVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSR------CAKSAYsnskqkfeSPVFLLFLDCVWQ 224
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1346-1481 6.27e-25

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatases 10, 11, and 12; This subgroup of enzymatically inactive phosphatase domains of myotubularins consists of MTMR10, MTMR11, MTMR12, and similar proteins. Beside the phosphatase domain, they contain an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR10, MTMR11, and MTMR12 are pseudophosphatases that lack the catalytic cysteine in their catalytic pocket. MTMR12 functions as an adapter for the catalytically active myotubularin to regulate its intracellular location.


Pssm-ID: 350385  Cd Length: 200  Bit Score: 104.35  E-value: 6.27e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1346 IRQVKASFKKLMRACIPSTiPTDSEVT---FLKALGDSEWFPQLHRIMQLAVVVSEVLEN-GSSVLVCLEEGWDITAQVT 1421
Cdd:cd14537   61 LQDVQAAYLKLRELCTPDS-SEQFWVQdskWYSLLENTKWLHYVSACLKKASEAAEALESrGRSVVLQESDGRDLSCVVS 139

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 29788755 1422 SLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSLTLNCQG-SGFAPVFLQFLDCVHQ 1481
Cdd:cd14537  140 SLVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKTeSEESPVFLLFLDCVWQ 200
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 25-84 3.61e-23

uDENN domain; This region is always found associated with pfam02141. It is predicted to form an all beta domain.


Pssm-ID: 460926  Cd Length: 59  Bit Score: 94.21  E-value: 3.61e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755     25 GKIIQRFPQKDWDDTPFPQGIELFCQPGGWQLSRERKqPTFFVVVLTDIDSDRHYCSCLT 84
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSRE-PTFFSFVLTDEDGSRLYGACLT 59
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1296-1482 7.82e-22

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 11; Myotubularin related phosphoinositide phosphatase 11 (MTMR11), also called cisplatin resistance-associated protein (hCRA) in humans, is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR11 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket.


Pssm-ID: 350443  Cd Length: 195  Bit Score: 95.28  E-value: 7.82e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1296 SASFSNSSYLQNQLLkRQAALYIFGEKSQlrnfkvefalnCEFVPV--EFHEIRQVKASFKKLMRACIPSTIPTDSEVTF 1373
Cdd:cd14595   19 MAGFYTNSDPEKEDI-RSVELLLQAGHSQ-----------CVIVDTseELPSPADIQLAYLKLRTLCLPDISVSVSDEKW 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1374 LKALGDSEWFPQLHRIMQLAVVVSEVLENGSSVLVCLE-EGWDITAQVTSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHK 1452
Cdd:cd14595   87 LSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQEsEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEWVVAGHP 166

                        170       180       190
                 ....*....|....*....|....*....|
gi 29788755 1453 FSQRSSLTLNcQGSGFAPVFLQFLDCVHQV 1482
Cdd:cd14595  167 FLQRLNLTRE-SDKEESPVFLLFLDCVWQL 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1345-1482 8.65e-21

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 12; Myotubularin related phosphoinositide phosphatase 12 (MTMR12), also called phosphatidylinositol 3 phosphate 3-phosphatase adapter subunit (3-PAP), is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR12 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It functions as an adapter for the catalytically active myotubularin to regulate its intracellular location.


Pssm-ID: 350442  Cd Length: 203  Bit Score: 92.21  E-value: 8.65e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1345 EIRQVKASFKKLMrACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVLVCLEEGWDITAQVTSL 1423
Cdd:cd14594   67 EIQTAYNRFKQLF-LIDNSTDFWDTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEkQNTNVLLTEEEATDLCCVISSL 145

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 29788755 1424 VQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSlTLNCQGSGFAPVFLQFLDCVHQV 1482
Cdd:cd14594  146 VQIMMDPYCRTKSGFQSLIQKEWVMGGHCFLDRCN-HLRQNDKEEVPVFLLFLDCVWQL 203
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 352-420 1.11e-18

Domain always found downstream of DENN domain, found in a variety of signalling proteins; The dDENN domain is part of the tripartite DENN domain. It is always found downstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.


Pssm-ID: 129037  Cd Length: 69  Bit Score: 81.57  E-value: 1.11e-18
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29788755     352 DKEVRAVFLRLFAQLFQGYRSCLQLIRIHAEPVIHFHKTAFLGQRGLVENDFLTKVLSGMAFAGFVSER 420
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1346-1481 5.49e-18

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 10; Myotubularin related phosphoinositide phosphatase 10 (MTMR10) is enzymatically inactive and contains an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR10 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket.


Pssm-ID: 350441  Cd Length: 195  Bit Score: 84.17  E-value: 5.49e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1346 IRQVKASFKKLMRACIPSTIpTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENGS-SVLVCLEEGWDITAQVTSLV 1424
Cdd:cd14593   61 IQEIQAAFVKLKQLCVNEPF-EETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHvSVILQEEEGRDLSCVVASLV 139

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 29788755 1425 QLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSSlTLNCQGSGFAPVFLQFLDCVHQ 1481
Cdd:cd14593  140 QVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCN-HLKKSSKKESPLFLLFLDCVWQ 195
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1747-1847 4.35e-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: 75.66  E-value: 4.35e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    1747 EGTLYKRGA-LLKGWKPRWFVLdvTKHQLRYYDS---GEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTsdkafFDLKTSK 1822
Cdd:smart00233    4 EGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKPHC-----FEIKTSD 76

                            90       100
                    ....*....|....*....|....*.
gi 29788755    1823 R-VYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:smart00233   77 RkTLLLQAESEEEREKWVEALRKAIA 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1747-1842 6.35e-13

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: 66.03  E-value: 6.35e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGA-LLKGWKPRWFVLDvtKHQLRYYDSGEDTS--CKGHIDLAEVEMVIPagpsmgaPKHTSDKAFFDLKTSK- 1822
Cdd:cd00821    2 EGYLLKRGGgGLKSWKKRWFVLF--EGVLLYYKSKKDSSykPKGSIPLSGILEVEE-------VSPKERPHCFELVTPDg 72

                         90       100
                 ....*....|....*....|
gi 29788755 1823 RVYNFCAQDGQSAQQWMDKI 1842
Cdd:cd00821   73 RTYYLQADSEEERQEWLKAL 92
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 1745-1844 6.48e-13

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: 66.19  E-value: 6.48e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1745 SFEGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVipagpsmgAPKHTSDKAF-FDLKTSKR 1823
Cdd:cd10573    4 SKEGYLTKLGGIVKNWKTRWFVL--RRNELKYFKTRGDTKPIRVLDLRECSSV--------QRDYSQGKVNcFCLVFPER 73

                         90       100
                 ....*....|....*....|.
gi 29788755 1824 VYNFCAQDGQSAQQWMDKIQS 1844
Cdd:cd10573   74 TFYMYANTEEEADEWVKLLKW 94
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 1748-1844 7.52e-13

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: 66.19  E-value: 7.52e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1748 GTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAgpsmGAPKHTsdkafFDLKTSKRVYNF 1827
Cdd:cd01265    7 NKLETRGLGLKGWKRRWFVLDESKCQLYYYRSPQDATPLGSIDLSGAAFSYDP----EAEPGQ-----FEIHTPGRVHIL 77

                         90
                 ....*....|....*..
gi 29788755 1828 CAQDGQSAQQWMDKIQS 1844
Cdd:cd01265   78 KASTRQAMLYWLQALQS 94
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1747-1847 7.62e-13

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.43  E-value: 7.62e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755   1747 EGTLYKRG-ALLKGWKPRWFVLdvTKHQLRYYD---SGEDTSCKGHIDLAEVEMVIPAGPSMGAPKHTsdkafFDLKTS- 1821
Cdd:pfam00169    4 EGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFC-----FELRTGe 76

                           90       100
                   ....*....|....*....|....*....
gi 29788755   1822 ---KRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:pfam00169   77 rtgKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 1747-1846 2.81e-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: 65.01  E-value: 2.81e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAgpsmgaPKHTSDKAFFDLKTSKRVYN 1826
Cdd:cd13273   11 KGYLWKKGHLLPTWTERWFVL--KPNSLSYYKSEDLKEKKGEIALDSNCCVESL------PDREGKKCRFLVKTPDKTYE 82

                         90       100
                 ....*....|....*....|
gi 29788755 1827 FCAQDGQSAQQWMDKIQSCI 1846
Cdd:cd13273   83 LSASDHKTRQEWIAAIQTAI 102
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 1747-1848 5.41e-12

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: 63.56  E-value: 5.41e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGAL--LKGWKPRWFVLDVTkhQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMgapkhtsdkafFDLKTSKRV 1824
Cdd:cd13253    3 SGYLDKQGGQgnNKGFQKRWVVFDGL--SLRYFDSEKDAYSKRIIPLSAISTVRAVGDNK-----------FELVTTNRT 69

                         90       100
                 ....*....|....*....|....
gi 29788755 1825 YNFCAQDGQSAQQWMDKIQSCISD 1848
Cdd:cd13253   70 FVFRAESDDERNLWCSTLQAAISE 93
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 1748-1842 2.81e-10

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: 59.18  E-value: 2.81e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1748 GTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPagpsmgAPKHTSDKAFFdLKTSKRVYNF 1827
Cdd:cd13298   10 GYLLKRSRKTKNWKKRWVVL--RPCQLSYYKDEKEYKLRRVINLSELLAVAP------LKDKKRKNVFG-IYTPSKNLHF 80

                         90
                 ....*....|....*
gi 29788755 1828 CAQDGQSAQQWMDKI 1842
Cdd:cd13298   81 RATSEKDANEWVEAL 95
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 1748-1847 5.38e-10

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: 58.25  E-value: 5.38e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1748 GTLYKRG---ALL--KGWKPRWFVLDVTKhqLRYYDSGEDTS-CKGHIDLAEVEMVIPAGPSMGApkhtsdkafFDLKTS 1821
Cdd:cd13296    3 GWLTKKGggsSTLsrRNWKSRWFVLRDTV--LKYYENDQEGEkLLGTIDIRSAKEIVDNDPKENR---------LSITTE 71

                         90       100
                 ....*....|....*....|....*.
gi 29788755 1822 KRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd13296   72 ERTYHLVAESPEDASQWVNVLTRVIS 97
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 1744-1842 5.92e-10

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: 58.35  E-value: 5.92e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1744 RSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIpAGPSMGAPKHTSDKAFFDLKTSKR 1823
Cdd:cd14673    3 KRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVY-YDHLRSAAKSPNPALTFCVKTHDR 81

                         90
                 ....*....|....*....
gi 29788755 1824 VYNFCAQDGQSAQQWMDKI 1842
Cdd:cd14673   82 LYYMVAPSPEAMRIWMDVI 100
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 1747-1844 9.90e-10

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: 57.30  E-value: 9.90e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTS--CKGHIDLAEVEMVIpagpsmgapkHTSDKAFFDLKTSKRV 1824
Cdd:cd13283    2 RGVLSKWTNYIHGWQDRYFVL--KDGTLSYYKSESEKEygCRGSISLSKAVIKP----------HEFDECRFDVSVNDSV 69

                         90       100
                 ....*....|....*....|
gi 29788755 1825 YNFCAQDGQSAQQWMDKIQS 1844
Cdd:cd13283   70 WYLRAESPEERQRWIDALES 89
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 1760-1842 1.12e-09

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. 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: 241535  Cd Length: 115  Bit Score: 57.84  E-value: 1.12e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1760 WKPRWFVLDVT----KHQLRYYDSGEDTSCKGHIDLAEVEMViPAGPSMGAPKHTSDKAFFDLKTSKRVYNFCAQDGQSA 1835
Cdd:cd13384   23 WRRRYFVLRQSeipgQYFLEYYTDRTCRKLKGSIDLDQCEQV-DAGLTFETKNKLKDQHIFDIRTPKRTYYLVADTEDEM 101


                 ....*..
gi 29788755 1836 QQWMDKI 1842
Cdd:cd13384  102 NKWVNCI 108
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
 1747-1845 1.89e-09

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: 56.92  E-value: 1.89e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCK--GHIDLAEVEMVipagPSMGAPkHTsdkaFFDLKTSKRV 1824
Cdd:cd13291    2 EGQLLKYTNVVKGWQNRWFVLDPDTGILEYFLSEESKNQKprGSLSLAGAVIS----PSDEDS-HT----FTVNAANGEM 72

                         90       100
                 ....*....|....*....|.
gi 29788755 1825 YNFCAQDGQSAQQWMDKIQSC 1845
Cdd:cd13291   73 YKLRAADAKERQEWVNRLRAV 93
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
 1747-1839 1.97e-09

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: 56.64  E-value: 1.97e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLDvtKHQLRYYDSGEDTS--CKGHIDLAEVEMVIpagpsmgapkHTSDKAFFDL--KTSK 1822
Cdd:cd01247    2 EGVLWKWTNYLSGWQPRWFVLD--DGVLSYYKSQEEVNqgCKGSVKMSVCEIIV----------HPTDPTRMDLiiPGEQ 69

                         90
                 ....*....|....*..
gi 29788755 1823 RVYnFCAQDGQSAQQWM 1839
Cdd:cd01247   70 HFY-LKASSAAERQRWL 85
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 1747-1847 2.88e-09

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second 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: 241282  Cd Length: 105  Bit Score: 56.06  E-value: 2.88e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLK-GWKPRWFVLDVTKhqLRYYDSGEDTSCKGHIDLAEVE---MVipagpSMGAPKHTSDKAF--FDLKT 1820
Cdd:cd01251    5 EGYLEKTGPKQTdGFRKRWFTLDDRR--LMYFKDPLDAFPKGEIFIGSKEegySV-----REGLPPGIKGHWGfgFTLVT 77

                         90       100
                 ....*....|....*....|....*..
gi 29788755 1821 SKRVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd01251   78 PDRTFLLSAETEEERREWITAIQKVLE 104
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 1745-1845 8.60e-09

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


Pssm-ID: 270080  Cd Length: 103  Bit Score: 54.66  E-value: 8.60e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1745 SFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEmVIPAGPSM-GAPK--HTSDKAFFDLkts 1821
Cdd:cd13260    4 DKKGYLLKKGGKNKKWKNLYFVLEGKEQHLYFFDNEKRTKPKGLIDLSYCS-LYPVHDSLfGRPNcfQIVVRALNES--- 79

                         90       100
                 ....*....|....*....|....
gi 29788755 1822 kRVYNFCAQDGQSAQQWMDKIQSC 1845
Cdd:cd13260   80 -TITYLCADTAELAQEWMRALRAF 102
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 1747-1847 1.68e-08

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: 53.84  E-value: 1.68e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLDVTkhQLRYYDSGEDTSCK--GHIDLAEVEMVIPAgpsmgapkhtSDKAFFDLKTSKRV 1824
Cdd:cd13282    2 AGYLTKLGGKVKTWKRRWFVLKNG--ELFYYKSPNDVIRKpqGQIALDGSCEIARA----------EGAQTFEIVTEKRT 69

                         90       100
                 ....*....|....*....|...
gi 29788755 1825 YNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd13282   70 YYLTADSENDLDEWIRVIQNVLR 92
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 1745-1840 4.67e-08

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: 52.66  E-value: 4.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1745 SFEGTLYKR-GALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVeMVIPAGPSmgapKHTSDK-AFFDLKTSK 1822
Cdd:cd13248    8 VMSGWLHKQgGSGLKNWRKRWFVL--KDNCLYYYKDPEEEKALGSILLPSY-TISPAPPS----DEISRKfAFKAEHANM 80

                         90
                 ....*....|....*...
gi 29788755 1823 RVYNFCAQDGQSAQQWMD 1840
Cdd:cd13248   81 RTYYFAADTAEEMEQWMN 98
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 1747-1847 2.03e-07

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. 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: 269954  Cd Length: 119  Bit Score: 51.16  E-value: 2.03e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEV--------------EMVIPAGPS-MGAPKHTS 1811
Cdd:cd01252    6 EGWLLKLGGRVKSWKRRWFIL--TDNCLYYFEYTTDKEPRGIIPLENLsvrevedkkkpfcfELYSPSNGQvIKACKTDS 83

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 29788755 1812 DKAFFDLKTSkrVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd01252   84 DGKVVEGNHT--VYRISAASEEERDEWIKSIKASIS 117
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 1760-1842 3.10e-07

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. 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: 270133  Cd Length: 112  Bit Score: 50.49  E-value: 3.10e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1760 WKPRWFVLDVTK-----HQLRYYDSGEDTSCKGHIDLAEVEMViPAGPSMGApKHTSDKAFFDLKTSKRVYNFCAQDGQS 1834
Cdd:cd13324   21 WRRRWFVLRSGRlsggqDVLEYYTDDHCKKLKGIIDLDQCEQV-DAGLTFEK-KKFKNQFIFDIRTPKRTYYLVAETEEE 98


                 ....*...
gi 29788755 1835 AQQWMDKI 1842
Cdd:cd13324   99 MNKWVRCI 106
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 1747-1791 3.51e-07

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: 50.45  E-value: 3.51e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDL 1791
Cdd:cd13301    6 EGYLVKKGHVVNNWKARWFVL--KEDGLEYYKKKTDSSPKGMIPL 48
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 1740-1842 1.81e-06

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: 48.18  E-value: 1.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1740 NDENRSFEGTLYKRGALLKGWKPRWFVLDVTKhqLRYYDSGEDTSCKGHIDLAEVEMVIPAgpSMGAPKHTsdkafFDLK 1819
Cdd:cd13255    2 ISEAVLKAGYLEKKGERRKTWKKRWFVLRPTK--LAYYKNDKEYRLLRLIDLTDIHTCTEV--QLKKHDNT-----FGIV 72

                         90       100
                 ....*....|....*....|...
gi 29788755 1820 TSKRVYNFCAQDGQSAQQWMDKI 1842
Cdd:cd13255   73 TPARTFYVQADSKAEMESWISAI 95
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 1747-1849 2.82e-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: 47.60  E-value: 2.82e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGA-LLKGWKPRWFVLDvtKHQLRYYDSGEDTSCKGHID---LAEVEMVipagpsmgapkHTSDKAF-FDLKTS 1821
Cdd:cd13250    2 EGYLFKRSSnAFKTWKRRWFSLQ--NGQLYYQKRDKKDEPTVMVEdlrLCTVKPT-----------EDSDRRFcFEVISP 68

                         90       100
                 ....*....|....*....|....*...
gi 29788755 1822 KRVYNFCAQDGQSAQQWMDKIQSCISDA 1849
Cdd:cd13250   69 TKSYMLQAESEEDRQAWIQAIQSAIASA 96
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 1746-1846 4.56e-06

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: 46.93  E-value: 4.56e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1746 FEGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCK---GHIDLAEVEMVipagpsMGAPKHTSDKAFFDLKTSK 1822
Cdd:cd13276    1 KAGWLEKQGEFIKTWRRRWFVL--KQGKLFWFKEPDVTPYSkprGVIDLSKCLTV------KSAEDATNKENAFELSTPE 72

                         90       100
                 ....*....|....*....|....
gi 29788755 1823 RVYNFCAQDGQSAQQWMDKIQSCI 1846
Cdd:cd13276   73 ETFYFIADNEKEKEEWIGAIGRAI 96
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 1736-1843 4.62e-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: 47.23  E-value: 4.62e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1736 YTSKNDENRSFEGTLYKRGALLKGWKPRWFVLdvtKHQ-LRYYDSGEDTSC-KGHIDLAEVEMVIPAGPSMGAPKHtsdk 1813
Cdd:cd13215   13 YLPKRSGAVIKSGYLSKRSKRTLRYTRYWFVL---KGDtLSWYNSSTDLYFpAGTIDLRYATSIELSKSNGEATTS---- 85

                         90       100       110
                 ....*....|....*....|....*....|
gi 29788755 1814 afFDLKTSKRVYNFCAQDGQSAQQWMDKIQ 1843
Cdd:cd13215   86 --FKIVTNSRTYKFKADSETSADEWVKALK 113
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 1747-1794 6.98e-06

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: 47.61  E-value: 6.98e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 29788755 1747 EGTLYKR--GALLKG---WKPRWFVLdvTKHQLRYYDS--GEDTSCKGHIDLAEV 1794
Cdd:cd01238    2 EGLLVKRsqGKKRFGpvnYKERWFVL--TKSSLSYYEGdgEKRGKEKGSIDLSKV 54
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
 1747-1846 1.55e-05

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: 45.51  E-value: 1.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSC---KGHIDLAEVEMVIpagpsmgapkHTSDKAFFDLKTSKR 1823
Cdd:cd13290    2 EGPLSKWTNVMKGWQYRWFVLDDNAGLLSYYTSKEKMMRgsrRGCVRLKGAVVGI----------DDEDDSTFTITVDQK 71

                         90       100
                 ....*....|....*....|...
gi 29788755 1824 VYNFCAQDGQSAQQWMDKIQSCI 1846
Cdd:cd13290   72 TFHFQARDAEERERWIRALEDTI 94
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 915-1000 2.37e-05

Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold.


Pssm-ID: 275393  Cd Length: 94  Bit Score: 44.68  E-value: 2.37e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755  915 EGALFLTTYRILFrgtpHDQLVGEQTVVrSFPIASITKEKKITMQNQLQQnmqeGLQITSASFQLIKVAFDEEvsPEVVE 994
Cdd:cd10570   20 EGTLYLSTYRLIF----SSKADGDETKL-VIPLVDITDVEKIAGASFLPS----GLIITCKDFRTIKFSFDSE--DEAVK 88


                 ....*.
gi 29788755  995 IFKKQL 1000
Cdd:cd10570   89 VIARVL 94
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 1746-1839 2.45e-05

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: 44.67  E-value: 2.45e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1746 FEGTLYKRGALLKGWKPRWFVLDVTkhQLRYYDSGEDTSCKGHIDLA--EVEMVIPAGPSMGapkhtsdKAFFDL--KTS 1821
Cdd:cd13316    2 HSGWMKKRGERYGTWKTRYFVLKGT--RLYYLKSENDDKEKGLIDLTghRVVPDDSNSPFRG-------SYGFKLvpPAV 72

                         90
                 ....*....|....*...
gi 29788755 1822 KRVYNFCAQDGQSAQQWM 1839
Cdd:cd13316   73 PKVHYFAVDEKEELREWM 90
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
 1748-1839 3.28e-05

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: 44.60  E-value: 3.28e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1748 GTLYKRGALLKGWKPRWFVLdVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAG---PSMGAPKHTSDKAFFDLKTSKR- 1823
Cdd:cd13265    7 GWLLRQSTILKRWKKNWFVL-YGDGNLVYYEDETRREVEGRINMPRECRNIRVGlecRDVQPPEGRSRDCLLQIVLRDGs 85

                         90
                 ....*....|....*.
gi 29788755 1824 VYNFCAQDGQSAQQWM 1839
Cdd:cd13265   86 TLFLCAESADDALAWK 101
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
 1746-1843 5.42e-05

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: 43.91  E-value: 5.42e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1746 FEGTLYKRGALLKGWKPRWFVLDvtKHQLRYYDSGEDTS--CKGHIDLAevemvipagpsmGAPKHTSDKAFFDLKT-SK 1822
Cdd:cd13284    1 MKGWLLKWTNYIKGYQRRWFVLS--NGLLSYYRNQAEMAhtCRGTINLA------------GAEIHTEDSCNFVISNgGT 66

                         90       100
                 ....*....|....*....|.
gi 29788755 1823 RVYNFCAQDGQSAQQWMDKIQ 1843
Cdd:cd13284   67 QTFHLKASSEVERQRWVTALE 87
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 1746-1847 5.57e-05

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: 44.32  E-value: 5.57e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1746 FEGTLYKRGA---LLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEmvIPAGPSMGAPKHTSDKaFFDLKTSK 1822
Cdd:cd13308   11 HSGTLTKKGGsqkTLQNWQLRYVII--HQGCVYYYKNDQSAKPKGVFSLNGYN--RRAAEERTSKLKFVFK-IIHLSPDH 85

                         90       100
                 ....*....|....*....|....*
gi 29788755 1823 RVYNFCAQDGQSAQQWMDKIQSCIS 1847
Cdd:cd13308   86 RTWYFAAKSEDEMSEWMEYIRREID 110
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
879-957 5.87e-05

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 42.58  E-value: 5.87e-05
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 29788755     879 LPGEEIVCEGLRVLLDPDGReeatggllggpqllpAEGALFLTTYRILFRGTPHDQLvgeqtVVRSFPIASITKEKKIT 957
Cdd:smart00568    2 LPEEEKLIADYSCYLSRTGP---------------VQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
 1732-1848 7.76e-05

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. 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-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 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: 270181  Cd Length: 106  Bit Score: 43.79  E-value: 7.76e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1732 LYSQYTSKNDENRSFEGTlykrgallkGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKhts 1811
Cdd:cd13381    2 LKAGYLEKRRKDHSFFGF---------EWQKRWCAL--SNSVFYYYGSDKDKQQKGEFAIDGYDVKMNNTLRKDAKK--- 67

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 29788755 1812 DKAFFDLKTSKRVYNFCAQDGQSAQQWMDKIQSCISD 1848
Cdd:cd13381   68 DCCFEICAPDKRVYQFTAASPKEAEEWVQQIKFILQD 104
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 387-433 9.38e-05

dDENN domain; This region is always found associated with pfam02141. It is predicted to form a globular domain. Although not statistically supported it has been suggested that this domain may be similar to members of the Rho/Rac/Cdc42 GEF family. This N-terminal region of DENN folds into a longin module, consisting of a central antiparallel beta-sheet layered between helix H1 and helices H2 and H3 (strands S1-S5). Rab35 interacts with dDENN via residues in helix 1 and in the loop S3-S4.


Pssm-ID: 460925  Cd Length: 48  Bit Score: 41.41  E-value: 9.38e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 29788755    387 FHKTAFLGQRGLVENDFLTKVLSGMAFAGFVSERG-PPYRSCDLFDEL 433
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
 1741-1846 1.30e-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: 46.91  E-value: 1.30e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1741 DENRSFEGTLYKRGALLKGWKPRWFVLDvTKHQLRYYDSGED----TSCKGHIDLAEVEMVIpagpSMGAPKHTSDKAFF 1816
Cdd:cd23949   59 DRKVIFSGKLSKYGEDSKKWKERFCVVR-GDYNLEYYESKEAyergKKPKGSINLAGYKVLT----SPEEYLELVDRKFP 133

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 29788755 1817 DLK-----------------------TSKRVYNFCAQDGQSAQQWMDKIQSCI 1846
Cdd:cd23949  134 DLAgksekasvpfperpppftlelyhPYRRHYYFCFETEKEQEEWVAVLQDCI 186
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
 1748-1842 4.44e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 270057  Cd Length: 91  Bit Score: 40.86  E-value: 4.44e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1748 GTLYKRGALLKGWKPRWFVLdvtKHQLRY-YDSGEDTSCKGHIDLAEVEMVipagPSMGAPKHTSDKAFFDLKTSKRVYN 1826
Cdd:cd13237    3 GYLQRRKKSKKSWKRLWFVL---KDKVLYtYKASEDVVALESVPLLGFTVV----TIDESFEEDESLVFQLLHKGQLPII 75

                         90
                 ....*....|....*.
gi 29788755 1827 FCAQDGQSAQQWMDKI 1842
Cdd:cd13237   76 FRADDAETAQRWIEAL 91
SPA pfam08616
Stabilization of polarity axis; Swiss:Q99222 has been shown to interact with the outer plaque ...
 208-302 4.80e-04

Stabilization of polarity axis; Swiss:Q99222 has been shown to interact with the outer plaque of the spindle pole body. In Aspergillus nidulans the protein member is necessary for stabilization of the polarity axes during septation. and in S. cerevisiae it functions as a polarization-specific docking factor.


Pssm-ID: 400783  Cd Length: 113  Bit Score: 41.51  E-value: 4.80e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    208 IQNVLSLFCAVLTENKVLF--HSASFQRLSDACRALESLMFPL-------KYSYPYIPIlpaQLLEVLSSPTPFIIGVHS 278
Cdd:pfam08616   12 TPPIILLINALLTSKRIIFlsYQRSAGEVSEFVLALCNLISGGfvlrgftNNSFPYVDL---SKLDALRKVPGYIAGVTN 88

                           90       100
                   ....*....|....*....|....
gi 29788755    279 VFKTDVHELLDVIIaDLDGGTIKI 302
Cdd:pfam08616   89 PIFENQDQWWDVLC-DLDSGSVKL 111
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
 1748-1846 4.83e-04

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270109  Cd Length: 126  Bit Score: 42.04  E-value: 4.83e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1748 GTLYK--RGALLKGW---KPRWFVLdvTKHQLRYYDSGEDTSCK-GHIDLAEVEMVIPAGPSMGapKHTSDKAFfDLKTS 1821
Cdd:cd13297   17 GWLYKegGKGGARGNltkKKRWFVL--TGNSLDYYKSSEKNSLKlGTLVLNSLCSVVPPDEKMA--KETGYWTF-TVHGR 91

                         90       100
                 ....*....|....*....|....*
gi 29788755 1822 KRVYNFCAQDGQSAQQWMDKIQSCI 1846
Cdd:cd13297   92 KHSFRLYTKLQEEAMRWVNAIQDVI 116
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 914-1006 7.52e-04

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.


Pssm-ID: 397160  Cd Length: 112  Bit Score: 40.81  E-value: 7.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755    914 AEGALFLTTYRILFRGTPHDQLvgeQTVVrsFPIASITKEKKITmqnQLQQNMQEGLQITSASFQliKVAFDEEVSPEVV 993
Cdd:pfam02893   30 VQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDIEEIEKLK---GGANLFPNGIQVETGSND--KFSFAGFVTRDEA 99

                           90
                   ....*....|...
gi 29788755    994 EIFKKQLMKFRYP 1006
Cdd:pfam02893  100 IEFILALLKNAHP 112
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 1747-1845 2.08e-03

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: 39.91  E-value: 2.08e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1747 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAE--VEMvipagpSMGAPKHtsdkAF---FDLKTS 1821
Cdd:cd13288   11 EGYLWKKGERNTSYQKRWFVL--KGNLLFYFEKKGDREPLGVIVLEGctVEL------AEDAEPY----AFairFDGPGA 78

                         90       100
                 ....*....|....*....|....
gi 29788755 1822 kRVYNFCAQDGQSAQQWMDKIQSC 1845
Cdd:cd13288   79 -RSYVLAAENQEDMESWMKALSRA 101
PH_Gab3 cd13385
Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes ...
 1760-1845 2.16e-03

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


Pssm-ID: 270184  Cd Length: 125  Bit Score: 39.95  E-value: 2.16e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1760 WKPRWFVL---------DVtkhqLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMgAPKHTSDKAFFDLKTSKRVYNFCAQ 1830
Cdd:cd13385   26 WRKRWFVLrrgrmsgnpDV----LEYYRNNHSKKPIRVIDLSECEVLKHSGPNF-IRKEFQNNFVFIVKTTYRTFYLVAK 100

                         90
                 ....*....|....*.
gi 29788755 1831 DGQSAQQWMDKI-QSC 1845
Cdd:cd13385  101 TEEEMQVWVHNIsQIC 116
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 1752-1846 3.65e-03

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: 38.87  E-value: 3.65e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1752 KRGALLKGWKPRWFVLDVtkHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSmgaPKHTSDKaFFDLKTSKRVYNFCAQD 1831
Cdd:cd13271   16 KQGAVRKNWKRRFFILDD--NTISYYKSETDKEPLRTIPLREVLKVHECLVK---SLLMRDN-LFEIITTSRTFYIQADS 89

                         90
                 ....*....|....*
gi 29788755 1832 GQSAQQWMDKIQSCI 1846
Cdd:cd13271   90 PEEMHSWIKAISGAI 104
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 1744-1849 4.98e-03

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: 38.44  E-value: 4.98e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29788755 1744 RSFEGTLYKRGALLKGWKPRWFVLDvtKHQLRYYDSGED--TSCKGHIDLAEVEMVIPAgpsmgapkhtSDKAFFDL--K 1819
Cdd:cd13292    2 PTMKGYLKKWTNYAKGYKTRWFVLE--DGVLSYYRHQDDegSACRGSINMKNARLVSDP----------SEKLRFEVssK 69

                         90       100       110
                 ....*....|....*....|....*....|.
gi 29788755 1820 TSKRV-YNFCAQDGQSAQQWMDKIQSCISDA 1849
Cdd:cd13292   70 TSGSPkWYLKANHPVEAARWIQALQKAIEWA 100
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 1812-1849 5.00e-03

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) 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: 270071  Cd Length: 108  Bit Score: 38.50  E-value: 5.00e-03
                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 29788755 1812 DKAFFDLKTSKRVYNFCAQDGQSAQQWMDKIQSCISDA 1849
Cdd:cd13251   67 DKKCFDLISHNRTYHFQAEDENDANAWMSVLKNSKEQA 104
 
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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