NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|755522772|ref|XP_011240132|]
View 

myotubularin-related protein 13 isoform X7 [Mus musculus]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 892-1296 2.08e-178

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


The actual alignment was detected with superfamily member cd14589:

Pssm-ID: 475123  Cd Length: 297  Bit Score: 536.81  E-value: 2.08e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 971
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  972 VSTSSLESSSsIEQEKYLQALLTAVIVHQKLRGSSTLtvrpalalspgterrssrmstvlkqvvpghldvnpsnsfargv 1051
Cdd:cd14589    81 APASSESSSS-IEQEKYLQALLNAISVHQKMNGNSTL------------------------------------------- 116

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1052 hgyrdksftqsnpkssakepvhnqgvwaslrsstrlissptsfidvgarlagkdhsasfsnstyLQNQLLKRQAALYIFG 1131
Cdd:cd14589   117 ----------------------------------------------------------------LQSQLLKRQAALYIFG 132

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1132 EKSQLRSSKVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVL 1211
Cdd:cd14589   133 EKSQLRGFKLDFALNCEFVPVEFHDIRQVKASFKKLMRACVPSTIPTDSEVTFLKALGESEWFLQLHRIMQLAVVISELL 212

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1212 ENGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQGGGFAPIFLQFLDCVH 1291
Cdd:cd14589   213 ESGSSVMVCLEDGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSGFAPIFLQFLDCVH 292


                  ....*
gi 755522772 1292 QVHNQ 1296
Cdd:cd14589   293 QIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 286-508 8.53e-141

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: 433.28  E-value: 8.53e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   286 GPPVVSIMEKVITVF-NSAQRLEVVRNCISFIFENKTLETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 364
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   365 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 444
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755522772   445 KDDNHIPHLKQKLP---DGQHQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 508
Cdd:pfam12335  161 DEKNPHISAQGKNTaslASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 636-754 1.91e-65

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: 217.15  E-value: 1.91e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  636 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 715
Cdd:cd13339     1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 755522772  716 LQQSVQEGLQITSASFQLIKVAFDEEVSPEVVDIFKKQL 754
Cdd:cd13339    81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1553-1658 3.07e-63

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: 210.27  E-value: 3.07e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1553 ENRSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTSDKAFFDLKTS 1632
Cdd:cd01235     1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                          90       100
                  ....*....|....*....|....*.
gi 755522772 1633 KRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd01235    81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 108-176 6.77e-19

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: 82.34  E-value: 6.77e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755522772    108 DKEVRAVFLRLFAQLFQGYRSCLQLIRIHAEPVIHFHKTAFLGQRGLVENDFLTKVLNGMAFAGFVSER 176
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
DENN super family cl11519
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 1-54 1.92e-18

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.


The actual alignment was detected with superfamily member smart00799:

Pssm-ID: 472208  Cd Length: 183  Bit Score: 84.94  E-value: 1.92e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 755522772      1 MFPLKYSYPYIPILPAQLLEVLSSPTPFIIGVHSIFKTDVHELL--DVIIADLDGG 54
Cdd:smart00799  128 LYPFVWQHIYIPILPASLLDVLSAPTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
 
Name Accession Description Interval E-value
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 892-1296 2.08e-178

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: 536.81  E-value: 2.08e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 971
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  972 VSTSSLESSSsIEQEKYLQALLTAVIVHQKLRGSSTLtvrpalalspgterrssrmstvlkqvvpghldvnpsnsfargv 1051
Cdd:cd14589    81 APASSESSSS-IEQEKYLQALLNAISVHQKMNGNSTL------------------------------------------- 116

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1052 hgyrdksftqsnpkssakepvhnqgvwaslrsstrlissptsfidvgarlagkdhsasfsnstyLQNQLLKRQAALYIFG 1131
Cdd:cd14589   117 ----------------------------------------------------------------LQSQLLKRQAALYIFG 132

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1132 EKSQLRSSKVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVL 1211
Cdd:cd14589   133 EKSQLRGFKLDFALNCEFVPVEFHDIRQVKASFKKLMRACVPSTIPTDSEVTFLKALGESEWFLQLHRIMQLAVVISELL 212

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1212 ENGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQGGGFAPIFLQFLDCVH 1291
Cdd:cd14589   213 ESGSSVMVCLEDGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSGFAPIFLQFLDCVH 292


                  ....*
gi 755522772 1292 QVHNQ 1296
Cdd:cd14589   293 QIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 286-508 8.53e-141

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: 433.28  E-value: 8.53e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   286 GPPVVSIMEKVITVF-NSAQRLEVVRNCISFIFENKTLETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 364
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   365 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 444
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755522772   445 KDDNHIPHLKQKLP---DGQHQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 508
Cdd:pfam12335  161 DEKNPHISAQGKNTaslASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 870-1331 1.25e-82

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: 275.13  E-value: 1.25e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   870 RDYQRLGLGTisgnssrskPEYFRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 949
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   950 RSGgfhgKGVVGLFKSQNspqavstsslessssIEQEKYLQALltavivhqklrgsstltvrpalalspgteRRSSRMST 1029
Cdd:pfam06602   83 RSS----QPLVGLNGKRS---------------IEDEKLLQAI-----------------------------FKSSNPYS 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1030 VLKQVVpghLDvnpsnsfARgvhgyrdksftqsnPKSSAkepvhnqgvwaslrsstrlissptsfidVGARLAGKdhsaS 1109
Cdd:pfam06602  115 AKKLYI---VD-------AR--------------PKLNA----------------------------MANRAKGG----G 138

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1110 FSNstylqnqllkrqaalyifgeksqlrsskVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSevtFLKALG 1189
Cdd:pfam06602  139 YEN----------------------------EDNYPNCKKIFLGIENIHVMRDSLNKLVEACNDRSPSMDK---WLSRLE 187

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1190 DSEWFPQLHRIMQLAVVVSEVLE-NGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRS 1268
Cdd:pfam06602  188 SSGWLKHIKAILDGACLIAQAVDlEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRC 267

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755522772  1269 S-LALNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEFNLYYLKFLAFHYVSNRFKTFLLDSDYER 1331
Cdd:pfam06602  268 GhLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGTFLCNSEKER 331
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 636-754 1.91e-65

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: 217.15  E-value: 1.91e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  636 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 715
Cdd:cd13339     1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 755522772  716 LQQSVQEGLQITSASFQLIKVAFDEEVSPEVVDIFKKQL 754
Cdd:cd13339    81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1553-1658 3.07e-63

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: 210.27  E-value: 3.07e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1553 ENRSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTSDKAFFDLKTS 1632
Cdd:cd01235     1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                          90       100
                  ....*....|....*....|....*.
gi 755522772 1633 KRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd01235    81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 108-176 6.77e-19

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: 82.34  E-value: 6.77e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755522772    108 DKEVRAVFLRLFAQLFQGYRSCLQLIRIHAEPVIHFHKTAFLGQRGLVENDFLTKVLNGMAFAGFVSER 176
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 1-54 1.92e-18

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: 84.94  E-value: 1.92e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 755522772      1 MFPLKYSYPYIPILPAQLLEVLSSPTPFIIGVHSIFKTDVHELL--DVIIADLDGG 54
Cdd:smart00799  128 LYPFVWQHIYIPILPASLLDVLSAPTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 1-54 4.31e-18

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: 83.78  E-value: 4.31e-18
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 755522772     1 MFPLKYSYPYIPILPAQLLEVLSSPTPFIIGVHS-IFKTDVHELLDVIIADLDGG 54
Cdd:pfam02141  132 LYPFVWQHIYIPVLPASLLDVLSAPTPFIIGVHSrYFDLLEDPLDDVVLVDLDTG 186
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1558-1658 1.04e-15

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: 74.51  E-value: 1.04e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   1558 EGTLYKRGA-LLKGWKPRWFVLdvTKHQLRYYDS---GEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTsdkafFDLKTSK 1633
Cdd:smart00233    4 EGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKPHC-----FEIKTSD 76

                            90       100
                    ....*....|....*....|....*.
gi 755522772   1634 R-VYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:smart00233   77 RkTLLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1558-1658 1.02e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.05  E-value: 1.02e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1558 EGTLYKRG-ALLKGWKPRWFVLdvTKHQLRYYD---SGEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTsdkafFDLKTS- 1632
Cdd:pfam00169    4 EGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFC-----FELRTGe 76

                           90       100
                   ....*....|....*....|....*....
gi 755522772  1633 ---KRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:pfam00169   77 rtgKRTYLLQAESEEERKDWIKAIQSAIR 105
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
633-711 3.45e-05

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 42.97  E-value: 3.45e-05
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755522772    633 LPGEEIVCEGLRVLLDPDGReeatggllggpqllpAEGALFLTTYRILFRGTPHDQLvgeqtVVRSFPIASITKEKKIT 711
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 ...
 143-189 8.59e-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: 8.59e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 755522772   143 FHKTAFLGQRGLVENDFLTKVLNGMAFAGFVSERG-PPYRACDLFDEL 189
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 668-760 3.65e-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: 41.58  E-value: 3.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   668 AEGALFLTTYRILFRGTPHDQLvgeQTVVrsFPIASITKEKKITMQNQLQQSvqeGLQITSASFQliKVAFDEEVSPEVV 747
Cdd:pfam02893   30 VQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDIEEIEKLKGGANLFPN---GIQVETGSND--KFSFAGFVTRDEA 99

                           90
                   ....*....|...
gi 755522772   748 DIFKKQLMKFRYP 760
Cdd:pfam02893  100 IEFILALLKNAHP 112
 
Name Accession Description Interval E-value
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 892-1296 2.08e-178

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: 536.81  E-value: 2.08e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 971
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  972 VSTSSLESSSsIEQEKYLQALLTAVIVHQKLRGSSTLtvrpalalspgterrssrmstvlkqvvpghldvnpsnsfargv 1051
Cdd:cd14589    81 APASSESSSS-IEQEKYLQALLNAISVHQKMNGNSTL------------------------------------------- 116

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1052 hgyrdksftqsnpkssakepvhnqgvwaslrsstrlissptsfidvgarlagkdhsasfsnstyLQNQLLKRQAALYIFG 1131
Cdd:cd14589   117 ----------------------------------------------------------------LQSQLLKRQAALYIFG 132

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1132 EKSQLRSSKVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVL 1211
Cdd:cd14589   133 EKSQLRGFKLDFALNCEFVPVEFHDIRQVKASFKKLMRACVPSTIPTDSEVTFLKALGESEWFLQLHRIMQLAVVISELL 212

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1212 ENGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQGGGFAPIFLQFLDCVH 1291
Cdd:cd14589   213 ESGSSVMVCLEDGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSGFAPIFLQFLDCVH 292


                  ....*
gi 755522772 1292 QVHNQ 1296
Cdd:cd14589   293 QIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 286-508 8.53e-141

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: 433.28  E-value: 8.53e-141
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   286 GPPVVSIMEKVITVF-NSAQRLEVVRNCISFIFENKTLETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 364
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   365 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 444
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755522772   445 KDDNHIPHLKQKLP---DGQHQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 508
Cdd:pfam12335  161 DEKNPHISAQGKNTaslASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 892-1296 2.76e-135

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: 420.23  E-value: 2.76e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQ- 970
Cdd:cd14534     1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFHGKGVMGMLKSANTSTs 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  971 AVSTSSLESSSSIEQEKYLQALltavivhqklrgsstltvrpalalspgterrssrmstvlkqvvpghldvnpsnsfarg 1050
Cdd:cd14534    81 SPTVSSSETSSSLEQEKYLSAL---------------------------------------------------------- 102

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1051 vhgyrdksftqsnpkssakepvhnqgvwaslrsstrlissptsfidvgarlagkdhsasfsnstylqnqllkrqaALYIF 1130
Cdd:cd14534   103 ---------------------------------------------------------------------------VLYVL 107

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1131 GEKSQLRSSKVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEV 1210
Cdd:cd14534   108 GEKSQMKGVKAESDPKCEFIPVEYPEVRQVKASFKKLLRACVPSSAPTEPEQSFLKAVEDSEWLQQLQCLMQLSGAVVDL 187

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1211 LE-NGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQGGGFAPIFLQFLDC 1289
Cdd:cd14534   188 LDvQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVEKEWLAFGHRFSHRSNLTAASQSSGFAPVFLQFLDA 267


                  ....*..
gi 755522772 1290 VHQVHNQ 1296
Cdd:cd14534   268 VHQIHRQ 274
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 892-1296 8.98e-116

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: 367.37  E-value: 8.98e-116
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 971
Cdd:cd14588     1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  972 vsTSSLESSSSIEQEKYLQALLTAVIVHQKLRGSSTLTvrpalalspgterrssrmstvlkqvvpghldvnpsnsfargv 1051
Cdd:cd14588    81 --GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLS------------------------------------------ 116

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1052 hGYRdksftqsnpkssakepvhnqgvwaslrsstrlissptsfidvgarlagkdhsasfsnstylqnqllkrqAALYIFG 1131
Cdd:cd14588   117 -GFR---------------------------------------------------------------------AALYIIG 126

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1132 EKSQLRSSKVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVL 1211
Cdd:cd14588   127 DKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASFKKLMKACVPSCPSTDPSQTYLRTLEESEWLSQLHKLLQVSVLVVELL 206

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1212 ENGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQGGGFAPIFLQFLDCVH 1291
Cdd:cd14588   207 DSGSSVLVSLEDGWDITTQVVSLVQLLSDPYYRTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVH 286


                  ....*
gi 755522772 1292 QVHNQ 1296
Cdd:cd14588   287 QIHLQ 291
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 870-1331 1.25e-82

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: 275.13  E-value: 1.25e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   870 RDYQRLGLGTisgnssrskPEYFRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 949
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   950 RSGgfhgKGVVGLFKSQNspqavstsslessssIEQEKYLQALltavivhqklrgsstltvrpalalspgteRRSSRMST 1029
Cdd:pfam06602   83 RSS----QPLVGLNGKRS---------------IEDEKLLQAI-----------------------------FKSSNPYS 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1030 VLKQVVpghLDvnpsnsfARgvhgyrdksftqsnPKSSAkepvhnqgvwaslrsstrlissptsfidVGARLAGKdhsaS 1109
Cdd:pfam06602  115 AKKLYI---VD-------AR--------------PKLNA----------------------------MANRAKGG----G 138

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1110 FSNstylqnqllkrqaalyifgeksqlrsskVEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSevtFLKALG 1189
Cdd:pfam06602  139 YEN----------------------------EDNYPNCKKIFLGIENIHVMRDSLNKLVEACNDRSPSMDK---WLSRLE 187

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1190 DSEWFPQLHRIMQLAVVVSEVLE-NGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRS 1268
Cdd:pfam06602  188 SSGWLKHIKAILDGACLIAQAVDlEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRC 267

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755522772  1269 S-LALNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEFNLYYLKFLAFHYVSNRFKTFLLDSDYER 1331
Cdd:pfam06602  268 GhLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGTFLCNSEKER 331
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 636-754 1.91e-65

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: 217.15  E-value: 1.91e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  636 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 715
Cdd:cd13339     1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 755522772  716 LQQSVQEGLQITSASFQLIKVAFDEEVSPEVVDIFKKQL 754
Cdd:cd13339    81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1553-1658 3.07e-63

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: 210.27  E-value: 3.07e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1553 ENRSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTSDKAFFDLKTS 1632
Cdd:cd01235     1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                          90       100
                  ....*....|....*....|....*.
gi 755522772 1633 KRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd01235    81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 1122-1292 2.22e-60

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: 207.01  E-value: 2.22e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1122 KRQAALYIFGEKSQLrSSKVEFAFNC--------EFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEW 1193
Cdd:cd14507    47 PSSKKLYIVDARPKL-NAVANRAKGGgyenteyyPNCELEFLNIENIHAMRDSLNKLRDACLSPNDEESNWLSALESSGW 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1194 FPQLHRIMQLAVVVSEVLEN-GSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLAL 1272
Cdd:cd14507   126 LEHIRLILKGAVRVADLLEKeGTSVLVHCSDGWDRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGD 205

                         170       180
                  ....*....|....*....|.
gi 755522772 1273 NSQGGG-FAPIFLQFLDCVHQ 1292
Cdd:cd14507   206 KNSSDEeRSPIFLQFLDCVWQ 226
PH-GRAM_MTMR5_MTMR13 cd13208
Myotubularian (MTM) related 5 and 13 proteins (MTMR5 and MTMR13) Pleckstrin ...
 636-754 2.45e-53

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: 182.55  E-value: 2.45e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  636 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLpAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQN- 714
Cdd:cd13208     1 EELVMEGLRVYLLPDGREEGTGGNGGPNLLP-AEGALFLTNYRVIFKGTPCDPLACEQTVVRSFPIASLTKEKKIAVQKl 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 755522772  715 -QLQQSVQEGLQITSASFQLIKVAFDEEVSPEVVDIFKKQL 754
Cdd:cd13208    80 aHLDQKLQEGLQLRSATFQLIKVAFDEEVSSEKIEKFRKQL 120
PH-GRAM_MTMR5 cd13340
Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, ...
 636-754 8.86e-47

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: 163.49  E-value: 8.86e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  636 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 715
Cdd:cd13340     1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 755522772  716 LQQSVQEGLQITSASFQLIKVAFDEEVSPEVVDIFKKQL 754
Cdd:cd13340    81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1146-1308 7.94e-46

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: 167.90  E-value: 7.94e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSEVLENGSSVWVCLEEGW 1225
Cdd:cd14532   134 NIKFQFFGIENIHVMRSSLQKLLEVCELKNPSMSA---FLSGLESSGWLKHIKAVMDTSVFIAKAVSEGASVLVHCSDGW 210

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1226 DITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLaLNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEFNL 1305
Cdd:cd14532   211 DRTAQTCSLASLLLDPYYRTIKGFQVLIEKEWLSFGHKFTDRCGH-LQGDAKEVSPVFTQFLDCVWQLMQQFPRAFEFNE 289


                  ...
gi 755522772 1306 YYL 1308
Cdd:cd14532   290 RFL 292
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 1146-1308 1.56e-40

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: 150.68  E-value: 1.56e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVWVCLEEG 1224
Cdd:cd14535    81 NAELVFLDIHNIHVMRESLRKLKDICFPNI----DDSHWLSNLESTHWLEHIKLILAGAVRIADKVESGkTSVVVHCSDG 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1225 WDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLA-LNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEF 1303
Cdd:cd14535   157 WDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGHGdKNHSDADRSPVFLQFIDCVWQMTRQFPNAFEF 236


                  ....*
gi 755522772 1304 NLYYL 1308
Cdd:cd14535   237 NEHFL 241
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1146-1308 3.97e-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: 138.63  E-value: 3.97e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVWVCLEEG 1224
Cdd:cd14590    94 NAELVFLDIHNIHVMRESLRKLKEIVYPNI----EESHWLSNLESTHWLEHIKLILAGALRIADKVESGkTSVVVHCSDG 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1225 WDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLA-LNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEF 1303
Cdd:cd14590   170 WDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGdKNHADADRSPVFLQFIDCVWQMTRQFPTAFEF 249


                  ....*
gi 755522772 1304 NLYYL 1308
Cdd:cd14590   250 NEYFL 254
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 1146-1308 8.87e-36

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: 137.08  E-value: 8.87e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVWVCLEEG 1224
Cdd:cd14591    81 NAELVFLDIHNIHVMRESLKKLKDIVYPNV----EESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLVHCSDG 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1225 WDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLA-LNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEF 1303
Cdd:cd14591   157 WDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGdKNHADADRSPIFLQFIDCVWQMSKQFPTAFEF 236


                  ....*
gi 755522772 1304 NLYYL 1308
Cdd:cd14591   237 NEQFL 241
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1146-1308 3.05e-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: 132.80  E-value: 3.05e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiptdSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENG-SSVWVCLEEG 1224
Cdd:cd14592    81 NAELVFLEIHNIHVMRESLRKLKEIVYPSI----DEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGkTSVVVHCSDG 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1225 WDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLA-LNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEF 1303
Cdd:cd14592   157 WDRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGdDNHADADRSPIFLQFIDCVWQMTRQFPSAFEF 236


                  ....*
gi 755522772 1304 NLYYL 1308
Cdd:cd14592   237 NELFL 241
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1141-1292 8.18e-34

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: 130.60  E-value: 8.18e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1141 VEFAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTdsevTFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVWV 1219
Cdd:cd14533    80 PEYYPNCEVVFMNLANIHAIRKSFHSLRALCSSAPDQP----NWLSNLESTKWLHHLSGLLKAALLVVNAVDeEGRPVLV 155

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755522772 1220 CLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRS-----SLALNSQgggfAPIFLQFLDCVHQ 1292
Cdd:cd14533   156 HCSDGWDRTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCghgvnSEDINER----CPVFLQWLDCVHQ 229
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1146-1308 9.77e-34

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: 133.07  E-value: 9.77e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACIPSTiPTDSEvtFLKALGDSEWFPQLHRIMQLAVVVSE-VLENGSSVWVCLEEG 1224
Cdd:cd14584   140 NIRFQFIGIENIHVMRSSLQKLLEVCEMKS-PSMSD--FLTGLENSGWLRHIKAVMDAGVFLAKaVKEEKASVLVHCSDG 216

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1225 WDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSlALNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEFN 1304
Cdd:cd14584   217 WDRTAQVCSLASLLLDPFYRTIKGLMVLIEKEWISMGHKFSQRCG-HLDGDPKEVSPVFTQFLECVWQLMEQFPCAFEFN 295


                  ....
gi 755522772 1305 LYYL 1308
Cdd:cd14584   296 EHFL 299
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1146-1317 1.76e-33

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: 132.01  E-value: 1.76e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1146 NCEFVPVEFHEIRQVKASFKKLMRACipsTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSE-VLENGSSVWVCLEEG 1224
Cdd:cd14583   134 NIKFQFIGIENIHVMRNSLQKMLEVC---ELRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKaVAEEGASVLVHCSDG 210

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1225 WDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSlALNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEFN 1304
Cdd:cd14583   211 WDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVSFGHKFNHRYG-HLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFN 289

                         170
                  ....*....|...
gi 755522772 1305 LYYLKFLAFHYVS 1317
Cdd:cd14583   290 ERFLIHIHHHIYS 302
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 892-1292 3.68e-33

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: 131.31  E-value: 3.68e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGgfhgKGVVGLFKSQNSpqa 971
Cdd:cd14587     3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCS----QPEISWWGWRNA--- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  972 vstsslessssieQEKYLqalltavivhqklrgssTLTVRPALALSPGTERRSSRMSTvlkqvvpGHLDVNPSNsfargv 1051
Cdd:cd14587    76 -------------DDEYL-----------------VTSIAKACALDPGTRAPGGSPSK-------GNSDGSDAS------ 112

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1052 hgyrDKSFTQSNPKSSAKEPVhnqgvwaslrsstrliSSPTSFIDVGARlagkDHSASFSNSTYlqnqllkrqaalyifG 1131
Cdd:cd14587   113 ----DTDFDSSLTACSAVESG----------------AAPQKLLILDAR----SYTAAVANRAK---------------G 153

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1132 EKSQLRsskvEFAFNCEFVPVEFHEIRQVKASFKKLMRACipSTIPTDSevTFLKALGDSEWFPQLHRIMQLAVVVSEVL 1211
Cdd:cd14587   154 GGCECE----EYYPNCEVMFMGMANIHSIRNSFQYLRAVC--SQMPDPG--NWLSALESTKWLQHLSVMLKAAVLVASAV 225

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1212 E-NGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQG-GGFAPIFLQFLDC 1289
Cdd:cd14587   226 DrEGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDqNEQCPVFLQWLDC 305


                  ...
gi 755522772 1290 VHQ 1292
Cdd:cd14587   306 VHQ 308
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1148-1308 1.78e-32

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: 129.28  E-value: 1.78e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1148 EFVPVEfhEIRQVKASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSE-VLENGSSVWVCLEEGWD 1226
Cdd:cd14585   138 QFVGIE--NIHVMRSSLQKLLEVCGTKALSVND---FLSGLESSGWLRHIKAVLDAAVFLAKaVAVEGASVLVHCSDGWD 212

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1227 ITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSlALNSQGGGFAPIFLQFLDCVHQVHNQYPTEFEFNLY 1306
Cdd:cd14585   213 RTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGHKFSDRCG-QLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEA 291


                  ..
gi 755522772 1307 YL 1308
Cdd:cd14585   292 FL 293
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 892-1292 5.20e-32

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: 128.22  E-value: 5.20e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  892 FRVTASNRLYSLCRSYPGLLVIPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGgfhgkgvvglfksqnspqa 971
Cdd:cd14586     8 WRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCG------------------- 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  972 vstsslessssieqekylqalltavivhqklrgsstltvrpalalspgterrssrmstvlkqvvpghldvNPSNSFargv 1051
Cdd:cd14586    69 ----------------------------------------------------------------------QPEVSW---- 74

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1052 HGYR---DKSFTQSNPKSSAKEPVHNQGVwaslrSSTRliSSPTSFIDvGARLAGKDHSASFSNSTYLQN------QLLK 1122
Cdd:cd14586    75 WGWRnadDEHLVQSVAKACASDSSSCKSV-----LMTG--NCSRDFPN-GGDLSDVEFDSSMSNASGVESlaiqpqKLLI 146

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1123 RQAALYIFGEKSQLRSSKVE---FAFNCEFVPVEFHEIRQVKASFKKLMRACIPSTIPTDsevtFLKALGDSEWFPQLHR 1199
Cdd:cd14586   147 LDARSYAAAVANRAKGGGCEcpeYYPNCEVVFMGMANIHSIRKSFQSLRLLCTQMPDPAN----WLSALESTKWLQHLSM 222

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1200 IMQLAVVVSEVLE-NGSSVWVCLEEGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQG-G 1277
Cdd:cd14586   223 LLKSALLVVHAVDrDQRPVLVHCSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDDlN 302

                         410
                  ....*....|....*
gi 755522772 1278 GFAPIFLQFLDCVHQ 1292
Cdd:cd14586   303 ERCPVFLQWLDCVHQ 317
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 1157-1292 4.51e-29

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: 117.16  E-value: 4.51e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1157 IRQVKASFKKLMRACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAV-VVSEVLENGSSVWVCLEEGWDITTQVTSLA 1235
Cdd:cd17666    99 IHVMRDSLNKVTEALKDGDDSNPSYPPLINALKKSNWLKYLAIILQGADlIAKSIHFNHSHVLIHCSDGWDRTSQLSALA 178

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 755522772 1236 QLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSqgggfaPIFLQFLDCVHQ 1292
Cdd:cd17666   179 QLCLDPYYRTLEGFMVLVEKDWLSFGHRFAERSGHKETS------PVFHQFLDCVYQ 229
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1151-1292 1.07e-27

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: 112.82  E-value: 1.07e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1151 PVEFHEIRQvkASFKKLMRACIPSTIPTDSevtFLKALGDSEWFPQLHRIMQLAVVVSEVLEN-GSSVWVCLEEGWDITT 1229
Cdd:cd14536    85 PIERYNVLQ--ESLIKLVEACNDQGHSMDK---WLSKLESSNWLSHVKEILTTACLVAQCIDReGASVLVHGSEGMDSTL 159

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755522772 1230 QVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQR--SSLALNSQGGGFAPIFLQFLDCVHQ 1292
Cdd:cd14536   160 QVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRcaKSAYSNSKQKFESPVFLLFLDCVWQ 224
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1157-1292 4.24e-22

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: 95.87  E-value: 4.24e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1157 IRQVKASFKKLMRACIPSTiPTDSEVT---FLKALGDSEWFPQLHRIMQLAVVVSEVLEN-GSSVWVCLEEGWDITTQVT 1232
Cdd:cd14537    61 LQDVQAAYLKLRELCTPDS-SEQFWVQdskWYSLLENTKWLHYVSACLKKASEAAEALESrGRSVVLQESDGRDLSCVVS 139

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755522772 1233 SLAQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSLALNSQGGG-FAPIFLQFLDCVHQ 1292
Cdd:cd14537   140 SLVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKTESeESPVFLLFLDCVWQ 200
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1107-1293 4.21e-20

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: 89.89  E-value: 4.21e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1107 SASFSNSTYLQNQLLkRQAALYIFGEKSQlrsskvefafnCEFVPV--EFHEIRQVKASFKKLMRACIPSTIPTDSEVTF 1184
Cdd:cd14595    19 MAGFYTNSDPEKEDI-RSVELLLQAGHSQ-----------CVIVDTseELPSPADIQLAYLKLRTLCLPDISVSVSDEKW 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1185 LKALGDSEWFPQLHRIMQLAVVVSEVLENGSSVWVCLE-EGWDITTQVTSLAQLLSDPFYRTIAGFRTLVEKEWLSFGHK 1263
Cdd:cd14595    87 LSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQEsEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEWVVAGHP 166

                         170       180       190
                  ....*....|....*....|....*....|...
gi 755522772 1264 FSQRsslaLNSQGGGF---APIFLQFLDCVHQV 1293
Cdd:cd14595   167 FLQR----LNLTRESDkeeSPVFLLFLDCVWQL 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1156-1293 1.56e-19

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: 88.74  E-value: 1.56e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1156 EIRQVKASFKKLMrACIPSTIPTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLE-NGSSVWVCLEEGWDITTQVTSL 1234
Cdd:cd14594    67 EIQTAYNRFKQLF-LIDNSTDFWDTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEkQNTNVLLTEEEATDLCCVISSL 145

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 755522772 1235 AQLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSlALNSQGGGFAPIFLQFLDCVHQV 1293
Cdd:cd14594   146 VQIMMDPYCRTKSGFQSLIQKEWVMGGHCFLDRCN-HLRQNDKEEVPVFLLFLDCVWQL 203
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 108-176 6.77e-19

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: 82.34  E-value: 6.77e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755522772    108 DKEVRAVFLRLFAQLFQGYRSCLQLIRIHAEPVIHFHKTAFLGQRGLVENDFLTKVLNGMAFAGFVSER 176
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 1-54 1.92e-18

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: 84.94  E-value: 1.92e-18
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 755522772      1 MFPLKYSYPYIPILPAQLLEVLSSPTPFIIGVHSIFKTDVHELL--DVIIADLDGG 54
Cdd:smart00799  128 LYPFVWQHIYIPILPASLLDVLSAPTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 1-54 4.31e-18

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: 83.78  E-value: 4.31e-18
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 755522772     1 MFPLKYSYPYIPILPAQLLEVLSSPTPFIIGVHS-IFKTDVHELLDVIIADLDGG 54
Cdd:pfam02141  132 LYPFVWQHIYIPVLPASLLDVLSAPTPFIIGVHSrYFDLLEDPLDDVVLVDLDTG 186
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1157-1292 6.62e-17

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: 80.71  E-value: 6.62e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1157 IRQVKASFKKLMRACIPSTIpTDSEVTFLKALGDSEWFPQLHRIMQLAVVVSEVLENGS-SVWVCLEEGWDITTQVTSLA 1235
Cdd:cd14593    61 IQEIQAAFVKLKQLCVNEPF-EETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHvSVILQEEEGRDLSCVVASLV 139

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 755522772 1236 QLLSDPFYRTIAGFRTLVEKEWLSFGHKFSQRSSlALNSQGGGFAPIFLQFLDCVHQ 1292
Cdd:cd14593   140 QVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCN-HLKKSSKKESPLFLLFLDCVWQ 195
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1558-1658 1.04e-15

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: 74.51  E-value: 1.04e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   1558 EGTLYKRGA-LLKGWKPRWFVLdvTKHQLRYYDS---GEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTsdkafFDLKTSK 1633
Cdd:smart00233    4 EGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKPHC-----FEIKTSD 76

                            90       100
                    ....*....|....*....|....*.
gi 755522772   1634 R-VYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:smart00233   77 RkTLLLQAESEEEREKWVEALRKAIA 102
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 1556-1655 3.11e-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: 66.96  E-value: 3.11e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1556 SFEGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVipagpsmgAPKYTSDKAF-FDLKTSKR 1634
Cdd:cd10573     4 SKEGYLTKLGGIVKNWKTRWFVL--RRNELKYFKTRGDTKPIRVLDLRECSSV--------QRDYSQGKVNcFCLVFPER 73

                          90       100
                  ....*....|....*....|.
gi 755522772 1635 VYNFCAQDGQSAQQWMDRIQS 1655
Cdd:cd10573    74 TFYMYANTEEEADEWVKLLKW 94
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1558-1653 4.25e-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: 66.41  E-value: 4.25e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGA-LLKGWKPRWFVLDvtKHQLRYYDSGEDTS--CKGHIDLAEVEMVIPAGPSmgapkytSDKAFFDLKTSK- 1633
Cdd:cd00821     2 EGYLLKRGGgGLKSWKKRWFVLF--EGVLLYYKSKKDSSykPKGSIPLSGILEVEEVSPK-------ERPHCFELVTPDg 72

                          90       100
                  ....*....|....*....|
gi 755522772 1634 RVYNFCAQDGQSAQQWMDRI 1653
Cdd:cd00821    73 RTYYLQADSEEERQEWLKAL 92
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1558-1658 1.02e-12

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 66.05  E-value: 1.02e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  1558 EGTLYKRG-ALLKGWKPRWFVLdvTKHQLRYYD---SGEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTsdkafFDLKTS- 1632
Cdd:pfam00169    4 EGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKddkSGKSKEPKGSISLSGCEVVEVVASDSPKRKFC-----FELRTGe 76

                           90       100
                   ....*....|....*....|....*....
gi 755522772  1633 ---KRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:pfam00169   77 rtgKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 1559-1655 1.27e-12

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: 65.42  E-value: 1.27e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1559 GTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGApkytsdkafFDLKTSKRVYNF 1638
Cdd:cd01265     7 NKLETRGLGLKGWKRRWFVLDESKCQLYYYRSPQDATPLGSIDLSGAAFSYDPEAEPGQ---------FEIHTPGRVHIL 77

                          90
                  ....*....|....*..
gi 755522772 1639 CAQDGQSAQQWMDRIQS 1655
Cdd:cd01265    78 KASTRQAMLYWLQALQS 94
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 1558-1657 4.29e-12

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 64.24  E-value: 4.29e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAgpsmgaPKYTSDKAFFDLKTSKRVYN 1637
Cdd:cd13273    11 KGYLWKKGHLLPTWTERWFVL--KPNSLSYYKSEDLKEKKGEIALDSNCCVESL------PDREGKKCRFLVKTPDKTYE 82

                          90       100
                  ....*....|....*....|
gi 755522772 1638 FCAQDGQSAQQWMDRIQSCI 1657
Cdd:cd13273    83 LSASDHKTRQEWIAAIQTAI 102
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 1558-1659 1.48e-11

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: 62.02  E-value: 1.48e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGAL--LKGWKPRWFVLDVTkhQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMgapkytsdkafFDLKTSKRV 1635
Cdd:cd13253     3 SGYLDKQGGQgnNKGFQKRWVVFDGL--SLRYFDSEKDAYSKRIIPLSAISTVRAVGDNK-----------FELVTTNRT 69

                          90       100
                  ....*....|....*....|....
gi 755522772 1636 YNFCAQDGQSAQQWMDRIQSCISD 1659
Cdd:cd13253    70 FVFRAESDDERNLWCSTLQAAISE 93
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
 1558-1656 1.62e-10

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: 59.61  E-value: 1.62e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCK--GHIDLAevemvipagpsmGAPKYTSDKA---FFDLKTS 1632
Cdd:cd13291     2 EGQLLKYTNVVKGWQNRWFVLDPDTGILEYFLSEESKNQKprGSLSLA------------GAVISPSDEDshtFTVNAAN 69

                          90       100
                  ....*....|....*....|....
gi 755522772 1633 KRVYNFCAQDGQSAQQWMDRIQSC 1656
Cdd:cd13291    70 GEMYKLRAADAKERQEWVNRLRAV 93
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 1555-1653 5.25e-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: 5.25e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1555 RSFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEMV----IPAGPSMGAPKYTsdkafFDLK 1630
Cdd:cd14673     3 KRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVyydhLRSAAKSPNPALT-----FCVK 77

                          90       100
                  ....*....|....*....|...
gi 755522772 1631 TSKRVYNFCAQDGQSAQQWMDRI 1653
Cdd:cd14673    78 THDRLYYMVAPSPEAMRIWMDVI 100
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 1559-1658 5.58e-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: 57.86  E-value: 5.58e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1559 GTLYKRG---ALL--KGWKPRWFVLDVTKhqLRYYDSGEDTS-CKGHIDLAEVEMVIPAGPSMGApkytsdkafFDLKTS 1632
Cdd:cd13296     3 GWLTKKGggsSTLsrRNWKSRWFVLRDTV--LKYYENDQEGEkLLGTIDIRSAKEIVDNDPKENR---------LSITTE 71

                          90       100
                  ....*....|....*....|....*.
gi 755522772 1633 KRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd13296    72 ERTYHLVAESPEDASQWVNVLTRVIS 97
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 1559-1653 8.92e-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: 57.64  E-value: 8.92e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1559 GTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAgpsmgapKYTSDKAFFDLKTSKRVYNF 1638
Cdd:cd13298    10 GYLLKRSRKTKNWKKRWVVL--RPCQLSYYKDEKEYKLRRVINLSELLAVAPL-------KDKKRKNVFGIYTPSKNLHF 80

                          90
                  ....*....|....*
gi 755522772 1639 CAQDGQSAQQWMDRI 1653
Cdd:cd13298    81 RATSEKDANEWVEAL 95
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 1571-1653 1.91e-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: 57.07  E-value: 1.91e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1571 WKPRWFVLDVT----KHQLRYYDSGEDTSCKGHIDLAEVEMViPAGPSMGAPKYTSDKAFFDLKTSKRVYNFCAQDGQSA 1646
Cdd:cd13384    23 WRRRYFVLRQSeipgQYFLEYYTDRTCRKLKGSIDLDQCEQV-DAGLTFETKNKLKDQHIFDIRTPKRTYYLVADTEDEM 101


                  ....*..
gi 755522772 1647 QQWMDRI 1653
Cdd:cd13384   102 NKWVNCI 108
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 1558-1658 4.75e-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: 55.29  E-value: 4.75e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLK-GWKPRWFVLDVTKhqLRYYDSGEDTSCKGHIDLAEVE---MVipagpSMGAPKYTSDKAF--FDLKT 1631
Cdd:cd01251     5 EGYLEKTGPKQTdGFRKRWFTLDDRR--LMYFKDPLDAFPKGEIFIGSKEegySV-----REGLPPGIKGHWGfgFTLVT 77

                          90       100
                  ....*....|....*....|....*..
gi 755522772 1632 SKRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd01251    78 PDRTFLLSAETEEERREWITAIQKVLE 104
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 1556-1656 1.28e-08

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: 54.27  E-value: 1.28e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1556 SFEGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSCKGHIDLAEVEmVIPAGPSM-GAPK--YTSDKAFFDLkts 1632
Cdd:cd13260     4 DKKGYLLKKGGKNKKWKNLYFVLEGKEQHLYFFDNEKRTKPKGLIDLSYCS-LYPVHDSLfGRPNcfQIVVRALNES--- 79

                          90       100
                  ....*....|....*....|....
gi 755522772 1633 kRVYNFCAQDGQSAQQWMDRIQSC 1656
Cdd:cd13260    80 -TITYLCADTAELAQEWMRALRAF 102
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 1558-1658 1.92e-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: 53.46  E-value: 1.92e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLDVTkhQLRYYDSGEDTSCK--GHIDLAEVEMVIPAgpsmgapkytSDKAFFDLKTSKRV 1635
Cdd:cd13282     2 AGYLTKLGGKVKTWKRRWFVLKNG--ELFYYKSPNDVIRKpqGQIALDGSCEIARA----------EGAQTFEIVTEKRT 69

                          90       100
                  ....*....|....*....|...
gi 755522772 1636 YNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd13282    70 YYLTADSENDLDEWIRVIQNVLR 92
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
 1558-1609 2.72e-08

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: 53.18  E-value: 2.72e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLDvtKHQLRYYDSGEDTS--CKGHIDLAEVEMVI 1609
Cdd:cd01247     2 EGVLWKWTNYLSGWQPRWFVLD--DGVLSYYKSQEEVNqgCKGSVKMSVCEIIV 53
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 1558-1655 3.10e-08

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: 53.06  E-value: 3.10e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTS--CKGHIDLAEVEMVIpagpsmgapkYTSDKAFFDLKTSKRV 1635
Cdd:cd13283     2 RGVLSKWTNYIHGWQDRYFVL--KDGTLSYYKSESEKEygCRGSISLSKAVIKP----------HEFDECRFDVSVNDSV 69

                          90       100
                  ....*....|....*....|
gi 755522772 1636 YNFCAQDGQSAQQWMDRIQS 1655
Cdd:cd13283    70 WYLRAESPEERQRWIDALES 89
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 1558-1658 5.68e-08

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: 52.70  E-value: 5.68e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEV--------------EMVIPAGPS-MGAPKYTS 1622
Cdd:cd01252     6 EGWLLKLGGRVKSWKRRWFIL--TDNCLYYFEYTTDKEPRGIIPLENLsvrevedkkkpfcfELYSPSNGQvIKACKTDS 83

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 755522772 1623 DKAFFDLKTSkrVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd01252    84 DGKVVEGNHT--VYRISAASEEERDEWIKSIKASIS 117
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 1558-1602 3.14e-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: 3.14e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDL 1602
Cdd:cd13301     6 EGYLVKKGHVVNNWKARWFVL--KEDGLEYYKKKTDSSPKGMIPL 48
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 1571-1660 3.15e-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: 3.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1571 WKPRWFVLDVTK-----HQLRYYDSGEDTSCKGHIDLAEVEMViPAGPSMGAPKYtSDKAFFDLKTSKRVYNFCAQDGQS 1645
Cdd:cd13324    21 WRRRWFVLRSGRlsggqDVLEYYTDDHCKKLKGIIDLDQCEQV-DAGLTFEKKKF-KNQFIFDIRTPKRTYYLVAETEEE 98

                          90
                  ....*....|....*
gi 755522772 1646 AQQWMDriqsCISDA 1660
Cdd:cd13324    99 MNKWVR----CICQV 109
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 1556-1651 3.70e-07

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: 49.96  E-value: 3.70e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1556 SFEGTLYKR-GALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVeMVIPAGPSMGAPKYTSDKAFfdlKTSKR 1634
Cdd:cd13248     8 VMSGWLHKQgGSGLKNWRKRWFVL--KDNCLYYYKDPEEEKALGSILLPSY-TISPAPPSDEISRKFAFKAE---HANMR 81

                          90
                  ....*....|....*..
gi 755522772 1635 VYNFCAQDGQSAQQWMD 1651
Cdd:cd13248    82 TYYFAADTAEEMEQWMN 98
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 1558-1605 6.12e-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: 6.12e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 755522772 1558 EGTLYKR--GALLKG---WKPRWFVLdvTKHQLRYYDS--GEDTSCKGHIDLAEV 1605
Cdd:cd01238     2 EGLLVKRsqGKKRFGpvnYKERWFVL--TKSSLSYYEGdgEKRGKEKGSIDLSKV 54
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 1557-1657 6.83e-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: 46.54  E-value: 6.83e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1557 FEGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCK---GHIDLAEVEMVipagpsMGAPKYTSDKAFFDLKTSK 1633
Cdd:cd13276     1 KAGWLEKQGEFIKTWRRRWFVL--KQGKLFWFKEPDVTPYSkprGVIDLSKCLTV------KSAEDATNKENAFELSTPE 72

                          90       100
                  ....*....|....*....|....
gi 755522772 1634 RVYNFCAQDGQSAQQWMDRIQSCI 1657
Cdd:cd13276    73 ETFYFIADNEKEKEEWIGAIGRAI 96
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
 1558-1657 7.98e-06

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: 46.28  E-value: 7.98e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLDVTKHQLRYYDSGEDTSC---KGHIDLAEVEMVIPagpsmgapkyTSDKAFFDLKTSKR 1634
Cdd:cd13290     2 EGPLSKWTNVMKGWQYRWFVLDDNAGLLSYYTSKEKMMRgsrRGCVRLKGAVVGID----------DEDDSTFTITVDQK 71

                          90       100
                  ....*....|....*....|...
gi 755522772 1635 VYNFCAQDGQSAQQWMDRIQSCI 1657
Cdd:cd13290    72 TFHFQARDAEERERWIRALEDTI 94
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 1547-1654 8.88e-06

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


Pssm-ID: 275402  Cd Length: 116  Bit Score: 46.46  E-value: 8.88e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1547 YTSKNDENRSFEGTLYKRGALLKGWKPRWFVLdvtKHQ-LRYYDSGEDTSC-KGHIDLAEVEMVIPAGPSMGAPKYtsdk 1624
Cdd:cd13215    13 YLPKRSGAVIKSGYLSKRSKRTLRYTRYWFVL---KGDtLSWYNSSTDLYFpAGTIDLRYATSIELSKSNGEATTS---- 85

                          90       100       110
                  ....*....|....*....|....*....|
gi 755522772 1625 afFDLKTSKRVYNFCAQDGQSAQQWMDRIQ 1654
Cdd:cd13215    86 --FKIVTNSRTYKFKADSETSADEWVKALK 113
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 669-754 1.06e-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: 45.45  E-value: 1.06e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772  669 EGALFLTTYRILFrgtpHDQLVGEQTVVrSFPIASITKEKKItmqnQLQQSVQEGLQITSASFQLIKVAFDEEvsPEVVD 748
Cdd:cd10570    20 EGTLYLSTYRLIF----SSKADGDETKL-VIPLVDITDVEKI----AGASFLPSGLIITCKDFRTIKFSFDSE--DEAVK 88


                  ....*.
gi 755522772  749 IFKKQL 754
Cdd:cd10570    89 VIARVL 94
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 1557-1650 1.93e-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: 45.06  E-value: 1.93e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1557 FEGTLYKRGALLKGWKPRWFVLDVTkhQLRYYDSGEDTSCKGHIDLA--EVEMVIPAGPSMGapKYtsdkaFFDL--KTS 1632
Cdd:cd13316     2 HSGWMKKRGERYGTWKTRYFVLKGT--RLYYLKSENDDKEKGLIDLTghRVVPDDSNSPFRG--SY-----GFKLvpPAV 72

                          90
                  ....*....|....*...
gi 755522772 1633 KRVYNFCAQDGQSAQQWM 1650
Cdd:cd13316    73 PKVHYFAVDEKEELREWM 90
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 1558-1660 2.73e-05

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 44.52  E-value: 2.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGA-LLKGWKPRWFVLDvtKHQLRYYDSGEDTSCKGHID---LAEVEMVIPagpsmgapkytSDKAF-FDLKTS 1632
Cdd:cd13250     2 EGYLFKRSSnAFKTWKRRWFSLQ--NGQLYYQKRDKKDEPTVMVEdlrLCTVKPTED-----------SDRRFcFEVISP 68

                          90       100
                  ....*....|....*....|....*...
gi 755522772 1633 KRVYNFCAQDGQSAQQWMDRIQSCISDA 1660
Cdd:cd13250    69 TKSYMLQAESEEDRQAWIQAIQSAIASA 96
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
633-711 3.45e-05

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 42.97  E-value: 3.45e-05
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755522772    633 LPGEEIVCEGLRVLLDPDGReeatggllggpqllpAEGALFLTTYRILFRGTPHDQLvgeqtVVRSFPIASITKEKKIT 711
Cdd:smart00568    2 LPEEEKLIADYSCYLSRTGP---------------VQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 1551-1660 4.54e-05

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: 44.33  E-value: 4.54e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1551 NDENRSFEGTLYKRGALLKGWKPRWFVLDVTKhqLRYYDSGEDTSCKGHIDLAEVEMVIPAgpSMGAPKYTsdkafFDLK 1630
Cdd:cd13255     2 ISEAVLKAGYLEKKGERRKTWKKRWFVLRPTK--LAYYKNDKEYRLLRLIDLTDIHTCTEV--QLKKHDNT-----FGIV 72

                          90       100       110
                  ....*....|....*....|....*....|
gi 755522772 1631 TSKRVYNFCAQDGQSAQQWMdriqSCISDA 1660
Cdd:cd13255    73 TPARTFYVQADSKAEMESWI----SAINLA 98
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
 1543-1659 7.08e-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: 7.08e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1543 LYSQYTSKNDENRSFEGTlykrgallkGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKyts 1622
Cdd:cd13381     2 LKAGYLEKRRKDHSFFGF---------EWQKRWCAL--SNSVFYYYGSDKDKQQKGEFAIDGYDVKMNNTLRKDAKK--- 67

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 755522772 1623 DKAFFDLKTSKRVYNFCAQDGQSAQQWMDRIQSCISD 1659
Cdd:cd13381    68 DCCFEICAPDKRVYQFTAASPKEAEEWVQQIKFILQD 104
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 143-189 8.59e-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: 8.59e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 755522772   143 FHKTAFLGQRGLVENDFLTKVLNGMAFAGFVSERG-PPYRACDLFDEL 189
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
 1552-1657 1.33e-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: 46.52  E-value: 1.33e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1552 DENRSFEGTLYKRGALLKGWKPRWFVLDvTKHQLRYYDSGED----TSCKGHIDLAEVEMVIpagpSMGAPKYTSDKAFF 1627
Cdd:cd23949    59 DRKVIFSGKLSKYGEDSKKWKERFCVVR-GDYNLEYYESKEAyergKKPKGSINLAGYKVLT----SPEEYLELVDRKFP 133

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 755522772 1628 DLK-----------------------TSKRVYNFCAQDGQSAQQWMDRIQSCI 1657
Cdd:cd23949   134 DLAgksekasvpfperpppftlelyhPYRRHYYFCFETEKEQEEWVAVLQDCI 186
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
 1557-1603 1.92e-04

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: 41.98  E-value: 1.92e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 755522772 1557 FEGTLYKRGALLKGWKPRWFVLDvtKHQLRYYDSGEDTS--CKGHIDLA 1603
Cdd:cd13284     1 MKGWLLKWTNYIKGYQRRWFVLS--NGLLSYYRNQAEMAhtCRGTINLA 47
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 1557-1658 1.97e-04

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270118  Cd Length: 113  Bit Score: 42.39  E-value: 1.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1557 FEGTLYKRGA---LLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMVipagpsmGAPKYTSDKAF----FDL 1629
Cdd:cd13308    11 HSGTLTKKGGsqkTLQNWQLRYVII--HQGCVYYYKNDQSAKPKGVFSLNGYNRR-------AAEERTSKLKFvfkiIHL 81

                          90       100
                  ....*....|....*....|....*....
gi 755522772 1630 KTSKRVYNFCAQDGQSAQQWMDRIQSCIS 1658
Cdd:cd13308    82 SPDHRTWYFAAKSEDEMSEWMEYIRREID 110
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
 1559-1650 2.44e-04

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: 41.90  E-value: 2.44e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1559 GTLYKRGALLKGWKPRWFVLdVTKHQLRYYDSGEDTSCKGHIDLAEVEMVIPAG---PSMGAPKYTSDKAFFDLKTSKR- 1634
Cdd:cd13265     7 GWLLRQSTILKRWKKNWFVL-YGDGNLVYYEDETRREVEGRINMPRECRNIRVGlecRDVQPPEGRSRDCLLQIVLRDGs 85

                          90
                  ....*....|....*.
gi 755522772 1635 VYNFCAQDGQSAQQWM 1650
Cdd:cd13265    86 TLFLCAESADDALAWK 101
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 668-760 3.65e-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: 41.58  E-value: 3.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772   668 AEGALFLTTYRILFRGTPHDQLvgeQTVVrsFPIASITKEKKITMQNQLQQSvqeGLQITSASFQliKVAFDEEVSPEVV 747
Cdd:pfam02893   30 VQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDIEEIEKLKGGANLFPN---GIQVETGSND--KFSFAGFVTRDEA 99

                           90
                   ....*....|...
gi 755522772   748 DIFKKQLMKFRYP 760
Cdd:pfam02893  100 IEFILALLKNAHP 112
PH_Gab3 cd13385
Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes ...
 1571-1656 7.90e-04

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: 41.11  E-value: 7.90e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1571 WKPRWFVL---------DVtkhqLRYYDSGEDTSCKGHIDLAEVEMVIPAGPSMGAPKYTSDKAFFdLKTSKRVYNFCAQ 1641
Cdd:cd13385    26 WRKRWFVLrrgrmsgnpDV----LEYYRNNHSKKPIRVIDLSECEVLKHSGPNFIRKEFQNNFVFI-VKTTYRTFYLVAK 100

                          90
                  ....*....|....*.
gi 755522772 1642 DGQSAQQWMDRI-QSC 1656
Cdd:cd13385   101 TEEEMQVWVHNIsQIC 116
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
 1559-1657 8.31e-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: 40.88  E-value: 8.31e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1559 GTLYK--RGALLKGW---KPRWFVLdvTKHQLRYYDSGEDTSCK-GHIDLAEVEMVIPAGPSMGAPK--YTsdkafFDLK 1630
Cdd:cd13297    17 GWLYKegGKGGARGNltkKKRWFVL--TGNSLDYYKSSEKNSLKlGTLVLNSLCSVVPPDEKMAKETgyWT-----FTVH 89

                          90       100
                  ....*....|....*....|....*..
gi 755522772 1631 TSKRVYNFCAQDGQSAQQWMDRIQSCI 1657
Cdd:cd13297    90 GRKHSFRLYTKLQEEAMRWVNAIQDVI 116
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 1558-1650 1.14e-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: 40.30  E-value: 1.14e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1558 EGTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAE--VEMvipagpSMGAPKYtsdkAF---FDLKTS 1632
Cdd:cd13288    11 EGYLWKKGERNTSYQKRWFVL--KGNLLFYFEKKGDREPLGVIVLEGctVEL------AEDAEPY----AFairFDGPGA 78

                          90
                  ....*....|....*...
gi 755522772 1633 kRVYNFCAQDGQSAQQWM 1650
Cdd:cd13288    79 -RSYVLAAENQEDMESWM 95
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
 1559-1653 1.22e-03

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: 39.70  E-value: 1.22e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1559 GTLYKRGALLKGWKPRWFVLdvtKHQLRY-YDSGEDTSCKGHIDLAEVEMVipagPSMGAPKYTSDKAFFDLKTSKRVYN 1637
Cdd:cd13237     3 GYLQRRKKSKKSWKRLWFVL---KDKVLYtYKASEDVVALESVPLLGFTVV----TIDESFEEDESLVFQLLHKGQLPII 75

                          90
                  ....*....|....*.
gi 755522772 1638 FCAQDGQSAQQWMDRI 1653
Cdd:cd13237    76 FRADDAETAQRWIEAL 91
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
 1559-1613 1.37e-03

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


Pssm-ID: 241529  Cd Length: 116  Bit Score: 40.31  E-value: 1.37e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 755522772 1559 GTLYKRGALLKGWKPRWFVLdvTKHQLRYYDSGEDTSCKGHIDLAEVEMV-IPAGP 1613
Cdd:cd13378     7 GWLKKQRSIMKNWQQRWFVL--RGDQLFYYKDEEETKPQGCISLQGSQVNeLPPNP 60
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 1555-1660 5.47e-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: 38.06  E-value: 5.47e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755522772 1555 RSFEGTLYKRGALLKGWKPRWFVLDvtKHQLRYYDSGED--TSCKGHIDLAEVEMVIPAgpsmgapkytSDKAFFDL--K 1630
Cdd:cd13292     2 PTMKGYLKKWTNYAKGYKTRWFVLE--DGVLSYYRHQDDegSACRGSINMKNARLVSDP----------SEKLRFEVssK 69

                          90       100       110
                  ....*....|....*....|....*....|.
gi 755522772 1631 TSKRV-YNFCAQDGQSAQQWMDRIQSCISDA 1660
Cdd:cd13292    70 TSGSPkWYLKANHPVEAARWIQALQKAIEWA 100
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 1623-1660 5.76e-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: 38.11  E-value: 5.76e-03
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 755522772 1623 DKAFFDLKTSKRVYNFCAQDGQSAQQWMDRIQSCISDA 1660
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH