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Conserved domains on  [gi|18497296|ref|NP_569729|]
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synaptojanin, isoform B [Drosophila melanogaster]

Protein Classification

endonuclease/exonuclease/phosphatase family protein; exonuclease/endonuclease/phosphatase family protein( domain architecture ID 13429219)

endonuclease/exonuclease/phosphatase (EEP) family protein is among a diverse set of enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds; their substrates range from nucleic acids to phospholipids and perhaps proteins| endonuclease/exonuclease/phosphatase (EEP) family protein is among a diverse set of enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds; their substrates range from nucleic acids to phospholipids and perhaps proteins

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 538-863 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This subfamily contains the INPP5c domains of two human synaptojanins, synaptojanin 1 (Synj1) and synaptojanin 2 (Synj2), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs). They belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, Synjs contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25 (a mitochondrial outer membrane protein). Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


:

Pssm-ID: 197323 [Multi-domain]  Cd Length: 328  Bit Score: 641.36  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  538 ARVAVGTYNVNGGKHFRSIVFKD-SLADWLLD-CHALARSKalvdvnNPSENVDHPVDIYAIGFEEIVDLNASNIMAAST 615
Cdd:cd09089    1 LRVFVGTWNVNGGKHFRSIAFKHqSMTDWLLDnPKLAGQCS------NDSEEDEKPVDIFAIGFEEMVDLNASNIVSAST 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  616 DNAKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCF 695
Cdd:cd09089   75 TNQKEWGEELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCF 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  696 VCAHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQE 775
Cdd:cd09089  155 VCSHFAAGQSQVKERNEDFAEIARKLSFPMGRTLDSHDYVFWCGDFNYRIDLPNDEVKELVRNGDWLKLLEFDQLTKQKA 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  776 AGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRKALAEGDF------AASAWNPGKLIHYGRSEL 849
Cdd:cd09089  235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPSDKTEeslvetNDPTWNPGTLLYYGRAEL 314

                        330
                 ....*....|....
gi 18497296  850 KQSDHRPVIAIIDA 863
Cdd:cd09089  315 KTSDHRPVVAIIDI 328
COG5329 super family cl34984
Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];
61-493 1.86e-90

Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];


The actual alignment was detected with superfamily member COG5329:

Pssm-ID: 227637 [Multi-domain]  Cd Length: 570  Bit Score: 303.54  E-value: 1.86e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   61 YGCLGALQLNAGEstvlFLVLVTGCVSMGKIGDIEIFRITQTTFVSL-QNAAPNE--------DKISEVRKLLNSGTFYF 131
Cdd:COG5329   61 YGVIGLIKLKGDI----YLIVITGASLVGVIPGHSIYKILDVDFISLnNNKWDDEleedeanyDKLSELKKLLSNGTFYF 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  132 AhtnasasasgassYRFDITLCAQRRQQTQET------DNRFFWNRMM------HI-HLMRFGIDCQSWLLQAMCGSVEV 198
Cdd:COG5329  137 S-------------YDFDITNSLQKNLSEGLEasvdraDLIFMWNSFLleefinHRsKLSSLEKQFDNFLTTVIRGFAET 203

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  199 RTVYIGAKQARAAIISRLSCERAGTRFNVRGTNDEGYVANFVETEQVIYVDGDVTSYVQTRGSVPLFWEQpGVQVGSHKV 278
Cdd:COG5329  204 VDIKVGGNTISLTLISRRSSERAGTRYLSRGIDDDGNVSNFVETEQIVTDSQYIFSFTQVRGSIPLFWEQ-SNLLYGPKI 282

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  279 KLSRGFETSAAAFDRHMSMMRQRYGYQTVVNLLgsslvGSKEGEAMLSNEFQRHHGMSAHKDVPHVVFDYHQECRGGNFS 358
Cdd:COG5329  283 KVTRSSEAAQSAFDKHFDKLREKYGDVYVVNLL-----KTKGYEAPLLELYEKHLDLSKKPKIHYTEFDFHKETSQDGFD 357

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  359 ALAKLKERIVACGANYGVFHA--SNGQVLREQFGVVRTNCLDCLDRTNCVQTYLGLdtlgIQLEALKMGGKQQNI-SRFE 435
Cdd:COG5329  358 DVKKLLYLIEQDLLEFGYFAYdiNEGKSISEQDGVFRTNCLDCLDRTNVIQSLISR----VLLEQFRSEGVISDGySPFL 433

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18497296  436 EIFRQMWINNGNEVSKIYAGTGAIQG----------GSKLMDGARSAARTIQNNLLDNSKQEAIDVLL 493
Cdd:COG5329  434 QIHRELWADNGDAISRLYTGTGALKSsftrrgrrsfAGALNDFIKSFSRYYINNFTDGQRQDAIDLLL 501
DUF1866 pfam08952
Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known ...
 862-1008 3.09e-73

Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known function.


:

Pssm-ID: 286093  Cd Length: 146  Bit Score: 239.71  E-value: 3.09e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    862 DAEIMEIDQQRRRAVFEQVIRDLGPPDSTIVVHVLEssatGDEDGPTIYDENVMSALITELSKMGEVTLVRYVEDTMWVT 941
Cdd:pfam08952    1 DVEIQEVDPEARRRVFKEVIRDQGPPDGTIVVSLCS----GDLDEKNIFDENLMDELIQELTSFGEVTLVRFVEDTMWVT 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18497296    942 FRDGESALNASSKKSIQVCGLDLILELKSKDWQHLVDSEIELCTTNTIPL--CANPVEHAQLLQAITPE 1008
Cdd:pfam08952   77 FRDGHSALNALSKDGMKVCGRALKIRLKSKDWIKGLEEEIILCTDNTIPVspCANSTLLAEDFDFGSPD 145
 
Name Accession Description Interval E-value
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 538-863 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This subfamily contains the INPP5c domains of two human synaptojanins, synaptojanin 1 (Synj1) and synaptojanin 2 (Synj2), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs). They belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, Synjs contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25 (a mitochondrial outer membrane protein). Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197323 [Multi-domain]  Cd Length: 328  Bit Score: 641.36  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  538 ARVAVGTYNVNGGKHFRSIVFKD-SLADWLLD-CHALARSKalvdvnNPSENVDHPVDIYAIGFEEIVDLNASNIMAAST 615
Cdd:cd09089    1 LRVFVGTWNVNGGKHFRSIAFKHqSMTDWLLDnPKLAGQCS------NDSEEDEKPVDIFAIGFEEMVDLNASNIVSAST 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  616 DNAKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCF 695
Cdd:cd09089   75 TNQKEWGEELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCF 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  696 VCAHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQE 775
Cdd:cd09089  155 VCSHFAAGQSQVKERNEDFAEIARKLSFPMGRTLDSHDYVFWCGDFNYRIDLPNDEVKELVRNGDWLKLLEFDQLTKQKA 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  776 AGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRKALAEGDF------AASAWNPGKLIHYGRSEL 849
Cdd:cd09089  235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPSDKTEeslvetNDPTWNPGTLLYYGRAEL 314

                        330
                 ....*....|....
gi 18497296  850 KQSDHRPVIAIIDA 863
Cdd:cd09089  315 KTSDHRPVVAIIDI 328
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 536-865 1.55e-98

Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+)-sensitive enzymes.


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 315.83  E-value: 1.55e-98
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     536 RMARVAVGTYNVNGGkhFRSivfKDSLADWLLDchalarskalvdvnNPSENVDHPVDIYAIGFEEIVDLNASNIMAAST 615
Cdd:smart00128    1 RDIKVLIGTWNVGGL--ESP---KVDVTSWLFQ--------------KIEVKQSEKPDIYVIGLQEVVGLAPGVILETIA 61

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     616 DNAKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCF 695
Cdd:smart00128   62 GKERLWSDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCF 141

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     696 VCAHFAAGQSQVAERNADYAEITRKLAFPMGRTL--KSHDWVFWCGDFNYRIDME-KDELKECVRNGDLSTVLEFDQLRK 772
Cdd:smart00128  142 VNSHLAAGASNVEQRNQDYKTILRALSFPERALLsqFDHDVVFWFGDLNFRLDSPsYEEVRRKISKKEFDDLLEKDQLNR 221

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     773 EQEAGNVFGEFLEGEITFDPTYKYDLF-SDDYDTSEKQRAPAWTDRVLWRRrkalaegdfaaSAWNPGKL-IHYGRSELK 850
Cdd:smart00128  222 QREAGKVFKGFQEGPITFPPTYKYDSVgTETYDTSEKKRVPAWCDRILYRS-----------NGPELIQLsEYHSGMEIT 290

                           330
                    ....*....|....*
gi 18497296     851 QSDHRPVIAIIDAEI 865
Cdd:smart00128  291 TSDHKPVFATFRLKV 305
COG5329 COG5329
Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];
61-493 1.86e-90

Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];


Pssm-ID: 227637 [Multi-domain]  Cd Length: 570  Bit Score: 303.54  E-value: 1.86e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   61 YGCLGALQLNAGEstvlFLVLVTGCVSMGKIGDIEIFRITQTTFVSL-QNAAPNE--------DKISEVRKLLNSGTFYF 131
Cdd:COG5329   61 YGVIGLIKLKGDI----YLIVITGASLVGVIPGHSIYKILDVDFISLnNNKWDDEleedeanyDKLSELKKLLSNGTFYF 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  132 AhtnasasasgassYRFDITLCAQRRQQTQET------DNRFFWNRMM------HI-HLMRFGIDCQSWLLQAMCGSVEV 198
Cdd:COG5329  137 S-------------YDFDITNSLQKNLSEGLEasvdraDLIFMWNSFLleefinHRsKLSSLEKQFDNFLTTVIRGFAET 203

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  199 RTVYIGAKQARAAIISRLSCERAGTRFNVRGTNDEGYVANFVETEQVIYVDGDVTSYVQTRGSVPLFWEQpGVQVGSHKV 278
Cdd:COG5329  204 VDIKVGGNTISLTLISRRSSERAGTRYLSRGIDDDGNVSNFVETEQIVTDSQYIFSFTQVRGSIPLFWEQ-SNLLYGPKI 282

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  279 KLSRGFETSAAAFDRHMSMMRQRYGYQTVVNLLgsslvGSKEGEAMLSNEFQRHHGMSAHKDVPHVVFDYHQECRGGNFS 358
Cdd:COG5329  283 KVTRSSEAAQSAFDKHFDKLREKYGDVYVVNLL-----KTKGYEAPLLELYEKHLDLSKKPKIHYTEFDFHKETSQDGFD 357

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  359 ALAKLKERIVACGANYGVFHA--SNGQVLREQFGVVRTNCLDCLDRTNCVQTYLGLdtlgIQLEALKMGGKQQNI-SRFE 435
Cdd:COG5329  358 DVKKLLYLIEQDLLEFGYFAYdiNEGKSISEQDGVFRTNCLDCLDRTNVIQSLISR----VLLEQFRSEGVISDGySPFL 433

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18497296  436 EIFRQMWINNGNEVSKIYAGTGAIQG----------GSKLMDGARSAARTIQNNLLDNSKQEAIDVLL 493
Cdd:COG5329  434 QIHRELWADNGDAISRLYTGTGALKSsftrrgrrsfAGALNDFIKSFSRYYINNFTDGQRQDAIDLLL 501
Syja_N pfam02383
SacI homology domain; This Pfam family represents a protein domain which shows homology to the ...
 61-353 2.82e-82

SacI homology domain; This Pfam family represents a protein domain which shows homology to the yeast protein SacI. The SacI homology domain is most notably found at the amino terminal of the inositol 5'-phosphatase synaptojanin.


Pssm-ID: 460545  Cd Length: 295  Bit Score: 270.98  E-value: 2.82e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     61 YGCLGALQLNAGestvLFLVLVTGCVSMGKIGDIEIFRITQTTFVSL----------QNAAPNEDKI-SEVRKLLNSGTF 129
Cdd:pfam02383    1 YGILGLIRLLSG----YYLIVITKREQVGQIGGHPIYKITDVEFIPLnsslsdtqlaKKEHPDEERLlKLLKLFLSSGSF 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    130 YFAhtnasasasgassYRFDITLCAQRRQQTQET------DNRFFWNRMMHIHLMRFGIDCQSWLLQAMCGSVEVRTVYI 203
Cdd:pfam02383   77 YFS-------------YDYDLTNSLQRNLTRSRSpsfdslDDRFFWNRHLLKPLIDFQLDLDRWILPLIQGFVEQGKLSV 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    204 GAKQARAAIISRLSCERAGTRFNVRGTNDEGYVANFVETEQVIYV-----DGDVTSYVQTRGSVPLFWEQPGVQVGSHKV 278
Cdd:pfam02383  144 FGRSVTLTLISRRSRKRAGTRYLRRGIDDDGNVANFVETEQIVSLntsnsEGKIFSFVQIRGSIPLFWSQDPNLKYKPKI 223

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18497296    279 KLSRgFETSAAAFDRHMSMMRQRYGYQTVVNllgssLVGSKEGEAMLSNEFQRH---HGMSAHKDVPHVVFDYHQECR 353
Cdd:pfam02383  224 QITR-PEATQPAFKKHFDDLIERYGPVHIVN-----LVEKKGRESKLSEAYEEAvkyLNQFLPDKLRYTAFDFHHECK 295
DUF1866 pfam08952
Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known ...
 862-1008 3.09e-73

Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known function.


Pssm-ID: 286093  Cd Length: 146  Bit Score: 239.71  E-value: 3.09e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    862 DAEIMEIDQQRRRAVFEQVIRDLGPPDSTIVVHVLEssatGDEDGPTIYDENVMSALITELSKMGEVTLVRYVEDTMWVT 941
Cdd:pfam08952    1 DVEIQEVDPEARRRVFKEVIRDQGPPDGTIVVSLCS----GDLDEKNIFDENLMDELIQELTSFGEVTLVRFVEDTMWVT 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18497296    942 FRDGESALNASSKKSIQVCGLDLILELKSKDWQHLVDSEIELCTTNTIPL--CANPVEHAQLLQAITPE 1008
Cdd:pfam08952   77 FRDGHSALNALSKDGMKVCGRALKIRLKSKDWIKGLEEEIILCTDNTIPVspCANSTLLAEDFDFGSPD 145
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
507-881 1.01e-66

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 233.14  E-value: 1.01e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  507 RILLPSNMLHAPTTVLRELCKRYTEYVRprmARVAVGTYNVNGGkhfrsiVFKDSLADWLLdchalarskalvdvnnPSE 586
Cdd:COG5411    2 PVPIYDPRHPYIVAVLRQRRSKYVIEKD---VSIFVSTFNPPGK------PPKASTKRWLF----------------PEI 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  587 NVDHPVDIYAIGFEEIVDLNASNIMAAstDNAKLWAEELQKTIS------RDNDYVLLTYQQLVGVCLYIYIRPEHAPHI 660
Cdd:COG5411   57 EATELADLYVVGLQEVVELTPGSILSA--DPYDRLRIWESKVLDclngaqSDEKYSLLRSPQLGGILLRVFSLATNLPVV 134

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  661 RDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGD 740
Cdd:COG5411  135 KPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDHDTIFWLGD 214

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  741 FNYRIDMEKDELKECVRNGD--LSTVLEFDQLRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRV 818
Cdd:COG5411  215 LNYRVTSTNEEVRPEIASDDgrLDKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRI 294

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18497296  819 LWRrrkalaegdfaASAWNPG--KLIHygrsELKQSDHRPVIAIIDAEIMEIDQQRRRAVFEQVI 881
Cdd:COG5411  295 LYK-----------SEQLTPHsySSIP----HLMISDHRPVYATFRAKIKVVDPSKKEGLIEKLY 344
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 635-876 3.48e-49

Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 185.88  E-value: 3.48e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   635 YVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAE--RNA 712
Cdd:PLN03191  364 YVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRNA 443

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   713 DYAEITRKLAFP------MGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQEAGNVFGEFLEG 786
Cdd:PLN03191  444 DVYEIIRRTRFSsvldtdQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEG 523

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   787 EITFDPTYKYDLFSDDY-----DTSEKQRAPAWTDRVLWrrrkaLAEGDfaasawnpgKLIHYGRSELKQSDHRPVIAII 861
Cdd:PLN03191  524 PIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILW-----LGKGI---------KQLCYKRSEIRLSDHRPVSSMF 589

                         250
                  ....*....|....*.
gi 18497296   862 DAEIMEIDQQR-RRAV 876
Cdd:PLN03191  590 LVEVEVFDHRKlQRAL 605
RRM_SYNJ1 cd12719
RNA recognition motif (RRM) found in synaptojanin-1 and similar proteins; This subgroup ...
 888-969 1.06e-33

RNA recognition motif (RRM) found in synaptojanin-1 and similar proteins; This subgroup corresponds to the RRM of synaptojanin-1, also termed synaptojanin, or synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1, originally identified as one of the major Grb2-binding proteins that may participate in synaptic vesicle endocytosis. It also acts as a Src homology 3 (SH3) domain-binding brain-specific inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p, a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2. Synaptojanin-1 has two tissue-specific alternative splicing isoforms, synaptojanin-145 expressed in brain and synaptojanin-170 expressed in peripheral tissues. Synaptojanin-145 is very abundant in nerve terminals and may play an essential role in the clathrin-mediated endocytosis of synaptic vesicles. In contrast to synaptojanin-145, synaptojanin-170 contains three unique asparagine-proline-phenylalanine (NPF) motifs in the C-terminal region and may functions as a potential binding partner for Eps15, a clathrin coat-associated protein acting as a major substrate for the tyrosine kinase activity of the epidermal growth factor receptor.


Pssm-ID: 410118  Cd Length: 77  Bit Score: 124.44  E-value: 1.06e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  888 DSTIVVHVLESSATgdedgPTIYDENVMSALITELSKMGEVTLVRYVEDTMWVTFRDGESALNASSKKSIQVCGLDLILE 967
Cdd:cd12719    1 DGTVVVSVLSSSPE-----PNYFDDNLIDALLQQFSSFGEVILIRFVEDKMWVTFLEGSSALAALSLNGTEVLGRTIIIS 75


                 ..
gi 18497296  968 LK 969
Cdd:cd12719   76 LK 77
 
Name Accession Description Interval E-value
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 538-863 0e+00

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This subfamily contains the INPP5c domains of two human synaptojanins, synaptojanin 1 (Synj1) and synaptojanin 2 (Synj2), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs). They belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, Synjs contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25 (a mitochondrial outer membrane protein). Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197323 [Multi-domain]  Cd Length: 328  Bit Score: 641.36  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  538 ARVAVGTYNVNGGKHFRSIVFKD-SLADWLLD-CHALARSKalvdvnNPSENVDHPVDIYAIGFEEIVDLNASNIMAAST 615
Cdd:cd09089    1 LRVFVGTWNVNGGKHFRSIAFKHqSMTDWLLDnPKLAGQCS------NDSEEDEKPVDIFAIGFEEMVDLNASNIVSAST 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  616 DNAKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCF 695
Cdd:cd09089   75 TNQKEWGEELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCF 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  696 VCAHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQE 775
Cdd:cd09089  155 VCSHFAAGQSQVKERNEDFAEIARKLSFPMGRTLDSHDYVFWCGDFNYRIDLPNDEVKELVRNGDWLKLLEFDQLTKQKA 234

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  776 AGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRKALAEGDF------AASAWNPGKLIHYGRSEL 849
Cdd:cd09089  235 AGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPSDKTEeslvetNDPTWNPGTLLYYGRAEL 314

                        330
                 ....*....|....
gi 18497296  850 KQSDHRPVIAIIDA 863
Cdd:cd09089  315 KTSDHRPVVAIIDI 328
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 539-862 3.71e-164

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This subfamily contains the INPP5c domains of human synaptojanin 1 (Synj1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro.


Pssm-ID: 197332  Cd Length: 336  Bit Score: 491.09  E-value: 3.71e-164
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  539 RVAVGTYNVNGGKHFRSIVFKD-SLADWLLDCHALARSKALVDVNNpsenvdHPVDIYAIGFEEIVDLNASNIMAASTDN 617
Cdd:cd09098    2 RVCVGTWNVNGGKQFRSIAFKNqTLTDWLLDAPKKAGIPEFQDVRS------KPVDIFAIGFEEMVELNAGNIVSASTTN 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  618 AKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVC 697
Cdd:cd09098   76 QKLWAAELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVC 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  698 AHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQEAG 777
Cdd:cd09098  156 SHFAAGQSQVKERNEDFIEIARKLSFPMGRMLFSHDYVFWCGDFNYRIDIPNEEVKELIRQQNWDSLIAGDQLINQKNAG 235

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  778 NVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRK----------ALAEGDFAASA-----WNPGKLI 842
Cdd:cd09098  236 QVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKwpfdrsaedlDLLNASFPDNSkeqytWSPGTLL 315

                        330       340
                 ....*....|....*....|
gi 18497296  843 HYGRSELKQSDHRPVIAIID 862
Cdd:cd09098  316 HYGRAELKTSDHRPVVALID 335
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 539-862 2.68e-144

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This subfamily contains the INPP5c domains of human synaptojanin 2 (Synj2) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj2 can hydrolyze phosphatidylinositol diphosphate (PIP2) to phosphatidylinositol phosphate (PIP). In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro. Synj2 occurs as multiple alternative splice variants in various tissues. These variants share the INPP5c domain and the Sac1 domain. Synj2A is recruited to the mitochondria via its interaction with OMP25, a mitochondrial outer membrane protein. Synj2B is found at nerve terminals in the brain and at the spermatid manchette in testis. Synj2B undergoes further alternative splicing to give 2B1 and 2B2. In clathrin-mediated endocytosis, Synj2 participates in the formation of clathrin-coated pits, and perhaps also in vesicle decoating. Rac1 GTPase regulates the intracellular localization of Synj2 forms, but not Synj1. Synj2 may contribute to the role of Rac1 in cell migration and invasion, and is a potential target for therapeutic intervention in malignant tumors.


Pssm-ID: 197333  Cd Length: 336  Bit Score: 439.07  E-value: 2.68e-144
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  539 RVAVGTYNVNGGKHFRSIVFKDS-LADWLLDchalarSKALVDVNNPSENVDHPVDIYAIGFEEIVDLNASNIMAASTDN 617
Cdd:cd09099    2 RVAMGTWNVNGGKQFRSNILGTSeLTDWLLD------SPKLSGTPDFQDDESNPPDIFAVGFEEMVELSAGNIVNASTTN 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  618 AKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVC 697
Cdd:cd09099   76 RKMWGEQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFIC 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  698 AHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQEAG 777
Cdd:cd09099  156 SHLTAGQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDWKKLLEFDQLQLQKSSG 235

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  778 NVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRK----------ALAEGDFAASA-----WNPGKLI 842
Cdd:cd09099  236 KIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKwpfektageiNLLDSDLDFDTkirhtWTPGALM 315

                        330       340
                 ....*....|....*....|
gi 18497296  843 HYGRSELKQSDHRPVIAIID 862
Cdd:cd09099  316 YYGRAELQASDHRPVLAIVE 335
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 539-863 4.61e-103

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae Inp51p, Inp52p, and Inp53p, and related proteins; This subfamily contains the INPP5c domain of three Saccharomyces cerevisiae synaptojanin-like inositol polyphosphate 5-phosphatases (INP51, INP52, and INP53), Schizosaccharomyces pombe synaptojanin (SPsynaptojanin), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In addition to this INPP5c domain, these proteins have an N-terminal catalytic Sac1-like domain (found in other proteins including the phophoinositide phosphatase Sac1p), and a C-terminal proline-rich domain (PRD). The Sac1 domain allows Inp52p and Inp53p to recognize and dephosphorylate a wider range of substrates including PI3P, PI4P, and PI(3,5)P2. The Sac1 domain of Inp51p is non-functional. Disruption of any two of INP51, INP52, and INP53, in S. cerevisiae leads to abnormal vacuolar and plasma membrane morphology. During hyperosmotic stress, Inp52p and Inp53p localize at actin patches, where they may facilitate the hydrolysis of PI(4,5)P2, and consequently promote actin rearrangement to regulate cell growth. SPsynaptojanin is also active against a range of soluble and lipid inositol phosphates, including I(1,4,5)P3, I(1,3,4,5)P4, I(1,4,5,6)P4, PI(4,5)P2, and PIP3. Transformation of S. cerevisiae with a plasmid expressing the SPsynaptojanin 5-phosphatase domain rescues inp51/inp52/inp53 triple-mutant strains.


Pssm-ID: 197324  Cd Length: 291  Bit Score: 327.76  E-value: 4.61e-103
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  539 RVAVGTYNVNGGkhfrsiVFKDSLADWLLdchalarskalvdvnnPSENvDHPVDIYAIGFEEIVDLNASNIMAASTDNA 618
Cdd:cd09090    2 NIFVGTFNVNGK------SYKDDLSSWLF----------------PEEN-DELPDIVVIGLQEVVELTAGQILNSDPSKS 58

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  619 KLWAEELQKTISR--DNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFV 696
Cdd:cd09090   59 SFWEKKIKTTLNGrgGEKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFV 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  697 CAHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQEA 776
Cdd:cd09090  139 TSHLAAGLTNYEERNNDYKTIARGLRFSRGRTIKDHDHVIWLGDFNYRISLTNEDVRRFILNGKLDKLLEYDQLNQQMNA 218

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  777 GNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRrrkalaegdfaasawnpGKLIH---YGRSELKQSD 853
Cdd:cd09090  219 GEVFPGFSEGPITFPPTYKYDKGTDNYDTSEKQRIPAWTDRILYR-----------------GENLRqlsYNSAPLRFSD 281

                        330
                 ....*....|
gi 18497296  854 HRPVIAIIDA 863
Cdd:cd09090  282 HRPVYATFEA 291
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 539-860 1.33e-102

Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate 5-phosphatases (5-phosphatases) are signal-modifying enzymes, which hydrolyze the 5-phosphate from the inositol ring of specific 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), such as PI(4,5)P2, PI(3,4,5)P3, PI(3,5)P2, I(1,4,5)P3, and I(1,3,4,5)P4. These enzymes are Mg2+-dependent, and belong to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In addition to this INPP5c domain, 5-phosphatases often contain additional domains and motifs, such as the SH2 domain, the Sac-1 domain, the proline-rich domain (PRD), CAAX, RhoGAP (RhoGTPase-activating protein), and SKICH [SKIP (skeletal muscle- and kidney-enriched inositol phosphatase) carboxyl homology] domains, that are important for protein-protein interactions and/or for the subcellular localization of these enzymes. 5-phosphatases incorporate into large signaling complexes, and regulate diverse cellular processes including postsynaptic vesicular trafficking, insulin signaling, cell growth and survival, and endocytosis. Loss or gain of function of 5-phosphatases is implicated in certain human diseases. This family also contains a functionally unrelated nitric oxide transport protein, Cimex lectularius (bedbug) nitrophorin, which catalyzes a heme-assisted S-nitrosation of a proximal thiolate; the heme however binds at a site distinct from the active site of the 5-phosphatases.


Pssm-ID: 197308 [Multi-domain]  Cd Length: 299  Bit Score: 326.60  E-value: 1.33e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  539 RVAVGTYNVNGGkhfrsIVFKDSLADWLldchalarskalvdvnnpSENVDHPVDIYAIGFEEIVDLNASNIMAASTDNA 618
Cdd:cd09074    2 KIFVVTWNVGGG-----ISPPENLENWL------------------SPKGTEAPDIYAVGVQEVDMSVQGFVGNDDSAKA 58

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  619 KLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRD--VAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFV 696
Cdd:cd09074   59 REWVDNIQEALNEKENYVLLGSAQLVGIFLFVFVKKEHLPQIKDleVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFV 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  697 CAHFAAGQSQVAERNADYAEITRKLAFPMG----RTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRK 772
Cdd:cd09074  139 NSHLAAGQEEVERRNQDYRDILSKLKFYRGdpaiDSIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDLDDLLEKDQLKK 218

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  773 EQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRkalaegdfaasAWNPGKLIHYGRSEL-KQ 851
Cdd:cd09074  219 QKEKGKVFDGFQELPITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYKSK-----------AGSEIQPLSYTSVPLyKT 287


                 ....*....
gi 18497296  852 SDHRPVIAI 860
Cdd:cd09074  288 SDHKPVRAT 296
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 536-865 1.55e-98

Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+)-sensitive enzymes.


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 315.83  E-value: 1.55e-98
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     536 RMARVAVGTYNVNGGkhFRSivfKDSLADWLLDchalarskalvdvnNPSENVDHPVDIYAIGFEEIVDLNASNIMAAST 615
Cdd:smart00128    1 RDIKVLIGTWNVGGL--ESP---KVDVTSWLFQ--------------KIEVKQSEKPDIYVIGLQEVVGLAPGVILETIA 61

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     616 DNAKLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCF 695
Cdd:smart00128   62 GKERLWSDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCF 141

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     696 VCAHFAAGQSQVAERNADYAEITRKLAFPMGRTL--KSHDWVFWCGDFNYRIDME-KDELKECVRNGDLSTVLEFDQLRK 772
Cdd:smart00128  142 VNSHLAAGASNVEQRNQDYKTILRALSFPERALLsqFDHDVVFWFGDLNFRLDSPsYEEVRRKISKKEFDDLLEKDQLNR 221

                           250       260       270       280       290       300       310       320
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     773 EQEAGNVFGEFLEGEITFDPTYKYDLF-SDDYDTSEKQRAPAWTDRVLWRRrkalaegdfaaSAWNPGKL-IHYGRSELK 850
Cdd:smart00128  222 QREAGKVFKGFQEGPITFPPTYKYDSVgTETYDTSEKKRVPAWCDRILYRS-----------NGPELIQLsEYHSGMEIT 290

                           330
                    ....*....|....*
gi 18497296     851 QSDHRPVIAIIDAEI 865
Cdd:smart00128  291 TSDHKPVFATFRLKV 305
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 539-862 1.53e-95

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol polyphosphate 5-phosphatase I, Oculocerebrorenal syndrome of Lowe 1, and related proteins; This subfamily contains the INPP5c domain of type II inositol polyphosphate 5-phosphatase I (INPP5B), Oculocerebrorenal syndrome of Lowe 1 (OCRL-1), and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5B and OCRL1 preferentially hydrolyze the 5-phosphate of phosphatidylinositol (4,5)- bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)- trisphosphate [PI(3,4,5)P3]. INPP5B can also hydrolyze soluble inositol (1,4,5)-trisphosphate [I(1,4,5)P3] and inositol (1,3,4,5)-tetrakisphosphate [I(1,3,4,5)P4]. INPP5B participates in the endocytic pathway and in the early secretory pathway. In the latter, it may function in retrograde ERGIC (ER-to-Golgi intermediate compartment)-to-ER transport; it binds specific RAB proteins within the secretory pathway. In the endocytic pathway, it binds RAB5 and during endocytosis, may function in a RAB5-controlled cascade for converting PI(3,4,5)P3 to phosphatidylinositol 3-phosphate (PI3P). This cascade may link growth factor signaling and membrane dynamics. Mutation in OCRL1 is implicated in Lowe syndrome, an X-linked recessive multisystem disorder, which includes defects in eye, brain, and kidney function, and in Type 2 Dent's disease, a disorder with only the renal symptoms. OCRL-1 may have a role in membrane trafficking within the endocytic pathway and at the trans-Golgi network, and may participate in actin dynamics or signaling from endomembranes. OCRL1 and INPP5B have overlapping functions: deletion of both 5-phosphatases in mice is embryonic lethal, deletion of OCRL1 alone has no phenotype, and deletion of Inpp5b alone has only a mild phenotype (male sterility). Several of the proteins that interact with OCRL1 also bind INPP5B, for examples, inositol polyphosphate phosphatase interacting protein of 27kDa (IPIP27)A and B (also known as Ses1 and 2), and endocytic signaling adaptor APPL1. OCRL1, but not INPP5B, binds clathrin heavy chain, the plasma membrane AP2 adaptor subunit alpha-adaptin. In addition to this INPP5c domain, most proteins in this subfamily have a C-terminal RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain.


Pssm-ID: 197327  Cd Length: 292  Bit Score: 307.32  E-value: 1.53e-95
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  539 RVAVGTYNVNGGKHfrsivfKDSLADWLldchalarskalvdvnNPSENvdhPVDIYAIGFEEIvDLNASNIMAASTDNA 618
Cdd:cd09093    2 RIFVGTWNVNGQSP------DESLRPWL----------------SCDEE---PPDIYAIGFQEL-DLSAEAFLFNDSSRE 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  619 KLWAEELQKTISRDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVCA 698
Cdd:cd09093   56 QEWVKAVERGLHPDAKYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNS 135

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  699 HFAAGQSQVAERNADYAEITRKLAFPMG----RTLKSHDWVFWCGDFNYRIDM-EKDELKECVRNGDLSTVLEFDQLRKE 773
Cdd:cd09093  136 HLAAHMEEVERRNQDYKDICARMKFEDPdgppLSISDHDVVFWLGDLNYRIQElPTEEVKELIEKNDLEELLKYDQLNIQ 215

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  774 QEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRrrkalaEGDFaasawnpgKLIHYGRS-ELKQS 852
Cdd:cd09093  216 RRAGKVFEGFTEGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILWR------GTNI--------VQLSYRSHmELKTS 281

                        330
                 ....*....|
gi 18497296  853 DHRPVIAIID 862
Cdd:cd09093  282 DHKPVSALFD 291
COG5329 COG5329
Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];
61-493 1.86e-90

Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];


Pssm-ID: 227637 [Multi-domain]  Cd Length: 570  Bit Score: 303.54  E-value: 1.86e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   61 YGCLGALQLNAGEstvlFLVLVTGCVSMGKIGDIEIFRITQTTFVSL-QNAAPNE--------DKISEVRKLLNSGTFYF 131
Cdd:COG5329   61 YGVIGLIKLKGDI----YLIVITGASLVGVIPGHSIYKILDVDFISLnNNKWDDEleedeanyDKLSELKKLLSNGTFYF 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  132 AhtnasasasgassYRFDITLCAQRRQQTQET------DNRFFWNRMM------HI-HLMRFGIDCQSWLLQAMCGSVEV 198
Cdd:COG5329  137 S-------------YDFDITNSLQKNLSEGLEasvdraDLIFMWNSFLleefinHRsKLSSLEKQFDNFLTTVIRGFAET 203

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  199 RTVYIGAKQARAAIISRLSCERAGTRFNVRGTNDEGYVANFVETEQVIYVDGDVTSYVQTRGSVPLFWEQpGVQVGSHKV 278
Cdd:COG5329  204 VDIKVGGNTISLTLISRRSSERAGTRYLSRGIDDDGNVSNFVETEQIVTDSQYIFSFTQVRGSIPLFWEQ-SNLLYGPKI 282

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  279 KLSRGFETSAAAFDRHMSMMRQRYGYQTVVNLLgsslvGSKEGEAMLSNEFQRHHGMSAHKDVPHVVFDYHQECRGGNFS 358
Cdd:COG5329  283 KVTRSSEAAQSAFDKHFDKLREKYGDVYVVNLL-----KTKGYEAPLLELYEKHLDLSKKPKIHYTEFDFHKETSQDGFD 357

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  359 ALAKLKERIVACGANYGVFHA--SNGQVLREQFGVVRTNCLDCLDRTNCVQTYLGLdtlgIQLEALKMGGKQQNI-SRFE 435
Cdd:COG5329  358 DVKKLLYLIEQDLLEFGYFAYdiNEGKSISEQDGVFRTNCLDCLDRTNVIQSLISR----VLLEQFRSEGVISDGySPFL 433

                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18497296  436 EIFRQMWINNGNEVSKIYAGTGAIQG----------GSKLMDGARSAARTIQNNLLDNSKQEAIDVLL 493
Cdd:COG5329  434 QIHRELWADNGDAISRLYTGTGALKSsftrrgrrsfAGALNDFIKSFSRYYINNFTDGQRQDAIDLLL 501
Syja_N pfam02383
SacI homology domain; This Pfam family represents a protein domain which shows homology to the ...
 61-353 2.82e-82

SacI homology domain; This Pfam family represents a protein domain which shows homology to the yeast protein SacI. The SacI homology domain is most notably found at the amino terminal of the inositol 5'-phosphatase synaptojanin.


Pssm-ID: 460545  Cd Length: 295  Bit Score: 270.98  E-value: 2.82e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296     61 YGCLGALQLNAGestvLFLVLVTGCVSMGKIGDIEIFRITQTTFVSL----------QNAAPNEDKI-SEVRKLLNSGTF 129
Cdd:pfam02383    1 YGILGLIRLLSG----YYLIVITKREQVGQIGGHPIYKITDVEFIPLnsslsdtqlaKKEHPDEERLlKLLKLFLSSGSF 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    130 YFAhtnasasasgassYRFDITLCAQRRQQTQET------DNRFFWNRMMHIHLMRFGIDCQSWLLQAMCGSVEVRTVYI 203
Cdd:pfam02383   77 YFS-------------YDYDLTNSLQRNLTRSRSpsfdslDDRFFWNRHLLKPLIDFQLDLDRWILPLIQGFVEQGKLSV 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    204 GAKQARAAIISRLSCERAGTRFNVRGTNDEGYVANFVETEQVIYV-----DGDVTSYVQTRGSVPLFWEQPGVQVGSHKV 278
Cdd:pfam02383  144 FGRSVTLTLISRRSRKRAGTRYLRRGIDDDGNVANFVETEQIVSLntsnsEGKIFSFVQIRGSIPLFWSQDPNLKYKPKI 223

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18497296    279 KLSRgFETSAAAFDRHMSMMRQRYGYQTVVNllgssLVGSKEGEAMLSNEFQRH---HGMSAHKDVPHVVFDYHQECR 353
Cdd:pfam02383  224 QITR-PEATQPAFKKHFDDLIERYGPVHIVN-----LVEKKGRESKLSEAYEEAvkyLNQFLPDKLRYTAFDFHHECK 295
DUF1866 pfam08952
Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known ...
 862-1008 3.09e-73

Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known function.


Pssm-ID: 286093  Cd Length: 146  Bit Score: 239.71  E-value: 3.09e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296    862 DAEIMEIDQQRRRAVFEQVIRDLGPPDSTIVVHVLEssatGDEDGPTIYDENVMSALITELSKMGEVTLVRYVEDTMWVT 941
Cdd:pfam08952    1 DVEIQEVDPEARRRVFKEVIRDQGPPDGTIVVSLCS----GDLDEKNIFDENLMDELIQELTSFGEVTLVRFVEDTMWVT 76

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18497296    942 FRDGESALNASSKKSIQVCGLDLILELKSKDWQHLVDSEIELCTTNTIPL--CANPVEHAQLLQAITPE 1008
Cdd:pfam08952   77 FRDGHSALNALSKDGMKVCGRALKIRLKSKDWIKGLEEEIILCTDNTIPVspCANSTLLAEDFDFGSPD 145
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 593-863 1.96e-68

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate 5-phosphatase J and related proteins; INPP5c domain of Inositol polyphosphate-5-phosphatase J (INPP5J), also known as PIB5PA or PIPP, and related proteins. This subfamily belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5J hydrolyzes PI(4,5)P2, I(1,4,5)P3, and I(1,3,4,5)P4 at ruffling membranes. These proteins contain a C-terminal, SKIP carboxyl homology domain (SKICH), which may direct plasma membrane ruffle localization.


Pssm-ID: 197328  Cd Length: 300  Bit Score: 232.26  E-value: 1.96e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  593 DIYAIGFEEIvdlnASNIMAASTDNAK--LWAEELQKTISrDNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKT 670
Cdd:cd09094   33 DIYIIGLQEV----NSKPVQFVSDLIFddPWSDLFMDILS-PKGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRT 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  671 GLGGATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAERNADYAEITRKLAFPMGRT--LKSHDWVFWCGDFNYRI-DM 747
Cdd:cd09094  108 GLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQVFNECNTpsILDHDYVFWFGDLNFRIeDV 187

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  748 EKDELKECVRNGDLSTVLEFDQLRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWrRRKALA 827
Cdd:cd09094  188 SIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILW-KVNPDA 266

                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 18497296  828 EGDFAASAWNPGKLIHYgrSELKQSDHRPVIAIIDA 863
Cdd:cd09094  267 STEEKFLSITQTSYKSH--MEYGISDHKPVTAQFRL 300
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
507-881 1.01e-66

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 233.14  E-value: 1.01e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  507 RILLPSNMLHAPTTVLRELCKRYTEYVRprmARVAVGTYNVNGGkhfrsiVFKDSLADWLLdchalarskalvdvnnPSE 586
Cdd:COG5411    2 PVPIYDPRHPYIVAVLRQRRSKYVIEKD---VSIFVSTFNPPGK------PPKASTKRWLF----------------PEI 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  587 NVDHPVDIYAIGFEEIVDLNASNIMAAstDNAKLWAEELQKTIS------RDNDYVLLTYQQLVGVCLYIYIRPEHAPHI 660
Cdd:COG5411   57 EATELADLYVVGLQEVVELTPGSILSA--DPYDRLRIWESKVLDclngaqSDEKYSLLRSPQLGGILLRVFSLATNLPVV 134

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  661 RDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAERNADYAEITRKLAFPMGRTLKSHDWVFWCGD 740
Cdd:COG5411  135 KPVSGTVKKTGFGGSSSNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDHDTIFWLGD 214

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  741 FNYRIDMEKDELKECVRNGD--LSTVLEFDQLRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRV 818
Cdd:COG5411  215 LNYRVTSTNEEVRPEIASDDgrLDKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRI 294

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18497296  819 LWRrrkalaegdfaASAWNPG--KLIHygrsELKQSDHRPVIAIIDAEIMEIDQQRRRAVFEQVI 881
Cdd:COG5411  295 LYK-----------SEQLTPHsySSIP----HLMISDHRPVYATFRAKIKVVDPSKKEGLIEKLY 344
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 536-862 5.81e-57

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol polyphosphate-5-phosphatase E and related proteins; INPP5c domain of Inositol polyphosphate-5-phosphatase E (also called type IV or 72 kDa 5-phosphatase), rat pharbin, and related proteins. This subfamily belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. INPP5E hydrolyzes the 5-phosphate from PI(3,5)P2, PI(4,5)P2 and PI(3,4,5)P3, forming PI3P, PI4P, and PI(3,4)P2, respectively. It is a very potent PI(3,4,5)P3 5-phosphatase. Its intracellular localization is chiefly cytosolic, with pronounced perinuclear/Golgi localization. INPP5E also has an N-terminal proline rich domain (PRD) and a C-terminal CAAX motif. This protein is expressed in a variety of tissues, including the breast, brain, testis, and haemopoietic cells. It is differentially expressed in several cancers, for example, it is up-regulated in cervical cancer and down-regulated in stomach cancer. It is a candidate target for therapeutics of obesity and related disorders, as it is expressed in the hypothalamus, and following insulin stimulation, it undergoes tyrosine phosphorylation, associates with insulin receptor substrate-1, -2, and PI3-kinase, and become active as a 5-phosphatase. INPP5E may play a role, along with other 5-phosphatases SHIP2 and SKIP, in regulating glucose homoeostasis and energy metabolism. Mice deficient in INPPE5 develop a multi-organ disorder associated with structural defects of the primary cilium.


Pssm-ID: 197329  Cd Length: 298  Bit Score: 199.57  E-value: 5.81e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  536 RMARVAVGTYNVNGGKHFrsivfKDSLADWLLdchalarskalvdvnnpSENVDHPVDIYAIGFEEivdlnasnimaaST 615
Cdd:cd09095    3 RNVGIFVATWNMQGQKEL-----PENLDDFLL-----------------PTSADFAQDIYVIGVQE------------GC 48

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  616 DNAKLWAEELQKTISrdNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCF 695
Cdd:cd09095   49 SDRREWEIRLQETLG--PSHVLLHSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLF 126

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  696 VCAHFAAGQSQVAERNADYAEITRKLAFP-----------MGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNG---DL 761
Cdd:cd09095  127 ITSHFTSGDGKVKERVLDYNKIIQALNLPrnvptnpykseSGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQGqevDV 206

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  762 STVLEFDQLRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRAPAWTDRVLWRRRKAlaegdfaasawNPGKL 841
Cdd:cd09095  207 SALLQHDQLTREMSKGSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRQK-----------GDVCC 275

                        330       340
                 ....*....|....*....|..
gi 18497296  842 IHYGR-SELKQSDHRPVIAIID 862
Cdd:cd09095  276 LKYNScPSIKTSDHRPVFALFR 297
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 635-876 3.48e-49

Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 185.88  E-value: 3.48e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   635 YVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAE--RNA 712
Cdd:PLN03191  364 YVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRNA 443

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   713 DYAEITRKLAFP------MGRTLKSHDWVFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLRKEQEAGNVFGEFLEG 786
Cdd:PLN03191  444 DVYEIIRRTRFSsvldtdQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEG 523

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296   787 EITFDPTYKYDLFSDDY-----DTSEKQRAPAWTDRVLWrrrkaLAEGDfaasawnpgKLIHYGRSELKQSDHRPVIAII 861
Cdd:PLN03191  524 PIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILW-----LGKGI---------KQLCYKRSEIRLSDHRPVSSMF 589

                         250
                  ....*....|....*.
gi 18497296   862 DAEIMEIDQQR-RRAV 876
Cdd:PLN03191  590 LVEVEVFDHRKlQRAL 605
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 540-859 1.43e-42

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol 5-phosphatase-2 and related proteins; This subfamily contains the INPP5c domain of SHIP2 (SH2 domain containing inositol 5-phosphatase-2, also called INPPL1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. SHIP2 catalyzes the dephosphorylation of the PI, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]. SHIP2 is widely expressed, most prominently in brain, heart and in skeletal muscle. SHIP2 is an inhibitor of the insulin signaling pathway. It is implicated in actin structure remodeling, cell adhesion and cell spreading, receptor endocytosis and degradation, and in the JIP1-mediated JNK pathway. Its interacting partners include filamin/actin, p130Cas, Shc, Vinexin, Interesectin 1, and c-Jun NH2-terminal kinase (JNK)-interacting protein 1 (JIP1). A large variety of extracellular stimuli appear to lead to the tyrosine phosphorylation of SHIP2, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin, macrophage colony-stimulating factor (M-CSF) and hepatocyte growth factor (HGF). SHIP2 is localized to the cytosol in quiescent cells; following growth factor stimulation and /or cell adhesion, it relocalizes to membrane ruffles. In addition to this INPP5c domain, SHIP2 has an N-terminal SH2 domain, a C-terminal proline-rich domain (PRD), which includes a WW-domain binding motif (PPLP), an NPXY motif and a sterile alpha motif (SAM) domain. The gene encoding SHIP2 is a candidate for conferring a predisposition for type 2 diabetes; it has been suggested that suppression of SHIP2 may be of benefit in the treatment of obesity and thereby prevent type 2 diabetes. SHIP2 and SHIP1 have little overlap in their in vivo functions.


Pssm-ID: 197335  Cd Length: 304  Bit Score: 158.21  E-value: 1.43e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  540 VAVGTYNVNggkhfrSIVFKDSLADWLLdchalarSKALVDVNNPSeNVDHPVDIYAIGFEEivdlnasnimaaSTDNAK 619
Cdd:cd09101    3 IFIGTWNMG------SVPPPKSLASWLT-------SRGLGKTLDET-TVTIPHDIYVFGTQE------------NSVGDR 56

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  620 LWAEELQKTISR--DNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFVC 697
Cdd:cd09101   57 EWVDFLRASLKEltDIDYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVN 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  698 AHFAAGQSQVAERNADYAEITRKLAFPmGRTLKSHDW------VFWCGDFNYRIDMEKDELKECVRNGDLSTVLEFDQLR 771
Cdd:cd09101  137 CHLTSGNEKTHRRNQNYLDILRSLSLG-DKQLNAFDIslrfthLFWFGDLNYRLDMDIQEILNYITRKEFDPLLAVDQLN 215

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  772 KEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRA-------PAWTDRVLWrrrKALAEGDFAASAwnpgklihY 844
Cdd:cd09101  216 LEREKNKVFLRFREEEISFPPTYRYERGSRDTYMWQKQKTtgmrtnvPSWCDRILW---KSYPETHIVCNS--------Y 284

                        330
                 ....*....|....*.
gi 18497296  845 G-RSELKQSDHRPVIA 859
Cdd:cd09101  285 GcTDDIVTSDHSPVFG 300
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 591-863 4.62e-39

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and -2, and related proteins; This subfamily contains the INPP5c domain of SHIP1 (SH2 domain containing inositol polyphosphate 5-phosphatase-1, also known as SHIP/INPP5D), and SHIP2 (also known as INPPL1). It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Both SHIP1 and -2 catalyze the dephosphorylation of the PI, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], to phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]. SHIP1 also converts inositol-1,3,4,5- polyphosphate [I(1,3,4,5)P4] to inositol-1,3,4-polyphosphate [I(1,3,4)P3]. SHIP1 and SHIP2 have little overlap in their in vivo functions. SHIP1 is a negative regulator of cell growth and plays a major part in mediating the inhibitory signaling in B cells; it is predominantly expressed in hematopoietic cells. SHIP2 is as an inhibitor of the insulin signaling pathway, and is implicated in actin structure remodeling, cell adhesion and cell spreading, receptor endocytosis and degradation, and in the JIP1-mediated JNK pathway. SHIP2 is widely expressed, most prominently in brain, heart and in skeletal muscle. In addition to this INPP5c domain, SHIP1 has an N-terminal SH2 domain, two NPXY motifs, and a C-terminal proline-rich region (PRD), while SHIP2 has an N-terminal SH2 domain, a C-terminal proline-rich domain (PRD), which includes a WW-domain binding motif (PPLP), an NPXY motif, and a sterile alpha motif (SAM) domain. The gene encoding SHIP2 is a candidate gene for conferring a predisposition for type 2 diabetes.


Pssm-ID: 197325  Cd Length: 307  Bit Score: 148.17  E-value: 4.62e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  591 PVDIYAIGFEEivdlnasnimaaSTDNAKLWAEELQKTISR--DNDYVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCV 668
Cdd:cd09091   40 PHDIYVIGTQE------------DPLGEKEWLDLLRHSLKEltSLDYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSV 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  669 KTGLGGATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAERNADYAEITRKLAFPmGRTLKSHDW------VFWCGDFN 742
Cdd:cd09091  108 KTGIANTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQNYLNILRFLSLG-DKKLSAFNIthrfthLFWLGDLN 186

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  743 YRIDMEKDELKECV---RNGDLSTVLEFDQLRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRA-------P 812
Cdd:cd09091  187 YRLDLPIQEAENIIqkiEQQQFEPLLRHDQLNLEREEHKVFLRFSEEEITFPPTYRYERGSRDTYAYTKQKAtgvkynlP 266

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 18497296  813 AWTDRVLWrrrKALAEGDFAASAwnpgklihYG-RSELKQSDHRPVIAIIDA 863
Cdd:cd09091  267 SWCDRILW---KSYPETHIICQS--------YGcTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 540-863 5.12e-37

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing inositol polyphosphate 5-phosphatase-1 and related proteins; This subfamily contains the INPP5c domain of SHIP1 (SH2 domain containing inositol polyphosphate 5-phosphatase-1, also known as SHIP/INPP5D) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. SHIP1's enzymic activity is restricted to phosphatidylinositol 3,4,5-trisphosphate [PI (3,4,5)P3] and inositol-1,3,4,5- polyphosphate [I(1,3,4,5)P4]. It converts these two phosphoinositides to phosphatidylinositol 3,4-bisphosphate [PI (3,4)P2] and inositol-1,3,4-polyphosphate [I(1,3,4)P3], respectively. SHIP1 is a negative regulator of cell growth and plays a major part in mediating the inhibitory signaling in B cells; it is predominantly expressed in hematopoietic cells. In addition to this INPP5c domain, SHIP1 has an N-terminal SH2 domain, two NPXY motifs, and a C-terminal proline-rich region (PRD). SHIP1's phosphorylated NPXY motifs interact with proteins with phosphotyrosine binding (PTB) domains, and facilitate the translocation of SHIP1 to the plasma membrane to hydrolyze PI(3,4,5)P3. SHIP1 generally acts to oppose the activity of phosphatidylinositol 3-kinase (PI3K). It acts as a negative signaling molecule, reducing the levels of PI(3,4,5)P3, thereby removing the latter as a membrane-targeting signal for PH domain-containing effector molecules. SHIP1 may also, in certain contexts, amplify PI3K signals. SHIP1 and SHIP2 have little overlap in their in vivo functions.


Pssm-ID: 197334  Cd Length: 307  Bit Score: 142.05  E-value: 5.12e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  540 VAVGTYNVNGGKHFRSIvfkdslADWLLdCHALARSKalvdvnnpSENVDH-PVDIYAIGFEEivdlnasnimaaSTDNA 618
Cdd:cd09100    3 IFIGTWNMGNAPPPKKI------TSWFQ-CKGQGKTR--------DDTADYiPHDIYVIGTQE------------DPLGE 55

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  619 KLWAEELQKTISRDND--YVLLTYQQLVGVCLYIYIRPEHAPHIRDVAIDCVKTGLGGATGNKGACAIRFVLHGTSMCFV 696
Cdd:cd09100   56 KEWLDTLKHSLREITSisFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFV 135

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  697 CAHFAAGQSQVAERNADYAEITRKLAF------PMGRTLK-SHdwVFWCGDFNYRIDM---EKDELKECVRNGDLSTVLE 766
Cdd:cd09100  136 NSHLTSGSEKKLRRNQNYFNILRFLVLgdkklsPFNITHRfTH--LFWLGDLNYRVELpntEAENIIQKIKQQQYQELLP 213

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  767 FDQLRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYDTSEKQRA-------PAWTDRVLWRRRkalaegdfaasawnpg 839
Cdd:cd09100  214 HDQLLIERKESKVFLQFEEEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWKSY---------------- 277

                        330       340       350
                 ....*....|....*....|....*....|
gi 18497296  840 KLIH-----YG-RSELKQSDHRPVIAIIDA 863
Cdd:cd09100  278 PLVHvvcqsYGcTDDITTSDHSPVFATFEV 307
RRM_SYNJ1 cd12719
RNA recognition motif (RRM) found in synaptojanin-1 and similar proteins; This subgroup ...
 888-969 1.06e-33

RNA recognition motif (RRM) found in synaptojanin-1 and similar proteins; This subgroup corresponds to the RRM of synaptojanin-1, also termed synaptojanin, or synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1, originally identified as one of the major Grb2-binding proteins that may participate in synaptic vesicle endocytosis. It also acts as a Src homology 3 (SH3) domain-binding brain-specific inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p, a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2. Synaptojanin-1 has two tissue-specific alternative splicing isoforms, synaptojanin-145 expressed in brain and synaptojanin-170 expressed in peripheral tissues. Synaptojanin-145 is very abundant in nerve terminals and may play an essential role in the clathrin-mediated endocytosis of synaptic vesicles. In contrast to synaptojanin-145, synaptojanin-170 contains three unique asparagine-proline-phenylalanine (NPF) motifs in the C-terminal region and may functions as a potential binding partner for Eps15, a clathrin coat-associated protein acting as a major substrate for the tyrosine kinase activity of the epidermal growth factor receptor.


Pssm-ID: 410118  Cd Length: 77  Bit Score: 124.44  E-value: 1.06e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  888 DSTIVVHVLESSATgdedgPTIYDENVMSALITELSKMGEVTLVRYVEDTMWVTFRDGESALNASSKKSIQVCGLDLILE 967
Cdd:cd12719    1 DGTVVVSVLSSSPE-----PNYFDDNLIDALLQQFSSFGEVILIRFVEDKMWVTFLEGSSALAALSLNGTEVLGRTIIIS 75


                 ..
gi 18497296  968 LK 969
Cdd:cd12719   76 LK 77
RRM_SYNJ cd12440
RNA recognition motif (RRM) found in synaptojanin-1, synaptojanin-2 and similar proteins; This ...
 888-969 9.43e-13

RNA recognition motif (RRM) found in synaptojanin-1, synaptojanin-2 and similar proteins; This subfamily corresponds to the RRM of two active phosphatidylinositol phosphate phosphatases, synaptojanin-1 and synaptojanin-2. They have different interaction partners and are likely to have different biological functions. Synaptojanin-1 was originally identified as one of the major Grb2-binding proteins that may participate in synaptic vesicle endocytosis. It also acts as a Src homology 3 (SH3) domain-binding brain-specific inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Synaptojanin-2 is a ubiquitously expressed homolog of synaptojanin-1. It is a novel Rac1 effector regulating the early step of clathrin-mediated endocytosis. Synaptojanin-2 directly and specifically interacts with Rac1 in a GTP-dependent manner. It mediates the inhibitory effect of Rac1 on endocytosis and plays an important role in the Rac1-mediated control of cell growth. Both, synaptojanin-1 and synaptojanin-2, have two tissue-specific alternative splicing isoforms, a shorter isoform expressed in brain and a longer isoform in peripheral tissues. Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p, a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2. Synaptojanin-2 shows high sequence homology to the N-terminal Sac1p homology domain, the central inositol 5-phosphatase domain, the putative RNA recognition motif (RRM) of synaptojanin-1, but differs in the proline-rich region.


Pssm-ID: 409874 [Multi-domain]  Cd Length: 77  Bit Score: 64.76  E-value: 9.43e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  888 DSTIVVHVLESSATGDEDgptiyDENVMSALITELSKMGEVTLVRYVEDTMWVTFRDGESALNASSKKSIQVCGLDLILE 967
Cdd:cd12440    1 DATVVVSLDSKSEEWNEF-----EDALIGELLRVLASYGDVVLVRFAHEGMLVTFRDGRSALAALALNGKQILGRTLKIR 75


                 ..
gi 18497296  968 LK 969
Cdd:cd12440   76 LK 77
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 609-857 6.89e-08

Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes the catalytic domain (exonuclease/endonuclease/phosphatase or EEP domain) of a diverse set of proteins including the ExoIII family of apurinic/apyrimidinic (AP) endonucleases, inositol polyphosphate 5-phosphatases (INPP5), neutral sphingomyelinases (nSMases), deadenylases (such as the vertebrate circadian-clock regulated nocturnin), bacterial cytolethal distending toxin B (CdtB), deoxyribonuclease 1 (DNase1), the endonuclease domain of the non-LTR retrotransposon LINE-1, and related domains. These diverse enzymes share a common catalytic mechanism of cleaving phosphodiester bonds; their substrates range from nucleic acids to phospholipids and perhaps proteins.


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 54.79  E-value: 6.89e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  609 NI-MAASTDNAKLWAEE----------LQKTISRDNDYVLLTyQQLVGVCLYIYIRPEHAPHIRDVAI-------DCVKT 670
Cdd:cd08372    5 NVnGLNAATRASGIARWvreldpdivcLQEVKDSQYSAVALN-QLLPEGYHQYQSGPSRKEGYEGVAIlsktpkfKIVEK 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  671 GLG----GATGNKGACAIRFVLHGTSMCFVCAHFAAGQSQVAERNADYAEITRKLAFpmgRTLKSHDWVFWCGDFNYRId 746
Cdd:cd08372   84 HQYkfgeGDSGERRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVLEFLKR---LRQPNSAPVVICGDFNVRP- 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  747 mekdelkecvRNGDLSTvlefdqlRKEQEAGNVFGEFLEGEITFDPTYKYDLFSDDYdtsekqraPAWTDRVLWrrRKAL 826
Cdd:cd08372  160 ----------SEVDSEN-------PSSMLRLFVALNLVDSFETLPHAYTFDTYMHNV--------KSRLDYIFV--SKSL 212

                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 18497296  827 aegdfaasawnpgkLIHYGRSELKQ--------SDHRPV 857
Cdd:cd08372  213 --------------LPSVKSSKILSdaararipSDHYPI 237
RRM_SYNJ2 cd12720
RNA recognition motif (RRM) found in synaptojanin-2 and similar proteins; This subgroup ...
 888-961 5.20e-05

RNA recognition motif (RRM) found in synaptojanin-2 and similar proteins; This subgroup corresponds to the RRM of synaptojanin-2, also termed synaptic inositol-1,4,5-trisphosphate 5-phosphatase 2, an ubiquitously expressed central regulatory enzyme in the phosphoinositide-signaling cascade. As a novel Rac1 effector regulating the early step of clathrin-mediated endocytosis, synaptojanin-2 acts as a polyphosphoinositide phosphatase directly and specifically interacting with Rac1 in a GTP-dependent manner. It mediates the inhibitory effect of Rac1 on endocytosis and plays an important role in the Rac1-mediated control of cell growth. Synaptojanin-2 shows high sequence homology to the N-terminal Sac1p homology domain, the central inositol 5-phosphatase domain, the putative RNA recognition motif (RRM) of synaptojanin-1, but differs in the proline-rich region.


Pssm-ID: 410119 [Multi-domain]  Cd Length: 78  Bit Score: 42.85  E-value: 5.20e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18497296  888 DSTIVVHVLESSATGDEDGPtiydENVMSALITELSKMGEVTLVRYVEDTMWVTFRDGESALNASSKKSIQVCG 961
Cdd:cd12720    1 DATVVVNLLSPTLEEKNDFP----EDLSTELVQCFQSYGTVILVRFNRGQMLVTFEDSRSALRVLDLDGIKVNG 70
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 677-819 3.52e-04

Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I (INPP5A) hydrolyzes the 5-phosphate from inositol 1,3,4,5-tetrakisphosphate [I(1,3,4,5)P4] and inositol 1,4,5-trisphosphate [I(1,4,5)P3]. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. As the substrates of INPP5A mobilize intracellular calcium ions, INPP5A is a calcium signal-terminating enzyme. In platelets, phosphorylated pleckstrin binds and activates INPP5A in a 1:1 complex, and accelerates the degradation of the calcium ion-mobilizing I(1,4,5)P3.


Pssm-ID: 197326  Cd Length: 383  Bit Score: 44.38  E-value: 3.52e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  677 GNKGACAIRFVLHGTSMCFVCAHFAAGQSQVA---ERNADYAEITRK-LAFPMGR-TLKSHDWV--FWCGDFNYRIDME- 748
Cdd:cd09092  153 SRKGFMRTRWKINNCVFDLVNIHLFHDASNLAaceSSPSVYSQNRHRaLGYVLERlTDERFEKVpfFVFGDFNFRLDTKs 232

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18497296  749 ---------------KDELKECVRN------GDLSTVLE--------FDQ-----------LRKEQEAGNVFGEFLEGEI 788
Cdd:cd09092  233 vvetlcakatmqtvrKADSNIVVKLefrekdNDNKVVLQiekkkfdyFNQdvfrdnngkalLKFDKELEVFKDVLYELDI 312

                        170       180       190
                 ....*....|....*....|....*....|....
gi 18497296  789 TFDPTYKYdlfSDDYDTSE---KQRAPAWTDRVL 819
Cdd:cd09092  313 SFPPSYPY---SEDPEQGTqymNTRCPAWCDRIL 343
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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