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Conserved domains on  [gi|2462611117|ref|XP_054212657|]
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synaptojanin-2 isoform X8 [Homo sapiens]

Protein Classification

endonuclease/exonuclease/phosphatase family protein( domain architecture ID 1014753)

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

CATH:  3.60.10.10
EC:  3.1.-.-
Gene Ontology:  GO:0046872|GO:0016787|GO:0003677
PubMed:  10838565
SCOP:  4002213

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EEP super family cl00490
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 530-816 0e+00

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.


The actual alignment was detected with superfamily member cd09099:

Pssm-ID: 469791  Cd Length: 336  Bit Score: 650.16  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKQFRSNVLRTAELTDWLLDSPQLSGATDSQDD-SSPADIFAVGFEEMVELSAGNIVNASTTNKKMWG 608
Cdd:cd09099     1 TRVAMGTWNVNGGKQFRSNILGTSELTDWLLDSPKLSGTPDFQDDeSNPPDIFAVGFEEMVELSAGNIVNASTTNRKMWG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 609 EQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTA 688
Cdd:cd09099    81 EQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 689 GQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKD 768
Cdd:cd09099   161 GQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDWKKLLEFDQLQLQKSSGKIFKD 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 2462611117 769 FHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKT 816
Cdd:cd09099   241 FHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPFEKT 288
COG5329 super family cl34984
Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];
13-485 1.59e-93

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: 305.08  E-value: 1.59e-93
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  13 LGAEGDCSVLLEARGRDDCLLFEAGTVATLAPEEKEVIKGQYGKLTdAYGCLGELRLKSGgtslSFLVLVTGCTSVGRIP 92
Cdd:COG5329    14 IVSNNYALSFRRLGVKNSERILCATELVGVRFEPDEGFSSLSSAHK-IYGVIGLIKLKGD----IYLIVITGASLVGVIP 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  93 DAEIYKITATDFYPLQEEAKEEER---------LIALKKILSSGVFYFSWPndgsrFDLTVRTQKQGDD--SSEWGN--- 158
Cdd:COG5329    89 GHSIYKILDVDFISLNNNKWDDELeedeanydkLSELKKLLSNGTFYFSYD-----FDITNSLQKNLSEglEASVDRadl 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 159 SFFWNQLLHVPLRQH-------QVSCCDWLLKIICGVVTIRTVYASHKQAKACLVSRVSCERTGTRFHTRGVNDDGHVSN 231
Cdd:COG5329   164 IFMWNSFLLEEFINHrsklsslEKQFDNFLTTVIRGFAETVDIKVGGNTISLTLISRRSSERAGTRYLSRGIDDDGNVSN 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 232 FVETEQMIYMDDGVSSFVQIRGSVPLFWEQPGLQVGShHLRLHRGLEANAPAFDRHMVLLKEQYGQQVVVNLLGSRGGEE 311
Cdd:COG5329   244 FVETEQIVTDSQYIFSFTQVRGSIPLFWEQSNLLYGP-KIKVTRSSEAAQSAFDKHFDKLREKYGDVYVVNLLKTKGYEA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 312 VLNRAFKKLlwasCHAGDTPMIN---FDFHQFAK---GGKLEKLETLLRPQLklhwEDFDVFTKGEN--VSPRFQKGTLR 383
Cdd:COG5329   323 PLLELYEKH----LDLSKKPKIHyteFDFHKETSqdgFDDVKKLLYLIEQDL----LEFGYFAYDINegKSISEQDGVFR 394

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 384 MNCLDCLDRTNTVQSFIALEVLHLQLKTLGLSSkpIVDRFVESFKAMWSLNGHSLSKVFTGSRALEGKAK-------VGK 456
Cdd:COG5329   395 TNCLDCLDRTNVIQSLISRVLLEQFRSEGVISD--GYSPFLQIHRELWADNGDAISRLYTGTGALKSSFTrrgrrsfAGA 472

                         490       500
                  ....*....|....*....|....*....
gi 2462611117 457 LKDGARSMSRTIQSNFFDGVKQEAIKLLL 485
Cdd:COG5329   473 LNDFIKSFSRYYINNFTDGQRQDAIDLLL 501
 
Name Accession Description Interval E-value
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 530-816 0e+00

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: 650.16  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKQFRSNVLRTAELTDWLLDSPQLSGATDSQDD-SSPADIFAVGFEEMVELSAGNIVNASTTNKKMWG 608
Cdd:cd09099     1 TRVAMGTWNVNGGKQFRSNILGTSELTDWLLDSPKLSGTPDFQDDeSNPPDIFAVGFEEMVELSAGNIVNASTTNRKMWG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 609 EQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTA 688
Cdd:cd09099    81 EQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 689 GQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKD 768
Cdd:cd09099   161 GQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDWKKLLEFDQLQLQKSSGKIFKD 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 2462611117 769 FHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKT 816
Cdd:cd09099   241 FHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPFEKT 288
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 528-806 2.96e-101

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 316.60  E-value: 2.96e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  528 KRIRIAMGTWNVNGgkQFRSNVLrtaeLTDWLLDSPQlsgatdsQDDSSPADIFAVGFEEMVELSAGNIVNASTTNKKMW 607
Cdd:smart00128   1 RDIKVLIGTWNVGG--LESPKVD----VTSWLFQKIE-------VKQSEKPDIYVIGLQEVVGLAPGVILETIAGKERLW 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  608 GEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:smart00128  68 SDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLA 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  688 AGQSQVKERNEDYKEITQKLCFPMGR--NVFSHDYVFWCGDFNYRIDL-TYEEVFYFVKRQDWKKLLEFDQLQLQKSSGK 764
Cdd:smart00128 148 AGASNVEQRNQDYKTILRALSFPERAllSQFDHDVVFWFGDLNFRLDSpSYEEVRRKISKKEFDDLLEKDQLNRQREAGK 227

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 2462611117  765 IFKDFHEGAINFGPTYKYDV-GSAAYDTSDKCRTPAWTDRVLW 806
Cdd:smart00128 228 VFKGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILY 270
COG5329 COG5329
Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];
13-485 1.59e-93

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


Pssm-ID: 227637 [Multi-domain]  Cd Length: 570  Bit Score: 305.08  E-value: 1.59e-93
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  13 LGAEGDCSVLLEARGRDDCLLFEAGTVATLAPEEKEVIKGQYGKLTdAYGCLGELRLKSGgtslSFLVLVTGCTSVGRIP 92
Cdd:COG5329    14 IVSNNYALSFRRLGVKNSERILCATELVGVRFEPDEGFSSLSSAHK-IYGVIGLIKLKGD----IYLIVITGASLVGVIP 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  93 DAEIYKITATDFYPLQEEAKEEER---------LIALKKILSSGVFYFSWPndgsrFDLTVRTQKQGDD--SSEWGN--- 158
Cdd:COG5329    89 GHSIYKILDVDFISLNNNKWDDELeedeanydkLSELKKLLSNGTFYFSYD-----FDITNSLQKNLSEglEASVDRadl 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 159 SFFWNQLLHVPLRQH-------QVSCCDWLLKIICGVVTIRTVYASHKQAKACLVSRVSCERTGTRFHTRGVNDDGHVSN 231
Cdd:COG5329   164 IFMWNSFLLEEFINHrsklsslEKQFDNFLTTVIRGFAETVDIKVGGNTISLTLISRRSSERAGTRYLSRGIDDDGNVSN 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 232 FVETEQMIYMDDGVSSFVQIRGSVPLFWEQPGLQVGShHLRLHRGLEANAPAFDRHMVLLKEQYGQQVVVNLLGSRGGEE 311
Cdd:COG5329   244 FVETEQIVTDSQYIFSFTQVRGSIPLFWEQSNLLYGP-KIKVTRSSEAAQSAFDKHFDKLREKYGDVYVVNLLKTKGYEA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 312 VLNRAFKKLlwasCHAGDTPMIN---FDFHQFAK---GGKLEKLETLLRPQLklhwEDFDVFTKGEN--VSPRFQKGTLR 383
Cdd:COG5329   323 PLLELYEKH----LDLSKKPKIHyteFDFHKETSqdgFDDVKKLLYLIEQDL----LEFGYFAYDINegKSISEQDGVFR 394

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 384 MNCLDCLDRTNTVQSFIALEVLHLQLKTLGLSSkpIVDRFVESFKAMWSLNGHSLSKVFTGSRALEGKAK-------VGK 456
Cdd:COG5329   395 TNCLDCLDRTNVIQSLISRVLLEQFRSEGVISD--GYSPFLQIHRELWADNGDAISRLYTGTGALKSSFTrrgrrsfAGA 472

                         490       500
                  ....*....|....*....|....*....
gi 2462611117 457 LKDGARSMSRTIQSNFFDGVKQEAIKLLL 485
Cdd:COG5329   473 LNDFIKSFSRYYINNFTDGQRQDAIDLLL 501
Syja_N pfam02383
SacI homology domain; This Pfam family represents a protein domain which shows homology to the ...
 61-342 2.72e-83

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: 268.67  E-value: 2.72e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  61 YGCLGELRLKSGgtslSFLVLVTGCTSVGRIPDAEIYKITATDFYPL----------QEEAKEEERLIALKKI-LSSGVF 129
Cdd:pfam02383   1 YGILGLIRLLSG----YYLIVITKREQVGQIGGHPIYKITDVEFIPLnsslsdtqlaKKEHPDEERLLKLLKLfLSSGSF 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 130 YFSWpndgsRFDLTVRTQKQGDDSSEWGNS-----FFWNQLLHVPLRQHQVSCCDWLLKIICGVVTIRTVYASHKQAKAC 204
Cdd:pfam02383  77 YFSY-----DYDLTNSLQRNLTRSRSPSFDslddrFFWNRHLLKPLIDFQLDLDRWILPLIQGFVEQGKLSVFGRSVTLT 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 205 LVSRVSCERTGTRFHTRGVNDDGHVSNFVETEQMIYMDDG-----VSSFVQIRGSVPLFWEQPGLQVGSHHLRLHRgLEA 279
Cdd:pfam02383 152 LISRRSRKRAGTRYLRRGIDDDGNVANFVETEQIVSLNTSnsegkIFSFVQIRGSIPLFWSQDPNLKYKPKIQITR-PEA 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462611117 280 NAPAFDRHMVLLKEQYGQQVVVNLLGSRGGEEVLNRAFKKLLWAS--CHAGDTPMINFDFHQFAK 342
Cdd:pfam02383 231 TQPAFKKHFDDLIERYGPVHIVNLVEKKGRESKLSEAYEEAVKYLnqFLPDKLRYTAFDFHHECK 295
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
509-805 4.20e-73

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 247.00  E-value: 4.20e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 509 VTPRILKAMTERQSEFTNFKRIRIAMGTWNVNGGKqfrsnvlRTAELTDWLldSPqlsgatDSQDDSSPaDIFAVGFEEM 588
Cdd:COG5411     9 RHPYIVAVLRQRRSKYVIEKDVSIFVSTFNPPGKP-------PKASTKRWL--FP------EIEATELA-DLYVVGLQEV 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 589 VELSAGNIVNASTtnKKMWGEQLQKAIS------RSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKA 662
Cdd:COG5411    73 VELTPGSILSADP--YDRLRIWESKVLDclngaqSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSS 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 663 GNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFV 742
Cdd:COG5411   151 SNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDHDTIFWLGDLNYRVTSTNEEVRPEI 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462611117 743 KRQDWK--KLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVL 805
Cdd:COG5411   231 ASDDGRldKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRIL 295
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 620-809 5.62e-40

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 156.99  E-value: 5.62e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 620 RYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKE--RN 697
Cdd:PLN03191  363 KYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRN 442

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 698 EDYKEITQKLCFP------MGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKDFHE 771
Cdd:PLN03191  443 ADVYEIIRRTRFSsvldtdQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKE 522

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2462611117 772 GAINFGPTYKYDVGSAAY-----DTSDKCRTPAWTDRVLWWRK 809
Cdd:PLN03191  523 GPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGK 565
 
Name Accession Description Interval E-value
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 530-816 0e+00

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: 650.16  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKQFRSNVLRTAELTDWLLDSPQLSGATDSQDD-SSPADIFAVGFEEMVELSAGNIVNASTTNKKMWG 608
Cdd:cd09099     1 TRVAMGTWNVNGGKQFRSNILGTSELTDWLLDSPKLSGTPDFQDDeSNPPDIFAVGFEEMVELSAGNIVNASTTNRKMWG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 609 EQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTA 688
Cdd:cd09099    81 EQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTSFCFICSHLTA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 689 GQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKD 768
Cdd:cd09099   161 GQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDWKKLLEFDQLQLQKSSGKIFKD 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 2462611117 769 FHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKT 816
Cdd:cd09099   241 FHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPFEKT 288
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 530-817 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: 578.96  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKQFRSNVLRTAELTDWLLDSPQLSGA--TDSQDDSSPADIFAVGFEEMVELSAGNIVNASTTNKKMW 607
Cdd:cd09089     1 LRVFVGTWNVNGGKHFRSIAFKHQSMTDWLLDNPKLAGQcsNDSEEDEKPVDIFAIGFEEMVDLNASNIVSASTTNQKEW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 608 GEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:cd09089    81 GEELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHSTSLCFVCSHFA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 688 AGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFK 767
Cdd:cd09089   161 AGQSQVKERNEDFAEIARKLSFPMGRTLDSHDYVFWCGDFNYRIDLPNDEVKELVRNGDWLKLLEFDQLTKQKAAGNVFK 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462611117 768 DFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKTD 817
Cdd:cd09089   241 GFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPSDKTE 290
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 530-816 5.39e-162

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: 474.91  E-value: 5.39e-162
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKQFRSNVLRTAELTDWLLDSPQLSGATDSQD-DSSPADIFAVGFEEMVELSAGNIVNASTTNKKMWG 608
Cdd:cd09098     1 IRVCVGTWNVNGGKQFRSIAFKNQTLTDWLLDAPKKAGIPEFQDvRSKPVDIFAIGFEEMVELNAGNIVSASTTNQKLWA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 609 EQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTA 688
Cdd:cd09098    81 AELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTSLCFVCSHFAA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 689 GQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKD 768
Cdd:cd09098   161 GQSQVKERNEDFIEIARKLSFPMGRMLFSHDYVFWCGDFNYRIDIPNEEVKELIRQQNWDSLIAGDQLINQKNAGQVFRG 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 2462611117 769 FHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKT 816
Cdd:cd09098   241 FLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPFDRS 288
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 530-810 1.22e-120

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: 366.66  E-value: 1.22e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKqfrsnvLRTAELTDWLldspqlsgatdSQDDSSPADIFAVGFEEMVELSAGNIVNASTTNKKMWGE 609
Cdd:cd09074     1 VKIFVVTWNVGGGI------SPPENLENWL-----------SPKGTEAPDIYAVGVQEVDMSVQGFVGNDDSAKAREWVD 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 610 QLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRD--VAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:cd09074    64 NIQEALNEKENYVLLGSAQLVGIFLFVFVKKEHLPQIKDleVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVNSHLA 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 688 AGQSQVKERNEDYKEITQKLCFPMG----RNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSG 763
Cdd:cd09074   144 AGQEEVERRNQDYRDILSKLKFYRGdpaiDSIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDLDDLLEKDQLKKQKEKG 223

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 2462611117 764 KIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKK 810
Cdd:cd09074   224 KVFDGFQELPITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYKSKA 270
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 530-806 9.22e-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: 319.67  E-value: 9.22e-103
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGkqfrsnvLRTAELTDWLLDSpqlsgatdsqDDSSPADIFAVGFEEMVELSAGNIVNASTTNKKMWGE 609
Cdd:cd09090     1 INIFVGTFNVNGK-------SYKDDLSSWLFPE----------ENDELPDIVVIGLQEVVELTAGQILNSDPSKSSFWEK 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 610 QLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:cd09090    64 KIKTTLNGrgGEKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLA 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 688 AGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFK 767
Cdd:cd09090   144 AGLTNYEERNNDYKTIARGLRFSRGRTIKDHDHVIWLGDFNYRISLTNEDVRRFILNGKLDKLLEYDQLNQQMNAGEVFP 223

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 2462611117 768 DFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLW 806
Cdd:cd09090   224 GFSEGPITFPPTYKYDKGTDNYDTSEKQRIPAWTDRILY 262
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 528-806 2.96e-101

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 316.60  E-value: 2.96e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  528 KRIRIAMGTWNVNGgkQFRSNVLrtaeLTDWLLDSPQlsgatdsQDDSSPADIFAVGFEEMVELSAGNIVNASTTNKKMW 607
Cdd:smart00128   1 RDIKVLIGTWNVGG--LESPKVD----VTSWLFQKIE-------VKQSEKPDIYVIGLQEVVGLAPGVILETIAGKERLW 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  608 GEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:smart00128  68 SDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLA 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  688 AGQSQVKERNEDYKEITQKLCFPMGR--NVFSHDYVFWCGDFNYRIDL-TYEEVFYFVKRQDWKKLLEFDQLQLQKSSGK 764
Cdd:smart00128 148 AGASNVEQRNQDYKTILRALSFPERAllSQFDHDVVFWFGDLNFRLDSpSYEEVRRKISKKEFDDLLEKDQLNRQREAGK 227

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 2462611117  765 IFKDFHEGAINFGPTYKYDV-GSAAYDTSDKCRTPAWTDRVLW 806
Cdd:smart00128 228 VFKGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILY 270
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 530-806 6.59e-94

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: 296.53  E-value: 6.59e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGgkQFRSNVLRTaeltdWLldspqlsgatdsQDDSSPADIFAVGFEEmVELSAGNIVNASTTNKKMWGE 609
Cdd:cd09093     1 FRIFVGTWNVNG--QSPDESLRP-----WL------------SCDEEPPDIYAIGFQE-LDLSAEAFLFNDSSREQEWVK 60

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 610 QLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAG 689
Cdd:cd09093    61 AVERGLHPDAKYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAH 140

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 690 QSQVKERNEDYKEITQKLCFPMG----RNVFSHDYVFWCGDFNYRI-DLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGK 764
Cdd:cd09093   141 MEEVERRNQDYKDICARMKFEDPdgppLSISDHDVVFWLGDLNYRIqELPTEEVKELIEKNDLEELLKYDQLNIQRRAGK 220

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 2462611117 765 IFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLW 806
Cdd:cd09093   221 VFEGFTEGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILW 262
COG5329 COG5329
Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms];
13-485 1.59e-93

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


Pssm-ID: 227637 [Multi-domain]  Cd Length: 570  Bit Score: 305.08  E-value: 1.59e-93
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  13 LGAEGDCSVLLEARGRDDCLLFEAGTVATLAPEEKEVIKGQYGKLTdAYGCLGELRLKSGgtslSFLVLVTGCTSVGRIP 92
Cdd:COG5329    14 IVSNNYALSFRRLGVKNSERILCATELVGVRFEPDEGFSSLSSAHK-IYGVIGLIKLKGD----IYLIVITGASLVGVIP 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  93 DAEIYKITATDFYPLQEEAKEEER---------LIALKKILSSGVFYFSWPndgsrFDLTVRTQKQGDD--SSEWGN--- 158
Cdd:COG5329    89 GHSIYKILDVDFISLNNNKWDDELeedeanydkLSELKKLLSNGTFYFSYD-----FDITNSLQKNLSEglEASVDRadl 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 159 SFFWNQLLHVPLRQH-------QVSCCDWLLKIICGVVTIRTVYASHKQAKACLVSRVSCERTGTRFHTRGVNDDGHVSN 231
Cdd:COG5329   164 IFMWNSFLLEEFINHrsklsslEKQFDNFLTTVIRGFAETVDIKVGGNTISLTLISRRSSERAGTRYLSRGIDDDGNVSN 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 232 FVETEQMIYMDDGVSSFVQIRGSVPLFWEQPGLQVGShHLRLHRGLEANAPAFDRHMVLLKEQYGQQVVVNLLGSRGGEE 311
Cdd:COG5329   244 FVETEQIVTDSQYIFSFTQVRGSIPLFWEQSNLLYGP-KIKVTRSSEAAQSAFDKHFDKLREKYGDVYVVNLLKTKGYEA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 312 VLNRAFKKLlwasCHAGDTPMIN---FDFHQFAK---GGKLEKLETLLRPQLklhwEDFDVFTKGEN--VSPRFQKGTLR 383
Cdd:COG5329   323 PLLELYEKH----LDLSKKPKIHyteFDFHKETSqdgFDDVKKLLYLIEQDL----LEFGYFAYDINegKSISEQDGVFR 394

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 384 MNCLDCLDRTNTVQSFIALEVLHLQLKTLGLSSkpIVDRFVESFKAMWSLNGHSLSKVFTGSRALEGKAK-------VGK 456
Cdd:COG5329   395 TNCLDCLDRTNVIQSLISRVLLEQFRSEGVISD--GYSPFLQIHRELWADNGDAISRLYTGTGALKSSFTrrgrrsfAGA 472

                         490       500
                  ....*....|....*....|....*....
gi 2462611117 457 LKDGARSMSRTIQSNFFDGVKQEAIKLLL 485
Cdd:COG5329   473 LNDFIKSFSRYYINNFTDGQRQDAIDLLL 501
Syja_N pfam02383
SacI homology domain; This Pfam family represents a protein domain which shows homology to the ...
 61-342 2.72e-83

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: 268.67  E-value: 2.72e-83
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117  61 YGCLGELRLKSGgtslSFLVLVTGCTSVGRIPDAEIYKITATDFYPL----------QEEAKEEERLIALKKI-LSSGVF 129
Cdd:pfam02383   1 YGILGLIRLLSG----YYLIVITKREQVGQIGGHPIYKITDVEFIPLnsslsdtqlaKKEHPDEERLLKLLKLfLSSGSF 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 130 YFSWpndgsRFDLTVRTQKQGDDSSEWGNS-----FFWNQLLHVPLRQHQVSCCDWLLKIICGVVTIRTVYASHKQAKAC 204
Cdd:pfam02383  77 YFSY-----DYDLTNSLQRNLTRSRSPSFDslddrFFWNRHLLKPLIDFQLDLDRWILPLIQGFVEQGKLSVFGRSVTLT 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 205 LVSRVSCERTGTRFHTRGVNDDGHVSNFVETEQMIYMDDG-----VSSFVQIRGSVPLFWEQPGLQVGSHHLRLHRgLEA 279
Cdd:pfam02383 152 LISRRSRKRAGTRYLRRGIDDDGNVANFVETEQIVSLNTSnsegkIFSFVQIRGSIPLFWSQDPNLKYKPKIQITR-PEA 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462611117 280 NAPAFDRHMVLLKEQYGQQVVVNLLGSRGGEEVLNRAFKKLLWAS--CHAGDTPMINFDFHQFAK 342
Cdd:pfam02383 231 TQPAFKKHFDDLIERYGPVHIVNLVEKKGRESKLSEAYEEAVKYLnqFLPDKLRYTAFDFHHECK 295
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
509-805 4.20e-73

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 247.00  E-value: 4.20e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 509 VTPRILKAMTERQSEFTNFKRIRIAMGTWNVNGGKqfrsnvlRTAELTDWLldSPqlsgatDSQDDSSPaDIFAVGFEEM 588
Cdd:COG5411     9 RHPYIVAVLRQRRSKYVIEKDVSIFVSTFNPPGKP-------PKASTKRWL--FP------EIEATELA-DLYVVGLQEV 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 589 VELSAGNIVNASTtnKKMWGEQLQKAIS------RSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKA 662
Cdd:COG5411    73 VELTPGSILSADP--YDRLRIWESKVLDclngaqSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSS 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 663 GNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFV 742
Cdd:COG5411   151 SNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDHDTIFWLGDLNYRVTSTNEEVRPEI 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462611117 743 KRQDWK--KLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVL 805
Cdd:COG5411   231 ASDDGRldKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRIL 295
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 572-806 8.00e-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: 227.25  E-value: 8.00e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 572 QDDSSPADIFAVGFEEMVELSAGNIVNASTTNKkmWGEQLQKAISrSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAI 651
Cdd:cd09094    26 QSPEVAPDIYIIGLQEVNSKPVQFVSDLIFDDP--WSDLFMDILS-PKGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQT 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 652 DTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGR--NVFSHDYVFWCGDFNY 729
Cdd:cd09094   103 NYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILSTQVFNECNtpSILDHDYVFWFGDLNF 182

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462611117 730 RI-DLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLW 806
Cdd:cd09094   183 RIeDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILW 260
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 528-814 2.36e-59

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: 204.19  E-value: 2.36e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 528 KRIRIAMGTWNVNGGKQFRSNvlrtaeLTDWLLdspqlsgatdSQDDSSPADIFAVGFEEmvelsagnivnaSTTNKKMW 607
Cdd:cd09095     3 RNVGIFVATWNMQGQKELPEN------LDDFLL----------PTSADFAQDIYVIGVQE------------GCSDRREW 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 608 GEQLQKAISRSHryILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:cd09095    55 EIRLQETLGPSH--VLLHSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFT 132

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 688 AGQSQVKERNEDYKEITQKLCFPmgRNVFSHDY-------------VFWCGDFNYRIDLTYEEVFYFVKR---QDWKKLL 751
Cdd:cd09095   133 SGDGKVKERVLDYNKIIQALNLP--RNVPTNPYksesgdvttrfdeVFWFGDFNFRLSGPRHLVDALINQgqeVDVSALL 210

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462611117 752 EFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLwWRKKHPFD 814
Cdd:cd09095   211 QHDQLTREMSKGSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRIL-YRSRQKGD 272
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 530-812 2.23e-43

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: 159.73  E-value: 2.23e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVnggkqfrSNVLRTAELTDWLLDSPQlsGAT-DSQDDSSPADIFAVGFEEmvelsagnivnaSTTNKKMWG 608
Cdd:cd09091     1 ISIFIGTWNM-------GSAPPPKNITSWFTSKGQ--GKTrDDVADYIPHDIYVIGTQE------------DPLGEKEWL 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 609 EQLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHL 686
Cdd:cd09091    60 DLLRHSLKEltSLDYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHL 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 687 TAGQSQVKERNEDYKEITQKLCF---PMGRNVFSH--DYVFWCGDFNYRIDLTYEEVFYFVKR---QDWKKLLEFDQLQL 758
Cdd:cd09091   140 TSGSEKKLRRNQNYLNILRFLSLgdkKLSAFNITHrfTHLFWLGDLNYRLDLPIQEAENIIQKieqQQFEPLLRHDQLNL 219

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462611117 759 QKSSGKIFKDFHEGAINFGPTYKYDVGSA---AYD----TSDKCRTPAWTDRVLWwrKKHP 812
Cdd:cd09091   220 EREEHKVFLRFSEEEITFPPTYRYERGSRdtyAYTkqkaTGVKYNLPSWCDRILW--KSYP 278
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 530-812 4.15e-43

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: 159.00  E-value: 4.15e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVnggkqfrSNVLRTAELTDWLLDSPQlsGAT-DSQDDSSPADIFAVGFEEmvelsagnivnaSTTNKKMWG 608
Cdd:cd09100     1 ITIFIGTWNM-------GNAPPPKKITSWFQCKGQ--GKTrDDTADYIPHDIYVIGTQE------------DPLGEKEWL 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 609 EQLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHL 686
Cdd:cd09100    60 DTLKHSLREitSISFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSHL 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 687 TAGQSQVKERNEDYKEITQKLCF---PMGRNVFSH--DYVFWCGDFNYRIDL---TYEEVFYFVKRQDWKKLLEFDQLQL 758
Cdd:cd09100   140 TSGSEKKLRRNQNYFNILRFLVLgdkKLSPFNITHrfTHLFWLGDLNYRVELpntEAENIIQKIKQQQYQELLPHDQLLI 219

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462611117 759 QKSSGKIFKDFHEGAINFGPTYKYDVGSA---AYD----TSDKCRTPAWTDRVLWwrKKHP 812
Cdd:cd09100   220 ERKESKVFLQFEEEEITFAPTYRFERGTReryAYTkqkaTGMKYNLPSWCDRVLW--KSYP 278
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 530-812 4.95e-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: 155.90  E-value: 4.95e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 530 IRIAMGTWNVNGGKQFRSnvlrtaeLTDWLLdSPQLSGATDSQDDSSPADIFAVGFEEmvelsagnivnaSTTNKKMWGE 609
Cdd:cd09101     1 ISIFIGTWNMGSVPPPKS-------LASWLT-SRGLGKTLDETTVTIPHDIYVFGTQE------------NSVGDREWVD 60

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 610 QLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLT 687
Cdd:cd09101    61 FLRASLKEltDIDYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLT 140

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 688 AGQSQVKERNEDYKEITQKLCFPMGR-NVFS----HDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSS 762
Cdd:cd09101   141 SGNEKTHRRNQNYLDILRSLSLGDKQlNAFDislrFTHLFWFGDLNYRLDMDIQEILNYITRKEFDPLLAVDQLNLEREK 220

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462611117 763 GKIFKDFHEGAINFGPTYKYDVGS-------AAYDTSDKCRTPAWTDRVLWwrKKHP 812
Cdd:cd09101   221 NKVFLRFREEEISFPPTYRYERGSrdtymwqKQKTTGMRTNVPSWCDRILW--KSYP 275
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 620-809 5.62e-40

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 156.99  E-value: 5.62e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 620 RYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKE--RN 697
Cdd:PLN03191  363 KYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRN 442

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 698 EDYKEITQKLCFP------MGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKDFHE 771
Cdd:PLN03191  443 ADVYEIIRRTRFSsvldtdQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKE 522

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 2462611117 772 GAINFGPTYKYDVGSAAY-----DTSDKCRTPAWTDRVLWWRK 809
Cdd:PLN03191  523 GPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGK 565
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 611-805 1.71e-10

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: 62.11  E-value: 1.71e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 611 LQKAISrSHRYILLTSAQLVGVCLYIFVRPYHVP-------FIRD--VAIDTVKTGMGGKA--GNKGAVGIRFQFHSTSF 679
Cdd:cd08372    32 LQEVKD-SQYSAVALNQLLPEGYHQYQSGPSRKEgyegvaiLSKTpkFKIVEKHQYKFGEGdsGERRAVVVKFDVHDKEL 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462611117 680 CFICSHLTAGQSQVKERNEDYKEITQKLcfpMGRNVFSHDYVFWCGDFNYRIDLTYEEVfyfvkrqdWKKLLEFdqlqlq 759
Cdd:cd08372   111 CVVNAHLQAGGTRADVRDAQLKEVLEFL---KRLRQPNSAPVVICGDFNVRPSEVDSEN--------PSSMLRL------ 173

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 2462611117 760 KSSGKiFKDFHEgAINFGPTYKydvgsaaydtSDKCRTPAWTDRVL 805
Cdd:cd08372   174 FVALN-LVDSFE-TLPHAYTFD----------TYMHNVKSRLDYIF 207
 
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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