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Conserved domains on  [gi|6324507|ref|NP_014576|]
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phosphoinositide 5-phosphatase INP54 [Saccharomyces cerevisiae S288C]

Protein Classification

COG5411 family protein( domain architecture ID 11475066)

COG5411 family protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
1-371 5.31e-153

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


:

Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 439.60  E-value: 5.31e-153
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    1 MNKTNWKVSVTTFNCGKEFPVENSKAIVKQLLFPYddgISQLELQDLYVLGFQEVVPIWQGSFPAVN-RDLIDRITTTAV 79
Cdd:COG5411  21 RSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPE---IEATELADLYVVGLQEVVELTPGSILSADpYDRLRIWESKVL 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   80 NCLNEKvsatQGDEQYSCLGVNSLGAITIIVLYNNNALKVKDDILKRNGKCGWFGTHLKggtlisfQMTRNGEENWERFS 159
Cdd:COG5411  98 DCLNGA----QSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSN-------KGAVAIRFNYERTS 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  160 YICAHLNANEGVNNRNQRIDDYKRIMSEVCDS---EVAKSDHFFFLGDLNFRVTSTYDPTTNYSSTTTlRRLLENHEELN 236
Cdd:COG5411 167 FCFVNSHLAAGVNNIEERIFDYRSIASNICFSrglRIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDD-GRLDKLFEYDQ 245

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  237 LLRKGEDEPLCKGFQELKITFPPTYKFKLFEKETYNTK--RIPSWCDRILYKSYAvptfAQEGTYHSVPRsnaLLFSDHQ 314
Cdd:COG5411 246 LLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDkgRIPSWTDRILYKSEQ----LTPHSYSSIPH---LMISDHR 318

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324507  315 PVNLTVRLPRSTGTPVPLSLHIEKYPLSWSSGLIGQIG----DAVIGYCGWLVTKNVHYWI 371
Cdd:COG5411 319 PVYATFRAKIKVVDPSKKEGLIEKLYAEYKTELGEAGDiscdNFTILVLYGHVDGKIAIFS 379
 
Name Accession Description Interval E-value
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
1-371 5.31e-153

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 439.60  E-value: 5.31e-153
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    1 MNKTNWKVSVTTFNCGKEFPVENSKAIVKQLLFPYddgISQLELQDLYVLGFQEVVPIWQGSFPAVN-RDLIDRITTTAV 79
Cdd:COG5411  21 RSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPE---IEATELADLYVVGLQEVVELTPGSILSADpYDRLRIWESKVL 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   80 NCLNEKvsatQGDEQYSCLGVNSLGAITIIVLYNNNALKVKDDILKRNGKCGWFGTHLKggtlisfQMTRNGEENWERFS 159
Cdd:COG5411  98 DCLNGA----QSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSN-------KGAVAIRFNYERTS 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  160 YICAHLNANEGVNNRNQRIDDYKRIMSEVCDS---EVAKSDHFFFLGDLNFRVTSTYDPTTNYSSTTTlRRLLENHEELN 236
Cdd:COG5411 167 FCFVNSHLAAGVNNIEERIFDYRSIASNICFSrglRIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDD-GRLDKLFEYDQ 245

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  237 LLRKGEDEPLCKGFQELKITFPPTYKFKLFEKETYNTK--RIPSWCDRILYKSYAvptfAQEGTYHSVPRsnaLLFSDHQ 314
Cdd:COG5411 246 LLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDkgRIPSWTDRILYKSEQ----LTPHSYSSIPH---LMISDHR 318

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324507  315 PVNLTVRLPRSTGTPVPLSLHIEKYPLSWSSGLIGQIG----DAVIGYCGWLVTKNVHYWI 371
Cdd:COG5411 319 PVYATFRAKIKVVDPSKKEGLIEKLYAEYKTELGEAGDiscdNFTILVLYGHVDGKIAIFS 379
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 4-325 4.72e-101

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 301.58  E-value: 4.72e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507       4 TNWKVSVTTFNCGKEFPvenSKAIVKQLLFPYDDgISQLELQDLYVLGFQEVVPIWQGSfpavnrdLIDRITTTAVNCLN 83
Cdd:smart00128   1 RDIKVLIGTWNVGGLES---PKVDVTSWLFQKIE-VKQSEKPDIYVIGLQEVVGLAPGV-------ILETIAGKERLWSD 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507      84 EKVSATQGDEQYSCLGVNSLGAITIIVLYNNNAL-KVKDDILKRNGKCGWFGTHLKGGTLISFQMTRNgeenweRFSYIC 162
Cdd:smart00128  70 LLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLvYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDT------SFCFVN 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507     163 AHLNAneGVNNRNQRIDDYKRIMSEVCDSEVAK-----SDHFFFLGDLNFRVTSTYDptTNYSSTTTLRRLLENHEELNL 237
Cdd:smart00128 144 SHLAA--GASNVEQRNQDYKTILRALSFPERALlsqfdHDVVFWFGDLNFRLDSPSY--EEVRRKISKKEFDDLLEKDQL 219

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507     238 LRKGEDEPLCKGFQELKITFPPTYKFKLFEKETYNT---KRIPSWCDRILYKSyAVPTFAQEGTYHSvprSNALLFSDHQ 314
Cdd:smart00128 220 NRQREAGKVFKGFQEGPITFPPTYKYDSVGTETYDTsekKRVPAWCDRILYRS-NGPELIQLSEYHS---GMEITTSDHK 295

                          330
                   ....*....|.
gi 6324507     315 PVNLTVRLPRS 325
Cdd:smart00128 296 PVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 6-322 7.06e-101

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: 300.79  E-value: 7.06e-101
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    6 WKVSVTTFNCGKEfpvENSKAIVKQLLFPYDDgisqlELQDLYVLGFQEVVPIWQGSFPAVNRDLIDRITTTAVNCLNEK 85
Cdd:cd09074   1 VKIFVVTWNVGGG---ISPPENLENWLSPKGT-----EAPDIYAVGVQEVDMSVQGFVGNDDSAKAREWVDNIQEALNEK 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   86 vsatqgdEQYSCLGVNSLGAITIIVLYNNNALKVKDDilkrngkCGWFGTHLKGG----TLISFQMTRNGEENWERFSYI 161
Cdd:cd09074  73 -------ENYVLLGSAQLVGIFLFVFVKKEHLPQIKD-------LEVEGVTVGTGgggkLGNKGGVAIRFQINDTSFCFV 138

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  162 CAHLNANEGvnNRNQRIDDYKRIMSEVCDSE-------VAKSDHFFFLGDLNFRVTSTYDPTTNYSSTTTLRRLLENHEE 234
Cdd:cd09074 139 NSHLAAGQE--EVERRNQDYRDILSKLKFYRgdpaidsIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDLDDLLEKDQL 216

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  235 LNLLRKGedePLCKGFQELKITFPPTYKFKLFEKETYNT--KRIPSWCDRILYKSYAvPTFAQEGTYHSVPRsnaLLFSD 312
Cdd:cd09074 217 KKQKEKG---KVFDGFQELPITFPPTYKFDPGTDEYDTSdkKRIPAWCDRILYKSKA-GSEIQPLSYTSVPL---YKTSD 289

                       330
                ....*....|
gi 6324507  313 HQPVNLTVRL 322
Cdd:cd09074 290 HKPVRATFRV 299
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 128-316 1.01e-12

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 69.55  E-value: 1.01e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   128 GKCGWFGThlKGGTLISFQMTRNgeenweRFSYICAHLNANEGVNNRNQRIDDYKRIM-----SEVCDSEVAKS----DH 198
Cdd:PLN03191 400 GLMGYMGN--KGSVSISMSLFQS------RLCFVCSHLTSGHKDGAEQRRNADVYEIIrrtrfSSVLDTDQPQTipshDQ 471

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   199 FFFLGDLNFRVTStydpttnysSTTTLRRL--------LENHEELNL-LRKGEdepLCKGFQELKITFPPTYKFKlFEKE 269
Cdd:PLN03191 472 IFWFGDLNYRLNM---------LDTEVRKLvaqkrwdeLINSDQLIKeLRSGH---VFDGWKEGPIKFPPTYKYE-INSD 538

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 6324507   270 TY--------NTKRIPSWCDRILYKSYAVptfAQEgtyhSVPRSNaLLFSDHQPV 316
Cdd:PLN03191 539 RYvgenpkegEKKRSPAWCDRILWLGKGI---KQL----CYKRSE-IRLSDHRPV 585
 
Name Accession Description Interval E-value
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
1-371 5.31e-153

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 439.60  E-value: 5.31e-153
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    1 MNKTNWKVSVTTFNCGKEFPVENSKAIVKQLLFPYddgISQLELQDLYVLGFQEVVPIWQGSFPAVN-RDLIDRITTTAV 79
Cdd:COG5411  21 RSKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPE---IEATELADLYVVGLQEVVELTPGSILSADpYDRLRIWESKVL 97

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   80 NCLNEKvsatQGDEQYSCLGVNSLGAITIIVLYNNNALKVKDDILKRNGKCGWFGTHLKggtlisfQMTRNGEENWERFS 159
Cdd:COG5411  98 DCLNGA----QSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSN-------KGAVAIRFNYERTS 166

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  160 YICAHLNANEGVNNRNQRIDDYKRIMSEVCDS---EVAKSDHFFFLGDLNFRVTSTYDPTTNYSSTTTlRRLLENHEELN 236
Cdd:COG5411 167 FCFVNSHLAAGVNNIEERIFDYRSIASNICFSrglRIYDHDTIFWLGDLNYRVTSTNEEVRPEIASDD-GRLDKLFEYDQ 245

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  237 LLRKGEDEPLCKGFQELKITFPPTYKFKLFEKETYNTK--RIPSWCDRILYKSYAvptfAQEGTYHSVPRsnaLLFSDHQ 314
Cdd:COG5411 246 LLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDkgRIPSWTDRILYKSEQ----LTPHSYSSIPH---LMISDHR 318

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6324507  315 PVNLTVRLPRSTGTPVPLSLHIEKYPLSWSSGLIGQIG----DAVIGYCGWLVTKNVHYWI 371
Cdd:COG5411 319 PVYATFRAKIKVVDPSKKEGLIEKLYAEYKTELGEAGDiscdNFTILVLYGHVDGKIAIFS 379
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 4-325 4.72e-101

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 301.58  E-value: 4.72e-101
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507       4 TNWKVSVTTFNCGKEFPvenSKAIVKQLLFPYDDgISQLELQDLYVLGFQEVVPIWQGSfpavnrdLIDRITTTAVNCLN 83
Cdd:smart00128   1 RDIKVLIGTWNVGGLES---PKVDVTSWLFQKIE-VKQSEKPDIYVIGLQEVVGLAPGV-------ILETIAGKERLWSD 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507      84 EKVSATQGDEQYSCLGVNSLGAITIIVLYNNNAL-KVKDDILKRNGKCGWFGTHLKGGTLISFQMTRNgeenweRFSYIC 162
Cdd:smart00128  70 LLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLvYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDT------SFCFVN 143

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507     163 AHLNAneGVNNRNQRIDDYKRIMSEVCDSEVAK-----SDHFFFLGDLNFRVTSTYDptTNYSSTTTLRRLLENHEELNL 237
Cdd:smart00128 144 SHLAA--GASNVEQRNQDYKTILRALSFPERALlsqfdHDVVFWFGDLNFRLDSPSY--EEVRRKISKKEFDDLLEKDQL 219

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507     238 LRKGEDEPLCKGFQELKITFPPTYKFKLFEKETYNT---KRIPSWCDRILYKSyAVPTFAQEGTYHSvprSNALLFSDHQ 314
Cdd:smart00128 220 NRQREAGKVFKGFQEGPITFPPTYKYDSVGTETYDTsekKRVPAWCDRILYRS-NGPELIQLSEYHS---GMEITTSDHK 295

                          330
                   ....*....|.
gi 6324507     315 PVNLTVRLPRS 325
Cdd:smart00128 296 PVFATFRLKVT 306
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 6-322 7.06e-101

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: 300.79  E-value: 7.06e-101
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    6 WKVSVTTFNCGKEfpvENSKAIVKQLLFPYDDgisqlELQDLYVLGFQEVVPIWQGSFPAVNRDLIDRITTTAVNCLNEK 85
Cdd:cd09074   1 VKIFVVTWNVGGG---ISPPENLENWLSPKGT-----EAPDIYAVGVQEVDMSVQGFVGNDDSAKAREWVDNIQEALNEK 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   86 vsatqgdEQYSCLGVNSLGAITIIVLYNNNALKVKDDilkrngkCGWFGTHLKGG----TLISFQMTRNGEENWERFSYI 161
Cdd:cd09074  73 -------ENYVLLGSAQLVGIFLFVFVKKEHLPQIKD-------LEVEGVTVGTGgggkLGNKGGVAIRFQINDTSFCFV 138

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  162 CAHLNANEGvnNRNQRIDDYKRIMSEVCDSE-------VAKSDHFFFLGDLNFRVTSTYDPTTNYSSTTTLRRLLENHEE 234
Cdd:cd09074 139 NSHLAAGQE--EVERRNQDYRDILSKLKFYRgdpaidsIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDLDDLLEKDQL 216

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  235 LNLLRKGedePLCKGFQELKITFPPTYKFKLFEKETYNT--KRIPSWCDRILYKSYAvPTFAQEGTYHSVPRsnaLLFSD 312
Cdd:cd09074 217 KKQKEKG---KVFDGFQELPITFPPTYKFDPGTDEYDTSdkKRIPAWCDRILYKSKA-GSEIQPLSYTSVPL---YKTSD 289

                       330
                ....*....|
gi 6324507  313 HQPVNLTVRL 322
Cdd:cd09074 290 HKPVRATFRV 299
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 7-322 1.33e-32

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: 123.99  E-value: 1.33e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    7 KVSVTTFN-CGKEFPVENSKaivkqLLFPyddgISQLELQDLYVLGFQEVVPIWQGSF----PAVNRDLIDRITTtavnC 81
Cdd:cd09090   2 NIFVGTFNvNGKSYKDDLSS-----WLFP----EENDELPDIVVIGLQEVVELTAGQIlnsdPSKSSFWEKKIKT----T 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   82 LNEkvsatQGDEQYSCLGVNSLGAITIIVLYNNNAL-KVK--DDILKRNGKCGWFGThlKGGTLISFQMTRNgeenweRF 158
Cdd:cd09090  69 LNG-----RGGEKYVLLRSEQLVGTALLFFVKESQLpKVKnvEGSTKKTGLGGMSGN--KGAVAIRFDYGDT------SF 135

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  159 SYICAHLNAneGVNNRNQRIDDYKRIMSEVCDSE---VAKSDHFFFLGDLNFRVTSTYDPTTNYSSTTTLRRLLENhEEL 235
Cdd:cd09090 136 CFVTSHLAA--GLTNYEERNNDYKTIARGLRFSRgrtIKDHDHVIWLGDFNYRISLTNEDVRRFILNGKLDKLLEY-DQL 212

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  236 NLLRK-GEDEPlckGFQELKITFPPTYKFKLFEKeTYNT---KRIPSWCDRILYKSYAVPTFAqegtYHSVPrsnaLLFS 311
Cdd:cd09090 213 NQQMNaGEVFP---GFSEGPITFPPTYKYDKGTD-NYDTsekQRIPAWTDRILYRGENLRQLS----YNSAP----LRFS 280

                       330
                ....*....|.
gi 6324507  312 DHQPVNLTVRL 322
Cdd:cd09090 281 DHRPVYATFEA 291
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 126-322 2.42e-25

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: 104.37  E-value: 2.42e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  126 RNGKCGWFGThlKGGTLISFQMtrngeeNWERFSYICAHLNANEgvNNRNQRIDDYKRIMS----EVCD-SEVAKSDHFF 200
Cdd:cd09094 106 RTGLGGYWGN--KGAVTVRFSL------YGHMICFLNCHLPAHM--EKWEQRIDDFETILStqvfNECNtPSILDHDYVF 175

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  201 FLGDLNFRVTSTydpttnysSTTTLRRLLeNHEELNLLRK-------GEDEPLCKGFQELKITFPPTYKFKLfEKETYNT 273
Cdd:cd09094 176 WFGDLNFRIEDV--------SIEFVRELV-NSKKYHLLLEkdqlnmaKRKEEAFQGFQEGPLNFAPTYKFDL-GTDEYDT 245

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 6324507  274 ---KRIPSWCDRILYKSYAVPTFAQE------GTYHSVPrsnALLFSDHQPVNLTVRL 322
Cdd:cd09094 246 sgkKRKPAWTDRILWKVNPDASTEEKflsitqTSYKSHM---EYGISDHKPVTAQFRL 300
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 46-316 4.34e-23

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: 97.77  E-value: 4.34e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   46 DLYVLGFQEVvpiwqgsfpavnrDLidrittTAVNCLNEKVSATQ-----------GDEQYSCLGVNSLGAITIIVLYNN 114
Cdd:cd09093  31 DIYAIGFQEL-------------DL------SAEAFLFNDSSREQewvkaverglhPDAKYKKVKLIRLVGMMLLVFVKK 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  115 nalKVKDDIlkRNGKCGWFGTHL------KGGTLISFQMtRNGEenwerFSYICAHLNAN-EGVNNRNQridDYKRIMSE 187
Cdd:cd09093  92 ---EHRQHI--KEVAAETVGTGImgkmgnKGGVAVRFQF-HNTT-----FCFVNSHLAAHmEEVERRNQ---DYKDICAR 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  188 V--CDSE-----VAKSDHFFFLGDLNFRVTstyDPTTN----YSSTTTLRRLLEnHEELNLLRKGEDepLCKGFQELKIT 256
Cdd:cd09093 158 MkfEDPDgpplsISDHDVVFWLGDLNYRIQ---ELPTEevkeLIEKNDLEELLK-YDQLNIQRRAGK--VFEGFTEGEIN 231

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6324507  257 FPPTYKF--KLFEKETYNTKRIPSWCDRILYKSYAVptfaQEGTYHSVPrsnALLFSDHQPV 316
Cdd:cd09093 232 FIPTYKYdpGTDNWDSSEKCRAPAWCDRILWRGTNI----VQLSYRSHM---ELKTSDHKPV 286
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 138-316 8.39e-23

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: 97.11  E-value: 8.39e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  138 KGGTLISFQMTrnGEEnwerFSYICAHLNANEGvnNRNQRIDDYKRI-----MSEVCDSEVAKS---------DHFFFLG 203
Cdd:cd09095 110 KGALAISFTFF--GTS----FLFITSHFTSGDG--KVKERVLDYNKIiqalnLPRNVPTNPYKSesgdvttrfDEVFWFG 181

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  204 DLNFRVT---STYDPTTNYSSTTTLRRLLENHEELNLLRKGEdepLCKGFQELKITFPPTYKFKLfEKETYNT---KRIP 277
Cdd:cd09095 182 DFNFRLSgprHLVDALINQGQEVDVSALLQHDQLTREMSKGS---IFKGFQEAPIHFPPTYKFDI-GSDVYDTsskQRVP 257

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 6324507  278 SWCDRILYKSyavptfAQEGT-----YHSVPrsnALLFSDHQPV 316
Cdd:cd09095 258 SYTDRILYRS------RQKGDvcclkYNSCP---SIKTSDHRPV 292
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 8-316 2.55e-19

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: 87.31  E-value: 2.55e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507    8 VSVTTFNCGKEFPVEN------SKAIVKQLlfpyDDGISQLElQDLYVLGFQEVvpiwqgsfPAVNRDLIDrittTAVNC 81
Cdd:cd09091   3 IFIGTWNMGSAPPPKNitswftSKGQGKTR----DDVADYIP-HDIYVIGTQED--------PLGEKEWLD----LLRHS 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   82 LNEKVSATqgdeqYSCLGVNSLGAITIIVL----YNNNALKVKDDILKrNGKCGWFGThlKGGTLISFQMtrngeeNWER 157
Cdd:cd09091  66 LKELTSLD-----YKPIAMQTLWNIRIVVLakpeHENRISHVCTSSVK-TGIANTLGN--KGAVGVSFMF------NGTS 131

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  158 FSYICAHLNA-NEGVNNRNQRIDDYKRIMSeVCDSEVAKSD------HFFFLGDLNFRVTSTYDPTTNYSSTTTLRRL-- 228
Cdd:cd09091 132 FGFVNSHLTSgSEKKLRRNQNYLNILRFLS-LGDKKLSAFNithrftHLFWLGDLNYRLDLPIQEAENIIQKIEQQQFep 210

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  229 LENHEELNLLRKgeDEPLCKGFQELKITFPPTYKFKLFEKETYN-TKR--------IPSWCDRILYKSYAvptfaqegTY 299
Cdd:cd09091 211 LLRHDQLNLERE--EHKVFLRFSEEEITFPPTYRYERGSRDTYAyTKQkatgvkynLPSWCDRILWKSYP--------ET 280

                       330       340
                ....*....|....*....|.
gi 6324507  300 HSVPRS----NALLFSDHQPV 316
Cdd:cd09091 281 HIICQSygctDDIVTSDHSPV 301
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 36-316 8.28e-18

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: 83.11  E-value: 8.28e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   36 DDGISQLElQDLYVLGFQEVvpiwqgsfPAVNRDLIDrittTAVNCLNEKVSATqgdeqYSCLGVNSLGAITIIVLYNNN 115
Cdd:cd09100  33 DDTADYIP-HDIYVIGTQED--------PLGEKEWLD----TLKHSLREITSIS-----FKVIAIQTLWNIRIVVLAKPE 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  116 ALKVKDDILKRNGKCGWFGT-HLKGGTLISFQMtrngeeNWERFSYICAHLNA-NEGVNNRNQRIDDYKRIMSeVCDSEV 193
Cdd:cd09100  95 HENRISHICTDSVKTGIANTlGNKGAVGVSFMF------NGTSFGFVNSHLTSgSEKKLRRNQNYFNILRFLV-LGDKKL 167

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  194 AKSD------HFFFLGDLNFRVTStydPTTNYSSTTTLRRL-----LENHEELNLLRKgeDEPLCKGFQELKITFPPTYK 262
Cdd:cd09100 168 SPFNithrftHLFWLGDLNYRVEL---PNTEAENIIQKIKQqqyqeLLPHDQLLIERK--ESKVFLQFEEEEITFAPTYR 242

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6324507  263 FKLFEKETYN-TKR--------IPSWCDRILYKSYA-VPTFAQegtyhSVPRSNALLFSDHQPV 316
Cdd:cd09100 243 FERGTRERYAyTKQkatgmkynLPSWCDRVLWKSYPlVHVVCQ-----SYGCTDDITTSDHSPV 301
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 138-316 9.14e-18

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: 83.21  E-value: 9.14e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  138 KGGTLISFQMTRNGeenwerFSYICAHLNAneGVNNRNQRIDDYKRI---MSEVCDSEVAKSDHFFFLGDLNFRVTSTYD 214
Cdd:cd09089 138 KGAVAIRFLLHSTS------LCFVCSHFAA--GQSQVKERNEDFAEIarkLSFPMGRTLDSHDYVFWCGDFNYRIDLPND 209

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  215 PTTNYSSTTTLRRLLENHEelnLLRKGEDEPLCKGFQELKITFPPTYKFKLFEKEtYNTK---RIPSWCDRILYKSYAVP 291
Cdd:cd09089 210 EVKELVRNGDWLKLLEFDQ---LTKQKAAGNVFKGFLEGEINFAPTYKYDLFSDD-YDTSekcRTPAWTDRVLWRRRKWP 285

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 6324507  292 TFAQEGTYHSVPRS----NALLF--------SDHQPV 316
Cdd:cd09089 286 SDKTEESLVETNDPtwnpGTLLYygraelktSDHRPV 322
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 92-316 3.52e-17

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: 81.17  E-value: 3.52e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   92 DEQYSCLGVNSLGAITIIVL----YNNNALKVKDDILKrNGKCGWFGThlKGGTLISFQMtrngeeNWERFSYICAHL-N 166
Cdd:cd09101  71 DIDYQPIALQCLWNIKMVVLvkpeHENRISHVHTSSVK-TGIANTLGN--KGAVGVSFMF------NGTSFGFVNCHLtS 141

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  167 ANEGVNNRNQRIDDYKRIMSeVCDSEVAKSD------HFFFLGDLNFRVTSTYDPTTNYSSTTTLRRLLEnHEELNLLRk 240
Cdd:cd09101 142 GNEKTHRRNQNYLDILRSLS-LGDKQLNAFDislrftHLFWFGDLNYRLDMDIQEILNYITRKEFDPLLA-VDQLNLER- 218

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  241 gEDEPLCKGFQELKITFPPTYKFKLFEKETYNTKR---------IPSWCDRILYKSYAvPTFAQEGTYHSvprSNALLFS 311
Cdd:cd09101 219 -EKNKVFLRFREEEISFPPTYRYERGSRDTYMWQKqkttgmrtnVPSWCDRILWKSYP-ETHIVCNSYGC---TDDIVTS 293


                ....*
gi 6324507  312 DHQPV 316
Cdd:cd09101 294 DHSPV 298
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 46-285 8.27e-17

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: 80.45  E-value: 8.27e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   46 DLYVLGFQEVVPIWQGSfpavnrdlIDRITTTAVNCLNEKVS-ATQGDEQYSCLGVNSLGAITIIVLYNNNALKVKDDIL 124
Cdd:cd09099  51 DIFAVGFEEMVELSAGN--------IVNASTTNRKMWGEQLQkAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVA 122

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  125 KRNGKCGWFG-THLKGGTLISFQMTRNGeenwerFSYICAHLNAneGVNNRNQRIDDYKRIMSEVC---DSEVAKSDHFF 200
Cdd:cd09099 123 IDTVKTGMGGkAGNKGAVAIRFQFYSTS------FCFICSHLTA--GQNQVKERNEDYKEITQKLSfpmGRNVFSHDYVF 194

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  201 FLGDLNFRVTSTYDPTTNYSSTTTLRRLLEnHEELNLLRKGEDepLCKGFQELKITFPPTYKFKLfEKETYNTK---RIP 277
Cdd:cd09099 195 WCGDFNYRIDLTYEEVFYFIKRQDWKKLLE-FDQLQLQKSSGK--IFKDFHEGTINFGPTYKYDV-GSEAYDTSdkcRTP 270


                ....*...
gi 6324507  278 SWCDRILY 285
Cdd:cd09099 271 AWTDRVLW 278
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 46-286 6.97e-14

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: 71.99  E-value: 6.97e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   46 DLYVLGFQEVVPIWQGsfpavnrDLIDRITTtavnclNEKVSATQ------GDEQYSCLGVNSLGAITIIVLYNNNALKV 119
Cdd:cd09098  51 DIFAIGFEEMVELNAG-------NIVSASTT------NQKLWAAElqktisRDQKYVLLASEQLVGVCLFVFIRPQHAPF 117

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  120 KDDILKRNGKCGWFG-THLKGGTLIS--FQMTRngeenwerFSYICAHLNANEG-VNNRNQRIDDYKRIMSEVCDSEVAK 195
Cdd:cd09098 118 IRDVAVDTVKTGMGGaTGNKGAVAIRmlFHTTS--------LCFVCSHFAAGQSqVKERNEDFIEIARKLSFPMGRMLFS 189

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  196 SDHFFFLGDLNFRVTSTYDPTTNYSSTTTLRRLLENHEELNLLRKGEdepLCKGFQELKITFPPTYKFKLFEkETYNTK- 274
Cdd:cd09098 190 HDYVFWCGDFNYRIDIPNEEVKELIRQQNWDSLIAGDQLINQKNAGQ---VFRGFLEGKLDFAPTYKYDLFS-DDYDTSe 265

                       250
                ....*....|....
gi 6324507  275 --RIPSWCDRILYK 286
Cdd:cd09098 266 kcRTPAWTDRVLWR 279
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 128-316 1.01e-12

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 69.55  E-value: 1.01e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   128 GKCGWFGThlKGGTLISFQMTRNgeenweRFSYICAHLNANEGVNNRNQRIDDYKRIM-----SEVCDSEVAKS----DH 198
Cdd:PLN03191 400 GLMGYMGN--KGSVSISMSLFQS------RLCFVCSHLTSGHKDGAEQRRNADVYEIIrrtrfSSVLDTDQPQTipshDQ 471

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507   199 FFFLGDLNFRVTStydpttnysSTTTLRRL--------LENHEELNL-LRKGEdepLCKGFQELKITFPPTYKFKlFEKE 269
Cdd:PLN03191 472 IFWFGDLNYRLNM---------LDTEVRKLvaqkrwdeLINSDQLIKeLRSGH---VFDGWKEGPIKFPPTYKYE-INSD 538

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 6324507   270 TY--------NTKRIPSWCDRILYKSYAVptfAQEgtyhSVPRSNaLLFSDHQPV 316
Cdd:PLN03191 539 RYvgenpkegEKKRSPAWCDRILWLGKGI---KQL----CYKRSE-IRLSDHRPV 585
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 199-322 1.22e-08

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: 56.32  E-value: 1.22e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  199 FFFLGDLNFRVTS-----------TYDPTTNYSSTTTLRRLLENHEE-----LNLLRKG--------------------- 241
Cdd:cd09092 218 FFVFGDFNFRLDTksvvetlcakaTMQTVRKADSNIVVKLEFREKDNdnkvvLQIEKKKfdyfnqdvfrdnngkallkfd 297

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6324507  242 -EDEPLCKGFQELKITFPPTYKFK--LFEKETYNTKRIPSWCDRILYKSYAVPTFAQEG----TYHSVPRsnALLFSDHQ 314
Cdd:cd09092 298 kELEVFKDVLYELDISFPPSYPYSedPEQGTQYMNTRCPAWCDRILMSHSARELKSENEeksvTYDMIGP--NVCMGDHK 375


                ....*...
gi 6324507  315 PVNLTVRL 322
Cdd:cd09092 376 PVFLTFRI 383
 
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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