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Conserved domains on  [gi|465836|sp|P34370|]
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RecName: Full=Inositol polyphosphate 5-phosphatase; AltName: Full=Ciliary localization protein 1

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-284 1.38e-100

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


:

Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 300.81  E-value: 1.38e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836        1 MDWKITIFTYNLAMKASDSEAVHNMLNGMI----DDHTHLVAIGLQEVAHS------ETIGGAVLTWATTIASWMNTNGR 70
Cdd:smart00128   1 RDIKVLIGTWNVGGLESPKVDVTSWLFQKIevkqSEKPDIYVIGLQEVVGLapgvilETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836       71 MVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQRNTMGGLTGHKGSIGVRLQLaSPYSIVFVDSHFIHGPENYGKRVEQ 150
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKL-SDTSFCFVNSHLAAGASNVEQRNQD 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836      151 YHTN-RNCSFPEDK-----SVRAAFWFGDFNFRVE----EDVNTVIRKIKngthLELLDTREQLKRALVERDAFIGFHEQ 220
Cdd:smart00128 160 YKTIlRALSFPERAllsqfDHDVVFWFGDLNFRLDspsyEEVRRKISKKE----FDDLLEKDQLNRQREAGKVFKGFQEG 235

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 465836      221 PVTFEPTYRV-TVGTTEQDG---KRVPSWTDRILYK--GDGITGLS-YTNNKKAVASDHLPVVAMFRVTAP 284
Cdd:smart00128 236 PITFPPTYKYdSVGTETYDTsekKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKVT 306
SKICH super family cl39277
SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The ...
 293-394 3.38e-10

SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.


The actual alignment was detected with superfamily member pfam17751:

Pssm-ID: 465482  Cd Length: 102  Bit Score: 56.87  E-value: 3.38e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836     293 VIFEHLPTWY-TSIPLVGRFQVNELYykeNGSYRDWIGVFP---SSINDCTTATnWIYAATCFEQVIEGS-KFLACEFNN 367
Cdd:pfam17751   1 VVFQNVGEWYpPDEDIECSYTLTPDF---TPSSWDWIGLFKvgwKSVNDYVTYV-WAKDDEVEGSNSVRQvLFKASYLPK 76

                          90       100
                  ....*....|....*....|....*..
gi 465836     368 IPAGNYRLGYFScHLHCLVGLSKVFQI 394
Cdd:pfam17751  77 EPEGFYQFCYVS-NLGSVVGISTPFQF 102
 
Name Accession Description Interval E-value
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-284 1.38e-100

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 300.81  E-value: 1.38e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836        1 MDWKITIFTYNLAMKASDSEAVHNMLNGMI----DDHTHLVAIGLQEVAHS------ETIGGAVLTWATTIASWMNTNGR 70
Cdd:smart00128   1 RDIKVLIGTWNVGGLESPKVDVTSWLFQKIevkqSEKPDIYVIGLQEVVGLapgvilETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836       71 MVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQRNTMGGLTGHKGSIGVRLQLaSPYSIVFVDSHFIHGPENYGKRVEQ 150
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKL-SDTSFCFVNSHLAAGASNVEQRNQD 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836      151 YHTN-RNCSFPEDK-----SVRAAFWFGDFNFRVE----EDVNTVIRKIKngthLELLDTREQLKRALVERDAFIGFHEQ 220
Cdd:smart00128 160 YKTIlRALSFPERAllsqfDHDVVFWFGDLNFRLDspsyEEVRRKISKKE----FDDLLEKDQLNRQREAGKVFKGFQEG 235

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 465836      221 PVTFEPTYRV-TVGTTEQDG---KRVPSWTDRILYK--GDGITGLS-YTNNKKAVASDHLPVVAMFRVTAP 284
Cdd:smart00128 236 PITFPPTYKYdSVGTETYDTsekKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 36-280 4.71e-46

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: 159.81  E-value: 4.71e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    36 LVAIGLQEVAhsETIGGAVL--------TWATTIASWMNTNG--RMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQR 105
Cdd:cd09090  34 IVVIGLQEVV--ELTAGQILnsdpskssFWEKKIKTTLNGRGgeKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKK 111

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   106 NTMGGLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYHT-NRNCSFPEDKSVR---AAFWFGDFNFRVEED 181
Cdd:cd09090 112 TGLGGMSGNKGAVAIRFDYGDT-SFCFVTSHLAAGLTNYEERNNDYKTiARGLRFSRGRTIKdhdHVIWLGDFNYRISLT 190

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   182 VNTVIRKIKNGTHLELLDtREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDG---KRVPSWTDRILYKGDGITG 258
Cdd:cd09090 191 NEDVRRFILNGKLDKLLE-YDQLNQQMNAGEVFPGFSEGPITFPPTYKYDKGTDNYDTsekQRIPAWTDRILYRGENLRQ 269

                       250       260
                ....*....|....*....|..
gi 465836   259 LSYtNNKKAVASDHLPVVAMFR 280
Cdd:cd09090 270 LSY-NSAPLRFSDHRPVYATFE 290
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
36-304 2.98e-35

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 134.91  E-value: 2.98e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    36 LVAIGLQEVAHsETIGGAV--------LTWATTIASWMN---TNGRMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQ 104
Cdd:COG5411  64 LYVVGLQEVVE-LTPGSILsadpydrlRIWESKVLDCLNgaqSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVK 142

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   105 RNTMGGLTGHKGSIGVRLQLASpYSIVFVDSHFIHGPENYGKRVEQYHTNRNC-SFPEDKSVR---AAFWFGDFNFRVEE 180
Cdd:COG5411 143 KTGFGGSSSNKGAVAIRFNYER-TSFCFVNSHLAAGVNNIEERIFDYRSIASNiCFSRGLRIYdhdTIFWLGDLNYRVTS 221

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   181 DVNTVIRKIKNGT-HLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDGK---RVPSWTDRILYKGDGI 256
Cdd:COG5411 222 TNEEVRPEIASDDgRLDKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSdkgRIPSWTDRILYKSEQL 301

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 465836   257 TGLSYTNNKKAVASDHLPVVAMFRV---TAPAAPKpqwEVIFEHLPTWYTS 304
Cdd:COG5411 302 TPHSYSSIPHLMISDHRPVYATFRAkikVVDPSKK---EGLIEKLYAEYKT 349
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 110-281 1.58e-18

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 87.66  E-value: 1.58e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    110 GLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKR---VEQYHTNRNCSF--------PED-KSVRAAFWFGDFNFR 177
Cdd:PLN03191 403 GYMGNKGSVSISMSLFQS-RLCFVCSHLTSGHKDGAEQrrnADVYEIIRRTRFssvldtdqPQTiPSHDQIFWFGDLNYR 481

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    178 VEEdVNTVIRKIKNGTHLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVT------VGTTEQDG--KRVPSWTDRI 249
Cdd:PLN03191 482 LNM-LDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEinsdryVGENPKEGekKRSPAWCDRI 560

                        170       180       190
                 ....*....|....*....|....*....|..
gi 465836    250 LYKGDGITGLSYTNNKKAVaSDHLPVVAMFRV 281
Cdd:PLN03191 561 LWLGKGIKQLCYKRSEIRL-SDHRPVSSMFLV 591
SKICH pfam17751
SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The ...
 293-394 3.38e-10

SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.


Pssm-ID: 465482  Cd Length: 102  Bit Score: 56.87  E-value: 3.38e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836     293 VIFEHLPTWY-TSIPLVGRFQVNELYykeNGSYRDWIGVFP---SSINDCTTATnWIYAATCFEQVIEGS-KFLACEFNN 367
Cdd:pfam17751   1 VVFQNVGEWYpPDEDIECSYTLTPDF---TPSSWDWIGLFKvgwKSVNDYVTYV-WAKDDEVEGSNSVRQvLFKASYLPK 76

                          90       100
                  ....*....|....*....|....*..
gi 465836     368 IPAGNYRLGYFScHLHCLVGLSKVFQI 394
Cdd:pfam17751  77 EPEGFYQFCYVS-NLGSVVGISTPFQF 102
 
Name Accession Description Interval E-value
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-284 1.38e-100

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 300.81  E-value: 1.38e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836        1 MDWKITIFTYNLAMKASDSEAVHNMLNGMI----DDHTHLVAIGLQEVAHS------ETIGGAVLTWATTIASWMNTNGR 70
Cdd:smart00128   1 RDIKVLIGTWNVGGLESPKVDVTSWLFQKIevkqSEKPDIYVIGLQEVVGLapgvilETIAGKERLWSDLLESSLNGDGQ 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836       71 MVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQRNTMGGLTGHKGSIGVRLQLaSPYSIVFVDSHFIHGPENYGKRVEQ 150
Cdd:smart00128  81 YNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKL-SDTSFCFVNSHLAAGASNVEQRNQD 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836      151 YHTN-RNCSFPEDK-----SVRAAFWFGDFNFRVE----EDVNTVIRKIKngthLELLDTREQLKRALVERDAFIGFHEQ 220
Cdd:smart00128 160 YKTIlRALSFPERAllsqfDHDVVFWFGDLNFRLDspsyEEVRRKISKKE----FDDLLEKDQLNRQREAGKVFKGFQEG 235

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 465836      221 PVTFEPTYRV-TVGTTEQDG---KRVPSWTDRILYK--GDGITGLS-YTNNKKAVASDHLPVVAMFRVTAP 284
Cdd:smart00128 236 PITFPPTYKYdSVGTETYDTsekKRVPAWCDRILYRsnGPELIQLSeYHSGMEITTSDHKPVFATFRLKVT 306
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 36-280 4.71e-46

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: 159.81  E-value: 4.71e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    36 LVAIGLQEVAhsETIGGAVL--------TWATTIASWMNTNG--RMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQR 105
Cdd:cd09090  34 IVVIGLQEVV--ELTAGQILnsdpskssFWEKKIKTTLNGRGgeKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKK 111

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   106 NTMGGLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYHT-NRNCSFPEDKSVR---AAFWFGDFNFRVEED 181
Cdd:cd09090 112 TGLGGMSGNKGAVAIRFDYGDT-SFCFVTSHLAAGLTNYEERNNDYKTiARGLRFSRGRTIKdhdHVIWLGDFNYRISLT 190

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   182 VNTVIRKIKNGTHLELLDtREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDG---KRVPSWTDRILYKGDGITG 258
Cdd:cd09090 191 NEDVRRFILNGKLDKLLE-YDQLNQQMNAGEVFPGFSEGPITFPPTYKYDKGTDNYDTsekQRIPAWTDRILYRGENLRQ 269

                       250       260
                ....*....|....*....|..
gi 465836   259 LSYtNNKKAVASDHLPVVAMFR 280
Cdd:cd09090 270 LSY-NSAPLRFSDHRPVYATFE 290
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 3-281 7.55e-44

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: 154.41  E-value: 7.55e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836     3 WKITIFTYNLAMKASDSEAVHNMLNGMIDDHTHLVAIGLQEVAHS-ETIGGAVLT-----WATTIASWMNTNGRMVLLaK 76
Cdd:cd09074   1 VKIFVVTWNVGGGISPPENLENWLSPKGTEAPDIYAVGVQEVDMSvQGFVGNDDSakareWVDNIQEALNEKENYVLL-G 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    77 TFQATNQVLI-FGRKQLIGQIKRID--YRFQRNTMGGLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYHT 153
Cdd:cd09074  80 SAQLVGIFLFvFVKKEHLPQIKDLEveGVTVGTGGGGKLGNKGGVAIRFQINDT-SFCFVNSHLAAGQEEVERRNQDYRD 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   154 NRN------CSFPEDKSVRA--AFWFGDFNFRVEEDvNTVIRKIKNGTHLELLDTREQLKRALVERDAFIGFHEQPVTFE 225
Cdd:cd09074 159 ILSklkfyrGDPAIDSIFDHdvVFWFGDLNYRIDST-DDEVRKLISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFP 237

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 465836   226 PTYRVTVGTTEQD---GKRVPSWTDRILYK---GDGITGLSYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09074 238 PTYKFDPGTDEYDtsdKKRIPAWCDRILYKskaGSEIQPLSYTSVPLYKTSDHKPVRATFRV 299
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 4-281 9.26e-39

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: 140.97  E-value: 9.26e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836     4 KITIFTYNLAmKASDSEAVHNMLNGMIDDH-THLVAIGLQEVAHS--ETIGGAVLT--WATTIASWMNTNGRMVLLAKTF 78
Cdd:cd09094   2 RVYVVTWNVA-TAPPPIDVRSLLGLQSPEVaPDIYIIGLQEVNSKpvQFVSDLIFDdpWSDLFMDILSPKGYVKVSSIRL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    79 QATnQVLIFGRKQLIGQIKRIDYRFQRNTMGGLTGHKGSIGVRLQLASpYSIVFVDSHFIHGPENYGKRVEQYHT----- 153
Cdd:cd09094  81 QGL-LLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYG-HMICFLNCHLPAHMEKWEQRIDDFETilstq 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   154 -NRNCSFPEDKSVRAAFWFGDFNFRVEEDVNTVIRKIKNGTHLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVTV 232
Cdd:cd09094 159 vFNECNTPSILDHDYVFWFGDLNFRIEDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTYKFDL 238

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 465836   233 GTTEQD---GKRVPSWTDRILYKGD----------GITGLSYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09094 239 GTDEYDtsgKKRKPAWTDRILWKVNpdasteekflSITQTSYKSHMEYGISDHKPVTAQFRL 300
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 36-281 1.40e-36

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: 134.75  E-value: 1.40e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    36 LVAIGLQEVAHSETiggAVLTWATTIAS-WM-------NTNGRMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRfQRNT 107
Cdd:cd09093  32 IYAIGFQELDLSAE---AFLFNDSSREQeWVkaverglHPDAKYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAE-TVGT 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   108 MG-GLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYH-TNRNCSF--PEDKSVRAA-----FWFGDFNFRV 178
Cdd:cd09093 108 GImGKMGNKGGVAVRFQFHNT-TFCFVNSHLAAHMEEVERRNQDYKdICARMKFedPDGPPLSISdhdvvFWLGDLNYRI 186

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   179 EE-DVNTVIRKIKNGtHLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQD--GK-RVPSWTDRILYKGD 254
Cdd:cd09093 187 QElPTEEVKELIEKN-DLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDPGTDNWDssEKcRAPAWCDRILWRGT 265

                       250       260
                ....*....|....*....|....*..
gi 465836   255 GITGLSYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09093 266 NIVQLSYRSHMELKTSDHKPVSALFDI 292
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
36-304 2.98e-35

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 134.91  E-value: 2.98e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    36 LVAIGLQEVAHsETIGGAV--------LTWATTIASWMN---TNGRMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQ 104
Cdd:COG5411  64 LYVVGLQEVVE-LTPGSILsadpydrlRIWESKVLDCLNgaqSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVK 142

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   105 RNTMGGLTGHKGSIGVRLQLASpYSIVFVDSHFIHGPENYGKRVEQYHTNRNC-SFPEDKSVR---AAFWFGDFNFRVEE 180
Cdd:COG5411 143 KTGFGGSSSNKGAVAIRFNYER-TSFCFVNSHLAAGVNNIEERIFDYRSIASNiCFSRGLRIYdhdTIFWLGDLNYRVTS 221

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   181 DVNTVIRKIKNGT-HLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDGK---RVPSWTDRILYKGDGI 256
Cdd:COG5411 222 TNEEVRPEIASDDgRLDKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSdkgRIPSWTDRILYKSEQL 301

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 465836   257 TGLSYTNNKKAVASDHLPVVAMFRV---TAPAAPKpqwEVIFEHLPTWYTS 304
Cdd:COG5411 302 TPHSYSSIPHLMISDHRPVYATFRAkikVVDPSKK---EGLIEKLYAEYKT 349
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 31-281 4.99e-30

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: 117.88  E-value: 4.99e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    31 DDH-THLVAIGLQEVA--HSETIGGAVLT----WATTIASWMNTNGRMVLLAKTfQATNQVL-IFGRKQLIGQIKRIDYR 102
Cdd:cd09089  47 DEKpVDIFAIGFEEMVdlNASNIVSASTTnqkeWGEELQKTISRDHKYVLLTSE-QLVGVCLfVFVRPQHAPFIRDVAVD 125

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   103 FQRNTMGGLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYH-TNRNCSFPEDKSVRA---AFWFGDFNFRV 178
Cdd:cd09089 126 TVKTGLGGAAGNKGAVAIRFLLHST-SLCFVCSHFAAGQSQVKERNEDFAeIARKLSFPMGRTLDShdyVFWCGDFNYRI 204

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   179 EEDVNTVIRKIKNGTHLELLdTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDGK---RVPSWTDRILYK--- 252
Cdd:cd09089 205 DLPNDEVKELVRNGDWLKLL-EFDQLTKQKAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSekcRTPAWTDRVLWRrrk 283

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 465836   253 -------GDGITGLSYTNNKKAV---------ASDHLPVVAMFRV 281
Cdd:cd09089 284 wpsdkteESLVETNDPTWNPGTLlyygraelkTSDHRPVVAIIDI 328
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 72-281 1.57e-29

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: 115.98  E-value: 1.57e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    72 VLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQRNTMGGLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQY 151
Cdd:cd09095  67 VLLHSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGT-SFLFITSHFTSGDGKVKERVLDY 145

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   152 H-TNRNCSFPE---DKSVRA-----------AFWFGDFNFRVEEDVNTVIRKIKNG---THLELLDTrEQLKRALVERDA 213
Cdd:cd09095 146 NkIIQALNLPRnvpTNPYKSesgdvttrfdeVFWFGDFNFRLSGPRHLVDALINQGqevDVSALLQH-DQLTREMSKGSI 224

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 465836   214 FIGFHEQPVTFEPTYRVTVGTTEQDG---KRVPSWTDRILYKG---DGITGLSYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09095 225 FKGFQEAPIHFPPTYKFDIGSDVYDTsskQRVPSYTDRILYRSrqkGDVCCLKYNSCPSIKTSDHRPVFALFRV 298
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 36-281 2.05e-23

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: 99.71  E-value: 2.05e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    36 LVAIGLQEVAhsETIGGAVLT--------WATTIASWMNTNGRMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQRNT 107
Cdd:cd09099  52 IFAVGFEEMV--ELSAGNIVNasttnrkmWGEQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTG 129

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   108 MGGLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQY-HTNRNCSFPEDKSVRA---AFWFGDFNFRVEEDVN 183
Cdd:cd09099 130 MGGKAGNKGAVAIRFQFYST-SFCFICSHLTAGQNQVKERNEDYkEITQKLSFPMGRNVFShdyVFWCGDFNYRIDLTYE 208

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   184 TVIRKIKNGTHLELLDTrEQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDGK---RVPSWTDRILY--------- 251
Cdd:cd09099 209 EVFYFIKRQDWKKLLEF-DQLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSdkcRTPAWTDRVLWwrkkwpfek 287

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*....
gi 465836   252 ----------KGDGITGLSYTNNKKAV---------ASDHLPVVAMFRV 281
Cdd:cd09099 288 tageinlldsDLDFDTKIRHTWTPGALmyygraelqASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 34-252 5.88e-23

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: 98.57  E-value: 5.88e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    34 THLVAIGLQEVA--HSETIGGAVLT----WATTIASWMNTNGRMVLLAKTFQATNQVLIFGRKQLIGQIKRIDYRFQRNT 107
Cdd:cd09098  50 VDIFAIGFEEMVelNAGNIVSASTTnqklWAAELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTG 129

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   108 MGGLTGHKGSIGVRLqLASPYSIVFVDSHFIHGPENYGKRVEQY-HTNRNCSFPEDK---SVRAAFWFGDFNFRVE---E 180
Cdd:cd09098 130 MGGATGNKGAVAIRM-LFHTTSLCFVCSHFAAGQSQVKERNEDFiEIARKLSFPMGRmlfSHDYVFWCGDFNYRIDipnE 208

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 465836   181 DVNTVIRKikngTHLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQDGK---RVPSWTDRILYK 252
Cdd:cd09098 209 EVKELIRQ----QNWDSLIAGDQLINQKNAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSekcRTPAWTDRVLWR 279
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 113-281 7.88e-22

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: 94.63  E-value: 7.88e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   113 GHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYHT--------NRNCSfPEDKSVRAA--FWFGDFNFRVE--- 179
Cdd:cd09091 116 GNKGAVGVSFMFNGT-SFGFVNSHLTSGSEKKLRRNQNYLNilrflslgDKKLS-AFNITHRFThlFWLGDLNYRLDlpi 193

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   180 EDVNTVIRKIKNGTHLELLdTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQ--------DGKR--VPSWTDRI 249
Cdd:cd09091 194 QEAENIIQKIEQQQFEPLL-RHDQLNLEREEHKVFLRFSEEEITFPPTYRYERGSRDTyaytkqkaTGVKynLPSWCDRI 272

                       170       180       190
                ....*....|....*....|....*....|....*
gi 465836   250 LYKGDGITGL---SYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09091 273 LWKSYPETHIicqSYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 98-281 2.95e-21

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: 93.13  E-value: 2.95e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    98 RIDYRFQRNTMGGLT---GHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKRVEQYHT---------NRNCSFPEDKSV 165
Cdd:cd09100  98 RISHICTDSVKTGIAntlGNKGAVGVSFMFNGT-SFGFVNSHLTSGSEKKLRRNQNYFNilrflvlgdKKLSPFNITHRF 176

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   166 RAAFWFGDFNFRVEE---DVNTVIRKIKNGTHLELLdTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQ----- 237
Cdd:cd09100 177 THLFWLGDLNYRVELpntEAENIIQKIKQQQYQELL-PHDQLLIERKESKVFLQFEEEEITFAPTYRFERGTRERyaytk 255

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 465836   238 ---DGKR--VPSWTDRILYKGDGITGL---SYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09100 256 qkaTGMKynLPSWCDRVLWKSYPLVHVvcqSYGCTDDITTSDHSPVFATFEV 307
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 110-281 1.58e-18

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 87.66  E-value: 1.58e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    110 GLTGHKGSIGVRLQLASPySIVFVDSHFIHGPENYGKR---VEQYHTNRNCSF--------PED-KSVRAAFWFGDFNFR 177
Cdd:PLN03191 403 GYMGNKGSVSISMSLFQS-RLCFVCSHLTSGHKDGAEQrrnADVYEIIRRTRFssvldtdqPQTiPSHDQIFWFGDLNYR 481

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    178 VEEdVNTVIRKIKNGTHLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVT------VGTTEQDG--KRVPSWTDRI 249
Cdd:PLN03191 482 LNM-LDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEinsdryVGENPKEGekKRSPAWCDRI 560

                        170       180       190
                 ....*....|....*....|....*....|..
gi 465836    250 LYKGDGITGLSYTNNKKAVaSDHLPVVAMFRV 281
Cdd:PLN03191 561 LWLGKGIKQLCYKRSEIRL-SDHRPVSSMFLV 591
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 113-281 4.36e-18

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: 83.87  E-value: 4.36e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   113 GHKGSIGVRLqLASPYSIVFVDSHFIHGPENYGKRVEQY-HTNRNCSFPE------DKSVRAA--FWFGDFNFRVEEDVN 183
Cdd:cd09101 116 GNKGAVGVSF-MFNGTSFGFVNCHLTSGNEKTHRRNQNYlDILRSLSLGDkqlnafDISLRFThlFWFGDLNYRLDMDIQ 194

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   184 TVIRKIkNGTHLELLDTREQLKRALVERDAFIGFHEQPVTFEPTYRVTVGTTEQ--------DGKR--VPSWTDRILYKG 253
Cdd:cd09101 195 EILNYI-TRKEFDPLLAVDQLNLEREKNKVFLRFREEEISFPPTYRYERGSRDTymwqkqktTGMRtnVPSWCDRILWKS 273

                       170       180       190
                ....*....|....*....|....*....|.
gi 465836   254 DGITGL---SYTNNKKAVASDHLPVVAMFRV 281
Cdd:cd09101 274 YPETHIvcnSYGCTDDIVTSDHSPVFGTFEV 304
SKICH pfam17751
SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The ...
 293-394 3.38e-10

SKICH domain; The SKICH domains of SKIP and PIPP mediate plasma membrane localization. The functions of the SKICH domains of NDP52 and CALCOCO1 are not known.


Pssm-ID: 465482  Cd Length: 102  Bit Score: 56.87  E-value: 3.38e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836     293 VIFEHLPTWY-TSIPLVGRFQVNELYykeNGSYRDWIGVFP---SSINDCTTATnWIYAATCFEQVIEGS-KFLACEFNN 367
Cdd:pfam17751   1 VVFQNVGEWYpPDEDIECSYTLTPDF---TPSSWDWIGLFKvgwKSVNDYVTYV-WAKDDEVEGSNSVRQvLFKASYLPK 76

                          90       100
                  ....*....|....*....|....*..
gi 465836     368 IPAGNYRLGYFScHLHCLVGLSKVFQI 394
Cdd:pfam17751  77 EPEGFYQFCYVS-NLGSVVGISTPFQF 102
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 84-277 1.12e-04

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: 43.24  E-value: 1.12e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836    84 VLIFGRKQLIGQIKRIDYRFQRNTMGGLTGHKGSIGVRlqlaspySIVFVDSHFIHGPENYGKRVEQYHTNRN-CSFPED 162
Cdd:cd08372  71 ILSKTPKFKIVEKHQYKFGEGDSGERRAVVVKFDVHDK-------ELCVVNAHLQAGGTRADVRDAQLKEVLEfLKRLRQ 143

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 465836   163 KSVRAAFWFGDFNFRVEEDVNTVIRKIKNGTHlelldtreqlKRALVerDAFIGFHEQPvtfeptyrvtvgTTEQDGKRV 242
Cdd:cd08372 144 PNSAPVVICGDFNVRPSEVDSENPSSMLRLFV----------ALNLV--DSFETLPHAY------------TFDTYMHNV 199

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 465836   243 PSWTDRILYKGD--------GITGLSYTNNkkaVASDHLPVVA 277
Cdd:cd08372 200 KSRLDYIFVSKSllpsvkssKILSDAARAR---IPSDHYPIEV 239
 
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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