NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|25151733|ref|NP_509008|]
View 

putative type I inositol 1,4,5-trisphosphate 5-phosphatase [Caenorhabditis elegans]

Protein Classification

inositol polyphosphate-5-phosphatase A( domain architecture ID 10173428)

inositol polyphosphate-5-phosphatase A (INPP5A) specifically hydrolyzes the 5-phosphate of inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, and inositol 1,3,4,5-tetrasphosphate to inositol 1,3,4-trisphosphate

CATH:  3.60.10.10
EC:  3.1.3.56
Gene Ontology:  GO:0043647|GO:0042731|GO:0052745|GO:0046856
PubMed:  10838565
SCOP:  4002213

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 2-409 0e+00

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: 582.12  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733   2 VQYLLITANVGSLFEPDARLHTSWIKTVADQVESVDPSFFVIHLQETGGKKFTECSQQVPIIINRLST--ALPKFDLLRA 79
Cdd:cd09092   1 VDVLLVTANVGSLFEDPENLEKNWLREFLQTVHAHKPSFVALHLQEVGGKNYEASMEHVEKFIRELLSsdAMKDFDRVRV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  80 YVDIDY-EAIEYTALGALCFIKRSLwSNVSQFNFHTKKYEQLTsPKEVVTHGLENYPYVVKHKFPKDFWPSIKWGRKGYM 158
Cdd:cd09092  81 YVDEDFkSAEHFTALGSLYFIHKSL-KNIYQFDFHAKKYKKVT-GKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFM 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 159 QTRWKIENKVFDFVNAHLFHDESNLALIHENPQLYSQNRKRALDFVLAELSSkENGCTPLLFVFGDLNFRLDSRSFLNRL 238
Cdd:cd09092 159 RTRWKINNCVFDLVNIHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTD-ERFEKVPFFVFGDFNFRLDTKSVVETL 237

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 239 TERTAQHPVADQeqmgsladglqasaanlqvithpsenlrrtVSAIEFRRESDSDDSQNSCVLRIEKKKFDYFNHKKLLD 318
Cdd:cd09092 238 CAKATMQTVRKA------------------------------DSNIVVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRD 287

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 319 DWRSYRD-DDKETENF-QSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLMNKNAY---SLVEEGEPQYRSFGM 393
Cdd:cd09092 288 NNGKALLkFDKELEVFkDVLYELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILMSHSARelkSENEEKSVTYDMIGP 367

                       410
                ....*....|....*.
gi 25151733 394 ETCTGDHKPVMLTFNI 409
Cdd:cd09092 368 NVCMGDHKPVFLTFRI 383
 
Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 2-409 0e+00

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: 582.12  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733   2 VQYLLITANVGSLFEPDARLHTSWIKTVADQVESVDPSFFVIHLQETGGKKFTECSQQVPIIINRLST--ALPKFDLLRA 79
Cdd:cd09092   1 VDVLLVTANVGSLFEDPENLEKNWLREFLQTVHAHKPSFVALHLQEVGGKNYEASMEHVEKFIRELLSsdAMKDFDRVRV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  80 YVDIDY-EAIEYTALGALCFIKRSLwSNVSQFNFHTKKYEQLTsPKEVVTHGLENYPYVVKHKFPKDFWPSIKWGRKGYM 158
Cdd:cd09092  81 YVDEDFkSAEHFTALGSLYFIHKSL-KNIYQFDFHAKKYKKVT-GKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFM 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 159 QTRWKIENKVFDFVNAHLFHDESNLALIHENPQLYSQNRKRALDFVLAELSSkENGCTPLLFVFGDLNFRLDSRSFLNRL 238
Cdd:cd09092 159 RTRWKINNCVFDLVNIHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTD-ERFEKVPFFVFGDFNFRLDTKSVVETL 237

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 239 TERTAQHPVADQeqmgsladglqasaanlqvithpsenlrrtVSAIEFRRESDSDDSQNSCVLRIEKKKFDYFNHKKLLD 318
Cdd:cd09092 238 CAKATMQTVRKA------------------------------DSNIVVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRD 287

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 319 DWRSYRD-DDKETENF-QSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLMNKNAY---SLVEEGEPQYRSFGM 393
Cdd:cd09092 288 NNGKALLkFDKELEVFkDVLYELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILMSHSARelkSENEEKSVTYDMIGP 367

                       410
                ....*....|....*.
gi 25151733 394 ETCTGDHKPVMLTFNI 409
Cdd:cd09092 368 NVCMGDHKPVFLTFRI 383
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-409 4.04e-93

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 282.32  E-value: 4.04e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733      1 MVQYLLITANVGSLFEPDaRLHTSWIKTVADQVESVDPSFFVIHLQETGGKKFtecsqqvpiiinrlstalpkfdllray 80
Cdd:smart00128   2 DIKVLIGTWNVGGLESPK-VDVTSWLFQKIEVKQSEKPDIYVIGLQEVVGLAP--------------------------- 53

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733     81 vdidYEAIEYTALGALCFIKRSLWSNV--SQFNFHTKKYeQLTSPKEVVTHGLENYPYVVKHKFPKDFWPSIKWGRKGYM 158
Cdd:smart00128  54 ----GVILETIAGKERLWSDLLESSLNgdGQYNVLAKVY-LVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAV 128

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733    159 QTRWKIENKVFDFVNAHLFHDESNlalIHENPQLYSQNrKRALDFVLAELSSKEngCTPLLFVFGDLNFRLDSRSFlnrl 238
Cdd:smart00128 129 AVRFKLSDTSFCFVNSHLAAGASN---VEQRNQDYKTI-LRALSFPERALLSQF--DHDVVFWFGDLNFRLDSPSY---- 198

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733    239 tertaqhpvadqeqmgsladglqasaanlqvithpsENLRRTVSAIEFrresdsddsqnscvlriekkkfdyfnhkKLLD 318
Cdd:smart00128 199 ------------------------------------EEVRRKISKKEF----------------------------DDLL 214

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733    319 DWRSYRDDDKETENFQSMFEMHINFPPTYPWseDPENSETLM---KTRAPAWCDRVLMNKNAYSLVEEGEpqyRSFGMET 395
Cdd:smart00128 215 EKDQLNRQREAGKVFKGFQEGPITFPPTYKY--DSVGTETYDtseKKRVPAWCDRILYRSNGPELIQLSE---YHSGMEI 289

                          410
                   ....*....|....
gi 25151733    396 CTGDHKPVMLTFNI 409
Cdd:smart00128 290 TTSDHKPVFATFRL 303
PTZ00312 PTZ00312
inositol-1,4,5-triphosphate 5-phosphatase; Provisional
 86-381 4.03e-14

inositol-1,4,5-triphosphate 5-phosphatase; Provisional


Pssm-ID: 140333  Cd Length: 356  Bit Score: 73.00  E-value: 4.03e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733   86 EAIEYTALGALCFIKRSLWSNVSQFNFHTKKYeqLTSPKEVVTHGLEnyPYVVKH--KFPkdfwpSIKWGRKGYMQTRWK 163
Cdd:PTZ00312   6 DAQRFTAIGSIVFLSPRMCPISSILSFPHRTF--VPVVDDPLTYGSS--PTRLFHggKFS-----GAGRSRKGFLLLSLR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  164 IENKVFDFVNAHLFHDESNLALIHENPQLYSQNRKRALDFVLAELSSKENGCTPlLFVFGDLNFRLDSRSFLNRLTERta 243
Cdd:PTZ00312  77 LGTVVVNVLNVHLYNDDDNRVAAASSPSLYTGQRQEALLEAIAECSAFISPSDP-LFIFGDFNVRLDGHNLLEWLKEK-- 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  244 qhpvaDQEQMGSLADGLQASAANLQVITHPS--ENLRRTvsAIEFRRESDSDDSQNSCVL-------------------- 301
Cdd:PTZ00312 154 -----MQIDVKIEVKRVRAPDRFWELFTNPQtqGEIRRF--DLELQRLMDVVAQQSGVELaefairfpptyprvaertnt 226

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  302 --RIEKKKFDYFNHKKLLDDWRSYRDDDKETENFQ-----------SMFEMHINFPPTYPWSEDpensetlmktRAPAWC 368
Cdd:PTZ00312 227 gaQIESAGANVAASVYGVKDVAAKLDNQQRKKAAKdlkgtadailaSVVLTRVTAIPHRNYCRD----------RLPAWC 296

                        330
                 ....*....|...
gi 25151733  369 DRVLMNKNAYSLV 381
Cdd:PTZ00312 297 DRVLWNPAGLELM 309
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
286-407 2.00e-06

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 49.78  E-value: 2.00e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 286 FRRESDSDDSQNSCVLriekkkfdyfnhKKLLDDWRSYRDDDKETENFQSMF----EMHINFPPTYPWSEDPENSETLMK 361
Cdd:COG5411 217 YRVTSTNEEVRPEIAS------------DDGRLDKLFEYDQLLWEMEVGNVFpgfkEPVITFPPTYKFDYGTDEYDTSDK 284

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 25151733 362 TRAPAWCDRVLMNKnaySLVEEGEpqYRSFGMETCTgDHKPVMLTF 407
Cdd:COG5411 285 GRIPSWTDRILYKS---EQLTPHS--YSSIPHLMIS-DHRPVYATF 324
 
Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 2-409 0e+00

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: 582.12  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733   2 VQYLLITANVGSLFEPDARLHTSWIKTVADQVESVDPSFFVIHLQETGGKKFTECSQQVPIIINRLST--ALPKFDLLRA 79
Cdd:cd09092   1 VDVLLVTANVGSLFEDPENLEKNWLREFLQTVHAHKPSFVALHLQEVGGKNYEASMEHVEKFIRELLSsdAMKDFDRVRV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  80 YVDIDY-EAIEYTALGALCFIKRSLwSNVSQFNFHTKKYEQLTsPKEVVTHGLENYPYVVKHKFPKDFWPSIKWGRKGYM 158
Cdd:cd09092  81 YVDEDFkSAEHFTALGSLYFIHKSL-KNIYQFDFHAKKYKKVT-GKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFM 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 159 QTRWKIENKVFDFVNAHLFHDESNLALIHENPQLYSQNRKRALDFVLAELSSkENGCTPLLFVFGDLNFRLDSRSFLNRL 238
Cdd:cd09092 159 RTRWKINNCVFDLVNIHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTD-ERFEKVPFFVFGDFNFRLDTKSVVETL 237

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 239 TERTAQHPVADQeqmgsladglqasaanlqvithpsenlrrtVSAIEFRRESDSDDSQNSCVLRIEKKKFDYFNHKKLLD 318
Cdd:cd09092 238 CAKATMQTVRKA------------------------------DSNIVVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRD 287

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 319 DWRSYRD-DDKETENF-QSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLMNKNAY---SLVEEGEPQYRSFGM 393
Cdd:cd09092 288 NNGKALLkFDKELEVFkDVLYELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILMSHSARelkSENEEKSVTYDMIGP 367

                       410
                ....*....|....*.
gi 25151733 394 ETCTGDHKPVMLTFNI 409
Cdd:cd09092 368 NVCMGDHKPVFLTFRI 383
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-409 4.04e-93

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 282.32  E-value: 4.04e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733      1 MVQYLLITANVGSLFEPDaRLHTSWIKTVADQVESVDPSFFVIHLQETGGKKFtecsqqvpiiinrlstalpkfdllray 80
Cdd:smart00128   2 DIKVLIGTWNVGGLESPK-VDVTSWLFQKIEVKQSEKPDIYVIGLQEVVGLAP--------------------------- 53

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733     81 vdidYEAIEYTALGALCFIKRSLWSNV--SQFNFHTKKYeQLTSPKEVVTHGLENYPYVVKHKFPKDFWPSIKWGRKGYM 158
Cdd:smart00128  54 ----GVILETIAGKERLWSDLLESSLNgdGQYNVLAKVY-LVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAV 128

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733    159 QTRWKIENKVFDFVNAHLFHDESNlalIHENPQLYSQNrKRALDFVLAELSSKEngCTPLLFVFGDLNFRLDSRSFlnrl 238
Cdd:smart00128 129 AVRFKLSDTSFCFVNSHLAAGASN---VEQRNQDYKTI-LRALSFPERALLSQF--DHDVVFWFGDLNFRLDSPSY---- 198

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733    239 tertaqhpvadqeqmgsladglqasaanlqvithpsENLRRTVSAIEFrresdsddsqnscvlriekkkfdyfnhkKLLD 318
Cdd:smart00128 199 ------------------------------------EEVRRKISKKEF----------------------------DDLL 214

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733    319 DWRSYRDDDKETENFQSMFEMHINFPPTYPWseDPENSETLM---KTRAPAWCDRVLMNKNAYSLVEEGEpqyRSFGMET 395
Cdd:smart00128 215 EKDQLNRQREAGKVFKGFQEGPITFPPTYKY--DSVGTETYDtseKKRVPAWCDRILYRSNGPELIQLSE---YHSGMEI 289

                          410
                   ....*....|....
gi 25151733    396 CTGDHKPVMLTFNI 409
Cdd:smart00128 290 TTSDHKPVFATFRL 303
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 2-409 1.90e-32

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: 123.98  E-value: 1.90e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733   2 VQYLLITANVGSLFEPDARLhTSWIktvaDQVESVDPSFFVIHLQE----TGGKKFTECSQQVPIIINRLSTALPKfdll 77
Cdd:cd09074   1 VKIFVVTWNVGGGISPPENL-ENWL----SPKGTEAPDIYAVGVQEvdmsVQGFVGNDDSAKAREWVDNIQEALNE---- 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  78 rayvDIDYEAIEYTALGALC---FIKRSLWSNVSQFNfhtkkyeqltspkevvthglenypyvvKHKFPKDFWPSIKWGR 154
Cdd:cd09074  72 ----KENYVLLGSAQLVGIFlfvFVKKEHLPQIKDLE---------------------------VEGVTVGTGGGGKLGN 120

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 155 KGYMQTRWKIENKVFDFVNAHLFHDESNLAlihenpqlysqNRKRALDFVLAELSSKENGCTP-------LLFVFGDLNF 227
Cdd:cd09074 121 KGGVAIRFQINDTSFCFVNSHLAAGQEEVE-----------RRNQDYRDILSKLKFYRGDPAIdsifdhdVVFWFGDLNY 189

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 228 RLDS-RSFLNRLTERTAQHPVADQEQmgsladglqasaanlqvithpsenlrrtvsaiefrresdsddsqnscvLRIEKK 306
Cdd:cd09074 190 RIDStDDEVRKLISQGDLDDLLEKDQ------------------------------------------------LKKQKE 221

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 307 KfdyfnhKKLLDDWRsyrdddketenfqsmfEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLMNKNAYSLVEEGep 386
Cdd:cd09074 222 K------GKVFDGFQ----------------ELPITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYKSKAGSEIQPL-- 277

                       410       420
                ....*....|....*....|...
gi 25151733 387 QYRSFgMETCTGDHKPVMLTFNI 409
Cdd:cd09074 278 SYTSV-PLYKTSDHKPVRATFRV 299
PTZ00312 PTZ00312
inositol-1,4,5-triphosphate 5-phosphatase; Provisional
 86-381 4.03e-14

inositol-1,4,5-triphosphate 5-phosphatase; Provisional


Pssm-ID: 140333  Cd Length: 356  Bit Score: 73.00  E-value: 4.03e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733   86 EAIEYTALGALCFIKRSLWSNVSQFNFHTKKYeqLTSPKEVVTHGLEnyPYVVKH--KFPkdfwpSIKWGRKGYMQTRWK 163
Cdd:PTZ00312   6 DAQRFTAIGSIVFLSPRMCPISSILSFPHRTF--VPVVDDPLTYGSS--PTRLFHggKFS-----GAGRSRKGFLLLSLR 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  164 IENKVFDFVNAHLFHDESNLALIHENPQLYSQNRKRALDFVLAELSSKENGCTPlLFVFGDLNFRLDSRSFLNRLTERta 243
Cdd:PTZ00312  77 LGTVVVNVLNVHLYNDDDNRVAAASSPSLYTGQRQEALLEAIAECSAFISPSDP-LFIFGDFNVRLDGHNLLEWLKEK-- 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  244 qhpvaDQEQMGSLADGLQASAANLQVITHPS--ENLRRTvsAIEFRRESDSDDSQNSCVL-------------------- 301
Cdd:PTZ00312 154 -----MQIDVKIEVKRVRAPDRFWELFTNPQtqGEIRRF--DLELQRLMDVVAQQSGVELaefairfpptyprvaertnt 226

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  302 --RIEKKKFDYFNHKKLLDDWRSYRDDDKETENFQ-----------SMFEMHINFPPTYPWSEDpensetlmktRAPAWC 368
Cdd:PTZ00312 227 gaQIESAGANVAASVYGVKDVAAKLDNQQRKKAAKdlkgtadailaSVVLTRVTAIPHRNYCRD----------RLPAWC 296

                        330
                 ....*....|...
gi 25151733  369 DRVLMNKNAYSLV 381
Cdd:PTZ00312 297 DRVLWNPAGLELM 309
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 333-409 8.24e-12

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: 65.41  E-value: 8.24e-12
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 25151733 333 FQSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVL-MNKNAYSLVeegepqYRSFgMETCTGDHKPVMLTFNI 409
Cdd:cd09093 222 FEGFTEGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILwRGTNIVQLS------YRSH-MELKTSDHKPVSALFDI 292
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 152-409 1.11e-09

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: 58.92  E-value: 1.11e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 152 WGRKGYMQTRWKIENKVFDFVNAHL-FHDES------NLALIHENPQLYSQNRKRALDfvlaelsskengcTPLLFVFGD 224
Cdd:cd09094 113 WGNKGAVTVRFSLYGHMICFLNCHLpAHMEKweqridDFETILSTQVFNECNTPSILD-------------HDYVFWFGD 179

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 225 LNFRLDSRSflnrltertaqhpvadqeqmgsladglqasaanlqvithpsenlrrtvsaIEFRRESDSDDSQNscvLRIE 304
Cdd:cd09094 180 LNFRIEDVS--------------------------------------------------IEFVRELVNSKKYH---LLLE 206

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 305 KkkfDYFNHkkllddwrsyrddDKETEN-FQSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLMNKNAYSLVEE 383
Cdd:cd09094 207 K---DQLNM-------------AKRKEEaFQGFQEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWKVNPDASTEE 270

                       250       260       270
                ....*....|....*....|....*....|.
gi 25151733 384 GEPQ-----YRSFgMETCTGDHKPVMLTFNI 409
Cdd:cd09094 271 KFLSitqtsYKSH-MEYGISDHKPVTAQFRL 300
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 333-409 1.15e-06

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: 50.08  E-value: 1.15e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 333 FQSMFEMHINFPPTYPW---SEDPENSEtlmKTRAPAWCDRVL-------MNKNAYSLVEEGEPQY---------RSfgm 393
Cdd:cd09089 239 FKGFLEGEINFAPTYKYdlfSDDYDTSE---KCRTPAWTDRVLwrrrkwpSDKTEESLVETNDPTWnpgtllyygRA--- 312

                        90
                ....*....|....*.
gi 25151733 394 ETCTGDHKPVMLTFNI 409
Cdd:cd09089 313 ELKTSDHRPVVAIIDI 328
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 331-407 1.86e-06

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: 49.26  E-value: 1.86e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 25151733 331 ENFQSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVL-MNKNAYSLVEEGEPQYRSfgmetctgDHKPVMLTF 407
Cdd:cd09090 220 EVFPGFSEGPITFPPTYKYDKGTDNYDTSEKQRIPAWTDRILyRGENLRQLSYNSAPLRFS--------DHRPVYATF 289
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
286-407 2.00e-06

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 49.78  E-value: 2.00e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 286 FRRESDSDDSQNSCVLriekkkfdyfnhKKLLDDWRSYRDDDKETENFQSMF----EMHINFPPTYPWSEDPENSETLMK 361
Cdd:COG5411 217 YRVTSTNEEVRPEIAS------------DDGRLDKLFEYDQLLWEMEVGNVFpgfkEPVITFPPTYKFDYGTDEYDTSDK 284

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 25151733 362 TRAPAWCDRVLMNKnaySLVEEGEpqYRSFGMETCTgDHKPVMLTF 407
Cdd:COG5411 285 GRIPSWTDRILYKS---EQLTPHS--YSSIPHLMIS-DHRPVYATF 324
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 333-409 1.77e-05

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 46.82  E-value: 1.77e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733  333 FQSMFEMHINFPPTYPWS--------EDPENSEtlmKTRAPAWCDRVLMnknayslVEEGEPQYRSFGMETCTGDHKPVM 404
Cdd:PLN03191 517 FDGWKEGPIKFPPTYKYEinsdryvgENPKEGE---KKRSPAWCDRILW-------LGKGIKQLCYKRSEIRLSDHRPVS 586


                 ....*
gi 25151733  405 LTFNI 409
Cdd:PLN03191 587 SMFLV 591
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 284-409 2.42e-05

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: 45.71  E-value: 2.42e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 284 IEFRRESDSDDSQNsCVLRIEKKKF-DYFNHKKLLDDwrsyrddDKETENFQSMFEMHINFPPTYPW---SEDP----EN 355
Cdd:cd09091 185 LNYRLDLPIQEAEN-IIQKIEQQQFePLLRHDQLNLE-------REEHKVFLRFSEEEITFPPTYRYergSRDTyaytKQ 256

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 25151733 356 SETLMKTRAPAWCDRVLMnkNAYSLVEEGEPQYRSFGmETCTGDHKPVMLTFNI 409
Cdd:cd09091 257 KATGVKYNLPSWCDRILW--KSYPETHIICQSYGCTD-DIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 328-409 3.68e-05

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: 45.36  E-value: 3.68e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 328 KETENFQSMFEMHINFPPTYPWSEDP-------ENSETLMKTRAPAWCDRVLmnKNAYSLVeegEPQYRSFGMET--CTG 398
Cdd:cd09100 222 KESKVFLQFEEEEITFAPTYRFERGTreryaytKQKATGMKYNLPSWCDRVL--WKSYPLV---HVVCQSYGCTDdiTTS 296

                        90
                ....*....|.
gi 25151733 399 DHKPVMLTFNI 409
Cdd:cd09100 297 DHSPVFATFEV 307
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 333-409 4.88e-05

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: 45.03  E-value: 4.88e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 333 FQSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLMNK---------------NAYSLVEEGEPQYRSFG----- 392
Cdd:cd09098 238 FRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRrkwpfdrsaedldllNASFPDNSKEQYTWSPGtllhy 317

                        90
                ....*....|....*....
gi 25151733 393 --METCTGDHKPVMLTFNI 409
Cdd:cd09098 318 grAELKTSDHRPVVALIDI 336
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 303-409 7.05e-05

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: 44.58  E-value: 7.05e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 303 IEKKKFDYFNHkklLDDWRSYRDDDKETENFQsmfEMHINFPPTYPWSEDPENS-------ETLMKTRAPAWCDRVLmnk 375
Cdd:cd09101 200 ITRKEFDPLLA---VDQLNLEREKNKVFLRFR---EEEISFPPTYRYERGSRDTymwqkqkTTGMRTNVPSWCDRIL--- 270

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 25151733 376 naYSLVEEGEPQYRSFGM--ETCTGDHKPVMLTFNI 409
Cdd:cd09101 271 --WKSYPETHIVCNSYGCtdDIVTSDHSPVFGTFEV 304
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 319-372 1.21e-04

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: 43.86  E-value: 1.21e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 319 DWRSYRDDDK------ETENFQSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVL 372
Cdd:cd09099 218 DWKKLLEFDQlqlqksSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVL 277
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 328-409 5.18e-04

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: 41.64  E-value: 5.18e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 25151733 328 KETENFQSMFEMHINFPPTYPWSEDPENSETLMKTRAPAWCDRVLmnknaYSLVEEGEPQYRSFgmETC----TGDHKPV 403
Cdd:cd09095 220 SKGSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRIL-----YRSRQKGDVCCLKY--NSCpsikTSDHRPV 292


                ....*.
gi 25151733 404 MLTFNI 409
Cdd:cd09095 293 FALFRV 298
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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