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Conserved domains on  [gi|1005261240|ref|NP_001307971|]
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inositol polyphosphate-5-phosphatase A isoform b [Homo sapiens]

Protein Classification

exonuclease/endonuclease/phosphatase family protein( domain architecture ID 662)

exonuclease/endonuclease/phosphatase (EEP) family protein may cleave phosphodiester bonds

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EEP super family cl00490
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 39-330 0e+00

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


The actual alignment was detected with superfamily member cd09092:

Pssm-ID: 469791  Cd Length: 383  Bit Score: 572.10  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  39 ALGSFYFLHESLKNIYQFDFKAKKYRKVAGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRTRWCIADCAFDLVN 118
Cdd:cd09092    94 ALGSLYFIHKSLKNIYQFDFHAKKYKKVTGKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFMRTRWKINNCVFDLVN 173

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 119 IHLFHDASNLVAWETSPSVYSGIRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTKATMQTVRAADTNE 198
Cdd:cd09092   174 IHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTDERFEKVPFFVFGDFNFRLDTKSVVETLCAKATMQTVRKADSNI 253

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 199 VVKLIFRESDNDRKVMLQLEKKLFDYFNQEVFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPYSEDARQGEQYMNT 278
Cdd:cd09092   254 VVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRDNNGKALLKFDKELEVFKDVLYELDISFPPSYPYSEDPEQGTQYMNT 333

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1005261240 279 RCPAWCDRILMSPSAKElvLRSESEEKVVTYDHIGPNVCMGDHKPVFLAFRI 330
Cdd:cd09092   334 RCPAWCDRILMSHSARE--LKSENEEKSVTYDMIGPNVCMGDHKPVFLTFRI 383
 
Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 39-330 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: 572.10  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  39 ALGSFYFLHESLKNIYQFDFKAKKYRKVAGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRTRWCIADCAFDLVN 118
Cdd:cd09092    94 ALGSLYFIHKSLKNIYQFDFHAKKYKKVTGKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFMRTRWKINNCVFDLVN 173

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 119 IHLFHDASNLVAWETSPSVYSGIRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTKATMQTVRAADTNE 198
Cdd:cd09092   174 IHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTDERFEKVPFFVFGDFNFRLDTKSVVETLCAKATMQTVRKADSNI 253

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 199 VVKLIFRESDNDRKVMLQLEKKLFDYFNQEVFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPYSEDARQGEQYMNT 278
Cdd:cd09092   254 VVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRDNNGKALLKFDKELEVFKDVLYELDISFPPSYPYSEDPEQGTQYMNT 333

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1005261240 279 RCPAWCDRILMSPSAKElvLRSESEEKVVTYDHIGPNVCMGDHKPVFLAFRI 330
Cdd:cd09092   334 RCPAWCDRILMSHSARE--LKSENEEKSVTYDMIGPNVCMGDHKPVFLTFRI 383
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 34-330 7.73e-72

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 225.70  E-value: 7.73e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240   34 RNTNMALGSFYFLHESLKNI--YQFDFKAKKYRKVAGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRTRWCIAD 111
Cdd:smart00128  57 LETIAGKERLWSDLLESSLNgdGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSD 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  112 CAFDLVNIHLFHDASNlvaWETSPSVYSGIrHKALGYVLDRIIDQrFEKVSYFVFGDFNFRLDSKSVvetlctkatmqtv 191
Cdd:smart00128 137 TSFCFVNSHLAAGASN---VEQRNQDYKTI-LRALSFPERALLSQ-FDHDVVFWFGDLNFRLDSPSY------------- 198

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  192 raadtnevvklifresdndrkvmLQLEKKLFDYFnqevFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPYseDARQ 271
Cdd:smart00128 199 -----------------------EEVRRKISKKE----FDDLLEKDQLNRQREAGKVFKGFQEGPITFPPTYKY--DSVG 249

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1005261240  272 GEQYMNT---RCPAWCDRILMSPSAKELVLRSEseekvvtyDHIGPNVCMGDHKPVFLAFRI 330
Cdd:smart00128 250 TETYDTSekkRVPAWCDRILYRSNGPELIQLSE--------YHSGMEITTSDHKPVFATFRL 303
PTZ00312 PTZ00312
inositol-1,4,5-triphosphate 5-phosphatase; Provisional
 92-297 9.88e-18

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


Pssm-ID: 140333  Cd Length: 356  Bit Score: 83.02  E-value: 9.88e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  92 FPECKWSRKGFIRTRWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGIRHKALGYVLDRIIDQRFEKVSYFVFGDFNF 171
Cdd:PTZ00312   60 FSGAGRSRKGFLLLSLRLGTVVVNVLNVHLYNDDDNRVAAASSPSLYTGQRQEALLEAIAECSAFISPSDPLFIFGDFNV 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 172 RLDSKSVVETLctKATMQ-TVRAADTNEVVKLIFRESDNDRKVMLQLEKklfdyFNQEVFRDNNGTALLEfdkelSVfkd 250
Cdd:PTZ00312  140 RLDGHNLLEWL--KEKMQiDVKIEVKRVRAPDRFWELFTNPQTQGEIRR-----FDLELQRLMDVVAQQS-----GV--- 204

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 251 RLYELDISFPPSYP-YSEDARQGEQ------------------------------------------------------- 274
Cdd:PTZ00312  205 ELAEFAIRFPPTYPrVAERTNTGAQiesaganvaasvygvkdvaakldnqqrkkaakdlkgtadailasvvltrvtaiph 284

                         250       260
                  ....*....|....*....|....*
gi 1005261240 275 --YMNTRCPAWCDRILMSPSAKELV 297
Cdd:PTZ00312  285 rnYCRDRLPAWCDRVLWNPAGLELM 309
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
103-329 7.78e-07

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 50.55  E-value: 7.78e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 103 IRTRWCiadcafdLVNIHLfhdASNLVAWETSPSVYSGIRhkalgyvlDRIIDQRFEKV----SYFVFGDFNFRLDSksv 178
Cdd:COG5411   163 ERTSFC-------FVNSHL---AAGVNNIEERIFDYRSIA--------SNICFSRGLRIydhdTIFWLGDLNYRVTS--- 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 179 vetlctkatmqtvraadTNEVVKlifRESDNDRKVMLQLEKklFDYFNQEVfrdnngtallEFDKELSVFKdrlyELDIS 258
Cdd:COG5411   222 -----------------TNEEVR---PEIASDDGRLDKLFE--YDQLLWEM----------EVGNVFPGFK----EPVIT 265

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1005261240 259 FPPSYPYseDARQGEQYMN--TRCPAWCDRIlmspsakeLVLRSESEEKvvTYDHIgPNVCMGDHKPVFLAFR 329
Cdd:COG5411   266 FPPTYKF--DYGTDEYDTSdkGRIPSWTDRI--------LYKSEQLTPH--SYSSI-PHLMISDHRPVYATFR 325
 
Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 39-330 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: 572.10  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  39 ALGSFYFLHESLKNIYQFDFKAKKYRKVAGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRTRWCIADCAFDLVN 118
Cdd:cd09092    94 ALGSLYFIHKSLKNIYQFDFHAKKYKKVTGKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFMRTRWKINNCVFDLVN 173

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 119 IHLFHDASNLVAWETSPSVYSGIRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTKATMQTVRAADTNE 198
Cdd:cd09092   174 IHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTDERFEKVPFFVFGDFNFRLDTKSVVETLCAKATMQTVRKADSNI 253

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 199 VVKLIFRESDNDRKVMLQLEKKLFDYFNQEVFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPYSEDARQGEQYMNT 278
Cdd:cd09092   254 VVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRDNNGKALLKFDKELEVFKDVLYELDISFPPSYPYSEDPEQGTQYMNT 333

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1005261240 279 RCPAWCDRILMSPSAKElvLRSESEEKVVTYDHIGPNVCMGDHKPVFLAFRI 330
Cdd:cd09092   334 RCPAWCDRILMSHSARE--LKSENEEKSVTYDMIGPNVCMGDHKPVFLTFRI 383
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 34-330 7.73e-72

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 225.70  E-value: 7.73e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240   34 RNTNMALGSFYFLHESLKNI--YQFDFKAKKYRKVAGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRTRWCIAD 111
Cdd:smart00128  57 LETIAGKERLWSDLLESSLNgdGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSD 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  112 CAFDLVNIHLFHDASNlvaWETSPSVYSGIrHKALGYVLDRIIDQrFEKVSYFVFGDFNFRLDSKSVvetlctkatmqtv 191
Cdd:smart00128 137 TSFCFVNSHLAAGASN---VEQRNQDYKTI-LRALSFPERALLSQ-FDHDVVFWFGDLNFRLDSPSY------------- 198

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  192 raadtnevvklifresdndrkvmLQLEKKLFDYFnqevFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPYseDARQ 271
Cdd:smart00128 199 -----------------------EEVRRKISKKE----FDDLLEKDQLNRQREAGKVFKGFQEGPITFPPTYKY--DSVG 249

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1005261240  272 GEQYMNT---RCPAWCDRILMSPSAKELVLRSEseekvvtyDHIGPNVCMGDHKPVFLAFRI 330
Cdd:smart00128 250 TETYDTSekkRVPAWCDRILYRSNGPELIQLSE--------YHSGMEITTSDHKPVFATFRL 303
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 39-330 1.30e-71

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: 224.90  E-value: 1.30e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  39 ALGSFYFLHESLKNIYQFDFkakkyrkvagkeiysdtlestpmLEKEKFPQDYFPECKWSRKGFIRTRWCIADCAFDLVN 118
Cdd:cd09074    83 LVGIFLFVFVKKEHLPQIKD-----------------------LEVEGVTVGTGGGGKLGNKGGVAIRFQINDTSFCFVN 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 119 IHLFHDASNlvaWETSPSVYSGIRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTKATMqtvraadtne 198
Cdd:cd09074   140 SHLAAGQEE---VERRNQDYRDILSKLKFYRGDPAIDSIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGD---------- 206

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 199 vvklifresdndrkvmlqlekklfdyfNQEVFRDNNGTALLEFDKelsvFKDRLYELDISFPPSYPYSEDARQGEQYMNT 278
Cdd:cd09074   207 ---------------------------LDDLLEKDQLKKQKEKGK----VFDGFQELPITFPPTYKFDPGTDEYDTSDKK 255

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1005261240 279 RCPAWCDRILMSPSAkelvlrsESEEKVVTYDHIgPNVCMGDHKPVFLAFRI 330
Cdd:cd09074   256 RIPAWCDRILYKSKA-------GSEIQPLSYTSV-PLYKTSDHKPVRATFRV 299
PTZ00312 PTZ00312
inositol-1,4,5-triphosphate 5-phosphatase; Provisional
 92-297 9.88e-18

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


Pssm-ID: 140333  Cd Length: 356  Bit Score: 83.02  E-value: 9.88e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  92 FPECKWSRKGFIRTRWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGIRHKALGYVLDRIIDQRFEKVSYFVFGDFNF 171
Cdd:PTZ00312   60 FSGAGRSRKGFLLLSLRLGTVVVNVLNVHLYNDDDNRVAAASSPSLYTGQRQEALLEAIAECSAFISPSDPLFIFGDFNV 139

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 172 RLDSKSVVETLctKATMQ-TVRAADTNEVVKLIFRESDNDRKVMLQLEKklfdyFNQEVFRDNNGTALLEfdkelSVfkd 250
Cdd:PTZ00312  140 RLDGHNLLEWL--KEKMQiDVKIEVKRVRAPDRFWELFTNPQTQGEIRR-----FDLELQRLMDVVAQQS-----GV--- 204

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 251 RLYELDISFPPSYP-YSEDARQGEQ------------------------------------------------------- 274
Cdd:PTZ00312  205 ELAEFAIRFPPTYPrVAERTNTGAQiesaganvaasvygvkdvaakldnqqrkkaakdlkgtadailasvvltrvtaiph 284

                         250       260
                  ....*....|....*....|....*
gi 1005261240 275 --YMNTRCPAWCDRILMSPSAKELV 297
Cdd:PTZ00312  285 rnYCRDRLPAWCDRVLWNPAGLELM 309
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 156-330 1.60e-09

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: 58.20  E-value: 1.60e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 156 QRFEKVsyFVFGDFNFRLDSksvvetlctkatmqtvraaDTNEVVKLIFRESDNDRKVMLQLEKklfdyfnqevfrdnng 235
Cdd:cd09095   172 TRFDEV--FWFGDFNFRLSG-------------------PRHLVDALINQGQEVDVSALLQHDQ---------------- 214

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 236 taLLEFDKELSVFKDrLYELDISFPPSYPYSEDARQGEQYMNTRCPAWCDRILMSPsakelvlRSESEEKVVTYDHIgPN 315
Cdd:cd09095   215 --LTREMSKGSIFKG-FQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYRS-------RQKGDVCCLKYNSC-PS 283

                         170
                  ....*....|....*
gi 1005261240 316 VCMGDHKPVFLAFRI 330
Cdd:cd09095   284 IKTSDHRPVFALFRV 298
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 164-330 9.19e-08

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: 52.70  E-value: 9.19e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 164 FVFGDFNFRLDSksvvetlctkatmqtvraADTNEVVKLIfreSDNDRKVMLQlekklFDYFNQEVfrdNNGTALLEFDk 243
Cdd:cd09093   177 FWLGDLNYRIQE------------------LPTEEVKELI---EKNDLEELLK-----YDQLNIQR---RAGKVFEGFT- 226

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 244 elsvfkdrlyELDISFPPSYPYSEDARQGEQYMNTRCPAWCDRILMSPS-AKELVLRSESEEKvvtydhigpnvcMGDHK 322
Cdd:cd09093   227 ----------EGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILWRGTnIVQLSYRSHMELK------------TSDHK 284


                  ....*...
gi 1005261240 323 PVFLAFRI 330
Cdd:cd09093   285 PVSALFDI 292
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 100-330 2.10e-07

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: 51.90  E-value: 2.10e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 100 KGFIRTRWCIADCAFDLVNIHLfhdASNLVAWETSPSVYSGI-RHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDsksv 178
Cdd:cd09101   118 KGAVGVSFMFNGTSFGFVNCHL---TSGNEKTHRRNQNYLDIlRSLSLGDKQLNAFDISLRFTHLFWFGDLNYRLD---- 190

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 179 vetlctkatmqtvraADTNEVVKLIFREsdnDRKVMLQLekklfDYFNQEvfRDNNGTALlefdkelsvfkdRLYELDIS 258
Cdd:cd09101   191 ---------------MDIQEILNYITRK---EFDPLLAV-----DQLNLE--REKNKVFL------------RFREEEIS 233

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 259 FPPSYPYSEDAR-------QGEQYMNTRCPAWCDRILMspsakelvlRSESEEKVVTYDH-IGPNVCMGDHKPVFLAFRI 330
Cdd:cd09101   234 FPPTYRYERGSRdtymwqkQKTTGMRTNVPSWCDRILW---------KSYPETHIVCNSYgCTDDIVTSDHSPVFGTFEV 304
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 154-330 3.08e-07

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: 51.49  E-value: 3.08e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 154 IDQRFEKVsyFVFGDFNFRLDsksvvetlctkatmqtvraADTNEVVKLIFRESDNDRKVMLQLEKKLFDYFNQEVFrdn 233
Cdd:cd09091   172 ITHRFTHL--FWLGDLNYRLD-------------------LPIQEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVF--- 227

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 234 ngtalLEFDKElsvfkdrlyelDISFPPSYPYSEDARQGEQY-------MNTRCPAWCDRILMS--PSAKELVLRSESEE 304
Cdd:cd09091   228 -----LRFSEE-----------EITFPPTYRYERGSRDTYAYtkqkatgVKYNLPSWCDRILWKsyPETHIICQSYGCTD 291

                         170       180
                  ....*....|....*....|....*.
gi 1005261240 305 KVVTydhigpnvcmGDHKPVFLAFRI 330
Cdd:cd09091   292 DIVT----------SDHSPVFGTFEV 307
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
103-329 7.78e-07

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 50.55  E-value: 7.78e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 103 IRTRWCiadcafdLVNIHLfhdASNLVAWETSPSVYSGIRhkalgyvlDRIIDQRFEKV----SYFVFGDFNFRLDSksv 178
Cdd:COG5411   163 ERTSFC-------FVNSHL---AAGVNNIEERIFDYRSIA--------SNICFSRGLRIydhdTIFWLGDLNYRVTS--- 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 179 vetlctkatmqtvraadTNEVVKlifRESDNDRKVMLQLEKklFDYFNQEVfrdnngtallEFDKELSVFKdrlyELDIS 258
Cdd:COG5411   222 -----------------TNEEVR---PEIASDDGRLDKLFE--YDQLLWEM----------EVGNVFPGFK----EPVIT 265

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1005261240 259 FPPSYPYseDARQGEQYMN--TRCPAWCDRIlmspsakeLVLRSESEEKvvTYDHIgPNVCMGDHKPVFLAFR 329
Cdd:COG5411   266 FPPTYKF--DYGTDEYDTSdkGRIPSWTDRI--------LYKSEQLTPH--SYSSI-PHLMISDHRPVYATFR 325
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 100-330 8.18e-07

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: 50.03  E-value: 8.18e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 100 KGFIRTRWCIADCAFDLVNIHLfhdASNLVAWETSPSVYSGIrHKALGYVLDRIIdqrFEKVSYFVFGDFNFRLDSksvv 179
Cdd:cd09090   121 KGAVAIRFDYGDTSFCFVTSHL---AAGLTNYEERNNDYKTI-ARGLRFSRGRTI---KDHDHVIWLGDFNYRISL---- 189

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 180 etlctkatmqtvraadTNEVVKlifresdndRKVMLQLEKKLF--DYFNQEVfrdNNGTALLEFdkelsvfkdrlYELDI 257
Cdd:cd09090   190 ----------------TNEDVR---------RFILNGKLDKLLeyDQLNQQM---NAGEVFPGF-----------SEGPI 230

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1005261240 258 SFPPSYPYSEDARQGEQYMNTRCPAWCDRILMspsaKELVLRSESeekvvtYDHIgPNVcMGDHKPVFLAFRI 330
Cdd:cd09090   231 TFPPTYKYDKGTDNYDTSEKQRIPAWTDRILY----RGENLRQLS------YNSA-PLR-FSDHRPVYATFEA 291
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 97-330 1.72e-05

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: 45.82  E-value: 1.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240  97 WSRKGFIRTRWCIADCAFDLVNIHLfhdASNLVAWETSPSVYSGIrhkalgyvldrIIDQRFEKVSY---------FVFG 167
Cdd:cd09094   113 WGNKGAVTVRFSLYGHMICFLNCHL---PAHMEKWEQRIDDFETI-----------LSTQVFNECNTpsildhdyvFWFG 178

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 168 DFNFRLDSKSvvetlctkatMQTVR-AADTNEVVKLIFResdnDRKVMLQLEKKLFDYFNqevfrdnngtallefdkels 246
Cdd:cd09094   179 DLNFRIEDVS----------IEFVReLVNSKKYHLLLEK----DQLNMAKRKEEAFQGFQ-------------------- 224

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 247 vfkdrlyELDISFPPSYPYSEDARQGEQYMNTRCPAWCDRILMSPSAKElvlRSESEEKVVTYD--HIGPNVCMGDHKPV 324
Cdd:cd09094   225 -------EGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWKVNPDA---STEEKFLSITQTsyKSHMEYGISDHKPV 294


                  ....*.
gi 1005261240 325 FLAFRI 330
Cdd:cd09094   295 TAQFRL 300
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 137-324 2.02e-05

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 46.44  E-value: 2.02e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 137 VYSGIRHKALGYVLDriIDQRFEKVSY---FVFGDFNFRLDsksvvetlctkatmqtvrAADTnEVVKLIFRESDNDRKV 213
Cdd:PLN03191  445 VYEIIRRTRFSSVLD--TDQPQTIPSHdqiFWFGDLNYRLN------------------MLDT-EVRKLVAQKRWDELIN 503

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 214 MLQLEKKLfdyfnqevfrdnngtallefdKELSVFkDRLYELDISFPPSYPYS--------EDARQGEQymnTRCPAWCD 285
Cdd:PLN03191  504 SDQLIKEL---------------------RSGHVF-DGWKEGPIKFPPTYKYEinsdryvgENPKEGEK---KRSPAWCD 558

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1005261240 286 RIL-MSPSAKELVL-RSEseekvvtydhigpnVCMGDHKPV 324
Cdd:PLN03191  559 RILwLGKGIKQLCYkRSE--------------IRLSDHRPV 585
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 154-330 9.21e-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: 43.82  E-value: 9.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 154 IDQRFEKVsyFVFGDFNFRLDSKSV-VETLCTKATMQtvraadtnEVVKLIFRESdndrkvmLQLEKKlfdyfNQEVFrd 232
Cdd:cd09100   172 ITHRFTHL--FWLGDLNYRVELPNTeAENIIQKIKQQ--------QYQELLPHDQ-------LLIERK-----ESKVF-- 227

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 233 nngtalLEFDKElsvfkdrlyelDISFPPSYPYSEDARQGEQY-------MNTRCPAWCDRILMspsakelvlRSESEEK 305
Cdd:cd09100   228 ------LQFEEE-----------EITFAPTYRFERGTRERYAYtkqkatgMKYNLPSWCDRVLW---------KSYPLVH 281

                         170       180
                  ....*....|....*....|....*.
gi 1005261240 306 VVTYDH-IGPNVCMGDHKPVFLAFRI 330
Cdd:cd09100   282 VVCQSYgCTDDITTSDHSPVFATFEV 307
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 226-330 2.73e-04

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: 42.38  E-value: 2.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1005261240 226 NQEVF---RDNNGTALLEFD-----KEL-SVFKDRLyELDISFPPSYPY---SEDARQGEQymnTRCPAWCDRILMSpSA 293
Cdd:cd09089   208 NDEVKelvRNGDWLKLLEFDqltkqKAAgNVFKGFL-EGEINFAPTYKYdlfSDDYDTSEK---CRTPAWTDRVLWR-RR 282

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1005261240 294 KELVLRSESEEKVVTYDHIGPNVCM---------GDHKPVFLAFRI 330
Cdd:cd09089   283 KWPSDKTEESLVETNDPTWNPGTLLyygraelktSDHRPVVAIIDI 328
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 227-288 7.47e-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: 41.16  E-value: 7.47e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1005261240 227 QEVF---RDNNGTALLEFDK------ELSVFKDrLYELDISFPPSYPYSEDARQGEQYMNTRCPAWCDRIL 288
Cdd:cd09099   208 EEVFyfiKRQDWKKLLEFDQlqlqksSGKIFKD-FHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVL 277
 
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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