NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|157821515|ref|NP_001102393|]
View 

inositol polyphosphate-5-phosphatase A [Rattus norvegicus]

Protein Classification

INPP5A domain-containing protein( domain architecture ID 10173428)

INPP5A domain-containing protein

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 ...
 10-394 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: 739.28  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  10 TAVLLVTANVGSLFDDPENLQKNWLREFYQVLHTHKPHFMALHCQEFGGKNYEASMSHVDKFVKELLSSDAMKEYNRARV 89
Cdd:cd09092    1 VDVLLVTANVGSLFEDPENLEKNWLREFLQTVHAHKPSFVALHLQEVGGKNYEASMEHVEKFIRELLSSDAMKDFDRVRV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  90 YLDENYKSQEHFTALGSFYFLHESLKNIYQFDFKAKKYKKVTGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRT 169
Cdd:cd09092   81 YVDEDFKSAEHFTALGSLYFIHKSLKNIYQFDFHAKKYKKVTGKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFMRT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 170 RWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGVRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTK 249
Cdd:cd09092  161 RWKINNCVFDLVNIHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTDERFEKVPFFVFGDFNFRLDTKSVVETLCAK 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 250 ATMQTVRAADTNEVVKLIFRESDNDRKVVLQLEKKLFDYFNQDVFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPY 329
Cdd:cd09092  241 ATMQTVRKADSNIVVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRDNNGKALLKFDKELEVFKDVLYELDISFPPSYPY 320

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157821515 330 SEDSSQGEQYMNTRCPAWCDRILMSLSAKElvLKSESEEKVATYDHIGPNVCMGDHKPVFLAFRI 394
Cdd:cd09092  321 SEDPEQGTQYMNTRCPAWCDRILMSHSARE--LKSENEEKSVTYDMIGPNVCMGDHKPVFLTFRI 383
 
Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 10-394 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: 739.28  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  10 TAVLLVTANVGSLFDDPENLQKNWLREFYQVLHTHKPHFMALHCQEFGGKNYEASMSHVDKFVKELLSSDAMKEYNRARV 89
Cdd:cd09092    1 VDVLLVTANVGSLFEDPENLEKNWLREFLQTVHAHKPSFVALHLQEVGGKNYEASMEHVEKFIRELLSSDAMKDFDRVRV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  90 YLDENYKSQEHFTALGSFYFLHESLKNIYQFDFKAKKYKKVTGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRT 169
Cdd:cd09092   81 YVDEDFKSAEHFTALGSLYFIHKSLKNIYQFDFHAKKYKKVTGKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFMRT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 170 RWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGVRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTK 249
Cdd:cd09092  161 RWKINNCVFDLVNIHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTDERFEKVPFFVFGDFNFRLDTKSVVETLCAK 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 250 ATMQTVRAADTNEVVKLIFRESDNDRKVVLQLEKKLFDYFNQDVFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPY 329
Cdd:cd09092  241 ATMQTVRKADSNIVVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRDNNGKALLKFDKELEVFKDVLYELDISFPPSYPY 320

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157821515 330 SEDSSQGEQYMNTRCPAWCDRILMSLSAKElvLKSESEEKVATYDHIGPNVCMGDHKPVFLAFRI 394
Cdd:cd09092  321 SEDPEQGTQYMNTRCPAWCDRILMSHSARE--LKSENEEKSVTYDMIGPNVCMGDHKPVFLTFRI 383
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 8-397 7.53e-92

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 279.24  E-value: 7.53e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515     8 PGTAVLLVTANVGSLFDdPENLQKNWLREFYQVLHTHKPHFMALHCQEFGGKNYeasmshvdkfvkellssdamkeynra 87
Cdd:smart00128   1 RDIKVLIGTWNVGGLES-PKVDVTSWLFQKIEVKQSEKPDIYVIGLQEVVGLAP-------------------------- 53

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515    88 rvyldenYKSQEHFTALGSFYFLHESLKNI--YQFDFKAKKYKKVTGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKG 165
Cdd:smart00128  54 -------GVILETIAGKERLWSDLLESSLNgdGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKG 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515   166 FIRTRWCIADCAFDLVNIHLFHDASNlvaWETSPSVYSGVrHKALGYVLDRIIDQrFEKVSYFVFGDFNFRLDSKSVvet 245
Cdd:smart00128 127 AVAVRFKLSDTSFCFVNSHLAAGASN---VEQRNQDYKTI-LRALSFPERALLSQ-FDHDVVFWFGDLNFRLDSPSY--- 198

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515   246 lctkatmqtvraadtnevvklifresDNDRKVVLQLEkklfdyfnqdvFRDNNGTALLEFDKELSVFKDRLYELDISFPP 325
Cdd:smart00128 199 --------------------------EEVRRKISKKE-----------FDDLLEKDQLNRQREAGKVFKGFQEGPITFPP 241

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157821515   326 SYPYseDSSQGEQYMNT---RCPAWCDRILMSLSAKELVLKSEseekvatyDHIGPNVCMGDHKPVFLAFRIAPG 397
Cdd:smart00128 242 TYKY--DSVGTETYDTSekkRVPAWCDRILYRSNGPELIQLSE--------YHSGMEITTSDHKPVFATFRLKVT 306
PTZ00312 PTZ00312
inositol-1,4,5-triphosphate 5-phosphatase; Provisional
 91-361 9.09e-17

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


Pssm-ID: 140333  Cd Length: 356  Bit Score: 81.09  E-value: 9.09e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  91 LDENYKSQEhFTALGSFYFLHESLKNIYQ-FDFKAKKYKKVTGKEIysdTLESTPMLekeKFPQDYFPECKWSRKGFIRT 169
Cdd:PTZ00312   1 MDENEDAQR-FTAIGSIVFLSPRMCPISSiLSFPHRTFVPVVDDPL---TYGSSPTR---LFHGGKFSGAGRSRKGFLLL 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 170 RWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGVRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLctK 249
Cdd:PTZ00312  74 SLRLGTVVVNVLNVHLYNDDDNRVAAASSPSLYTGQRQEALLEAIAECSAFISPSDPLFIFGDFNVRLDGHNLLEWL--K 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 250 ATMQ-TVRAADTNevvklifresdndrkvvLQLEKKLFDYF----NQDVFRdnngtallEFDKELSVFKD--------RL 316
Cdd:PTZ00312 152 EKMQiDVKIEVKR-----------------VRAPDRFWELFtnpqTQGEIR--------RFDLELQRLMDvvaqqsgvEL 206

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 317 YELDISFPPSYP-YSEDSSQGEQ--------------------------------------------------------- 338
Cdd:PTZ00312 207 AEFAIRFPPTYPrVAERTNTGAQiesaganvaasvygvkdvaakldnqqrkkaakdlkgtadailasvvltrvtaiphrn 286

                        330       340
                 ....*....|....*....|...
gi 157821515 339 YMNTRCPAWCDRILMSLSAKELV 361
Cdd:PTZ00312 287 YCRDRLPAWCDRVLWNPAGLELM 309
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
225-393 1.39e-06

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 50.17  E-value: 1.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 225 VSYFVFGDFNFRLDSksvvetlctkatmqtvraadTNEVVKlifRESDNDRKVVLQLEKklFDYFNQDVfrdnngtallE 304
Cdd:COG5411  207 DTIFWLGDLNYRVTS--------------------TNEEVR---PEIASDDGRLDKLFE--YDQLLWEM----------E 251

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 305 FDKELSVFKdrlyELDISFPPSYPYseDSSQGEQYMN--TRCPAWCDRIlmslsakeLVLKSESEEKvaTYDHIgPNVCM 382
Cdd:COG5411  252 VGNVFPGFK----EPVITFPPTYKF--DYGTDEYDTSdkGRIPSWTDRI--------LYKSEQLTPH--SYSSI-PHLMI 314

                        170
                 ....*....|.
gi 157821515 383 GDHKPVFLAFR 393
Cdd:COG5411  315 SDHRPVYATFR 325
 
Name Accession Description Interval E-value
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 10-394 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: 739.28  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  10 TAVLLVTANVGSLFDDPENLQKNWLREFYQVLHTHKPHFMALHCQEFGGKNYEASMSHVDKFVKELLSSDAMKEYNRARV 89
Cdd:cd09092    1 VDVLLVTANVGSLFEDPENLEKNWLREFLQTVHAHKPSFVALHLQEVGGKNYEASMEHVEKFIRELLSSDAMKDFDRVRV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  90 YLDENYKSQEHFTALGSFYFLHESLKNIYQFDFKAKKYKKVTGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKGFIRT 169
Cdd:cd09092   81 YVDEDFKSAEHFTALGSLYFIHKSLKNIYQFDFHAKKYKKVTGKEIYSGTLESVPTVEKEKFPQDFFPECKWSRKGFMRT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 170 RWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGVRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLCTK 249
Cdd:cd09092  161 RWKINNCVFDLVNIHLFHDASNLAACESSPSVYSQNRHRALGYVLERLTDERFEKVPFFVFGDFNFRLDTKSVVETLCAK 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 250 ATMQTVRAADTNEVVKLIFRESDNDRKVVLQLEKKLFDYFNQDVFRDNNGTALLEFDKELSVFKDRLYELDISFPPSYPY 329
Cdd:cd09092  241 ATMQTVRKADSNIVVKLEFREKDNDNKVVLQIEKKKFDYFNQDVFRDNNGKALLKFDKELEVFKDVLYELDISFPPSYPY 320

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157821515 330 SEDSSQGEQYMNTRCPAWCDRILMSLSAKElvLKSESEEKVATYDHIGPNVCMGDHKPVFLAFRI 394
Cdd:cd09092  321 SEDPEQGTQYMNTRCPAWCDRILMSHSARE--LKSENEEKSVTYDMIGPNVCMGDHKPVFLTFRI 383
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 10-394 1.52e-95

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: 288.46  E-value: 1.52e-95
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  10 TAVLLVTANVGSLFDDPENLqKNWLREFYqvlhTHKPHFMALHCQEFGGKNYEasmshvdkFVKELLSSDAMKEYNRARV 89
Cdd:cd09074    1 VKIFVVTWNVGGGISPPENL-ENWLSPKG----TEAPDIYAVGVQEVDMSVQG--------FVGNDDSAKAREWVDNIQE 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  90 YLDE--NYKSQEHFTALGSFYFLHESLKNIYQFDFkakkykkvtgkeiysdtlestpmLEKEKFPQDYFPECKWSRKGFI 167
Cdd:cd09074   68 ALNEkeNYVLLGSAQLVGIFLFVFVKKEHLPQIKD-----------------------LEVEGVTVGTGGGGKLGNKGGV 124

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 168 RTRWCIADCAFDLVNIHLFHDASNlvaWETSPSVYSGVRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLC 247
Cdd:cd09074  125 AIRFQINDTSFCFVNSHLAAGQEE---VERRNQDYRDILSKLKFYRGDPAIDSIFDHDVVFWFGDLNYRIDSTDDEVRKL 201

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 248 TKATMqtvraadtnevvklifresdndrkvvlqlekklfdyfNQDVFRDNNGTALLEFDKelsvFKDRLYELDISFPPSY 327
Cdd:cd09074  202 ISQGD-------------------------------------LDDLLEKDQLKKQKEKGK----VFDGFQELPITFPPTY 240

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157821515 328 PYSEDSSQGEQYMNTRCPAWCDRILMSLSAkelvlksESEEKVATYDHIgPNVCMGDHKPVFLAFRI 394
Cdd:cd09074  241 KFDPGTDEYDTSDKKRIPAWCDRILYKSKA-------GSEIQPLSYTSV-PLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 8-397 7.53e-92

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 279.24  E-value: 7.53e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515     8 PGTAVLLVTANVGSLFDdPENLQKNWLREFYQVLHTHKPHFMALHCQEFGGKNYeasmshvdkfvkellssdamkeynra 87
Cdd:smart00128   1 RDIKVLIGTWNVGGLES-PKVDVTSWLFQKIEVKQSEKPDIYVIGLQEVVGLAP-------------------------- 53

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515    88 rvyldenYKSQEHFTALGSFYFLHESLKNI--YQFDFKAKKYKKVTGKEIYSDTLESTPMLEKEKFPQDYFPECKWSRKG 165
Cdd:smart00128  54 -------GVILETIAGKERLWSDLLESSLNgdGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKG 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515   166 FIRTRWCIADCAFDLVNIHLFHDASNlvaWETSPSVYSGVrHKALGYVLDRIIDQrFEKVSYFVFGDFNFRLDSKSVvet 245
Cdd:smart00128 127 AVAVRFKLSDTSFCFVNSHLAAGASN---VEQRNQDYKTI-LRALSFPERALLSQ-FDHDVVFWFGDLNFRLDSPSY--- 198

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515   246 lctkatmqtvraadtnevvklifresDNDRKVVLQLEkklfdyfnqdvFRDNNGTALLEFDKELSVFKDRLYELDISFPP 325
Cdd:smart00128 199 --------------------------EEVRRKISKKE-----------FDDLLEKDQLNRQREAGKVFKGFQEGPITFPP 241

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157821515   326 SYPYseDSSQGEQYMNT---RCPAWCDRILMSLSAKELVLKSEseekvatyDHIGPNVCMGDHKPVFLAFRIAPG 397
Cdd:smart00128 242 TYKY--DSVGTETYDTSekkRVPAWCDRILYRSNGPELIQLSE--------YHSGMEITTSDHKPVFATFRLKVT 306
PTZ00312 PTZ00312
inositol-1,4,5-triphosphate 5-phosphatase; Provisional
 91-361 9.09e-17

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


Pssm-ID: 140333  Cd Length: 356  Bit Score: 81.09  E-value: 9.09e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515  91 LDENYKSQEhFTALGSFYFLHESLKNIYQ-FDFKAKKYKKVTGKEIysdTLESTPMLekeKFPQDYFPECKWSRKGFIRT 169
Cdd:PTZ00312   1 MDENEDAQR-FTAIGSIVFLSPRMCPISSiLSFPHRTFVPVVDDPL---TYGSSPTR---LFHGGKFSGAGRSRKGFLLL 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 170 RWCIADCAFDLVNIHLFHDASNLVAWETSPSVYSGVRHKALGYVLDRIIDQRFEKVSYFVFGDFNFRLDSKSVVETLctK 249
Cdd:PTZ00312  74 SLRLGTVVVNVLNVHLYNDDDNRVAAASSPSLYTGQRQEALLEAIAECSAFISPSDPLFIFGDFNVRLDGHNLLEWL--K 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 250 ATMQ-TVRAADTNevvklifresdndrkvvLQLEKKLFDYF----NQDVFRdnngtallEFDKELSVFKD--------RL 316
Cdd:PTZ00312 152 EKMQiDVKIEVKR-----------------VRAPDRFWELFtnpqTQGEIR--------RFDLELQRLMDvvaqqsgvEL 206

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 317 YELDISFPPSYP-YSEDSSQGEQ--------------------------------------------------------- 338
Cdd:PTZ00312 207 AEFAIRFPPTYPrVAERTNTGAQiesaganvaasvygvkdvaakldnqqrkkaakdlkgtadailasvvltrvtaiphrn 286

                        330       340
                 ....*....|....*....|...
gi 157821515 339 YMNTRCPAWCDRILMSLSAKELV 361
Cdd:PTZ00312 287 YCRDRLPAWCDRVLWNPAGLELM 309
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 220-394 2.61e-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: 57.82  E-value: 2.61e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 220 QRFEKVsyFVFGDFNFRLDSksvvetlctkatmqtvraadtnevvklifresdnDRKVVLQLekklfdyFNQDVFRDNNg 299
Cdd:cd09095  172 TRFDEV--FWFGDFNFRLSG----------------------------------PRHLVDAL-------INQGQEVDVS- 207

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 300 tALLEFD------KELSVFKDrLYELDISFPPSYPYSEDSSQGEQYMNTRCPAWCDRILMSlsakelvLKSESEEKVATY 373
Cdd:cd09095  208 -ALLQHDqltremSKGSIFKG-FQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRILYR-------SRQKGDVCCLKY 278

                        170       180
                 ....*....|....*....|.
gi 157821515 374 DHIgPNVCMGDHKPVFLAFRI 394
Cdd:cd09095  279 NSC-PSIKTSDHRPVFALFRV 298
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 228-394 4.63e-07

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: 51.16  E-value: 4.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 228 FVFGDFNFRLDSksvvetlctkatmqtvraADTNEVVKLIfreSDNDRKVVLQlekklFDYFNQDVfrdNNGTALLEFDk 307
Cdd:cd09093  177 FWLGDLNYRIQE------------------LPTEEVKELI---EKNDLEELLK-----YDQLNIQR---RAGKVFEGFT- 226

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 308 elsvfkdrlyELDISFPPSYPYSEDSSQGEQYMNTRCPAWCDRILMSLS-AKELVLKSESEEKvatydhigpnvcMGDHK 386
Cdd:cd09093  227 ----------EGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILWRGTnIVQLSYRSHMELK------------TSDHK 284


                 ....*...
gi 157821515 387 PVFLAFRI 394
Cdd:cd09093  285 PVSALFDI 292
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 228-394 9.15e-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: 50.36  E-value: 9.15e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 228 FVFGDFNFRLDsksvvetlctkatmqtvraADTNEVVKLIFRESDNDRKVVLQLekklfdyfnqDVFRDNNGTALlefdk 307
Cdd:cd09101  180 FWFGDLNYRLD-------------------MDIQEILNYITRKEFDPLLAVDQL----------NLEREKNKVFL----- 225

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 308 elsvfkdRLYELDISFPPSYPY---SEDS----SQGEQYMNTRCPAWCDRIL-MSLSAKELVLKSESeekvATYDhigpn 379
Cdd:cd09101  226 -------RFREEEISFPPTYRYergSRDTymwqKQKTTGMRTNVPSWCDRILwKSYPETHIVCNSYG----CTDD----- 289

                        170
                 ....*....|....*
gi 157821515 380 VCMGDHKPVFLAFRI 394
Cdd:cd09101  290 IVTSDHSPVFGTFEV 304
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
225-393 1.39e-06

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 50.17  E-value: 1.39e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 225 VSYFVFGDFNFRLDSksvvetlctkatmqtvraadTNEVVKlifRESDNDRKVVLQLEKklFDYFNQDVfrdnngtallE 304
Cdd:COG5411  207 DTIFWLGDLNYRVTS--------------------TNEEVR---PEIASDDGRLDKLFE--YDQLLWEM----------E 251

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 305 FDKELSVFKdrlyELDISFPPSYPYseDSSQGEQYMN--TRCPAWCDRIlmslsakeLVLKSESEEKvaTYDHIgPNVCM 382
Cdd:COG5411  252 VGNVFPGFK----EPVITFPPTYKF--DYGTDEYDTSdkGRIPSWTDRI--------LYKSEQLTPH--SYSSI-PHLMI 314

                        170
                 ....*....|.
gi 157821515 383 GDHKPVFLAFR 393
Cdd:COG5411  315 SDHRPVYATFR 325
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 164-394 2.96e-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: 48.49  E-value: 2.96e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 164 KGFIRTRWCIADCAFDLVNIHLfhdASNLVAWETSPSVYSGVrHKALGYVLDRIIdqrFEKVSYFVFGDFNFRLDSksvv 243
Cdd:cd09090  121 KGAVAIRFDYGDTSFCFVTSHL---AAGLTNYEERNNDYKTI-ARGLRFSRGRTI---KDHDHVIWLGDFNYRISL---- 189

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 244 etlctkatmqtvraadTNEVVKlifresdndRKVVLQLEKKLF--DYFNQDVfrdNNGTALLEFdkelsvfkdrlYELDI 321
Cdd:cd09090  190 ----------------TNEDVR---------RFILNGKLDKLLeyDQLNQQM---NAGEVFPGF-----------SEGPI 230

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 157821515 322 SFPPSYPYSEDSSQGEQYMNTRCPAWCDRILMslsaKELVLKSESEEKVATYdhigpnvcMGDHKPVFLAFRI 394
Cdd:cd09090  231 TFPPTYKYDKGTDNYDTSEKQRIPAWTDRILY----RGENLRQLSYNSAPLR--------FSDHRPVYATFEA 291
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 161-394 3.52e-06

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: 48.52  E-value: 3.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 161 WSRKGFIRTRWCIADCAFDLVNIHLfhdASNLVAWETSPSVYSgvrhkalgyvldRIID-QRFEKVSY---------FVF 230
Cdd:cd09094  113 WGNKGAVTVRFSLYGHMICFLNCHL---PAHMEKWEQRIDDFE------------TILStQVFNECNTpsildhdyvFWF 177

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 231 GDFNFRLDSKSvvetlctkatmqtvraadTNEVVKLIfresdNDRKVVLQLEKklfDYFNQDvfrdnngtallefdKELS 310
Cdd:cd09094  178 GDLNFRIEDVS------------------IEFVRELV-----NSKKYHLLLEK---DQLNMA--------------KRKE 217

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 311 VFKDRLYELDISFPPSYPYSEDSSQGEQYMNTRCPAWCDRILMSLSAKELVLKSESEEKVATYDHIgPNVCMGDHKPVFL 390
Cdd:cd09094  218 EAFQGFQEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWKVNPDASTEEKFLSITQTSYKSH-MEYGISDHKPVTA 296


                 ....
gi 157821515 391 AFRI 394
Cdd:cd09094  297 QFRL 300
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 218-394 4.47e-06

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: 48.02  E-value: 4.47e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 218 IDQRFEKVsyFVFGDFNFRLDsksvvetlctkatmqtvraADTNEVVKLIFRESDNDRKVVLQLEKKLFDYFNQDVFrdn 297
Cdd:cd09091  172 ITHRFTHL--FWLGDLNYRLD-------------------LPIQEAENIIQKIEQQQFEPLLRHDQLNLEREEHKVF--- 227

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 298 ngtalLEFDKElsvfkdrlyelDISFPPSYPYSEDSSQGEQY-------MNTRCPAWCDRIL-MSLSAKELVLKSESeek 369
Cdd:cd09091  228 -----LRFSEE-----------EITFPPTYRYERGSRDTYAYtkqkatgVKYNLPSWCDRILwKSYPETHIICQSYG--- 288

                        170       180
                 ....*....|....*....|....*
gi 157821515 370 vATYDhigpnVCMGDHKPVFLAFRI 394
Cdd:cd09091  289 -CTDD-----IVTSDHSPVFGTFEV 307
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 201-388 9.11e-05

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 44.51  E-value: 9.11e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 201 VYSGVRHKALGYVLDriIDQRFEKVSY---FVFGDFNFRLDsksvvetlctkatmqtvrAADTnEVVKLIFResdndrkv 277
Cdd:PLN03191 445 VYEIIRRTRFSSVLD--TDQPQTIPSHdqiFWFGDLNYRLN------------------MLDT-EVRKLVAQ-------- 495

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 278 vlqleKKLFDYFNQDvfrdnngtallEFDKELS---VFkDRLYELDISFPPSYPYS--------EDSSQGEQymnTRCPA 346
Cdd:PLN03191 496 -----KRWDELINSD-----------QLIKELRsghVF-DGWKEGPIKFPPTYKYEinsdryvgENPKEGEK---KRSPA 555

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 157821515 347 WCDRIL-MSLSAKELVLKsESEEKvatydhigpnvcMGDHKPV 388
Cdd:PLN03191 556 WCDRILwLGKGIKQLCYK-RSEIR------------LSDHRPV 585
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 218-394 3.03e-04

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: 42.28  E-value: 3.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 218 IDQRFEKVsyFVFGDFNFRLDSKSV-VETLCTKATMQtvraadtnEVVKLIFRESdndrkvvLQLEKKlfdyfNQDVFrd 296
Cdd:cd09100  172 ITHRFTHL--FWLGDLNYRVELPNTeAENIIQKIKQQ--------QYQELLPHDQ-------LLIERK-----ESKVF-- 227

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 297 nngtalLEFDKElsvfkdrlyelDISFPPSYPYSEDSSQGEQY-------MNTRCPAWCDRIL-MSLSAKELVLKSESee 368
Cdd:cd09100  228 ------LQFEEE-----------EITFAPTYRFERGTRERYAYtkqkatgMKYNLPSWCDRVLwKSYPLVHVVCQSYG-- 288

                        170       180
                 ....*....|....*....|....*.
gi 157821515 369 kvATYDhigpnVCMGDHKPVFLAFRI 394
Cdd:cd09100  289 --CTDD-----ITTSDHSPVFATFEV 307
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 295-394 5.10e-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: 41.99  E-value: 5.10e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157821515 295 RDNNGTALLEFD-----KEL-SVFKDRLyELDISFPPSYPY---SEDSSQGEQymnTRCPAWCDRIL-----MSLSAKEL 360
Cdd:cd09089  216 RNGDWLKLLEFDqltkqKAAgNVFKGFL-EGEINFAPTYKYdlfSDDYDTSEK---CRTPAWTDRVLwrrrkWPSDKTEE 291

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 157821515 361 VLKSESEE-----KVATYDHigPNVCMGDHKPVFLAFRI 394
Cdd:cd09089  292 SLVETNDPtwnpgTLLYYGR--AELKTSDHRPVVAIIDI 328
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 302-352 7.80e-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: 7.80e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 157821515 302 LLEFDK------ELSVFKDrLYELDISFPPSYPYSEDSSQGEQYMNTRCPAWCDRIL 352
Cdd:cd09099  222 LLEFDQlqlqksSGKIFKD-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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH