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Conserved domains on  [gi|530384177|ref|XP_005267257|]
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synaptojanin-2 isoform X7 [Homo sapiens]

Protein Classification

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 ...
 1-274 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 cd09099:

Pssm-ID: 469791  Cd Length: 336  Bit Score: 630.90  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:cd09099   60 MVELSAGNIVNASTTNRKMWGEQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDW 160
Cdd:cd09099  140 VAIRFQFYSTSFCFICSHLTAGQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDW 219

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 161 KKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKTAGELNLLDSDL 240
Cdd:cd09099  220 KKLLEFDQLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPFEKTAGEINLLDSDL 299

                        250       260       270
                 ....*....|....*....|....*....|....
gi 530384177 241 DVDTKVRHTWSPGALQYYGRAELQASDHRPVLAI 274
Cdd:cd09099  300 DFDTKIRHTWTPGALMYYGRAELQASDHRPVLAI 333
DUF1866 pfam08952
Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known ...
 285-421 4.10e-70

Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known function.


:

Pssm-ID: 286093  Cd Length: 146  Bit Score: 228.54  E-value: 4.10e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  285 GARERVFQEVSSFQGPLDATVVVNLQSPTLEEKNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDV 364
Cdd:pfam08952  10 EARRRVFKEVIRDQGPPDGTIVVSLCSGDLDEKNIFDENLMDELIQELTSFGEVTLVRFVEDTMWVTFRDGHSALNALSK 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530384177  365 DGMKVKGRAVKIRPKTKDWLKGLREEIIRKRDSMAPVSPTANSCLLEENFDFTSLDY 421
Cdd:pfam08952  90 DGMKVCGRALKIRLKSKDWIKGLEEEIILCTDNTIPVSPCANSTLLAEDFDFGSPDY 146
PRK12323 super family cl46901
DNA polymerase III subunit gamma/tau;
559-757 1.27e-03

DNA polymerase III subunit gamma/tau;


The actual alignment was detected with superfamily member PRK12323:

Pssm-ID: 481241 [Multi-domain]  Cd Length: 700  Bit Score: 42.56  E-value: 1.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 559 PGAPQQPPKARTGISKPYnvkqiKTTNAQEAEAAIRCLLEARGGASEEALSAVAprdleassePEPTPgAAKPETPQAPP 638
Cdd:PRK12323 407 AAAPAAAAAARAVAAAPA-----RRSPAPEALAAARQASARGPGGAPAPAPAPA---------AAPAA-AARPAAAGPRP 471

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 639 LLPRRPPPRVPAIKKPTLRRTGKPLSPEEQFeqqtvhftigpPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPShrK 718
Cdd:PRK12323 472 VAAAAAAAPARAAPAAAPAPADDDPPPWEEL-----------PPEFASPAPAQPDAAPAGWVAESIPDPATADPDDA--F 538

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 530384177 719 PASDEAPPGAGASvPPPLEAPPLVPKVPPRRKKSA-PAAF 757
Cdd:PRK12323 539 ETLAPAPAAAPAP-RAAAATEPVVAPRPPRASASGlPDMF 577
PHA03307 super family cl33723
transcriptional regulator ICP4; Provisional
 680-861 4.56e-03

transcriptional regulator ICP4; Provisional


The actual alignment was detected with superfamily member PHA03307:

Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 40.92  E-value: 4.56e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  680 PPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPSHRKPASDEAPPGAGASVPPPLEAPPLVPKVPPRRKKSAPAAFHL 759
Cdd:PHA03307   72 PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  760 QVLQSNSqllqgltynSSDSPSGHPPAAGTVFPQGdflSTSSATSPDSDGTKAMKPEAAPLLGDyqdpfwnllHHPKLLN 839
Cdd:PHA03307  152 PPAAGAS---------PAAVASDAASSRQAALPLS---SPEETARAPSSPPAEPPPSTPPAAAS---------PRPPRRS 210

                         170       180
                  ....*....|....*....|..
gi 530384177  840 NTWLSKSSDPLDSGTRSPKRDP 861
Cdd:PHA03307  211 SPISASASSPAPAPGRSAADDA 232
 
Name Accession Description Interval E-value
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 1-274 0e+00

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: 630.90  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:cd09099   60 MVELSAGNIVNASTTNRKMWGEQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDW 160
Cdd:cd09099  140 VAIRFQFYSTSFCFICSHLTAGQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDW 219

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 161 KKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKTAGELNLLDSDL 240
Cdd:cd09099  220 KKLLEFDQLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPFEKTAGEINLLDSDL 299

                        250       260       270
                 ....*....|....*....|....*....|....
gi 530384177 241 DVDTKVRHTWSPGALQYYGRAELQASDHRPVLAI 274
Cdd:cd09099  300 DFDTKIRHTWTPGALMYYGRAELQASDHRPVLAI 333
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-274 2.12e-93

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 296.96  E-value: 2.12e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177     1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:smart00128  48 VVGLAPGVILETIAGKERLWSDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGA 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177    81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGR--NVFSHDYVFWCGDFNYRIDL-TYEEVFYFVKR 157
Cdd:smart00128 128 VAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDYKTILRALSFPERAllSQFDHDVVFWFGDLNFRLDSpSYEEVRRKISK 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   158 QDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDV-GSAAYDTSDKCRTPAWTDRVLWwrkkhpfDKTAGELNLL 236
Cdd:smart00128 208 KEFDDLLEKDQLNRQREAGKVFKGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILY-------RSNGPELIQL 280

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 530384177   237 DSdldvdtkvrhtwspgalqYYGRAELQASDHRPVLAI 274
Cdd:smart00128 281 SE------------------YHSGMEITTSDHKPVFAT 300
DUF1866 pfam08952
Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known ...
 285-421 4.10e-70

Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known function.


Pssm-ID: 286093  Cd Length: 146  Bit Score: 228.54  E-value: 4.10e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  285 GARERVFQEVSSFQGPLDATVVVNLQSPTLEEKNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDV 364
Cdd:pfam08952  10 EARRRVFKEVIRDQGPPDGTIVVSLCSGDLDEKNIFDENLMDELIQELTSFGEVTLVRFVEDTMWVTFRDGHSALNALSK 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530384177  365 DGMKVKGRAVKIRPKTKDWLKGLREEIIRKRDSMAPVSPTANSCLLEENFDFTSLDY 421
Cdd:pfam08952  90 DGMKVCGRALKIRLKSKDWIKGLEEEIILCTDNTIPVSPCANSTLLAEDFDFGSPDY 146
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
2-218 1.63e-61

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 216.19  E-value: 1.63e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   2 VELSAGNIVNASTtnKKMWGEQLQKAIS------RSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKA 75
Cdd:COG5411   73 VELTPGSILSADP--YDRLRIWESKVLDclngaqSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSS 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  76 GNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFV 155
Cdd:COG5411  151 SNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDHDTIFWLGDLNYRVTSTNEEVRPEI 230

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530384177 156 KRQDWK--KLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVL 218
Cdd:COG5411  231 ASDDGRldKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRIL 295
RRM_SYNJ2 cd12720
RNA recognition motif (RRM) found in synaptojanin-2 and similar proteins; This subgroup ...
 302-379 1.16e-46

RNA recognition motif (RRM) found in synaptojanin-2 and similar proteins; This subgroup corresponds to the RRM of synaptojanin-2, also termed synaptic inositol-1,4,5-trisphosphate 5-phosphatase 2, an ubiquitously expressed central regulatory enzyme in the phosphoinositide-signaling cascade. As a novel Rac1 effector regulating the early step of clathrin-mediated endocytosis, synaptojanin-2 acts as a polyphosphoinositide phosphatase directly and specifically interacting with Rac1 in a GTP-dependent manner. It mediates the inhibitory effect of Rac1 on endocytosis and plays an important role in the Rac1-mediated control of cell growth. Synaptojanin-2 shows high sequence homology to the N-terminal Sac1p homology domain, the central inositol 5-phosphatase domain, the putative RNA recognition motif (RRM) of synaptojanin-1, but differs in the proline-rich region.


Pssm-ID: 410119 [Multi-domain]  Cd Length: 78  Bit Score: 160.72  E-value: 1.16e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530384177 302 DATVVVNLQSPTLEEKNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDVDGMKVKGRAVKIRPK 379
Cdd:cd12720    1 DATVVVNLLSPTLEEKNDFPEDLSTELVQCFQSYGTVILVRFNRGQMLVTFEDSRSALRVLDLDGIKVNGRAVKIKPK 78
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 33-274 1.20e-41

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 162.38  E-value: 1.20e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  33 RYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKE--RN 110
Cdd:PLN03191 363 KYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRN 442

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 111 EDYKEITQKLCFP------MGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKDFHE 184
Cdd:PLN03191 443 ADVYEIIRRTRFSsvldtdQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKE 522

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 185 GAINFGPTYKYDVGSAAY-----DTSDKCRTPAWTDRVLWWRKkhpfdktagelnlldsdldvdtkvrhtwspGALQ-YY 258
Cdd:PLN03191 523 GPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGK------------------------------GIKQlCY 572

                        250
                 ....*....|....*.
gi 530384177 259 GRAELQASDHRPVLAI 274
Cdd:PLN03191 573 KRSEIRLSDHRPVSSM 588
PRK12323 PRK12323
DNA polymerase III subunit gamma/tau;
559-757 1.27e-03

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237057 [Multi-domain]  Cd Length: 700  Bit Score: 42.56  E-value: 1.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 559 PGAPQQPPKARTGISKPYnvkqiKTTNAQEAEAAIRCLLEARGGASEEALSAVAprdleassePEPTPgAAKPETPQAPP 638
Cdd:PRK12323 407 AAAPAAAAAARAVAAAPA-----RRSPAPEALAAARQASARGPGGAPAPAPAPA---------AAPAA-AARPAAAGPRP 471

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 639 LLPRRPPPRVPAIKKPTLRRTGKPLSPEEQFeqqtvhftigpPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPShrK 718
Cdd:PRK12323 472 VAAAAAAAPARAAPAAAPAPADDDPPPWEEL-----------PPEFASPAPAQPDAAPAGWVAESIPDPATADPDDA--F 538

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 530384177 719 PASDEAPPGAGASvPPPLEAPPLVPKVPPRRKKSA-PAAF 757
Cdd:PRK12323 539 ETLAPAPAAAPAP-RAAAATEPVVAPRPPRASASGlPDMF 577
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 680-861 4.56e-03

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 40.92  E-value: 4.56e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  680 PPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPSHRKPASDEAPPGAGASVPPPLEAPPLVPKVPPRRKKSAPAAFHL 759
Cdd:PHA03307   72 PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  760 QVLQSNSqllqgltynSSDSPSGHPPAAGTVFPQGdflSTSSATSPDSDGTKAMKPEAAPLLGDyqdpfwnllHHPKLLN 839
Cdd:PHA03307  152 PPAAGAS---------PAAVASDAASSRQAALPLS---SPEETARAPSSPPAEPPPSTPPAAAS---------PRPPRRS 210

                         170       180
                  ....*....|....*....|..
gi 530384177  840 NTWLSKSSDPLDSGTRSPKRDP 861
Cdd:PHA03307  211 SPISASASSPAPAPGRSAADDA 232
 
Name Accession Description Interval E-value
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 1-274 0e+00

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: 630.90  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:cd09099   60 MVELSAGNIVNASTTNRKMWGEQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDW 160
Cdd:cd09099  140 VAIRFQFYSTSFCFICSHLTAGQNQVKERNEDYKEITQKLSFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFIKRQDW 219

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 161 KKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKTAGELNLLDSDL 240
Cdd:cd09099  220 KKLLEFDQLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKWPFEKTAGEINLLDSDL 299

                        250       260       270
                 ....*....|....*....|....*....|....
gi 530384177 241 DVDTKVRHTWSPGALQYYGRAELQASDHRPVLAI 274
Cdd:cd09099  300 DFDTKIRHTWTPGALMYYGRAELQASDHRPVLAI 333
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 1-274 0e+00

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: 544.68  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:cd09089   61 MVDLNASNIVSASTTNQKEWGEELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGA 140

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDW 160
Cdd:cd09089  141 VAIRFLLHSTSLCFVCSHFAAGQSQVKERNEDFAEIARKLSFPMGRTLDSHDYVFWCGDFNYRIDLPNDEVKELVRNGDW 220

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 161 KKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKTAGELNlldsdl 240
Cdd:cd09089  221 LKLLEFDQLTKQKAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPSDKTEESLV------ 294

                        250       260       270
                 ....*....|....*....|....*....|....
gi 530384177 241 dvdTKVRHTWSPGALQYYGRAELQASDHRPVLAI 274
Cdd:cd09089  295 ---ETNDPTWNPGTLLYYGRAELKTSDHRPVVAI 325
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 1-274 2.99e-152

Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This subfamily contains the INPP5c domains of human synaptojanin 1 (Synj1) and related proteins. It belongs to a family of Mg2+-dependent inositol polyphosphate 5-phosphatases, which hydrolyze the 5-phosphate from the inositol ring of various 5-position phosphorylated phosphoinositides (PIs) and inositol phosphates (IPs), and to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. Synj1 occurs as two main isoforms: a brain enriched 145 KDa protein (Synj1-145) and a ubiquitously expressed 170KDa protein (Synj1-170). Synj1-145 participates in clathrin-mediated endocytosis. The primary substrate of the Synj1-145 INPP5c domain is PI(4,5)P2, which it converts to PI4P. Synj1-145 may work with membrane curvature sensors/generators (such as endophilin) to remove PI(4,5)P2 from curved membranes. The recruitment of the INPP5c domain of Synj1-145 to endophilin-induced membranes leads to a fragmentation and condensation of these structures. The PI(4,5)P2 to PI4P conversion may cooperate with dynamin to produce membrane fission. In addition to this INPP5c domain, these proteins contain an N-terminal Sac1-like domain; the Sac1 domain can dephosphorylate a variety of phosphoinositides in vitro.


Pssm-ID: 197332  Cd Length: 336  Bit Score: 451.42  E-value: 2.99e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:cd09098   60 MVELNAGNIVSASTTNQKLWAAELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGA 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDW 160
Cdd:cd09098  140 VAIRMLFHTTSLCFVCSHFAAGQSQVKERNEDFIEIARKLSFPMGRMLFSHDYVFWCGDFNYRIDIPNEEVKELIRQQNW 219

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 161 KKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKHPFDKTAGELNLLDSDL 240
Cdd:cd09098  220 DSLIAGDQLINQKNAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPFDRSAEDLDLLNASF 299

                        250       260       270
                 ....*....|....*....|....*....|....
gi 530384177 241 DVDTKVRHTWSPGALQYYGRAELQASDHRPVLAI 274
Cdd:cd09098  300 PDNSKEQYTWSPGTLLHYGRAELKTSDHRPVVAL 333
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 1-274 6.59e-111

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: 342.77  E-value: 6.59e-111
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRD--VAIDTVKTGMGGKAGNK 78
Cdd:cd09074   42 VDMSVQGFVGNDDSAKAREWVDNIQEALNEKENYVLLGSAQLVGIFLFVFVKKEHLPQIKDleVEGVTVGTGGGGKLGNK 121

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  79 GAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMG----RNVFSHDYVFWCGDFNYRIDLTYEEVFYF 154
Cdd:cd09074  122 GGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDILSKLKFYRGdpaiDSIFDHDVVFWFGDLNYRIDSTDDEVRKL 201

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 155 VKRQDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWWRKKhpfdktageln 234
Cdd:cd09074  202 ISQGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYKSKA----------- 270

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 530384177 235 lldsdldvdtkvrhtWSPGALQYYGRAELQ-ASDHRPVLAI 274
Cdd:cd09074  271 ---------------GSEIQPLSYTSVPLYkTSDHKPVRAT 296
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 1-274 2.12e-93

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 296.96  E-value: 2.12e-93
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177     1 MVELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGA 80
Cdd:smart00128  48 VVGLAPGVILETIAGKERLWSDLLESSLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGA 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177    81 VGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGR--NVFSHDYVFWCGDFNYRIDL-TYEEVFYFVKR 157
Cdd:smart00128 128 VAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDYKTILRALSFPERAllSQFDHDVVFWFGDLNFRLDSpSYEEVRRKISK 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   158 QDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDV-GSAAYDTSDKCRTPAWTDRVLWwrkkhpfDKTAGELNLL 236
Cdd:smart00128 208 KEFDDLLEKDQLNRQREAGKVFKGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILY-------RSNGPELIQL 280

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 530384177   237 DSdldvdtkvrhtwspgalqYYGRAELQASDHRPVLAI 274
Cdd:smart00128 281 SE------------------YHSGMEITTSDHKPVFAT 300
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 2-274 1.57e-92

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: 294.25  E-value: 1.57e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   2 VELSAGNIVNASTTNKKMWGEQLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKG 79
Cdd:cd09090   43 VELTAGQILNSDPSKSSFWEKKIKTTLNGrgGEKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKG 122

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  80 AVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQD 159
Cdd:cd09090  123 AVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIARGLRFSRGRTIKDHDHVIWLGDFNYRISLTNEDVRRFILNGK 202

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 160 WKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLwwRKKHPFDKTAgelnlldsd 239
Cdd:cd09090  203 LDKLLEYDQLNQQMNAGEVFPGFSEGPITFPPTYKYDKGTDNYDTSEKQRIPAWTDRIL--YRGENLRQLS--------- 271

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530384177 240 ldvdtkvrhtwspgalqyYGRAELQASDHRPVLAI 274
Cdd:cd09090  272 ------------------YNSAPLRFSDHRPVYAT 288
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 2-273 1.10e-84

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: 273.42  E-value: 1.10e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   2 VELSAGNIVNASTTNKKMWGEQLQKAISRSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAV 81
Cdd:cd09093   40 LDLSAEAFLFNDSSREQEWVKAVERGLHPDAKYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGV 119

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  82 GIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMG----RNVFSHDYVFWCGDFNYRI-DLTYEEVFYFVK 156
Cdd:cd09093  120 AVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICARMKFEDPdgppLSISDHDVVFWLGDLNYRIqELPTEEVKELIE 199

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 157 RQDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWwrkkhpfdkTAGELNLL 236
Cdd:cd09093  200 KNDLEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILW---------RGTNIVQL 270

                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 530384177 237 DsdldvdtkvrhtwspgalqYYGRAELQASDHRPVLA 273
Cdd:cd09093  271 S-------------------YRSHMELKTSDHKPVSA 288
DUF1866 pfam08952
Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known ...
 285-421 4.10e-70

Domain of unknown function (DUF1866); This domain, found in Synaptojanin, has no known function.


Pssm-ID: 286093  Cd Length: 146  Bit Score: 228.54  E-value: 4.10e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  285 GARERVFQEVSSFQGPLDATVVVNLQSPTLEEKNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDV 364
Cdd:pfam08952  10 EARRRVFKEVIRDQGPPDGTIVVSLCSGDLDEKNIFDENLMDELIQELTSFGEVTLVRFVEDTMWVTFRDGHSALNALSK 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 530384177  365 DGMKVKGRAVKIRPKTKDWLKGLREEIIRKRDSMAPVSPTANSCLLEENFDFTSLDY 421
Cdd:pfam08952  90 DGMKVCGRALKIRLKSKDWIKGLEEEIILCTDNTIPVSPCANSTLLAEDFDFGSPDY 146
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 20-274 4.88e-68

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: 228.79  E-value: 4.88e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  20 WGEQLQKAISrSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHL 99
Cdd:cd09094   59 WSDLFMDILS-PKGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHL 137

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 100 TAGQSQVKERNEDYKEITQKLCFPMGR--NVFSHDYVFWCGDFNYRI-DLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSG 176
Cdd:cd09094  138 PAHMEKWEQRIDDFETILSTQVFNECNtpSILDHDYVFWFGDLNFRIeDVSIEFVRELVNSKKYHLLLEKDQLNMAKRKE 217

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 177 KIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLWwrkkhpfdktagELNLLDSDLDVDTKVRHTwspgalQ 256
Cdd:cd09094  218 EAFQGFQEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILW------------KVNPDASTEEKFLSITQT------S 279

                        250
                 ....*....|....*...
gi 530384177 257 YYGRAELQASDHRPVLAI 274
Cdd:cd09094  280 YKSHMEYGISDHKPVTAQ 297
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
2-218 1.63e-61

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 216.19  E-value: 1.63e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177   2 VELSAGNIVNASTtnKKMWGEQLQKAIS------RSHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKA 75
Cdd:COG5411   73 VELTPGSILSADP--YDRLRIWESKVLDclngaqSDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSS 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  76 GNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFV 155
Cdd:COG5411  151 SNKGAVAIRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLRIYDHDTIFWLGDLNYRVTSTNEEVRPEI 230

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530384177 156 KRQDWK--KLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVL 218
Cdd:COG5411  231 ASDDGRldKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRIL 295
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 10-274 1.38e-56

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: 197.26  E-value: 1.38e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  10 VNASTTNKKMWGEQLQKAISRSHryILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHS 89
Cdd:cd09095   44 VQEGCSDRREWEIRLQETLGPSH--VLLHSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFG 121

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  90 TSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPmgRNVFSHDY-------------VFWCGDFNYRIDLTYEEVFYFVK 156
Cdd:cd09095  122 TSFLFITSHFTSGDGKVKERVLDYNKIIQALNLP--RNVPTNPYksesgdvttrfdeVFWFGDFNFRLSGPRHLVDALIN 199

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 157 R---QDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSAAYDTSDKCRTPAWTDRVLwWRKKHPFDKTagel 233
Cdd:cd09095  200 QgqeVDVSALLQHDQLTREMSKGSIFKGFQEAPIHFPPTYKFDIGSDVYDTSSKQRVPSYTDRIL-YRSRQKGDVC---- 274

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 530384177 234 nlldsdldvdtkvrhtwspgALQYYGRAELQASDHRPVLAI 274
Cdd:cd09095  275 --------------------CLKYNSCPSIKTSDHRPVFAL 295
RRM_SYNJ2 cd12720
RNA recognition motif (RRM) found in synaptojanin-2 and similar proteins; This subgroup ...
 302-379 1.16e-46

RNA recognition motif (RRM) found in synaptojanin-2 and similar proteins; This subgroup corresponds to the RRM of synaptojanin-2, also termed synaptic inositol-1,4,5-trisphosphate 5-phosphatase 2, an ubiquitously expressed central regulatory enzyme in the phosphoinositide-signaling cascade. As a novel Rac1 effector regulating the early step of clathrin-mediated endocytosis, synaptojanin-2 acts as a polyphosphoinositide phosphatase directly and specifically interacting with Rac1 in a GTP-dependent manner. It mediates the inhibitory effect of Rac1 on endocytosis and plays an important role in the Rac1-mediated control of cell growth. Synaptojanin-2 shows high sequence homology to the N-terminal Sac1p homology domain, the central inositol 5-phosphatase domain, the putative RNA recognition motif (RRM) of synaptojanin-1, but differs in the proline-rich region.


Pssm-ID: 410119 [Multi-domain]  Cd Length: 78  Bit Score: 160.72  E-value: 1.16e-46
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530384177 302 DATVVVNLQSPTLEEKNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDVDGMKVKGRAVKIRPK 379
Cdd:cd12720    1 DATVVVNLLSPTLEEKNDFPEDLSTELVQCFQSYGTVILVRFNRGQMLVTFEDSRSALRVLDLDGIKVNGRAVKIKPK 78
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 33-274 1.20e-41

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 162.38  E-value: 1.20e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  33 RYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKE--RN 110
Cdd:PLN03191 363 KYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRN 442

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 111 EDYKEITQKLCFP------MGRNVFSHDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKDFHE 184
Cdd:PLN03191 443 ADVYEIIRRTRFSsvldtdQPQTIPSHDQIFWFGDLNYRLNMLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKE 522

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 185 GAINFGPTYKYDVGSAAY-----DTSDKCRTPAWTDRVLWWRKkhpfdktagelnlldsdldvdtkvrhtwspGALQ-YY 258
Cdd:PLN03191 523 GPIKFPPTYKYEINSDRYvgenpKEGEKKRSPAWCDRILWLGK------------------------------GIKQlCY 572

                        250
                 ....*....|....*.
gi 530384177 259 GRAELQASDHRPVLAI 274
Cdd:PLN03191 573 KRSEIRLSDHRPVSSM 588
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 17-273 1.78e-38

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: 145.86  E-value: 1.78e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  17 KKMWGEQLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCF 94
Cdd:cd09091   55 EKEWLDLLRHSLKEltSLDYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGF 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  95 ICSHLTAGQSQVKERNEDYKEITQKLCF---PMGRNVFSH--DYVFWCGDFNYRIDLTYEEVFYFVKR---QDWKKLLEF 166
Cdd:cd09091  135 VNSHLTSGSEKKLRRNQNYLNILRFLSLgdkKLSAFNITHrfTHLFWLGDLNYRLDLPIQEAENIIQKieqQQFEPLLRH 214

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 167 DQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSA---AYD----TSDKCRTPAWTDRVLWwrKKHPfdktagELNLLdsd 239
Cdd:cd09091  215 DQLNLEREEHKVFLRFSEEEITFPPTYRYERGSRdtyAYTkqkaTGVKYNLPSWCDRILW--KSYP------ETHII--- 283

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530384177 240 ldvdtkvrhtwspgaLQYYG-RAELQASDHRPVLA 273
Cdd:cd09091  284 ---------------CQSYGcTDDIVTSDHSPVFG 303
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 49-225 2.18e-38

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: 145.50  E-value: 2.18e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  49 IFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCFICSHLTAGQSQVKERNEDYKEITQKLCFPMGR-N 127
Cdd:cd09101   89 VLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQNYLDILRSLSLGDKQlN 168

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 128 VFS----HDYVFWCGDFNYRIDLTYEEVFYFVKRQDWKKLLEFDQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSA-AY 202
Cdd:cd09101  169 AFDislrFTHLFWFGDLNYRLDMDIQEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFREEEISFPPTYRYERGSRdTY 248

                        170       180
                 ....*....|....*....|....*....
gi 530384177 203 ------DTSDKCRTPAWTDRVLWwrKKHP 225
Cdd:cd09101  249 mwqkqkTTGMRTNVPSWCDRILW--KSYP 275
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 17-225 2.37e-38

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: 145.51  E-value: 2.37e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  17 KKMWGEQLQKAISR--SHRYILLTSAQLVGVCLYIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVGIRFQFHSTSFCF 94
Cdd:cd09100   55 EKEWLDTLKHSLREitSISFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGF 134

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  95 ICSHLTAGQSQVKERNEDYKEITQKLCF---PMGRNVFSH--DYVFWCGDFNYRIDL---TYEEVFYFVKRQDWKKLLEF 166
Cdd:cd09100  135 VNSHLTSGSEKKLRRNQNYFNILRFLVLgdkKLSPFNITHrfTHLFWLGDLNYRVELpntEAENIIQKIKQQQYQELLPH 214

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530384177 167 DQLQLQKSSGKIFKDFHEGAINFGPTYKYDVGSA---AYD----TSDKCRTPAWTDRVLWwrKKHP 225
Cdd:cd09100  215 DQLLIERKESKVFLQFEEEEITFAPTYRFERGTReryAYTkqkaTGMKYNLPSWCDRVLW--KSYP 278
RRM_SYNJ cd12440
RNA recognition motif (RRM) found in synaptojanin-1, synaptojanin-2 and similar proteins; This ...
 302-379 9.24e-33

RNA recognition motif (RRM) found in synaptojanin-1, synaptojanin-2 and similar proteins; This subfamily corresponds to the RRM of two active phosphatidylinositol phosphate phosphatases, synaptojanin-1 and synaptojanin-2. They have different interaction partners and are likely to have different biological functions. Synaptojanin-1 was originally identified as one of the major Grb2-binding proteins that may participate in synaptic vesicle endocytosis. It also acts as a Src homology 3 (SH3) domain-binding brain-specific inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Synaptojanin-2 is a ubiquitously expressed homolog of synaptojanin-1. It is a novel Rac1 effector regulating the early step of clathrin-mediated endocytosis. Synaptojanin-2 directly and specifically interacts with Rac1 in a GTP-dependent manner. It mediates the inhibitory effect of Rac1 on endocytosis and plays an important role in the Rac1-mediated control of cell growth. Both, synaptojanin-1 and synaptojanin-2, have two tissue-specific alternative splicing isoforms, a shorter isoform expressed in brain and a longer isoform in peripheral tissues. Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p, a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2. Synaptojanin-2 shows high sequence homology to the N-terminal Sac1p homology domain, the central inositol 5-phosphatase domain, the putative RNA recognition motif (RRM) of synaptojanin-1, but differs in the proline-rich region.


Pssm-ID: 409874 [Multi-domain]  Cd Length: 77  Bit Score: 121.38  E-value: 9.24e-33
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530384177 302 DATVVVNLQSPTlEEKNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDVDGMKVKGRAVKIRPK 379
Cdd:cd12440    1 DATVVVSLDSKS-EEWNEFEDALIGELLRVLASYGDVVLVRFAHEGMLVTFRDGRSALAALALNGKQILGRTLKIRLK 77
RRM_SYNJ1 cd12719
RNA recognition motif (RRM) found in synaptojanin-1 and similar proteins; This subgroup ...
 302-379 7.46e-12

RNA recognition motif (RRM) found in synaptojanin-1 and similar proteins; This subgroup corresponds to the RRM of synaptojanin-1, also termed synaptojanin, or synaptic inositol-1,4,5-trisphosphate 5-phosphatase 1, originally identified as one of the major Grb2-binding proteins that may participate in synaptic vesicle endocytosis. It also acts as a Src homology 3 (SH3) domain-binding brain-specific inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Synaptojanin-1 contains an N-terminal domain homologous to the cytoplasmic portion of the yeast protein Sac1p, a central inositol 5-phosphatase domain followed by a putative RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), and a C-terminal proline-rich region mediating the binding of synaptojanin-1 to various SH3 domain-containing proteins including amphiphysin, SH3p4, SH3p8, SH3p13, and Grb2. Synaptojanin-1 has two tissue-specific alternative splicing isoforms, synaptojanin-145 expressed in brain and synaptojanin-170 expressed in peripheral tissues. Synaptojanin-145 is very abundant in nerve terminals and may play an essential role in the clathrin-mediated endocytosis of synaptic vesicles. In contrast to synaptojanin-145, synaptojanin-170 contains three unique asparagine-proline-phenylalanine (NPF) motifs in the C-terminal region and may functions as a potential binding partner for Eps15, a clathrin coat-associated protein acting as a major substrate for the tyrosine kinase activity of the epidermal growth factor receptor.


Pssm-ID: 410118  Cd Length: 77  Bit Score: 61.65  E-value: 7.46e-12
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530384177 302 DATVVVNLQSPTLEEkNEFPEDLRTELMQTLGSYGTIVLVRINQGQMLVTFADSHSALSVLDVDGMKVKGRAVKIRPK 379
Cdd:cd12719    1 DGTVVVSVLSSSPEP-NYFDDNLIDALLQQFSSFGEVILIRFVEDKMWVTFLEGSSALAALSLNGTEVLGRTIIISLK 77
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 24-273 2.53e-11

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


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 64.81  E-value: 2.53e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  24 LQKAISrSHRYILLTSAQLVGVCLYIFVRPYHVP-------FIRD--VAIDTVKTGMGGKA--GNKGAVGIRFQFHSTSF 92
Cdd:cd08372   32 LQEVKD-SQYSAVALNQLLPEGYHQYQSGPSRKEgyegvaiLSKTpkFKIVEKHQYKFGEGdsGERRAVVVKFDVHDKEL 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  93 CFICSHLTAGQSQVKERNEDYKEITQKLcfpMGRNVFSHDYVFWCGDFNYRIDLTYEEVfyfvkrqdWKKLLEFdqlqlq 172
Cdd:cd08372  111 CVVNAHLQAGGTRADVRDAQLKEVLEFL---KRLRQPNSAPVVICGDFNVRPSEVDSEN--------PSSMLRL------ 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 173 KSSGKiFKDFHEgAINFGPTYKydvgsaaydtSDKCRTPAWTDRVLwwrkkhpfdktagelnlldSDLDVDTKVRHTWSp 252
Cdd:cd08372  174 FVALN-LVDSFE-TLPHAYTFD----------TYMHNVKSRLDYIF-------------------VSKSLLPSVKSSKI- 221

                        250       260
                 ....*....|....*....|.
gi 530384177 253 gaLQYYGRAELqASDHRPVLA 273
Cdd:cd08372  222 --LSDAARARI-PSDHYPIEV 239
PRK12323 PRK12323
DNA polymerase III subunit gamma/tau;
559-757 1.27e-03

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237057 [Multi-domain]  Cd Length: 700  Bit Score: 42.56  E-value: 1.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 559 PGAPQQPPKARTGISKPYnvkqiKTTNAQEAEAAIRCLLEARGGASEEALSAVAprdleassePEPTPgAAKPETPQAPP 638
Cdd:PRK12323 407 AAAPAAAAAARAVAAAPA-----RRSPAPEALAAARQASARGPGGAPAPAPAPA---------AAPAA-AARPAAAGPRP 471

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 639 LLPRRPPPRVPAIKKPTLRRTGKPLSPEEQFeqqtvhftigpPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPShrK 718
Cdd:PRK12323 472 VAAAAAAAPARAAPAAAPAPADDDPPPWEEL-----------PPEFASPAPAQPDAAPAGWVAESIPDPATADPDDA--F 538

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 530384177 719 PASDEAPPGAGASvPPPLEAPPLVPKVPPRRKKSA-PAAF 757
Cdd:PRK12323 539 ETLAPAPAAAPAP-RAAAATEPVVAPRPPRASASGlPDMF 577
PRK07003 PRK07003
DNA polymerase III subunit gamma/tau;
559-764 2.00e-03

DNA polymerase III subunit gamma/tau;


Pssm-ID: 235906 [Multi-domain]  Cd Length: 830  Bit Score: 42.14  E-value: 2.00e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 559 PGAPQQPPKARtgiskpynvkQIKTTNAQEAEAAIRCLLEARGGASEEALSAVAPRDLEASSEPEPTPGAAKPETPQAPP 638
Cdd:PRK07003 368 PGGGVPARVAG----------AVPAPGARAAAAVGASAVPAVTAVTGAAGAALAPKAAAAAAATRAEAPPAAPAPPATAD 437

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 639 LLPRRPPPRVPAIKKPTLRRTGKPLSPEEQFEQQTVHFTIGPPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPShRK 718
Cdd:PRK07003 438 RGDDAADGDAPVPAKANARASADSRCDERDAQPPADSGSASAPASDAPPDAAFEPAPRAAAPSAATPAAVPDARAPA-AA 516

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 530384177 719 PASDEAPPGAgasvPPPLEAPPLVPKV--PPRRKKSAPAAfhLQVLQS 764
Cdd:PRK07003 517 SREDAPAAAA----PPAPEARPPTPAAaaPAARAGGAAAA--LDVLRN 558
PHA03247 PHA03247
large tegument protein UL36; Provisional
 448-820 2.04e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.23  E-value: 2.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  448 ELGGDDLSDVPGPTALAPPSKSPALTKKKQHPTykddadlvelKRELEAVGEFRHRSPsrslSVPNRPRPPqppqrpppp 527
Cdd:PHA03247 2542 ELASDDAGDPPPPLPPAAPPAAPDRSVPPPRPA----------PRPSEPAVTSRARRP----DAPPQSARP--------- 2598

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  528 tglmvKKSASDASISSGThgqysiLQTARLLPGAPQQPPKARTGISKPYNVKQIKTTNAQEAEAAIRCllEARGGASEEA 607
Cdd:PHA03247 2599 -----RAPVDDRGDPRGP------APPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDD--PAPGRVSRPR 2665

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  608 LSAVAPRDLEASSEPE-PTPGAAKPETpqappllprrppprvpaikkPTLRRTGKPLSPEEQFEQQTVHFTIGPPetsve 686
Cdd:PHA03247 2666 RARRLGRAAQASSPPQrPRRRAARPTV--------------------GSLTSLADPPPPPPTPEPAPHALVSATP----- 2720

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  687 APPVVTAPRVPPVPKPRTFQPGKAAERPShrKPASDEAPPGAGASVPPPLEAPPLVPKVPPRRKKSAPAAFHLQVlqsns 766
Cdd:PHA03247 2721 LPPGPAAARQASPALPAAPAPPAVPAGPA--TPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSE----- 2793

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....
gi 530384177  767 qllqglTYNSSDSPSGHPPAAGTVFPQGDFLSTSSATSPDSDGTKAMKPEAAPL 820
Cdd:PHA03247 2794 ------SRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPP 2841
PRK12727 PRK12727
flagellar biosynthesis protein FlhF;
552-770 2.37e-03

flagellar biosynthesis protein FlhF;


Pssm-ID: 237182 [Multi-domain]  Cd Length: 559  Bit Score: 41.51  E-value: 2.37e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 552 LQTARL-LPGAPQQPPKARTGISKPYNVKQIKTTNAQEAEAAIRcllEARGGASEEALSAVAPRdlEASSEPEPTPgAAK 630
Cdd:PRK12727  55 LETARSdTPATAAAPAPAPQAPTKPAAPVHAPLKLSANANMSQR---QRVASAAEDMIAAMALR--QPVSVPRQAP-AAA 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 631 PETPQAPPLLPRRPPPRVPAIKKPTLRRTGKPLSPEEQFEQqtvhFTIGPPetsVEAPPVVTAPRVPPVPKPRTFQPGKA 710
Cdd:PRK12727 129 PVRAASIPSPAAQALAHAAAVRTAPRQEHALSAVPEQLFAD----FLTTAP---VPRAPVQAPVVAAPAPVPAIAAALAA 201

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530384177 711 AERPSHRKPASDEAPPGAGASVPPPLEAPPLVPKV---PPRRKKSAPAAFHLQVLQSNSQLLQ 770
Cdd:PRK12727 202 HAAYAQDDDEQLDDDGFDLDDALPQILPPAALPPIvvaPAAPAALAAVAAAAPAPQNDEELKQ 264
PRK12323 PRK12323
DNA polymerase III subunit gamma/tau;
601-821 3.53e-03

DNA polymerase III subunit gamma/tau;


Pssm-ID: 237057 [Multi-domain]  Cd Length: 700  Bit Score: 41.01  E-value: 3.53e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 601 GGASEEALSAVAPRDLEASSEPEPTPGAAKPETPQAPPLLPRRPpprvpAIKKPTLRRTGKPLSPEEQFEQQTVHFTIGP 680
Cdd:PRK12323 369 GGGAGPATAAAAPVAQPAPAAAAPAAAAPAPAAPPAAPAAAPAA-----AAAARAVAAAPARRSPAPEALAAARQASARG 443

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177 681 PETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPSHRKPASDEAPPGAGASVPPPLE-APPLVPKVPPRRKKSAPAAFhl 759
Cdd:PRK12323 444 PGGAPAPAPAPAAAPAAAARPAAAGPRPVAAAAAAAPARAAPAAAPAPADDDPPPWEeLPPEFASPAPAQPDAAPAGW-- 521

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530384177 760 qVLQSNSQLLQGLTYNSSDSPSGHPPAAGTVFPQGDFLSTSSATSPD--SDGTKAMKPEAAPLL 821
Cdd:PRK12323 522 -VAESIPDPATADPDDAFETLAPAPAAAPAPRAAAATEPVVAPRPPRasASGLPDMFDGDWPAL 584
PHA03307 PHA03307
transcriptional regulator ICP4; Provisional
 680-861 4.56e-03

transcriptional regulator ICP4; Provisional


Pssm-ID: 223039 [Multi-domain]  Cd Length: 1352  Bit Score: 40.92  E-value: 4.56e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  680 PPETSVEAPPVVTAPRVPPVPKPRTFQPGKAAERPSHRKPASDEAPPGAGASVPPPLEAPPLVPKVPPRRKKSAPAAFHL 759
Cdd:PHA03307   72 PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384177  760 QVLQSNSqllqgltynSSDSPSGHPPAAGTVFPQGdflSTSSATSPDSDGTKAMKPEAAPLLGDyqdpfwnllHHPKLLN 839
Cdd:PHA03307  152 PPAAGAS---------PAAVASDAASSRQAALPLS---SPEETARAPSSPPAEPPPSTPPAAAS---------PRPPRRS 210

                         170       180
                  ....*....|....*....|..
gi 530384177  840 NTWLSKSSDPLDSGTRSPKRDP 861
Cdd:PHA03307  211 SPISASASSPAPAPGRSAADDA 232
 
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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