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Conserved domains on  [gi|24663242|ref|NP_648566|]
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inositol polyphosphate 5-phosphatase E, isoform A [Drosophila melanogaster]

Protein Classification

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

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

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EEP super family cl00490
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 387-703 1.96e-163

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 cd09095:

Pssm-ID: 469791  Cd Length: 298  Bit Score: 473.45  E-value: 1.96e-163
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 387 PQKEITVFVGTWNMNG-HSPPKQLNDFVLPANVEHVPDIVVMGTQESTPDRFEWEVTIQETLGPSHVLFHATTLGTLHLA 465
Cdd:cd09095   1 PDRNVGIFVATWNMQGqKELPENLDDFLLPTSADFAQDIYVIGVQEGCSDRREWEIRLQETLGPSHVLLHSASHGVLHLA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 466 VYMRRDLIWYCSVPEDASMSVRTGSAFRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIINALDLPRNLPN 545
Cdd:cd09095  81 VFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 546 Q--RHKNKDVTQNFDNVFWCGDLNFRLGEPREKLLEWIQNTkfplPSHLPHGYMHTDQLTSVLADGAAFRGFMEANITFP 623
Cdd:cd09095 161 NpyKSESGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQG----QEVDVSALLQHDQLTREMSKGSIFKGFQEAPIHFP 236

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 624 PTYKYDPGSQNFDTSSKQRAPAYTDRILYKYRQmqglvirrqtlvpgvstptQPHVQCLLYDSVPSITTSDHKPVWALFR 703
Cdd:cd09095 237 PTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRQ-------------------KGDVCCLKYNSCPSIKTSDHRPVFALFR 297
 
Name Accession Description Interval E-value
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 387-703 1.96e-163

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: 473.45  E-value: 1.96e-163
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 387 PQKEITVFVGTWNMNG-HSPPKQLNDFVLPANVEHVPDIVVMGTQESTPDRFEWEVTIQETLGPSHVLFHATTLGTLHLA 465
Cdd:cd09095   1 PDRNVGIFVATWNMQGqKELPENLDDFLLPTSADFAQDIYVIGVQEGCSDRREWEIRLQETLGPSHVLLHSASHGVLHLA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 466 VYMRRDLIWYCSVPEDASMSVRTGSAFRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIINALDLPRNLPN 545
Cdd:cd09095  81 VFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 546 Q--RHKNKDVTQNFDNVFWCGDLNFRLGEPREKLLEWIQNTkfplPSHLPHGYMHTDQLTSVLADGAAFRGFMEANITFP 623
Cdd:cd09095 161 NpyKSESGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQG----QEVDVSALLQHDQLTREMSKGSIFKGFQEAPIHFP 236

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 624 PTYKYDPGSQNFDTSSKQRAPAYTDRILYKYRQmqglvirrqtlvpgvstptQPHVQCLLYDSVPSITTSDHKPVWALFR 703
Cdd:cd09095 237 PTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRQ-------------------KGDVCCLKYNSCPSIKTSDHRPVFALFR 297
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 391-703 2.95e-61

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 208.36  E-value: 2.95e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    391 ITVFVGTWNMNGHSPPKQL--NDF--VLPANVEHVPDIVVMGTQE------------STPDRFEWEVTIQETL-GPSHVL 453
Cdd:smart00128   3 IKVLIGTWNVGGLESPKVDvtSWLfqKIEVKQSEKPDIYVIGLQEvvglapgviletIAGKERLWSDLLESSLnGDGQYN 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    454 FHATT-LGTLHLAVYMRRDLIWYcsVPEDASMSVRTGSAF--RTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDV 530
Cdd:smart00128  83 VLAKVyLVGILVLVFVKANHLVY--IKDVETFTVKTGMGGlwGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    531 KRIINALDLPRN-LPNQRHknkdvtqnFDNVFWCGDLNFRLGEPR-EKLLEWIQNTKF-PLpshlphgyMHTDQLTSVLA 607
Cdd:smart00128 161 KTILRALSFPERaLLSQFD--------HDVVFWFGDLNFRLDSPSyEEVRRKISKKEFdDL--------LEKDQLNRQRE 224

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    608 DGAAFRGFMEANITFPPTYKYDP-GSQNFDTSSKQRAPAYTDRILYKyrqmqglvirrqtlvpgvstPTQPHV-QCLLYD 685
Cdd:smart00128 225 AGKVFKGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYR--------------------SNGPELiQLSEYH 284

                          330
                   ....*....|....*...
gi 24663242    686 SVPSITTSDHKPVWALFR 703
Cdd:smart00128 285 SGMEITTSDHKPVFATFR 302
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
383-746 1.79e-45

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 169.19  E-value: 1.79e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 383 SRVLPQKEITVFVGTWNMNGHSPPKQLNDFVLPANVEHV-PDIVVMGTQES---TPDRF----------EWEVTIQETL- 447
Cdd:COG5411  22 SKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEATElADLYVVGLQEVvelTPGSIlsadpydrlrIWESKVLDCLn 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 448 ----GPSHVLFHATTLGTLHLAVYMRRDLIwycSVPEDASMSVR-TGSAFRT--KGAVAISFCLFGTSMLFVTSHLTAHQ 520
Cdd:COG5411 102 gaqsDEKYSLLRSPQLGGILLRVFSLATNL---PVVKPVSGTVKkTGFGGSSsnKGAVAIRFNYERTSFCFVNSHLAAGV 178

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 521 QKVKERVSDVKRIINALDLPRNLPNQRHknkdvtqnfDNVFWCGDLNFRLGEPREKLLEWIQNTKFPLPSHLphgymHTD 600
Cdd:COG5411 179 NNIEERIFDYRSIASNICFSRGLRIYDH---------DTIFWLGDLNYRVTSTNEEVRPEIASDDGRLDKLF-----EYD 244

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 601 QLTSVLADGAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKyrqmqglvirrqtlvpgvSTPTQPHVq 680
Cdd:COG5411 245 QLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYK------------------SEQLTPHS- 305

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24663242 681 cllYDSVPSITTSDHKPVWALFRTLIRAgTDAIPLAagLFSRDIYLEGMRRRLNNQYSGASAVCVL 746
Cdd:COG5411 306 ---YSSIPHLMISDHRPVYATFRAKIKV-VDPSKKE--GLIEKLYAEYKTELGEAGDISCDNFTIL 365
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 495-702 1.44e-21

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 99.60  E-value: 1.44e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242  495 KGAVAISFCLFGTSMLFVTSHLTAHQQKVKE--RVSDVKRIINAL--------DLPRNLPNQrhknkdvtqnfDNVFWCG 564
Cdd:PLN03191 408 KGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRNADVYEIIRRTrfssvldtDQPQTIPSH-----------DQIFWFG 476

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242  565 DLNFRL----GEPRE--KLLEWIQntkfplpshlphgYMHTDQLTSVLADGAAFRGFMEANITFPPTYKYDPGS-----Q 633
Cdd:PLN03191 477 DLNYRLnmldTEVRKlvAQKRWDE-------------LINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSdryvgE 543

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24663242  634 NFDTSSKQRAPAYTDRILYKYRQMQGLVIRRQtlvpgvstptqphvqcllydsvpSITTSDHKPVWALF 702
Cdd:PLN03191 544 NPKEGEKKRSPAWCDRILWLGKGIKQLCYKRS-----------------------EIRLSDHRPVSSMF 589
 
Name Accession Description Interval E-value
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 387-703 1.96e-163

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: 473.45  E-value: 1.96e-163
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 387 PQKEITVFVGTWNMNG-HSPPKQLNDFVLPANVEHVPDIVVMGTQESTPDRFEWEVTIQETLGPSHVLFHATTLGTLHLA 465
Cdd:cd09095   1 PDRNVGIFVATWNMQGqKELPENLDDFLLPTSADFAQDIYVIGVQEGCSDRREWEIRLQETLGPSHVLLHSASHGVLHLA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 466 VYMRRDLIWYCSVPEDASMSVRTGSAFRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIINALDLPRNLPN 545
Cdd:cd09095  81 VFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKERVLDYNKIIQALNLPRNVPT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 546 Q--RHKNKDVTQNFDNVFWCGDLNFRLGEPREKLLEWIQNTkfplPSHLPHGYMHTDQLTSVLADGAAFRGFMEANITFP 623
Cdd:cd09095 161 NpyKSESGDVTTRFDEVFWFGDFNFRLSGPRHLVDALINQG----QEVDVSALLQHDQLTREMSKGSIFKGFQEAPIHFP 236

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 624 PTYKYDPGSQNFDTSSKQRAPAYTDRILYKYRQmqglvirrqtlvpgvstptQPHVQCLLYDSVPSITTSDHKPVWALFR 703
Cdd:cd09095 237 PTYKFDIGSDVYDTSSKQRVPSYTDRILYRSRQ-------------------KGDVCCLKYNSCPSIKTSDHRPVFALFR 297
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 391-703 1.14e-78

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: 254.56  E-value: 1.14e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNG-HSPPKQLNDFVLPANvEHVPDIVVMGTQE------------STPDRFEWEVTIQETLGPSH--VLFH 455
Cdd:cd09074   1 VKIFVVTWNVGGgISPPENLENWLSPKG-TEAPDIYAVGVQEvdmsvqgfvgndDSAKAREWVDNIQEALNEKEnyVLLG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 456 ATTLGTLHLAVYMRRDLIWYCSVPEDASMSVRTGSAFRT--KGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRI 533
Cdd:cd09074  80 SAQLVGIFLFVFVKKEHLPQIKDLEVEGVTVGTGGGGKLgnKGGVAIRFQINDTSFCFVNSHLAAGQEEVERRNQDYRDI 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 534 INALDLPRNLPNqrhknKDVTQNFDNVFWCGDLNFRLGEPREKLLEWIQNTKFplpshlpHGYMHTDQLTSVLADGAAFR 613
Cdd:cd09074 160 LSKLKFYRGDPA-----IDSIFDHDVVFWFGDLNYRIDSTDDEVRKLISQGDL-------DDLLEKDQLKKQKEKGKVFD 227

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 614 GFMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKyrqmqglvirrqtlvpgVSTPTqpHVQCLLYDSVPSITTS 693
Cdd:cd09074 228 GFQELPITFPPTYKFDPGTDEYDTSDKKRIPAWCDRILYK-----------------SKAGS--EIQPLSYTSVPLYKTS 288

                       330
                ....*....|
gi 24663242 694 DHKPVWALFR 703
Cdd:cd09074 289 DHKPVRATFR 298
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 391-703 1.17e-63

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: 214.13  E-value: 1.17e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSPPKQLNDFVLPANVEHVPDIVVMGTQE-----------STPDRFE-WEVTIQETL----GPSHVLF 454
Cdd:cd09090   1 INIFVGTFNVNGKSYKDDLSSWLFPEENDELPDIVVIGLQEvveltagqilnSDPSKSSfWEKKIKTTLngrgGEKYVLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 455 HATTLGTLHLAVYMRRDLIWYCSVPEDASMSVRTGSAFRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRII 534
Cdd:cd09090  81 RSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNYEERNNDYKTIA 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 535 NALDLPRNLPNQRHknkdvtqnfDNVFWCGDLNFRLGEPREKLLEWIQNTKFPlpshlphGYMHTDQLTSVLADGAAFRG 614
Cdd:cd09090 161 RGLRFSRGRTIKDH---------DHVIWLGDFNYRISLTNEDVRRFILNGKLD-------KLLEYDQLNQQMNAGEVFPG 224

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 615 FMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKyrqmqGLVIRRqtlvpgvstptqphvqcLLYDSVPSItTSD 694
Cdd:cd09090 225 FSEGPITFPPTYKYDKGTDNYDTSEKQRIPAWTDRILYR-----GENLRQ-----------------LSYNSAPLR-FSD 281


                ....*....
gi 24663242 695 HKPVWALFR 703
Cdd:cd09090 282 HRPVYATFE 290
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 391-703 2.95e-61

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 208.36  E-value: 2.95e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    391 ITVFVGTWNMNGHSPPKQL--NDF--VLPANVEHVPDIVVMGTQE------------STPDRFEWEVTIQETL-GPSHVL 453
Cdd:smart00128   3 IKVLIGTWNVGGLESPKVDvtSWLfqKIEVKQSEKPDIYVIGLQEvvglapgviletIAGKERLWSDLLESSLnGDGQYN 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    454 FHATT-LGTLHLAVYMRRDLIWYcsVPEDASMSVRTGSAF--RTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDV 530
Cdd:smart00128  83 VLAKVyLVGILVLVFVKANHLVY--IKDVETFTVKTGMGGlwGNKGAVAVRFKLSDTSFCFVNSHLAAGASNVEQRNQDY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    531 KRIINALDLPRN-LPNQRHknkdvtqnFDNVFWCGDLNFRLGEPR-EKLLEWIQNTKF-PLpshlphgyMHTDQLTSVLA 607
Cdd:smart00128 161 KTILRALSFPERaLLSQFD--------HDVVFWFGDLNFRLDSPSyEEVRRKISKKEFdDL--------LEKDQLNRQRE 224

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242    608 DGAAFRGFMEANITFPPTYKYDP-GSQNFDTSSKQRAPAYTDRILYKyrqmqglvirrqtlvpgvstPTQPHV-QCLLYD 685
Cdd:smart00128 225 AGKVFKGFQEGPITFPPTYKYDSvGTETYDTSEKKRVPAWCDRILYR--------------------SNGPELiQLSEYH 284

                          330
                   ....*....|....*...
gi 24663242    686 SVPSITTSDHKPVWALFR 703
Cdd:smart00128 285 SGMEITTSDHKPVFATFR 302
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 391-702 1.30e-60

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: 207.24  E-value: 1.30e-60
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNG----HSPP---KQLNDFVLPA------------NVEHVPDIVVMGTQE------------STPDRFEW 439
Cdd:cd09089   1 LRVFVGTWNVNGgkhfRSIAfkhQSMTDWLLDNpklagqcsndseEDEKPVDIFAIGFEEmvdlnasnivsaSTTNQKEW 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 440 EVTIQETLGPSH--VLFHATTLGTLHLAVYMRRDLIWYcsVPEDASMSVRTG--SAFRTKGAVAISFCLFGTSMLFVTSH 515
Cdd:cd09089  81 GEELQKTISRDHkyVLLTSEQLVGVCLFVFVRPQHAPF--IRDVAVDTVKTGlgGAAGNKGAVAIRFLLHSTSLCFVCSH 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 516 LTAHQQKVKERVSDVKRIINALDLP--RNLPNQrhknkdvtqnfDNVFWCGDLNFRLGEPREKLLEWIQNTKFPlpshlp 593
Cdd:cd09089 159 FAAGQSQVKERNEDFAEIARKLSFPmgRTLDSH-----------DYVFWCGDFNYRIDLPNDEVKELVRNGDWL------ 221

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 594 hGYMHTDQLTSVLADGAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKYRQMqgLVIRRQTLVPGVST 673
Cdd:cd09089 222 -KLLEFDQLTKQKAAGNVFKGFLEGEINFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKW--PSDKTEESLVETND 298

                       330       340
                ....*....|....*....|....*....
gi 24663242 674 PTQPHVQCLLYDSVpSITTSDHKPVWALF 702
Cdd:cd09089 299 PTWNPGTLLYYGRA-ELKTSDHRPVVAII 326
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 391-702 3.22e-57

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: 196.77  E-value: 3.22e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSPPKQLNDFVlpANVEHVPDIVVMGTQE-----------STPDRFEWEVTIQETLGP--SHVLFHAT 457
Cdd:cd09093   1 FRIFVGTWNVNGQSPDESLRPWL--SCDEEPPDIYAIGFQEldlsaeaflfnDSSREQEWVKAVERGLHPdaKYKKVKLI 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 458 TLGTLHLAVYMRRDLIWYcsVPEDASMSVRTGSAFRT--KGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIIN 535
Cdd:cd09093  79 RLVGMMLLVFVKKEHRQH--IKEVAAETVGTGIMGKMgnKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQDYKDICA 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 536 ALDLPRnlPNQRHKNKDvtqNFDNVFWCGDLNFRLGE-PREKLLEWIQNtkfplpSHLPHGYMHtDQLTSVLADGAAFRG 614
Cdd:cd09093 157 RMKFED--PDGPPLSIS---DHDVVFWLGDLNYRIQElPTEEVKELIEK------NDLEELLKY-DQLNIQRRAGKVFEG 224

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 615 FMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKyrqmqglvirrqtlvpgvstptQPHVQCLLYDSVPSITTSD 694
Cdd:cd09093 225 FTEGEINFIPTYKYDPGTDNWDSSEKCRAPAWCDRILWR----------------------GTNIVQLSYRSHMELKTSD 282


                ....*...
gi 24663242 695 HKPVWALF 702
Cdd:cd09093 283 HKPVSALF 290
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 393-703 2.13e-55

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: 192.20  E-value: 2.13e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 393 VFVGTWNMNGHSPPKQLNDFVLPANVEHVPDIVVMGTQE--STPDRF--------EWEVTIQETLGPSH-VLFHATTLGT 461
Cdd:cd09094   3 VYVVTWNVATAPPPIDVRSLLGLQSPEVAPDIYIIGLQEvnSKPVQFvsdlifddPWSDLFMDILSPKGyVKVSSIRLQG 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 462 LHLAVYMRRDliwycSVP--EDASMS-VRTG--SAFRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIINA 536
Cdd:cd09094  83 LLLLVFVKIQ-----HLPfiRDVQTNyTRTGlgGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRIDDFETILST 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 537 ldlpRNLPNQRHKNkdvTQNFDNVFWCGDLNFRLGE-PREKLLEWIQNTKFplpshlpHGYMHTDQLTSVLADGAAFRGF 615
Cdd:cd09094 158 ----QVFNECNTPS---ILDHDYVFWFGDLNFRIEDvSIEFVRELVNSKKY-------HLLLEKDQLNMAKRKEEAFQGF 223

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 616 MEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKyrqMQGLVIRRQTLVpgvstptqpHVQCLLYDSVPSITTSDH 695
Cdd:cd09094 224 QEGPLNFAPTYKFDLGTDEYDTSGKKRKPAWTDRILWK---VNPDASTEEKFL---------SITQTSYKSHMEYGISDH 291


                ....*...
gi 24663242 696 KPVWALFR 703
Cdd:cd09094 292 KPVTAQFR 299
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
383-746 1.79e-45

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 169.19  E-value: 1.79e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 383 SRVLPQKEITVFVGTWNMNGHSPPKQLNDFVLPANVEHV-PDIVVMGTQES---TPDRF----------EWEVTIQETL- 447
Cdd:COG5411  22 SKYVIEKDVSIFVSTFNPPGKPPKASTKRWLFPEIEATElADLYVVGLQEVvelTPGSIlsadpydrlrIWESKVLDCLn 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 448 ----GPSHVLFHATTLGTLHLAVYMRRDLIwycSVPEDASMSVR-TGSAFRT--KGAVAISFCLFGTSMLFVTSHLTAHQ 520
Cdd:COG5411 102 gaqsDEKYSLLRSPQLGGILLRVFSLATNL---PVVKPVSGTVKkTGFGGSSsnKGAVAIRFNYERTSFCFVNSHLAAGV 178

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 521 QKVKERVSDVKRIINALDLPRNLPNQRHknkdvtqnfDNVFWCGDLNFRLGEPREKLLEWIQNTKFPLPSHLphgymHTD 600
Cdd:COG5411 179 NNIEERIFDYRSIASNICFSRGLRIYDH---------DTIFWLGDLNYRVTSTNEEVRPEIASDDGRLDKLF-----EYD 244

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 601 QLTSVLADGAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKyrqmqglvirrqtlvpgvSTPTQPHVq 680
Cdd:COG5411 245 QLLWEMEVGNVFPGFKEPVITFPPTYKFDYGTDEYDTSDKGRIPSWTDRILYK------------------SEQLTPHS- 305

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24663242 681 cllYDSVPSITTSDHKPVWALFRTLIRAgTDAIPLAagLFSRDIYLEGMRRRLNNQYSGASAVCVL 746
Cdd:COG5411 306 ---YSSIPHLMISDHRPVYATFRAKIKV-VDPSKKE--GLIEKLYAEYKTELGEAGDISCDNFTIL 365
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 391-702 9.85e-43

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: 157.45  E-value: 9.85e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSPPKQLNDFVLPA--------NVEHVP-DIVVMGTQESTPDRFEWEVTIQETL-GPSHVLFHATTLG 460
Cdd:cd09100   1 ITIFIGTWNMGNAPPPKKITSWFQCKgqgktrddTADYIPhDIYVIGTQEDPLGEKEWLDTLKHSLrEITSISFKVIAIQ 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 461 TLhlavYMRRdlIWYCSVPEDA-------SMSVRTG--SAFRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVK 531
Cdd:cd09100  81 TL----WNIR--IVVLAKPEHEnrishicTDSVKTGiaNTLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRRNQNYF 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 532 RIINALdlprNLPNQRHKNKDVTQNFDNVFWCGDLNFRLGEPR---EKLLEWIQNTKFPlpSHLPHgymhtDQLTSVLAD 608
Cdd:cd09100 155 NILRFL----VLGDKKLSPFNITHRFTHLFWLGDLNYRVELPNteaENIIQKIKQQQYQ--ELLPH-----DQLLIERKE 223

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 609 GAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRA-------PAYTDRILYKyrqmqglvirrqtlvpgvSTPtQPHVQC 681
Cdd:cd09100 224 SKVFLQFEEEEITFAPTYRFERGTRERYAYTKQKAtgmkynlPSWCDRVLWK------------------SYP-LVHVVC 284

                       330       340
                ....*....|....*....|.
gi 24663242 682 LLYDSVPSITTSDHKPVWALF 702
Cdd:cd09100 285 QSYGCTDDITTSDHSPVFATF 305
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 391-701 2.20e-41

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: 154.43  E-value: 2.20e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSPPKQ-------LNDFVLPA----------NVEHVP-DIVVMGTQE------------STPDRFEWE 440
Cdd:cd09098   1 IRVCVGTWNVNGGKQFRSiafknqtLTDWLLDApkkagipefqDVRSKPvDIFAIGFEEmvelnagnivsaSTTNQKLWA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 441 VTIQETLGPS--HVLFHATTLGTLHLAVYMR-------RDLiwycsvpedASMSVRTG--SAFRTKGAVAISFCLFGTSM 509
Cdd:cd09098  81 AELQKTISRDqkYVLLASEQLVGVCLFVFIRpqhapfiRDV---------AVDTVKTGmgGATGNKGAVAIRMLFHTTSL 151

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 510 LFVTSHLTAHQQKVKERVSDVKRIINALDLPRNLPNQRHknkdvtqnfDNVFWCGDLNFRLGEPREKLLEWIQNTKFplp 589
Cdd:cd09098 152 CFVCSHFAAGQSQVKERNEDFIEIARKLSFPMGRMLFSH---------DYVFWCGDFNYRIDIPNEEVKELIRQQNW--- 219

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 590 shlpHGYMHTDQLTSVLADGAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKYRQMQGLVIRRQTLVP 669
Cdd:cd09098 220 ----DSLIAGDQLINQKNAGQVFRGFLEGKLDFAPTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPFDRSAEDLDLL 295

                       330       340       350
                ....*....|....*....|....*....|....*...
gi 24663242 670 GVSTPTQPHVQ------CLLYDSVPSITTSDHKPVWAL 701
Cdd:cd09098 296 NASFPDNSKEQytwspgTLLHYGRAELKTSDHRPVVAL 333
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 391-701 5.93e-41

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: 153.25  E-value: 5.93e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSP-------PKQLNDFVLPA-----------NVEHVPDIVVMGTQE------------STPDRFEWE 440
Cdd:cd09099   1 TRVAMGTWNVNGGKQfrsnilgTSELTDWLLDSpklsgtpdfqdDESNPPDIFAVGFEEmvelsagnivnaSTTNRKMWG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 441 VTIQETLGPSH--VLFHATTLGTLHLAVYMRRDLIWYcsVPEDASMSVRTGSAFRT--KGAVAISFCLFGTSMLFVTSHL 516
Cdd:cd09099  81 EQLQKAISRSHryILLTSAQLVGVCLFIFVRPYHVPF--IRDVAIDTVKTGMGGKAgnKGAVAIRFQFYSTSFCFICSHL 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 517 TAHQQKVKERVSDVKRIINALDLP--RNLPNQrhknkdvtqnfDNVFWCGDLNFRLGEPREKLLEWIQNTKFplpshlpH 594
Cdd:cd09099 159 TAGQNQVKERNEDYKEITQKLSFPmgRNVFSH-----------DYVFWCGDFNYRIDLTYEEVFYFIKRQDW-------K 220

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 595 GYMHTDQLTSVLADGAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKYRQ----------------MQ 658
Cdd:cd09099 221 KLLEFDQLQLQKSSGKIFKDFHEGTINFGPTYKYDVGSEAYDTSDKCRTPAWTDRVLWWRKKwpfektageinlldsdLD 300

                       330       340       350       360
                ....*....|....*....|....*....|....*....|...
gi 24663242 659 GLVIRRQTLVPGVstptqphvqcLLYDSVPSITTSDHKPVWAL 701
Cdd:cd09099 301 FDTKIRHTWTPGA----------LMYYGRAELQASDHRPVLAI 333
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 391-702 3.10e-40

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: 150.10  E-value: 3.10e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSPPKQLNDFVLPAN-----------VEHvpDIVVMGTQESTPDRFEWEVTIQETLGP-SHVLFHATT 458
Cdd:cd09091   1 ISIFIGTWNMGSAPPPKNITSWFTSKGqgktrddvadyIPH--DIYVIGTQEDPLGEKEWLDLLRHSLKElTSLDYKPIA 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 459 LGTL---HLAVYMRrdliwycsvPEDA-------SMSVRTGSA--FRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKER 526
Cdd:cd09091  79 MQTLwniRIVVLAK---------PEHEnrishvcTSSVKTGIAntLGNKGAVGVSFMFNGTSFGFVNSHLTSGSEKKLRR 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 527 VSDVKRIINALdlprNLPNQRHKNKDVTQNFDNVFWCGDLNFRLGEPREKLLEWIQNTKF----PLpshLPHgymhtDQL 602
Cdd:cd09091 150 NQNYLNILRFL----SLGDKKLSAFNITHRFTHLFWLGDLNYRLDLPIQEAENIIQKIEQqqfePL---LRH-----DQL 217

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 603 TSVLADGAAFRGFMEANITFPPTYKYDPGSQNFDTSSKQRA-------PAYTDRILYKyrqmqglvirrqtlvpgvSTPt 675
Cdd:cd09091 218 NLEREEHKVFLRFSEEEITFPPTYRYERGSRDTYAYTKQKAtgvkynlPSWCDRILWK------------------SYP- 278

                       330       340
                ....*....|....*....|....*..
gi 24663242 676 QPHVQCLLYDSVPSITTSDHKPVWALF 702
Cdd:cd09091 279 ETHIICQSYGCTDDIVTSDHSPVFGTF 305
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 391-702 3.18e-37

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: 141.65  E-value: 3.18e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 391 ITVFVGTWNMNGHSPPKQLNDFVLPANVEH--------VP-DIVVMGTQESTPDRFEW----EVTIQETLGPSHVLFHAT 457
Cdd:cd09101   1 ISIFIGTWNMGSVPPPKSLASWLTSRGLGKtldettvtIPhDIYVFGTQENSVGDREWvdflRASLKELTDIDYQPIALQ 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 458 TLGTLHLAVYMRRDliWYCSVPEDASMSVRTGSA--FRTKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIIN 535
Cdd:cd09101  81 CLWNIKMVVLVKPE--HENRISHVHTSSVKTGIAntLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTHRRNQNYLDILR 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 536 ALdlprNLPNQRHKNKDVTQNFDNVFWCGDLNFRLGEPREKLLEWIQNTKF-PLpshlphgyMHTDQLTSVLADGAAFRG 614
Cdd:cd09101 159 SL----SLGDKQLNAFDISLRFTHLFWFGDLNYRLDMDIQEILNYITRKEFdPL--------LAVDQLNLEREKNKVFLR 226

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 615 FMEANITFPPTYKYDPGSQNFDTSSKQRA-------PAYTDRILYKyrqmqglvirrqtlvpgvSTPtQPHVQCLLYDSV 687
Cdd:cd09101 227 FREEEISFPPTYRYERGSRDTYMWQKQKTtgmrtnvPSWCDRILWK------------------SYP-ETHIVCNSYGCT 287

                       330
                ....*....|....*
gi 24663242 688 PSITTSDHKPVWALF 702
Cdd:cd09101 288 DDIVTSDHSPVFGTF 302
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 495-702 1.44e-21

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 99.60  E-value: 1.44e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242  495 KGAVAISFCLFGTSMLFVTSHLTAHQQKVKE--RVSDVKRIINAL--------DLPRNLPNQrhknkdvtqnfDNVFWCG 564
Cdd:PLN03191 408 KGSVSISMSLFQSRLCFVCSHLTSGHKDGAEqrRNADVYEIIRRTrfssvldtDQPQTIPSH-----------DQIFWFG 476

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242  565 DLNFRL----GEPRE--KLLEWIQntkfplpshlphgYMHTDQLTSVLADGAAFRGFMEANITFPPTYKYDPGS-----Q 633
Cdd:PLN03191 477 DLNYRLnmldTEVRKlvAQKRWDE-------------LINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSdryvgE 543

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24663242  634 NFDTSSKQRAPAYTDRILYKYRQMQGLVIRRQtlvpgvstptqphvqcllydsvpSITTSDHKPVWALF 702
Cdd:PLN03191 544 NPKEGEKKRSPAWCDRILWLGKGIKQLCYKRS-----------------------EIRLSDHRPVSSMF 589
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 529-703 2.01e-06

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: 50.54  E-value: 2.01e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 529 DVKRIINALDLprNLPNQRHKNKDVTQNFDNVFwcgdlnfRLGEPREKLLEWIQNTKFplpSHLPHGYMHTDQLTSVLAD 608
Cdd:cd09092 229 DTKSVVETLCA--KATMQTVRKADSNIVVKLEF-------REKDNDNKVVLQIEKKKF---DYFNQDVFRDNNGKALLKF 296

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 609 GAAFRGF----MEANITFPPTYKYDPGSQNFDTSSKQRAPAYTDRILYKYrQMQGLVIRRQTLVPgvstptqphvqclLY 684
Cdd:cd09092 297 DKELEVFkdvlYELDISFPPSYPYSEDPEQGTQYMNTRCPAWCDRILMSH-SARELKSENEEKSV-------------TY 362

                       170       180
                ....*....|....*....|
gi 24663242 685 DSV-PSITTSDHKPVWALFR 703
Cdd:cd09092 363 DMIgPNVCMGDHKPVFLTFR 382
EEP cd08372
Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily; This large superfamily includes ...
 395-698 3.19e-04

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


Pssm-ID: 197306 [Multi-domain]  Cd Length: 241  Bit Score: 42.85  E-value: 3.19e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 395 VGTWNMNGHSPPKQLndFVLPANV-EHVPDIVvmGTQESTPDRFEWEVTIQETLGPSHVLFHAT--TLGTLHLAVYMRRD 471
Cdd:cd08372   1 VASYNVNGLNAATRA--SGIARWVrELDPDIV--CLQEVKDSQYSAVALNQLLPEGYHQYQSGPsrKEGYEGVAILSKTP 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 472 LIWYCSVPEDASMSVRTGSafrtKGAVAISFCLFGTSMLFVTSHLTAHQQKVKERVSDVKRIINALdlpRNLPNQRHknk 551
Cdd:cd08372  77 KFKIVEKHQYKFGEGDSGE----RRAVVVKFDVHDKELCVVNAHLQAGGTRADVRDAQLKEVLEFL---KRLRQPNS--- 146

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24663242 552 dvtqnfDNVFWCGDLNfrlgeprekllewiqntkfplpSHLPHGYMHTDQltsVLADGAAFRGFMEANITFPPTYKYDpg 631
Cdd:cd08372 147 ------APVVICGDFN----------------------VRPSEVDSENPS---SMLRLFVALNLVDSFETLPHAYTFD-- 193

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24663242 632 sqnfdtSSKQRAPAYTDRILYKyRQMQGLVIRRQtlvpgvstptqphvqcLLYDSVPSITTSDHKPV 698
Cdd:cd08372 194 ------TYMHNVKSRLDYIFVS-KSLLPSVKSSK----------------ILSDAARARIPSDHYPI 237
 
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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