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Conserved domains on  [gi|1063696119|ref|NP_001321558|]
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Endonuclease/exonuclease/phosphatase family protein [Arabidopsis thaliana]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 272-618 4.76e-107

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: 330.83  E-value: 4.76e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGRASTDSLVSWLGCAAT-GVEIVVVGLQEVEMGAGvlamsaakETVGLEGSPLGQWWLDMIGKTLDEG 350
Cdd:cd09074     1 VKIFVVTWNVGGGISPPENLENWLSPKGTeAPDIYAVGVQEVDMSVQ--------GFVGNDDSAKAREWVDNIQEALNEK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 351 SSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRA--IGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAVNRR 428
Cdd:cd09074    73 ENYVLLGSAQLVGIFLFVFVKKEHLPQIKDLEVEGVTVGTGGGgkLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERR 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 429 NADFDHVYRTMTFSRQSSSLNagvagasfgvtmprggnalgvntiearpELSEADMVIFLGDFNYRLdDITYDETRDFIS 508
Cdd:cd09074   153 NQDYRDILSKLKFYRGDPAID----------------------------SIFDHDVVFWFGDLNYRI-DSTDDEVRKLIS 203

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 509 QRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERhqaGLAGYDSGEKKRIPAWCDRILYRDNKKHLGAECSld 588
Cdd:cd09074   204 QGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFPPTYKFDP---GTDEYDTSDKKRIPAWCDRILYKSKAGSEIQPLS-- 278

                         330       340       350
                  ....*....|....*....|....*....|
gi 1063696119 589 cpvvssisqYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09074   279 ---------YTSVPLYKTSDHKPVRATFRV 299
WD40 super family cl43672
WD40 repeat [General function prediction only];
144-251 7.07e-06

WD40 repeat [General function prediction only];


The actual alignment was detected with superfamily member COG2319:

Pssm-ID: 441893 [Multi-domain]  Cd Length: 403  Bit Score: 49.14  E-value: 7.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 144 AIVISVDG-MIWTGSSNGILMRWD-GNGNCLQEFAYESSGILCMfTF---CSRLWVGYSNGTVQVWDLE-GKLLGGWVAH 217
Cdd:COG2319   209 SVAFSPDGkLLASGSADGTVRLWDlATGKLLRTLTGHSGSVRSV-AFspdGRLLASGSADGTVRLWDLAtGELLRTLTGH 287

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063696119 218 SGPVIKMAIGAG--YLFTLANHGGIRGWNVTSPGPL 251
Cdd:COG2319   288 SGGVNSVAFSPDgkLLASGSDDGTVRLWDLATGKLL 323
Motile_Sperm super family cl44412
MSP (Major sperm protein) domain; Major sperm proteins are involved in sperm motility. These ...
 653-777 2.33e-03

MSP (Major sperm protein) domain; Major sperm proteins are involved in sperm motility. These proteins oligomerise to form filaments. This family contains many other proteins.


The actual alignment was detected with superfamily member pfam00635:

Pssm-ID: 459882  Cd Length: 109  Bit Score: 38.50  E-value: 2.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 653 PETIVStnNIILQNQDSTILRITNKSEKNIAfFKIICEGqskieedgqahdhrargsfgfPQWLEVSPGTGTIKPNQIAE 732
Cdd:pfam00635   7 PDLIFF--AAPGNKQGTSTLTLKNTSDKRVA-FKVKTTN---------------------PKKYRVRPNYGIIKPGESVT 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063696119 733 VSVHLEDFPTVEEfvdgvaqnswcEDTRDKEVILVLVVHGRFSTE 777
Cdd:pfam00635  63 ITITRQPFDEEPG-----------DAKKDKFVIQYAVAPGDEKDA 96
 
Name Accession Description Interval E-value
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 272-618 4.76e-107

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: 330.83  E-value: 4.76e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGRASTDSLVSWLGCAAT-GVEIVVVGLQEVEMGAGvlamsaakETVGLEGSPLGQWWLDMIGKTLDEG 350
Cdd:cd09074     1 VKIFVVTWNVGGGISPPENLENWLSPKGTeAPDIYAVGVQEVDMSVQ--------GFVGNDDSAKAREWVDNIQEALNEK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 351 SSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRA--IGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAVNRR 428
Cdd:cd09074    73 ENYVLLGSAQLVGIFLFVFVKKEHLPQIKDLEVEGVTVGTGGGgkLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERR 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 429 NADFDHVYRTMTFSRQSSSLNagvagasfgvtmprggnalgvntiearpELSEADMVIFLGDFNYRLdDITYDETRDFIS 508
Cdd:cd09074   153 NQDYRDILSKLKFYRGDPAID----------------------------SIFDHDVVFWFGDLNYRI-DSTDDEVRKLIS 203

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 509 QRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERhqaGLAGYDSGEKKRIPAWCDRILYRDNKKHLGAECSld 588
Cdd:cd09074   204 QGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFPPTYKFDP---GTDEYDTSDKKRIPAWCDRILYKSKAGSEIQPLS-- 278

                         330       340       350
                  ....*....|....*....|....*....|
gi 1063696119 589 cpvvssisqYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09074   279 ---------YTSVPLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 271-621 3.79e-104

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 323.54  E-value: 3.79e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  271 NLKILAGTWNVGEGRASTDSLVSWLGCAATGVE-----IVVVGLQEVEMGAGvlamSAAKETVGLEGSPlgqwWLDMIGK 345
Cdd:smart00128   2 DIKVLIGTWNVGGLESPKVDVTSWLFQKIEVKQsekpdIYVIGLQEVVGLAP----GVILETIAGKERL----WSDLLES 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  346 TLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAV 425
Cdd:smart00128  74 SLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNV 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  426 NRRNADFDHVYRTMTFSRqssslnagvagasfgvtmprggnalgvntieaRPELSE--ADMVIFLGDFNYRLDDITYDET 503
Cdd:smart00128 154 EQRNQDYKTILRALSFPE--------------------------------RALLSQfdHDVVFWFGDLNFRLDSPSYEEV 201

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  504 RDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhQAGLAGYDSGEKKRIPAWCDRILYRDNKKHLGA 583
Cdd:smart00128 202 RRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGPITFPPTYKYD--SVGTETYDTSEKKRVPAWCDRILYRSNGPELIQ 279

                          330       340       350
                   ....*....|....*....|....*....|....*...
gi 1063696119  584 ECSldcpvvssisqYDACMEVTDSDHKPVRCVFSVKIA 621
Cdd:smart00128 280 LSE-----------YHSGMEITTSDHKPVFATFRLKVT 306
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
248-727 3.26e-56

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 200.39  E-value: 3.26e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 248 PGPLDNVLRAELAGKEFLYSRIENLKILAGTWNVgEGRASTDSLVSWL---GCAATGVEIVVVGLQEVemgagvLAMSAA 324
Cdd:COG5411     6 YDPRHPYIVAVLRQRRSKYVIEKDVSIFVSTFNP-PGKPPKASTKRWLfpeIEATELADLYVVGLQEV------VELTPG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 325 KEtVGLEGSPLGQWWLDMIGKTLDE---GSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVG 401
Cdd:COG5411    79 SI-LSADPYDRLRIWESKVLDCLNGaqsDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 402 VRLRMYDRVLCFVNCHFAAHLEAVNRRNADFDHVYRTMTFSRQSSslnagvagasfgvtmprggnalgvntiearpeLSE 481
Cdd:COG5411   158 IRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLR--------------------------------IYD 205

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 482 ADMVIFLGDFNYRLDdITYDETRDFISQ--RCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhqAGLAGYDS 559
Cdd:COG5411   206 HDTIFWLGDLNYRVT-STNEEVRPEIASddGRLDKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFD---YGTDEYDT 281

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 560 GEKKRIPAWCDRILYRdnkkhlgaecsldcpvvSSISQ---YDACMEVTDSDHKPVRCVFSVKIARVDESVRRQEYGNII 636
Cdd:COG5411   282 SDKGRIPSWTDRILYK-----------------SEQLTphsYSSIPHLMISDHRPVYATFRAKIKVVDPSKKEGLIEKLY 344

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 637 nsNKKIKVLLGELSKVPEtivstnniilqnqDSTILRITNKSEKNIAFFK------IICEGQSKI-----EEDG------ 699
Cdd:COG5411   345 --AEYKTELGEAGDISCD-------------NFTILVLYGHVDGKIAIFSlgqprlLELIGSDVIvgptlWMIYvpdvsl 409

                         490       500       510
                  ....*....|....*....|....*....|....*
gi 1063696119 700 ------QAHDHRARGSFGFPQ-WLEVSPGTGTIKP 727
Cdd:COG5411   410 ksppghKASHNGATPILKRLQvVSSVSPAMGATEM 444
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 322-624 4.55e-40

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 157.38  E-value: 4.55e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 322 SAAKETVGLEGSPLGQWWLDMIGKTLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVG 401
Cdd:PLN03191  333 SSEAEDDTFKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVS 412

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 402 VRLRMYDRVLCFVNCHFAAHLE--AVNRRNADfdhVYRTMTFSRQSSSLNAgvagasfgvTMPRggnalgvnTIEARpel 479
Cdd:PLN03191  413 ISMSLFQSRLCFVCSHLTSGHKdgAEQRRNAD---VYEIIRRTRFSSVLDT---------DQPQ--------TIPSH--- 469

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 480 seaDMVIFLGDFNYRLDdITYDETRDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERHQAGLAGYD- 558
Cdd:PLN03191  470 ---DQIFWFGDLNYRLN-MLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYVGENp 545

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063696119 559 -SGEKKRIPAWCDRILYrdnkkhLGAECSLDCPVVSsisqydacmEVTDSDHKPVRCVFSVKIARVD 624
Cdd:PLN03191  546 kEGEKKRSPAWCDRILW------LGKGIKQLCYKRS---------EIRLSDHRPVSSMFLVEVEVFD 597
WD40 COG2319
WD40 repeat [General function prediction only];
144-251 7.07e-06

WD40 repeat [General function prediction only];


Pssm-ID: 441893 [Multi-domain]  Cd Length: 403  Bit Score: 49.14  E-value: 7.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 144 AIVISVDG-MIWTGSSNGILMRWD-GNGNCLQEFAYESSGILCMfTF---CSRLWVGYSNGTVQVWDLE-GKLLGGWVAH 217
Cdd:COG2319   209 SVAFSPDGkLLASGSADGTVRLWDlATGKLLRTLTGHSGSVRSV-AFspdGRLLASGSADGTVRLWDLAtGELLRTLTGH 287

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063696119 218 SGPVIKMAIGAG--YLFTLANHGGIRGWNVTSPGPL 251
Cdd:COG2319   288 SGGVNSVAFSPDgkLLASGSDDGTVRLWDLATGKLL 323
WD40 cd00200
WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions ...
 155-244 2.55e-04

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.


Pssm-ID: 238121 [Multi-domain]  Cd Length: 289  Bit Score: 43.86  E-value: 2.55e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 155 TGSSNGILMRWD-GNGNCLQEFAYESSGILCMFTFCSRLWV--GYSNGTVQVWDLE-GKLLGGWVAHSGPVIKMAI--GA 228
Cdd:cd00200   194 SSSSDGTIKLWDlSTGKCLGTLRGHENGVNSVAFSPDGYLLasGSEDGTIRVWDLRtGECVQTLSGHTNSVTSLAWspDG 273

                          90
                  ....*....|....*.
gi 1063696119 229 GYLFTLANHGGIRGWN 244
Cdd:cd00200   274 KRLASGSADGTIRIWD 289
Motile_Sperm pfam00635
MSP (Major sperm protein) domain; Major sperm proteins are involved in sperm motility. These ...
 653-777 2.33e-03

MSP (Major sperm protein) domain; Major sperm proteins are involved in sperm motility. These proteins oligomerise to form filaments. This family contains many other proteins.


Pssm-ID: 459882  Cd Length: 109  Bit Score: 38.50  E-value: 2.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 653 PETIVStnNIILQNQDSTILRITNKSEKNIAfFKIICEGqskieedgqahdhrargsfgfPQWLEVSPGTGTIKPNQIAE 732
Cdd:pfam00635   7 PDLIFF--AAPGNKQGTSTLTLKNTSDKRVA-FKVKTTN---------------------PKKYRVRPNYGIIKPGESVT 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063696119 733 VSVHLEDFPTVEEfvdgvaqnswcEDTRDKEVILVLVVHGRFSTE 777
Cdd:pfam00635  63 ITITRQPFDEEPG-----------DAKKDKFVIQYAVAPGDEKDA 96
 
Name Accession Description Interval E-value
INPP5c cd09074
Catalytic domain of inositol polyphosphate 5-phosphatases; Inositol polyphosphate ...
 272-618 4.76e-107

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: 330.83  E-value: 4.76e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGRASTDSLVSWLGCAAT-GVEIVVVGLQEVEMGAGvlamsaakETVGLEGSPLGQWWLDMIGKTLDEG 350
Cdd:cd09074     1 VKIFVVTWNVGGGISPPENLENWLSPKGTeAPDIYAVGVQEVDMSVQ--------GFVGNDDSAKAREWVDNIQEALNEK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 351 SSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRA--IGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAVNRR 428
Cdd:cd09074    73 ENYVLLGSAQLVGIFLFVFVKKEHLPQIKDLEVEGVTVGTGGGgkLGNKGGVAIRFQINDTSFCFVNSHLAAGQEEVERR 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 429 NADFDHVYRTMTFSRQSSSLNagvagasfgvtmprggnalgvntiearpELSEADMVIFLGDFNYRLdDITYDETRDFIS 508
Cdd:cd09074   153 NQDYRDILSKLKFYRGDPAID----------------------------SIFDHDVVFWFGDLNYRI-DSTDDEVRKLIS 203

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 509 QRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERhqaGLAGYDSGEKKRIPAWCDRILYRDNKKHLGAECSld 588
Cdd:cd09074   204 QGDLDDLLEKDQLKKQKEKGKVFDGFQELPITFPPTYKFDP---GTDEYDTSDKKRIPAWCDRILYKSKAGSEIQPLS-- 278

                         330       340       350
                  ....*....|....*....|....*....|
gi 1063696119 589 cpvvssisqYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09074   279 ---------YTSVPLYKTSDHKPVRATFRV 299
IPPc smart00128
Inositol polyphosphate phosphatase, catalytic domain homologues; Mg(2+)-dependent/Li(+) ...
 271-621 3.79e-104

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


Pssm-ID: 214525 [Multi-domain]  Cd Length: 306  Bit Score: 323.54  E-value: 3.79e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  271 NLKILAGTWNVGEGRASTDSLVSWLGCAATGVE-----IVVVGLQEVEMGAGvlamSAAKETVGLEGSPlgqwWLDMIGK 345
Cdd:smart00128   2 DIKVLIGTWNVGGLESPKVDVTSWLFQKIEVKQsekpdIYVIGLQEVVGLAP----GVILETIAGKERL----WSDLLES 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  346 TLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAV 425
Cdd:smart00128  74 SLNGDGQYNVLAKVYLVGILVLVFVKANHLVYIKDVETFTVKTGMGGLWGNKGAVAVRFKLSDTSFCFVNSHLAAGASNV 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  426 NRRNADFDHVYRTMTFSRqssslnagvagasfgvtmprggnalgvntieaRPELSE--ADMVIFLGDFNYRLDDITYDET 503
Cdd:smart00128 154 EQRNQDYKTILRALSFPE--------------------------------RALLSQfdHDVVFWFGDLNFRLDSPSYEEV 201

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119  504 RDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhQAGLAGYDSGEKKRIPAWCDRILYRDNKKHLGA 583
Cdd:smart00128 202 RRKISKKEFDDLLEKDQLNRQREAGKVFKGFQEGPITFPPTYKYD--SVGTETYDTSEKKRVPAWCDRILYRSNGPELIQ 279

                          330       340       350
                   ....*....|....*....|....*....|....*...
gi 1063696119  584 ECSldcpvvssisqYDACMEVTDSDHKPVRCVFSVKIA 621
Cdd:smart00128 280 LSE-----------YHSGMEITTSDHKPVFATFRLKVT 306
INPP5c_INPP5B cd09093
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Type II inositol ...
 272-618 1.94e-79

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: 258.01  E-value: 1.94e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVgEGRASTDSLVSWLGCAATGVEIVVVGLQEVEMgagvlamsaAKETVGLEGSPLGQWWLDMIGKTLDEGS 351
Cdd:cd09093     1 FRIFVGTWNV-NGQSPDESLRPWLSCDEEPPDIYAIGFQELDL---------SAEAFLFNDSSREQEWVKAVERGLHPDA 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 352 SFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAVNRRNAD 431
Cdd:cd09093    71 KYKKVKLIRLVGMMLLVFVKKEHRQHIKEVAAETVGTGIMGKMGNKGGVAVRFQFHNTTFCFVNSHLAAHMEEVERRNQD 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 432 FDHVYRTMTFSRQSsslnagvagasfgvtmprgGNALGVntiearpelSEADMVIFLGDFNYRLDDITYDETRDFISQRC 511
Cdd:cd09093   151 YKDICARMKFEDPD-------------------GPPLSI---------SDHDVVFWLGDLNYRIQELPTEEVKELIEKND 202

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 512 FDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFerhQAGLAGYDSGEKKRIPAWCDRILYR-DNKKHLgaecsldcp 590
Cdd:cd09093   203 LEELLKYDQLNIQRRAGKVFEGFTEGEINFIPTYKY---DPGTDNWDSSEKCRAPAWCDRILWRgTNIVQL--------- 270

                         330       340
                  ....*....|....*....|....*...
gi 1063696119 591 vvssisQYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09093   271 ------SYRSHMELKTSDHKPVSALFDI 292
INPP5c_ScInp51p-like cd09090
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Saccharomyces cerevisiae ...
 272-616 8.88e-69

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: 229.53  E-value: 8.88e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGeGRASTDSLVSWLgCAATGVE---IVVVGLQE-VEMGAGVLAMSAAKETvglegsplgQWWLDMIGKTL 347
Cdd:cd09090     1 INIFVGTFNVN-GKSYKDDLSSWL-FPEENDElpdIVVIGLQEvVELTAGQILNSDPSKS---------SFWEKKIKTTL 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 348 D--EGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAV 425
Cdd:cd09090    70 NgrGGEKYVLLRSEQLVGTALLFFVKESQLPKVKNVEGSTKKTGLGGMSGNKGAVAIRFDYGDTSFCFVTSHLAAGLTNY 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 426 NRRNADFDHVYRTMTFSRqssslnagvagasfGVTMPrggnalgvntiearpelsEADMVIFLGDFNYRLDdITYDETRD 505
Cdd:cd09090   150 EERNNDYKTIARGLRFSR--------------GRTIK------------------DHDHVIWLGDFNYRIS-LTNEDVRR 196

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 506 FISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERhqaGLAGYDSGEKKRIPAWCDRILYR-DNKKHLGae 584
Cdd:cd09090   197 FILNGKLDKLLEYDQLNQQMNAGEVFPGFSEGPITFPPTYKYDK---GTDNYDTSEKQRIPAWTDRILYRgENLRQLS-- 271

                         330       340       350
                  ....*....|....*....|....*....|..
gi 1063696119 585 csldcpvvssisqYDACMEVTdSDHKPVRCVF 616
Cdd:cd09090   272 -------------YNSAPLRF-SDHRPVYATF 289
INPP5c_INPP5J-like cd09094
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of inositol polyphosphate ...
 272-616 1.14e-65

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: 221.47  E-value: 1.14e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEgRASTDSLVSWLGCAATGVE--IVVVGLQEVEMGAGVLAMSAAKETVglegsplgqwWLDMIGKTLDE 349
Cdd:cd09094     1 LRVYVVTWNVAT-APPPIDVRSLLGLQSPEVApdIYIIGLQEVNSKPVQFVSDLIFDDP----------WSDLFMDILSP 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 350 gSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAVNRRN 429
Cdd:cd09094    70 -KGYVKVSSIRLQGLLLLVFVKIQHLPFIRDVQTNYTRTGLGGYWGNKGAVTVRFSLYGHMICFLNCHLPAHMEKWEQRI 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 430 ADFDHVYRTMTFSrqssslnagvagasfgvtmprggnalGVNTiearPELSEADMVIFLGDFNYRLDDITYDETRDFISQ 509
Cdd:cd09094   149 DDFETILSTQVFN--------------------------ECNT----PSILDHDYVFWFGDLNFRIEDVSIEFVRELVNS 198

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 510 RCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERhqaGLAGYDSGEKKRIPAWCDRILYRDNKKHLGAECSLdc 589
Cdd:cd09094   199 KKYHLLLEKDQLNMAKRKEEAFQGFQEGPLNFAPTYKFDL---GTDEYDTSGKKRKPAWTDRILWKVNPDASTEEKFL-- 273

                         330       340
                  ....*....|....*....|....*....
gi 1063696119 590 pvvsSISQ--YDACMEVTDSDHKPVRCVF 616
Cdd:cd09094   274 ----SITQtsYKSHMEYGISDHKPVTAQF 298
COG5411 COG5411
Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];
248-727 3.26e-56

Phosphatidylinositol 5-phosphate phosphatase [Signal transduction mechanisms];


Pssm-ID: 227698 [Multi-domain]  Cd Length: 460  Bit Score: 200.39  E-value: 3.26e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 248 PGPLDNVLRAELAGKEFLYSRIENLKILAGTWNVgEGRASTDSLVSWL---GCAATGVEIVVVGLQEVemgagvLAMSAA 324
Cdd:COG5411     6 YDPRHPYIVAVLRQRRSKYVIEKDVSIFVSTFNP-PGKPPKASTKRWLfpeIEATELADLYVVGLQEV------VELTPG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 325 KEtVGLEGSPLGQWWLDMIGKTLDE---GSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVG 401
Cdd:COG5411    79 SI-LSADPYDRLRIWESKVLDCLNGaqsDEKYSLLRSPQLGGILLRVFSLATNLPVVKPVSGTVKKTGFGGSSSNKGAVA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 402 VRLRMYDRVLCFVNCHFAAHLEAVNRRNADFDHVYRTMTFSRQSSslnagvagasfgvtmprggnalgvntiearpeLSE 481
Cdd:COG5411   158 IRFNYERTSFCFVNSHLAAGVNNIEERIFDYRSIASNICFSRGLR--------------------------------IYD 205

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 482 ADMVIFLGDFNYRLDdITYDETRDFISQ--RCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhqAGLAGYDS 559
Cdd:COG5411   206 HDTIFWLGDLNYRVT-STNEEVRPEIASddGRLDKLFEYDQLLWEMEVGNVFPGFKEPVITFPPTYKFD---YGTDEYDT 281

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 560 GEKKRIPAWCDRILYRdnkkhlgaecsldcpvvSSISQ---YDACMEVTDSDHKPVRCVFSVKIARVDESVRRQEYGNII 636
Cdd:COG5411   282 SDKGRIPSWTDRILYK-----------------SEQLTphsYSSIPHLMISDHRPVYATFRAKIKVVDPSKKEGLIEKLY 344

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 637 nsNKKIKVLLGELSKVPEtivstnniilqnqDSTILRITNKSEKNIAFFK------IICEGQSKI-----EEDG------ 699
Cdd:COG5411   345 --AEYKTELGEAGDISCD-------------NFTILVLYGHVDGKIAIFSlgqprlLELIGSDVIvgptlWMIYvpdvsl 409

                         490       500       510
                  ....*....|....*....|....*....|....*
gi 1063696119 700 ------QAHDHRARGSFGFPQ-WLEVSPGTGTIKP 727
Cdd:COG5411   410 ksppghKASHNGATPILKRLQvVSSVSPAMGATEM 444
INPP5c_Synj cd09089
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanins; This ...
 272-618 1.33e-52

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: 186.44  E-value: 1.33e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEG------RASTDSLVSWLGCAA--------------TGVEIVVVGLQE-VEMGAG-VLAMSAAKEtvg 329
Cdd:cd09089     1 LRVFVGTWNVNGGkhfrsiAFKHQSMTDWLLDNPklagqcsndseedeKPVDIFAIGFEEmVDLNASnIVSASTTNQ--- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 330 legsplgQWWLDMIGKTLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDR 409
Cdd:cd09089    78 -------KEWGEELQKTISRDHKYVLLTSEQLVGVCLFVFVRPQHAPFIRDVAVDTVKTGLGGAAGNKGAVAIRFLLHST 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 410 VLCFVNCHFAAHLEAVNRRNADFDHVYRTMTFSrqssslnagvagasfgvtMPRggnalgvntiearpELSEADMVIFLG 489
Cdd:cd09089   151 SLCFVCSHFAAGQSQVKERNEDFAEIARKLSFP------------------MGR--------------TLDSHDYVFWCG 198

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 490 DFNYRLDdITYDETRDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhqAGLAGYDSGEKKRIPAWC 569
Cdd:cd09089   199 DFNYRID-LPNDEVKELVRNGDWLKLLEFDQLTKQKAAGNVFKGFLEGEINFAPTYKYD---LFSDDYDTSEKCRTPAWT 274

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063696119 570 DRILYRDNKKHLGAECSLDCPVVSS------ISQYDACmEVTDSDHKPVRCVFSV 618
Cdd:cd09089   275 DRVLWRRRKWPSDKTEESLVETNDPtwnpgtLLYYGRA-ELKTSDHRPVVAIIDI 328
INPP5c_Synj2 cd09099
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 2; This ...
 272-618 8.89e-43

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: 159.03  E-value: 8.89e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGRA------STDSLVSWL--GCAATGV-----------EIVVVGLQE-VEMGAG-VLAMSAAKETVgl 330
Cdd:cd09099     1 TRVAMGTWNVNGGKQfrsnilGTSELTDWLldSPKLSGTpdfqddesnppDIFAVGFEEmVELSAGnIVNASTTNRKM-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 331 egsplgqwWLDMIGKTLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRV 410
Cdd:cd09099    79 --------WGEQLQKAISRSHRYILLTSAQLVGVCLFIFVRPYHVPFIRDVAIDTVKTGMGGKAGNKGAVAIRFQFYSTS 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 411 LCFVNCHFAAHLEAVNRRNADFDHVYRTMTFsrqssslnagvagasfgvtmPRGGNALgvntiearpelsEADMVIFLGD 490
Cdd:cd09099   151 FCFICSHLTAGQNQVKERNEDYKEITQKLSF--------------------PMGRNVF------------SHDYVFWCGD 198

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 491 FNYRLDdITYDETRDFISQRcfDW--LREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhqAGLAGYDSGEKKRIPAW 568
Cdd:cd09099   199 FNYRID-LTYEEVFYFIKRQ--DWkkLLEFDQLQLQKSSGKIFKDFHEGTINFGPTYKYD---VGSEAYDTSDKCRTPAW 272

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1063696119 569 CDRILYRdNKKH-----------LGAECSLDCPVVSSIS----QYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09099   273 TDRVLWW-RKKWpfektageinlLDSDLDFDTKIRHTWTpgalMYYGRAELQASDHRPVLAIVEV 336
INPP5c_Synj1 cd09098
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of synaptojanin 1; This ...
 272-618 4.16e-42

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: 157.12  E-value: 4.16e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGRA------STDSLVSWLGCA-------------ATGVEIVVVGLQE-VEMGAG-VLAMSAAKETVgl 330
Cdd:cd09098     1 IRVCVGTWNVNGGKQfrsiafKNQTLTDWLLDApkkagipefqdvrSKPVDIFAIGFEEmVELNAGnIVSASTTNQKL-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 331 egsplgqwWLDMIGKTLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRV 410
Cdd:cd09098    79 --------WAAELQKTISRDQKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKTGMGGATGNKGAVAIRMLFHTTS 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 411 LCFVNCHFAAHLEAVNRRNADFDHVYRTMTFsrqssslnagvagasfgvtmPRGgnalgvntiearPELSEADMVIFLGD 490
Cdd:cd09098   151 LCFVCSHFAAGQSQVKERNEDFIEIARKLSF--------------------PMG------------RMLFSHDYVFWCGD 198

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 491 FNYRLdDITYDETRDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERHQaglAGYDSGEKKRIPAWCD 570
Cdd:cd09098   199 FNYRI-DIPNEEVKELIRQQNWDSLIAGDQLINQKNAGQVFRGFLEGKLDFAPTYKYDLFS---DDYDTSEKCRTPAWTD 274

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1063696119 571 RILYRDNKKHL--GAEcSLDCPVVS----SISQYD---------ACMEVTDSDHKPVRCVFSV 618
Cdd:cd09098   275 RVLWRRRKWPFdrSAE-DLDLLNASfpdnSKEQYTwspgtllhyGRAELKTSDHRPVVALIDI 336
PLN03191 PLN03191
Type I inositol-1,4,5-trisphosphate 5-phosphatase 2; Provisional
 322-624 4.55e-40

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


Pssm-ID: 215624 [Multi-domain]  Cd Length: 621  Bit Score: 157.38  E-value: 4.55e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 322 SAAKETVGLEGSPLGQWWLDMIGKTLDEGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVG 401
Cdd:PLN03191  333 SSEAEDDTFKEVPSYQLPEDLIKDCRKVKQKYVRIVSKQMVGIYVSVWVRKRLRRHINNLKVSPVGVGLMGYMGNKGSVS 412

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 402 VRLRMYDRVLCFVNCHFAAHLE--AVNRRNADfdhVYRTMTFSRQSSSLNAgvagasfgvTMPRggnalgvnTIEARpel 479
Cdd:PLN03191  413 ISMSLFQSRLCFVCSHLTSGHKdgAEQRRNAD---VYEIIRRTRFSSVLDT---------DQPQ--------TIPSH--- 469

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 480 seaDMVIFLGDFNYRLDdITYDETRDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERHQAGLAGYD- 558
Cdd:PLN03191  470 ---DQIFWFGDLNYRLN-MLDTEVRKLVAQKRWDELINSDQLIKELRSGHVFDGWKEGPIKFPPTYKYEINSDRYVGENp 545

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1063696119 559 -SGEKKRIPAWCDRILYrdnkkhLGAECSLDCPVVSsisqydacmEVTDSDHKPVRCVFSVKIARVD 624
Cdd:PLN03191  546 kEGEKKRSPAWCDRILW------LGKGIKQLCYKRS---------EIRLSDHRPVSSMFLVEVEVFD 597
INPP5c_INPP5E-like cd09095
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol ...
 271-618 4.74e-34

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: 132.55  E-value: 4.74e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 271 NLKILAGTWNVGEGRASTDSLVSWL--GCAATGVEIVVVGLQEvemgagvlamsaaketvgleGSPLGQWWLDMIGKTLd 348
Cdd:cd09095     4 NVGIFVATWNMQGQKELPENLDDFLlpTSADFAQDIYVIGVQE--------------------GCSDRREWEIRLQETL- 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 349 eGSSFVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHFAAHLEAVNRR 428
Cdd:cd09095    63 -GPSHVLLHSASHGVLHLAVFIRRDLIWFCSEVESATVTTRIVSQIKTKGALAISFTFFGTSFLFITSHFTSGDGKVKER 141

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 429 NADFDHVyrtmtfsRQSsslnagvagasfgVTMPRGGNALGVNTIEARPeLSEADMVIFLGDFNYRLDDiTYDETRDFIS 508
Cdd:cd09095   142 VLDYNKI-------IQA-------------LNLPRNVPTNPYKSESGDV-TTRFDEVFWFGDFNFRLSG-PRHLVDALIN 199

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 509 QRCFDWLRE---KDQLHTEMEAGNVFQGMREAIIRFPPTYKFErhqAGLAGYDSGEKKRIPAWCDRILYRDnkKHLGAEC 585
Cdd:cd09095   200 QGQEVDVSAllqHDQLTREMSKGSIFKGFQEAPIHFPPTYKFD---IGSDVYDTSSKQRVPSYTDRILYRS--RQKGDVC 274

                         330       340       350
                  ....*....|....*....|....*....|...
gi 1063696119 586 SLdcpvvssisQYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09095   275 CL---------KYNSCPSIKTSDHRPVFALFRV 298
INPP5c_SHIP2-INPPL1 cd09101
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 272-618 4.53e-31

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: 123.93  E-value: 4.53e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGRASTdSLVSWLGCAATGV-----------EIVVVGLQEVEMGAgvlamsaaKEtvglegsplgqwWL 340
Cdd:cd09101     1 ISIFIGTWNMGSVPPPK-SLASWLTSRGLGKtldettvtiphDIYVFGTQENSVGD--------RE------------WV 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 341 DMIGKTLDEGSS--FVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCHF 418
Cdd:cd09101    60 DFLRASLKELTDidYQPIALQCLWNIKMVVLVKPEHENRISHVHTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHL 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 419 AAHLEAVNRRNADFDHVYRTMTFSRQSssLNAgvagasFGVTMprggnalgvntiearpelsEADMVIFLGDFNYRLD-D 497
Cdd:cd09101   140 TSGNEKTHRRNQNYLDILRSLSLGDKQ--LNA------FDISL-------------------RFTHLFWFGDLNYRLDmD 192

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 498 ItyDETRDFISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERHQAGLAGYD----SGEKKRIPAWCDRIL 573
Cdd:cd09101   193 I--QEILNYITRKEFDPLLAVDQLNLEREKNKVFLRFREEEISFPPTYRYERGSRDTYMWQkqktTGMRTNVPSWCDRIL 270

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 1063696119 574 YRDNkkhlgAECSLDCpvvssiSQYDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09101   271 WKSY-----PETHIVC------NSYGCTDDIVTSDHSPVFGTFEV 304
INPP5c_SHIP cd09091
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 272-618 1.08e-28

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: 117.35  E-value: 1.08e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGrASTDSLVSWLGCAATGV-----------EIVVVGLQEvemgagvlamsaaketvglegSPLGQW-W 339
Cdd:cd09091     1 ISIFIGTWNMGSA-PPPKNITSWFTSKGQGKtrddvadyiphDIYVIGTQE---------------------DPLGEKeW 58

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 340 LDMIGKTLDEGSS--FVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCH 417
Cdd:cd09091    59 LDLLRHSLKELTSldYKPIAMQTLWNIRIVVLAKPEHENRISHVCTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSH 138

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 418 FAAHLEAVNRRNADFDHVYRTMTFSRQSSSlnagvagaSFGVTMprggnalgvntiearpelsEADMVIFLGDFNYRLD- 496
Cdd:cd09091   139 LTSGSEKKLRRNQNYLNILRFLSLGDKKLS--------AFNITH-------------------RFTHLFWLGDLNYRLDl 191

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 497 DITydETRDFIS---QRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERHQAGLAGYD----SGEKKRIPAWC 569
Cdd:cd09091   192 PIQ--EAENIIQkieQQQFEPLLRHDQLNLEREEHKVFLRFSEEEITFPPTYRYERGSRDTYAYTkqkaTGVKYNLPSWC 269

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063696119 570 DRILYRDNkkhlgaecsldcPVVSSISQ-YDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09091   270 DRILWKSY------------PETHIICQsYGCTDDIVTSDHSPVFGTFEV 307
INPP5c_SHIP1-INPP5D cd09100
Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of SH2 domain containing ...
 272-618 1.84e-27

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: 113.54  E-value: 1.84e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 272 LKILAGTWNVGEGrASTDSLVSWLGCAATGV-----------EIVVVGLQEvemgagvlamsaaketvglegSPLGQ-WW 339
Cdd:cd09100     1 ITIFIGTWNMGNA-PPPKKITSWFQCKGQGKtrddtadyiphDIYVIGTQE---------------------DPLGEkEW 58

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 340 LDMIGKTLDEGSS--FVRVGSRQLAGLLICVWVRHDLKPHVGDVDAAAVPCGFGRAIGNKGAVGVRLRMYDRVLCFVNCH 417
Cdd:cd09100    59 LDTLKHSLREITSisFKVIAIQTLWNIRIVVLAKPEHENRISHICTDSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNSH 138

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 418 FAAHLEAVNRRNADFDHVYRTMTFSRQSSSlnagvagaSFGVTmprggnalgvntiearpelSEADMVIFLGDFNYRLDD 497
Cdd:cd09100   139 LTSGSEKKLRRNQNYFNILRFLVLGDKKLS--------PFNIT-------------------HRFTHLFWLGDLNYRVEL 191

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 498 ITYDETRDF--ISQRCFDWLREKDQLHTEMEAGNVFQGMREAIIRFPPTYKFERHQAGLAGYD----SGEKKRIPAWCDR 571
Cdd:cd09100   192 PNTEAENIIqkIKQQQYQELLPHDQLLIERKESKVFLQFEEEEITFAPTYRFERGTRERYAYTkqkaTGMKYNLPSWCDR 271

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1063696119 572 ILYRDNkkhlgaecsldcPVVSSISQ-YDACMEVTDSDHKPVRCVFSV 618
Cdd:cd09100   272 VLWKSY------------PLVHVVCQsYGCTDDITTSDHSPVFATFEV 307
INPP5A cd09092
Type I inositol polyphosphate 5-phosphatase I; Type I inositol polyphosphate 5-phosphatase I ...
 486-616 1.83e-08

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: 57.48  E-value: 1.83e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 486 IFLGDFNYRLD-------------------------------DITYD-------ETR--DFISQRCF-----DWLREKDQ 520
Cdd:cd09092   219 FVFGDFNFRLDtksvvetlcakatmqtvrkadsnivvklefrEKDNDnkvvlqiEKKkfDYFNQDVFrdnngKALLKFDK 298

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 521 lhtemEAGNVFQGMREAIIRFPPTYKFERHqaglagYDSGE---KKRIPAWCDRILYRDNKKHLGAEcsldcpVVSSISQ 597
Cdd:cd09092   299 -----ELEVFKDVLYELDISFPPSYPYSED------PEQGTqymNTRCPAWCDRILMSHSARELKSE------NEEKSVT 361

                         170       180
                  ....*....|....*....|
gi 1063696119 598 YDAC-MEVTDSDHKPVRCVF 616
Cdd:cd09092   362 YDMIgPNVCMGDHKPVFLTF 381
WD40 COG2319
WD40 repeat [General function prediction only];
144-251 7.07e-06

WD40 repeat [General function prediction only];


Pssm-ID: 441893 [Multi-domain]  Cd Length: 403  Bit Score: 49.14  E-value: 7.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 144 AIVISVDG-MIWTGSSNGILMRWD-GNGNCLQEFAYESSGILCMfTF---CSRLWVGYSNGTVQVWDLE-GKLLGGWVAH 217
Cdd:COG2319   209 SVAFSPDGkLLASGSADGTVRLWDlATGKLLRTLTGHSGSVRSV-AFspdGRLLASGSADGTVRLWDLAtGELLRTLTGH 287

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063696119 218 SGPVIKMAIGAG--YLFTLANHGGIRGWNVTSPGPL 251
Cdd:COG2319   288 SGGVNSVAFSPDgkLLASGSDDGTVRLWDLATGKLL 323
WD40 COG2319
WD40 repeat [General function prediction only];
144-247 8.79e-06

WD40 repeat [General function prediction only];


Pssm-ID: 441893 [Multi-domain]  Cd Length: 403  Bit Score: 49.14  E-value: 8.79e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 144 AIVISVDG-MIWTGSSNGILMRWD-GNGNCLQEFAYESSGILCMfTFC---SRLWVGYSNGTVQVWDLE-GKLLGGWVAH 217
Cdd:COG2319   293 SVAFSPDGkLLASGSDDGTVRLWDlATGKLLRTLTGHTGAVRSV-AFSpdgKTLASGSDDGTVRLWDLAtGELLRTLTGH 371

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1063696119 218 SGPVIKMAIGA--GYLFTLANHGGIRGWNVTS 247
Cdd:COG2319   372 TGAVTSVAFSPdgRTLASGSADGTVRLWDLAT 403
WD40 COG2319
WD40 repeat [General function prediction only];
144-251 1.57e-05

WD40 repeat [General function prediction only];


Pssm-ID: 441893 [Multi-domain]  Cd Length: 403  Bit Score: 47.98  E-value: 1.57e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 144 AIVISVDG-MIWTGSSNGILMRWD-GNGNCLQEFAYESSGILCMfTFC---SRLWVGYSNGTVQVWDLE-GKLLGGWVAH 217
Cdd:COG2319   125 SVAFSPDGkTLASGSADGTVRLWDlATGKLLRTLTGHSGAVTSV-AFSpdgKLLASGSDDGTVRLWDLAtGKLLRTLTGH 203

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1063696119 218 SGPVIKMAIGAG--YLFTLANHGGIRGWNVTSPGPL 251
Cdd:COG2319   204 TGAVRSVAFSPDgkLLASGSADGTVRLWDLATGKLL 239
WD40 cd00200
WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions ...
 155-244 2.55e-04

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.


Pssm-ID: 238121 [Multi-domain]  Cd Length: 289  Bit Score: 43.86  E-value: 2.55e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 155 TGSSNGILMRWD-GNGNCLQEFAYESSGILCMFTFCSRLWV--GYSNGTVQVWDLE-GKLLGGWVAHSGPVIKMAI--GA 228
Cdd:cd00200   194 SSSSDGTIKLWDlSTGKCLGTLRGHENGVNSVAFSPDGYLLasGSEDGTIRVWDLRtGECVQTLSGHTNSVTSLAWspDG 273

                          90
                  ....*....|....*.
gi 1063696119 229 GYLFTLANHGGIRGWN 244
Cdd:cd00200   274 KRLASGSADGTIRIWD 289
Motile_Sperm pfam00635
MSP (Major sperm protein) domain; Major sperm proteins are involved in sperm motility. These ...
 653-777 2.33e-03

MSP (Major sperm protein) domain; Major sperm proteins are involved in sperm motility. These proteins oligomerise to form filaments. This family contains many other proteins.


Pssm-ID: 459882  Cd Length: 109  Bit Score: 38.50  E-value: 2.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063696119 653 PETIVStnNIILQNQDSTILRITNKSEKNIAfFKIICEGqskieedgqahdhrargsfgfPQWLEVSPGTGTIKPNQIAE 732
Cdd:pfam00635   7 PDLIFF--AAPGNKQGTSTLTLKNTSDKRVA-FKVKTTN---------------------PKKYRVRPNYGIIKPGESVT 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1063696119 733 VSVHLEDFPTVEEfvdgvaqnswcEDTRDKEVILVLVVHGRFSTE 777
Cdd:pfam00635  63 ITITRQPFDEEPG-----------DAKKDKFVIQYAVAPGDEKDA 96
 
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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