ID I5P2_HUMAN Reviewed; 993 AA.
AC P32019; C9J6U5; Q5VSG9; Q5VSH0; Q5VSH1; Q658Q5; Q6P6D4; Q6PD53;
AC Q86YE1;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 4.
DT 01-MAY-2013, entry version 124.
DE RecName: Full=Type II inositol 1,4,5-trisphosphate 5-phosphatase;
DE EC=3.1.3.36;
DE AltName: Full=75 kDa inositol polyphosphate-5-phosphatase;
DE AltName: Full=Phosphoinositide 5-phosphatase;
DE Short=5PTase;
DE Flags: Precursor;
GN Name=INPP5B; Synonyms=OCRL2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-990, MUTAGENESIS OF
RP CYS-990, AND VARIANT THR-745.
RX PubMed=7721860; DOI=10.1074/jbc.270.16.9370;
RA Jefferson A.B., Majerus P.W.;
RT "Properties of type II inositol polyphosphate 5-phosphatase.";
RL J. Biol. Chem. 270:9370-9377(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT
RP THR-745.
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-178.
RC TISSUE=Stomach;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 284-954, PROTEIN SEQUENCE OF 321-339,
RP AND VARIANT THR-745.
RC TISSUE=Placenta;
RX PubMed=1718960;
RA Ross T.S., Jefferson A.B., Mitchell C.A., Majerus P.W.;
RT "Cloning and expression of human 75-kDa inositol polyphosphate-5-
RT phosphatase.";
RL J. Biol. Chem. 266:20283-20289(1991).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RAB GTPASES.
RX PubMed=17956944; DOI=10.1242/jcs.014423;
RA Williams C., Choudhury R., McKenzie E., Lowe M.;
RT "Targeting of the type II inositol polyphosphate 5-phosphatase INPP5B
RT to the early secretory pathway.";
RL J. Cell Sci. 120:3941-3951(2007).
RN [7]
RP INTERACTION WITH FAM109A.
RX PubMed=20133602; DOI=10.1073/pnas.0914658107;
RA Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P.;
RT "Two closely related endocytic proteins that share a common OCRL-
RT binding motif with APPL1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP INTERACTION WITH FAM109A AND FAM109B.
RX PubMed=21233288; DOI=10.1091/mbc.E10-08-0730;
RA Noakes C.J., Lee G., Lowe M.;
RT "The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling
RT in the endocytic pathway.";
RL Mol. Biol. Cell 22:606-623(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 339-646 IN COMPLEX WITH
RP MAGNESIUM AND PHOSPHATIDYLINOSITOL 4-PHOSPHATE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of INPP5B in complex with phosphatidylinositol 4-
RT phosphate (CASP target).";
RL Submitted (JUL-2010) to the PDB data bank.
CC -!- FUNCTION: Hydrolyzes phosphatidylinositol 4,5-bisphosphate
CC (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol
CC 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates
CC cellular signaling events.
CC -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5-
CC bisphosphate + H(2)O = 1-phosphatidyl-1D-myo-inositol 4-phosphate
CC + phosphate.
CC -!- SUBUNIT: Interacts with APPL1, FAM109A and FAM109B. Interacts with
CC several Rab GTPases, at least RAB1A, RAB2A, RAB5A, RAB6A, RAB8A,
CC RAB9A and RAB33B; these interactions may play a dual role in
CC targeting INPP5B to the specific membranes and stimulating the
CC phosphatase activity.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Endoplasmic reticulum-
CC Golgi intermediate compartment. Early endosome membrane. Membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasmic
CC vesicle, phagosome membrane (By similarity). Golgi apparatus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P32019-1; Sequence=Displayed;
CC Note=No experimental confirmation available;
CC Name=2;
CC IsoId=P32019-2; Sequence=VSP_012820;
CC Name=3;
CC IsoId=P32019-3; Sequence=VSP_012821;
CC Name=4;
CC IsoId=P32019-4; Sequence=VSP_013902, VSP_013903;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Platelets.
CC -!- DOMAIN: The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase
CC activating) domains form a single folding module. The ASH domain
CC has an immunoglobulin-like fold, the Rho-GAP domain lacks the
CC catalytic arginine and is catalytically inactive. The ASH-RhoGAP
CC module regulates the majority of the protein-protein interactions
CC currently described. The ASH domain mediates association with
CC membrane-targeting Rab GTPases. The Rho-GAP domain interacts with
CC the endocytic adapter APPL1, which is then displaced by FAM109A
CC and FAM109B as endosomes mature, all three interactions relie on
CC F&H motifs, an approximately 12-13 amino-acid sequence centered
CC around Phe and His residues essential for binding (By similarity).
CC -!- PTM: Isoprenylation at Cys-990 may be required for localization at
CC the membrane.
CC -!- PTM: May be proteolytically cleaved after Lys-320 as inferred from
CC N-terminal protein sequence of the 75 kda form (PubMed:1718960).
CC -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-
CC phosphatase type II family.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 1 Rho-GAP domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA79207.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; M74161; AAA79207.1; ALT_INIT; mRNA.
DR EMBL; AL603790; CAH69926.1; -; Genomic_DNA.
DR EMBL; AL929472; CAH69926.1; JOINED; Genomic_DNA.
DR EMBL; AL603790; CAH69928.1; -; Genomic_DNA.
DR EMBL; AL929472; CAH69928.1; JOINED; Genomic_DNA.
DR EMBL; AL603790; CAH69929.1; -; Genomic_DNA.
DR EMBL; AL929472; CAH69929.1; JOINED; Genomic_DNA.
DR EMBL; AL929472; CAH70076.1; -; Genomic_DNA.
DR EMBL; AL603790; CAH70076.1; JOINED; Genomic_DNA.
DR EMBL; AL929472; CAH70079.1; -; Genomic_DNA.
DR EMBL; AL603790; CAH70079.1; JOINED; Genomic_DNA.
DR EMBL; AL929472; CAH70080.1; -; Genomic_DNA.
DR EMBL; AL603790; CAH70080.1; JOINED; Genomic_DNA.
DR EMBL; BX296560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC042529; AAH42529.2; -; mRNA.
DR EMBL; BC058932; AAH58932.1; -; mRNA.
DR EMBL; AL833055; CAH56301.1; -; mRNA.
DR IPI; IPI00244111; -.
DR IPI; IPI00478376; -.
DR IPI; IPI00553072; -.
DR IPI; IPI00604769; -.
DR RefSeq; NP_005531.2; NM_005540.2.
DR UniGene; Hs.449942; -.
DR PDB; 3MTC; X-ray; 2.40 A; A=339-643.
DR PDB; 3N9V; X-ray; 2.65 A; A/B=342-646.
DR PDBsum; 3MTC; -.
DR PDBsum; 3N9V; -.
DR ProteinModelPortal; P32019; -.
DR SMR; P32019; 1-155, 339-643, 656-989.
DR STRING; 9606.ENSP00000362115; -.
DR PhosphoSite; P32019; -.
DR DMDM; 281185510; -.
DR PaxDb; P32019; -.
DR PRIDE; P32019; -.
DR Ensembl; ENST00000373023; ENSP00000362114; ENSG00000204084.
DR Ensembl; ENST00000373024; ENSP00000362115; ENSG00000204084.
DR Ensembl; ENST00000373026; ENSP00000362117; ENSG00000204084.
DR Ensembl; ENST00000373027; ENSP00000362118; ENSG00000204084.
DR GeneID; 3633; -.
DR KEGG; hsa:3633; -.
DR UCSC; uc001ccf.1; human.
DR UCSC; uc001ccg.1; human.
DR CTD; 3633; -.
DR GeneCards; GC01M038326; -.
DR HGNC; HGNC:6077; INPP5B.
DR HPA; HPA028803; -.
DR MIM; 147264; gene.
DR neXtProt; NX_P32019; -.
DR PharmGKB; PA29885; -.
DR eggNOG; COG5411; -.
DR HOVERGEN; HBG000070; -.
DR InParanoid; P32019; -.
DR KO; K01099; -.
DR OMA; SAYHNCL; -.
DR BioCyc; MetaCyc:HS05898-MONOMER; -.
DR BRENDA; 3.1.3.36; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P32019; -.
DR ChEMBL; CHEMBL2636; -.
DR ChiTaRS; INPP5B; human.
DR EvolutionaryTrace; P32019; -.
DR GenomeRNAi; 3633; -.
DR NextBio; 14219; -.
DR ArrayExpress; P32019; -.
DR Bgee; P32019; -.
DR CleanEx; HS_INPP5B; -.
DR Genevestigator; P32019; -.
DR GermOnline; ENSG00000204084; Homo sapiens.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:Compara.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0052658; F:inositol-1,4,5-trisphosphate 5-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004439; F:phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity; IDA:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Compara.
DR GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphorylation; IEA:InterPro.
DR GO; GO:0070613; P:regulation of protein processing; IEA:Compara.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0030317; P:sperm motility; IEA:Compara.
DR GO; GO:0007283; P:spermatogenesis; IEA:Compara.
DR Gene3D; 1.10.555.10; -; 1.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR000300; IPPc.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00128; IPPc; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF56219; Exo_endo_phos; 1.
DR SUPFAM; SSF48350; Rho_GAP; 1.
DR PROSITE; PS50003; PH_DOMAIN; FALSE_NEG.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Endosome;
KW Golgi apparatus; Hydrolase; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Methylation; Polymorphism; Prenylation;
KW Reference proteome.
FT CHAIN 1 990 Type II inositol 1,4,5-trisphosphate 5-
FT phosphatase.
FT /FTId=PRO_0000015640.
FT PROPEP 991 993 Removed in mature form (Potential).
FT /FTId=PRO_0000422293.
FT DOMAIN 22 148 PH.
FT DOMAIN 821 993 Rho-GAP.
FT REGION 342 668 5-phosphatase (By similarity).
FT REGION 459 460 Substrate binding.
FT REGION 582 583 Substrate binding.
FT REGION 596 598 Substrate binding.
FT REGION 669 782 ASH (By similarity).
FT METAL 355 355 Magnesium.
FT METAL 383 383 Magnesium.
FT BINDING 383 383 Substrate.
FT MOD_RES 990 990 Cysteine methyl ester (Potential).
FT LIPID 990 990 S-farnesyl cysteine (Potential).
FT VAR_SEQ 1 244 Missing (in isoform 3).
FT /FTId=VSP_012821.
FT VAR_SEQ 178 257 Missing (in isoform 2).
FT /FTId=VSP_012820.
FT VAR_SEQ 810 828 TLMPVWTGDDGSQLDSPME -> LAYLAAYCFETQLVTKSL
FT I (in isoform 4).
FT /FTId=VSP_013902.
FT VAR_SEQ 829 993 Missing (in isoform 4).
FT /FTId=VSP_013903.
FT VARIANT 46 46 G -> S (in dbSNP:rs56993041).
FT /FTId=VAR_061270.
FT VARIANT 745 745 M -> T (in dbSNP:rs11488569).
FT /FTId=VAR_028002.
FT MUTAGEN 990 990 C->S: Loss of prenylation and membrane
FT localization.
FT CONFLICT 587 606 GSDDWDTSEKCRAPAWCDRI -> RALTTGIPVRSAVLLPG
FT VIGF (in Ref. 5; AA sequence).
FT CONFLICT 911 911 G -> P (in Ref. 5; AA sequence).
FT STRAND 340 353
FT HELIX 364 367
FT STRAND 368 370
FT STRAND 375 382
FT HELIX 388 391
FT HELIX 398 409
FT STRAND 416 424
FT STRAND 427 434
FT HELIX 435 440
FT STRAND 441 450
FT HELIX 453 455
FT STRAND 460 469
FT STRAND 472 480
FT HELIX 485 487
FT HELIX 488 501
FT STRAND 509 511
FT STRAND 518 527
FT HELIX 537 545
FT HELIX 549 553
FT HELIX 557 563
FT STRAND 588 591
FT STRAND 604 620
FT STRAND 626 629
FT STRAND 632 643
SQ SEQUENCE 993 AA; 112852 MW; ABD3581CC6CD29D6 CRC64;
MDQSVAIQET LAEGEYCVIA VQGVLCEGDS RQSRLLGLVR YRLEHGGQEH ALFLYTHRRM
AITGDDVSLD QIVPVSRDFT LEEVSPDGEL YILGSDVTVQ LDTAELSLVF QLPFGSQTRM
FLHEVARACP GFDSATRDPE FLWLSRYRCA ELELEMPTPR GCNSALVTWP GYATIGGGRY
PSRKKRWGLE EARPQGAGSV LFWGGAMEKT GFRLMERAHG GGFVWGRSAR DGRRDEELEE
AGREMSAAAG SRERNTAGGS NFDGLRPNGK GVPMDQSSRG QDKPESLQPR QNKSKSEITD
MVRSSTITVS DKAHILSMQK FGLRDTIVKS HLLQKEEDYT YIQNFRFFAG TYNVNGQSPK
ECLRLWLSNG IQAPDVYCVG FQELDLSKEA FFFHDTPKEE EWFKAVSEGL HPDAKYAKVK
LIRLVGIMLL LYVKQEHAAY ISEVEAETVG TGIMGRMGNK GGVAIRFQFH NTSICVVNSH
LAAHIEEYER RNQDYKDICS RMQFCQPDPS LPPLTISNHD VILWLGDLNY RIEELDVEKV
KKLIEEKDFQ MLYAYDQLKI QVAAKTVFEG FTEGELTFQP TYKYDTGSDD WDTSEKCRAP
AWCDRILWKG KNITQLSYQS HMALKTSDHK PVSSVFDIGV RVVNDELYRK TLEEIVRSLD
KMENANIPSV SLSKREFCFQ NVKYMQLKVE SFTIHNGQVP CHFEFINKPD EESYCKQWLN
ANPSRGFLLP DSDVEIDLEL FVNKMTATKL NSGEDKIEDI LVLHLDRGKD YFLSVSGNYL
PSCFGSPIHT LCYMREPILD LPLETISELT LMPVWTGDDG SQLDSPMEIP KELWMMVDYL
YRNAVQQEDL FQQPGLRSEF EHIRDCLDTG MIDNLSASNH SVAEALLLFL ESLPEPVICY
STYHNCLECS GNYTASKQVI STLPIFHKNV FHYLMAFLRE LLKNSAKNHL DENILASIFG
SLLLRNPAGH QKLDMTEKKK AQEFIHQFLC NPL
//
