ID   I5P2_HUMAN              Reviewed;         993 AA.
AC   P32019; C9J6U5; Q5VSG9; Q5VSH0; Q5VSH1; Q658Q5; Q6P6D4; Q6PD53; Q86YE1;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2009, sequence version 4.
DT   27-MAR-2024, entry version 199.
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; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   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 CYS-990,
RP   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., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., 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., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., 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., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., 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 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 project:
RT   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., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   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, AND
RP   VARIANT THR-745.
RC   TISSUE=Placenta;
RX   PubMed=1718960; DOI=10.1016/s0021-9258(18)54920-6;
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 to
RT   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-binding
RT   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., Buerckstuemmer T.,
RA   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 in
RT   the endocytic pathway.";
RL   Mol. Biol. Cell 22:606-623(2011).
RN   [10]
RP   INTERACTION WITH INPP5F.
RX   PubMed=25869668; DOI=10.1083/jcb.201409064;
RA   Nakatsu F., Messa M., Nandez R., Czapla H., Zou Y., Strittmatter S.M.,
RA   De Camilli P.;
RT   "Sac2/INPP5F is an inositol 4-phosphatase that functions in the endocytic
RT   pathway.";
RL   J. Cell Biol. 209:85-95(2015).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB8A.
RX   PubMed=26824392; DOI=10.7554/elife.12813;
RA   Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S.,
RA   Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J.,
RA   Morrow J.A., Reith A.D., Alessi D.R., Mann M.;
RT   "Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates
RT   a subset of Rab GTPases.";
RL   Elife 5:0-0(2016).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 339-646 IN COMPLEX WITH MAGNESIUM
RP   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 1,4,5-
CC       trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular
CC       signaling events. {ECO:0000269|PubMed:7721860}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC         bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC         inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178,
CC         ChEBI:CHEBI:58456; EC=3.1.3.36;
CC         Evidence={ECO:0000269|PubMed:7721860};
CC   -!- SUBUNIT: Interacts with APPL1, FAM109A and FAM109B (PubMed:20133602,
CC       PubMed:21233288). Interacts with several Rab GTPases, at least RAB1A,
CC       RAB2A, RAB5A, RAB6A, RAB8A, RAB9A and RAB33B; these interactions may
CC       play a dual role in targeting INPP5B to the specific membranes and
CC       stimulating its phosphatase activity (PubMed:17956944, PubMed:26824392,
CC       Ref.12). Interacts preferentially with non-phosphorylated RAB8A;
CC       phosphorylation of RAB8A on 'Thr-72' disrupts this interaction
CC       (PubMed:26824392). Interacts with INPP5F (PubMed:25869668).
CC       {ECO:0000269|PubMed:17956944, ECO:0000269|PubMed:20133602,
CC       ECO:0000269|PubMed:21233288, ECO:0000269|PubMed:25869668,
CC       ECO:0000269|PubMed:26824392, ECO:0000269|Ref.12}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:7721860}.
CC       Endoplasmic reticulum-Golgi intermediate compartment
CC       {ECO:0000269|PubMed:17956944}. Early endosome membrane
CC       {ECO:0000269|PubMed:17956944}. Membrane {ECO:0000269|PubMed:7721860};
CC       Peripheral membrane protein {ECO:0000305|PubMed:7721860}; Cytoplasmic
CC       side {ECO:0000305|PubMed:7721860}. Cytoplasmic vesicle, phagosome
CC       membrane {ECO:0000250|UniProtKB:Q8K337}. Golgi apparatus
CC       {ECO:0000269|PubMed:17956944}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=P32019-1; Sequence=Displayed;
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   -!- TISSUE SPECIFICITY: Platelets.
CC   -!- DOMAIN: The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating)
CC       domains form a single folding module. The ASH domain has an
CC       immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic
CC       arginine and is catalytically inactive. The ASH-RhoGAP module regulates
CC       the majority of the protein-protein interactions currently described.
CC       The ASH domain mediates association with membrane-targeting Rab
CC       GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1,
CC       which is then displaced by FAM109A and FAM109B as endosomes mature, all
CC       three interactions rely on F&H motifs, an approximately 12-13 amino-
CC       acid sequence centered around Phe and His residues essential for
CC       binding (By similarity). {ECO:0000250}.
CC   -!- PTM: Isoprenylation at Cys-990 may be required for localization at the
CC       membrane. {ECO:0000269|PubMed:7721860}.
CC   -!- PTM: May be proteolytically cleaved after Lys-320 as inferred from N-
CC       terminal protein sequence of the 75 kda form.
CC       {ECO:0000269|PubMed:1718960}.
CC   -!- SIMILARITY: Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase
CC       type II family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA79207.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M74161; AAA79207.1; ALT_INIT; mRNA.
DR   EMBL; AL603790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL929472; -; NOT_ANNOTATED_CDS; 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   CCDS; CCDS41306.1; -. [P32019-2]
DR   CCDS; CCDS72760.1; -. [P32019-3]
DR   RefSeq; NP_001284363.1; NM_001297434.1. [P32019-3]
DR   RefSeq; NP_005531.2; NM_005540.2. [P32019-2]
DR   PDB; 3MTC; X-ray; 2.40 A; A=339-643.
DR   PDB; 3N9V; X-ray; 2.65 A; A/B=342-646.
DR   PDB; 4CML; X-ray; 2.30 A; A=339-643.
DR   PDB; 5A7I; X-ray; 2.89 A; A=339-643.
DR   PDB; 5A7J; X-ray; 2.90 A; A/B=339-643.
DR   PDBsum; 3MTC; -.
DR   PDBsum; 3N9V; -.
DR   PDBsum; 4CML; -.
DR   PDBsum; 5A7I; -.
DR   PDBsum; 5A7J; -.
DR   AlphaFoldDB; P32019; -.
DR   SMR; P32019; -.
DR   BioGRID; 109845; 36.
DR   IntAct; P32019; 21.
DR   MINT; P32019; -.
DR   STRING; 9606.ENSP00000362115; -.
DR   BindingDB; P32019; -.
DR   ChEMBL; CHEMBL2636; -.
DR   DrugBank; DB03158; D-Myo-Inositol-1,4-Bisphosphate.
DR   DEPOD; INPP5B; -.
DR   GlyGen; P32019; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P32019; -.
DR   PhosphoSitePlus; P32019; -.
DR   BioMuta; INPP5B; -.
DR   DMDM; 281185510; -.
DR   EPD; P32019; -.
DR   jPOST; P32019; -.
DR   MassIVE; P32019; -.
DR   MaxQB; P32019; -.
DR   PaxDb; 9606-ENSP00000362115; -.
DR   PeptideAtlas; P32019; -.
DR   ProteomicsDB; 54832; -. [P32019-1]
DR   ProteomicsDB; 54833; -. [P32019-2]
DR   ProteomicsDB; 54834; -. [P32019-3]
DR   ProteomicsDB; 54835; -. [P32019-4]
DR   Pumba; P32019; -.
DR   ABCD; P32019; 1 sequenced antibody.
DR   Antibodypedia; 31808; 196 antibodies from 25 providers.
DR   DNASU; 3633; -.
DR   Ensembl; ENST00000373024.8; ENSP00000362115.3; ENSG00000204084.14. [P32019-2]
DR   Ensembl; ENST00000373026.5; ENSP00000362117.1; ENSG00000204084.14. [P32019-1]
DR   Ensembl; ENST00000373027.5; ENSP00000362118.1; ENSG00000204084.14. [P32019-3]
DR   GeneID; 3633; -.
DR   KEGG; hsa:3633; -.
DR   MANE-Select; ENST00000373024.8; ENSP00000362115.3; NM_005540.3; NP_005531.2. [P32019-2]
DR   UCSC; uc001ccf.1; human. [P32019-1]
DR   AGR; HGNC:6077; -.
DR   CTD; 3633; -.
DR   DisGeNET; 3633; -.
DR   GeneCards; INPP5B; -.
DR   HGNC; HGNC:6077; INPP5B.
DR   HPA; ENSG00000204084; Low tissue specificity.
DR   MIM; 147264; gene.
DR   neXtProt; NX_P32019; -.
DR   OpenTargets; ENSG00000204084; -.
DR   PharmGKB; PA29885; -.
DR   VEuPathDB; HostDB:ENSG00000204084; -.
DR   eggNOG; KOG0565; Eukaryota.
DR   eggNOG; KOG4270; Eukaryota.
DR   GeneTree; ENSGT00940000156762; -.
DR   HOGENOM; CLU_006779_2_0_1; -.
DR   InParanoid; P32019; -.
DR   OMA; VREDAWC; -.
DR   OrthoDB; 21647at2759; -.
DR   PhylomeDB; P32019; -.
DR   TreeFam; TF317034; -.
DR   BioCyc; MetaCyc:HS05898-MONOMER; -.
DR   BRENDA; 3.1.3.36; 2681.
DR   PathwayCommons; P32019; -.
DR   Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR   Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR   SABIO-RK; P32019; -.
DR   SignaLink; P32019; -.
DR   BioGRID-ORCS; 3633; 15 hits in 1169 CRISPR screens.
DR   ChiTaRS; INPP5B; human.
DR   EvolutionaryTrace; P32019; -.
DR   GeneWiki; INPP5B; -.
DR   GenomeRNAi; 3633; -.
DR   Pharos; P32019; Tbio.
DR   PRO; PR:P32019; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P32019; Protein.
DR   Bgee; ENSG00000204084; Expressed in left ovary and 150 other cell types or tissues.
DR   ExpressionAtlas; P32019; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
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:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0052659; F:inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity; TAS:Reactome.
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:0030317; P:flagellated sperm motility; IEA:Ensembl.
DR   GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR   GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR   GO; GO:0046856; P:phosphatidylinositol dephosphorylation; IDA:UniProtKB.
DR   GO; GO:0070613; P:regulation of protein processing; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   CDD; cd09093; INPP5c_INPP5B; 1.
DR   CDD; cd13383; PH_OCRL2; 1.
DR   CDD; cd04380; RhoGAP_OCRL1; 1.
DR   Gene3D; 2.30.29.110; -; 1.
DR   Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 1.10.555.10; Rho GTPase activation protein; 1.
DR   InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR031896; INPP5B_PH_dom.
DR   InterPro; IPR046985; IP5.
DR   InterPro; IPR000300; IPPc.
DR   InterPro; IPR048869; OCRL-1_2_ASH.
DR   InterPro; IPR037793; OCRL1/INPP5B_INPP5c.
DR   InterPro; IPR008936; Rho_GTPase_activation_prot.
DR   InterPro; IPR000198; RhoGAP_dom.
DR   InterPro; IPR047078; RhoGAP_OCRL1.
DR   PANTHER; PTHR11200; INOSITOL 5-PHOSPHATASE; 1.
DR   PANTHER; PTHR11200:SF163; TYPE II INOSITOL 1,4,5-TRISPHOSPHATE 5-PHOSPHATASE; 1.
DR   Pfam; PF16776; INPP5B_PH; 1.
DR   Pfam; PF21310; OCRL-like_ASH; 1.
DR   Pfam; PF00620; RhoGAP; 1.
DR   SMART; SM00128; IPPc; 1.
DR   SMART; SM00324; RhoGAP; 1.
DR   SUPFAM; SSF56219; DNase I-like; 1.
DR   SUPFAM; SSF48350; GTPase activation domain, GAP; 1.
DR   PROSITE; PS50238; RHOGAP; 1.
DR   Genevisible; P32019; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytoplasm; Cytoplasmic vesicle;
KW   Direct protein sequencing; Endosome; Golgi apparatus; Hydrolase;
KW   Lipid metabolism; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW   Methylation; Prenylation; Reference proteome.
FT   CHAIN           1..990
FT                   /note="Type II inositol 1,4,5-trisphosphate 5-phosphatase"
FT                   /id="PRO_0000015640"
FT   PROPEP          991..993
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000422293"
FT   DOMAIN          22..148
FT                   /note="PH"
FT   DOMAIN          821..993
FT                   /note="Rho-GAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT   REGION          224..302
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          342..668
FT                   /note="5-phosphatase"
FT                   /evidence="ECO:0000250"
FT   REGION          669..782
FT                   /note="ASH"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        228..247
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        279..302
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         355
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|Ref.12"
FT   BINDING         383
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|Ref.12"
FT   BINDING         383
FT                   /ligand="substrate"
FT   BINDING         459..460
FT                   /ligand="substrate"
FT   BINDING         582..583
FT                   /ligand="substrate"
FT   BINDING         596..598
FT                   /ligand="substrate"
FT   MOD_RES         990
FT                   /note="Cysteine methyl ester"
FT                   /evidence="ECO:0000255"
FT   LIPID           990
FT                   /note="S-farnesyl cysteine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..244
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_012821"
FT   VAR_SEQ         178..257
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7721860"
FT                   /id="VSP_012820"
FT   VAR_SEQ         810..828
FT                   /note="TLMPVWTGDDGSQLDSPME -> LAYLAAYCFETQLVTKSLI (in
FT                   isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013902"
FT   VAR_SEQ         829..993
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013903"
FT   VARIANT         46
FT                   /note="G -> S (in dbSNP:rs56993041)"
FT                   /id="VAR_061270"
FT   VARIANT         745
FT                   /note="M -> T (in dbSNP:rs11488569)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:1718960, ECO:0000269|PubMed:7721860"
FT                   /id="VAR_028002"
FT   MUTAGEN         990
FT                   /note="C->S: Loss of prenylation and membrane
FT                   localization."
FT                   /evidence="ECO:0000269|PubMed:7721860"
FT   CONFLICT        587..606
FT                   /note="GSDDWDTSEKCRAPAWCDRI -> RALTTGIPVRSAVLLPGVIGF (in
FT                   Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        911
FT                   /note="G -> P (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          340..353
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           364..367
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          368..370
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          375..382
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           388..391
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           397..409
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          416..424
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          427..434
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           435..440
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          441..450
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           453..455
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          460..469
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          472..480
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           485..487
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           488..501
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          509..511
FT                   /evidence="ECO:0007829|PDB:3MTC"
FT   STRAND          518..527
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           537..545
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           549..553
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   HELIX           557..563
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          566..568
FT                   /evidence="ECO:0007829|PDB:5A7J"
FT   STRAND          588..591
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          594..596
FT                   /evidence="ECO:0007829|PDB:5A7J"
FT   STRAND          604..620
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          626..629
FT                   /evidence="ECO:0007829|PDB:4CML"
FT   STRAND          632..643
FT                   /evidence="ECO:0007829|PDB:4CML"
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
//