INPP_HUMAN
ID INPP_HUMAN Reviewed; 399 AA.
AC P49441;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Inositol polyphosphate 1-phosphatase {ECO:0000305};
DE Short=IPP;
DE Short=IPPase;
DE EC=3.1.3.57 {ECO:0000269|PubMed:8390685};
GN Name=INPP1 {ECO:0000312|HGNC:HGNC:6071};
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], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8390685; DOI=10.1073/pnas.90.12.5833;
RA York J.D., Veile R.A., Donis-Keller H., Majerus P.W.;
RT "Cloning, heterologous expression, and chromosomal localization of human
RT inositol polyphosphate 1-phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:5833-5837(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10780272;
RA Lovlie R., Gulbrandsen A.-K., Molven A., Steen V.M.;
RT "Genomic structure and sequence analysis of a human inositol polyphosphate
RT 1-phosphatase gene (INPP1).";
RL Pharmacogenetics 9:517-528(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP VARIANT ALA-228.
RX PubMed=9682271;
RA Steen V.M., Lovlie R., Osher Y., Belmaker R.H., Berle J.O.,
RA Gulbrandsen A.K.;
RT "The polymorphic inositol polyphosphate 1-phosphatase gene as a candidate
RT for pharmacogenetic prediction of lithium-responsive manic-depressive
RT illness.";
RL Pharmacogenetics 8:259-268(1998).
CC -!- FUNCTION: Mg(2+)-dependent phosphatase that catalyzes the hydrolysis of
CC the 1-position phosphate from inositol 1,4-bisphosphate and inositol
CC 1,3,4-trisphosphate and participates in inositol phosphate metabolism.
CC {ECO:0000269|PubMed:8390685}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,4-bisphosphate + H2O = 1D-myo-inositol 4-
CC phosphate + phosphate; Xref=Rhea:RHEA:15553, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58282, ChEBI:CHEBI:58469; EC=3.1.3.57;
CC Evidence={ECO:0000269|PubMed:8390685};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15554;
CC Evidence={ECO:0000250|UniProtKB:P21327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + H2O = 1D-myo-inositol
CC 3,4-bisphosphate + phosphate; Xref=Rhea:RHEA:70319,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58414,
CC ChEBI:CHEBI:83241; Evidence={ECO:0000250|UniProtKB:P21327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70320;
CC Evidence={ECO:0000250|UniProtKB:P21327};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P21327};
CC -!- ACTIVITY REGULATION: Inhibited by Li(+).
CC {ECO:0000250|UniProtKB:P21327}.
CC -!- PATHWAY: Signal transduction; phosphatidylinositol signaling pathway.
CC {ECO:0000250|UniProtKB:P21327}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P21327}.
CC -!- INTERACTION:
CC P49441; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-725432, EBI-16439278;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC pancreas and kidney.
CC -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC {ECO:0000305}.
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DR EMBL; L08488; AAA36117.1; -; mRNA.
DR EMBL; AF141325; AAD46766.1; -; Genomic_DNA.
DR EMBL; BC015496; AAH15496.1; -; mRNA.
DR CCDS; CCDS2305.1; -.
DR RefSeq; NP_001122400.1; NM_001128928.1.
DR RefSeq; NP_002185.1; NM_002194.3.
DR RefSeq; XP_005246589.1; XM_005246532.1.
DR AlphaFoldDB; P49441; -.
DR SMR; P49441; -.
DR BioGRID; 109840; 26.
DR IntAct; P49441; 4.
DR MINT; P49441; -.
DR STRING; 9606.ENSP00000376142; -.
DR DEPOD; INPP1; -.
DR GlyGen; P49441; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49441; -.
DR PhosphoSitePlus; P49441; -.
DR BioMuta; INPP1; -.
DR DMDM; 1352464; -.
DR EPD; P49441; -.
DR jPOST; P49441; -.
DR MassIVE; P49441; -.
DR PaxDb; P49441; -.
DR PeptideAtlas; P49441; -.
DR PRIDE; P49441; -.
DR ProteomicsDB; 56010; -.
DR TopDownProteomics; P49441; -.
DR Antibodypedia; 34038; 151 antibodies from 22 providers.
DR DNASU; 3628; -.
DR Ensembl; ENST00000322522.8; ENSP00000325423.4; ENSG00000151689.13.
DR Ensembl; ENST00000392329.7; ENSP00000376142.2; ENSG00000151689.13.
DR GeneID; 3628; -.
DR KEGG; hsa:3628; -.
DR MANE-Select; ENST00000392329.7; ENSP00000376142.2; NM_001128928.2; NP_001122400.1.
DR CTD; 3628; -.
DR DisGeNET; 3628; -.
DR GeneCards; INPP1; -.
DR HGNC; HGNC:6071; INPP1.
DR HPA; ENSG00000151689; Low tissue specificity.
DR MIM; 147263; gene.
DR neXtProt; NX_P49441; -.
DR OpenTargets; ENSG00000151689; -.
DR PharmGKB; PA29880; -.
DR VEuPathDB; HostDB:ENSG00000151689; -.
DR eggNOG; KOG3099; Eukaryota.
DR GeneTree; ENSGT00940000156785; -.
DR HOGENOM; CLU_043868_2_0_1; -.
DR InParanoid; P49441; -.
DR OMA; ANIARVC; -.
DR OrthoDB; 1096950at2759; -.
DR PhylomeDB; P49441; -.
DR TreeFam; TF314300; -.
DR BioCyc; MetaCyc:HS07761-MON; -.
DR BRENDA; 3.1.3.57; 2681.
DR PathwayCommons; P49441; -.
DR Reactome; R-HSA-1855183; Synthesis of IP2, IP, and Ins in the cytosol.
DR SignaLink; P49441; -.
DR UniPathway; UPA00944; -.
DR BioGRID-ORCS; 3628; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; INPP1; human.
DR GeneWiki; INPP1; -.
DR GenomeRNAi; 3628; -.
DR Pharos; P49441; Tbio.
DR PRO; PR:P49441; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P49441; protein.
DR Bgee; ENSG00000151689; Expressed in sperm and 202 other tissues.
DR ExpressionAtlas; P49441; baseline and differential.
DR Genevisible; P49441; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0052829; F:inositol-1,3,4-trisphosphate 1-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0004441; F:inositol-1,4-bisphosphate 1-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046855; P:inositol phosphate dephosphorylation; IBA:GO_Central.
DR GO; GO:0006796; P:phosphate-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 4.10.460.10; -; 1.
DR InterPro; IPR020583; Inositol_monoP_metal-BS.
DR InterPro; IPR000760; Inositol_monophosphatase-like.
DR InterPro; IPR020550; Inositol_monophosphatase_CS.
DR InterPro; IPR044897; INPP1_dom_1.
DR Pfam; PF00459; Inositol_P; 1.
DR PROSITE; PS00629; IMP_1; 1.
DR PROSITE; PS00630; IMP_2; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Lithium; Magnesium; Metal-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..399
FT /note="Inositol polyphosphate 1-phosphatase"
FT /id="PRO_0000142510"
FT BINDING 54
FT /ligand="Li(+)"
FT /ligand_id="ChEBI:CHEBI:49713"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 79
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 80
FT /ligand="Li(+)"
FT /ligand_id="ChEBI:CHEBI:49713"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 153
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 153
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 155
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 156
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 157
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 158
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 267
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 269
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 289
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 290
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 293
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 311
FT /ligand="1D-myo-inositol 1,4-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58282"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT BINDING 316
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P21327"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT VARIANT 228
FT /note="T -> A (frequency not significantly different
FT between lithium-treated bipolar patients and healthy
FT controls; dbSNP:rs7592352)"
FT /evidence="ECO:0000269|PubMed:9682271"
FT /id="VAR_019669"
FT VARIANT 355
FT /note="V -> M (in dbSNP:rs35616200)"
FT /id="VAR_049599"
SQ SEQUENCE 399 AA; 43998 MW; AEFD592199A40C6C CRC64;
MSDILRELLC VSEKAANIAR ACRQQEALFQ LLIEEKKEGE KNKKFAVDFK TLADVLVQEV
IKQNMENKFP GLEKNIFGEE SNEFTNDWGE KITLRLCSTE EETAELLSKV LNGNKVASEA
LARVVHQDVA FTDPTLDSTE INVPQDILGI WVDPIDSTYQ YIKGSADIKS NQGIFPCGLQ
CVTILIGVYD IQTGVPLMGV INQPFVSRDP NTLRWKGQCY WGLSYMGTNM HSLQLTISRR
NGSETHTGNT GSEAAFSPSF SAVISTSEKE TIKAALSRVC GDRIFGAAGA GYKSLCVVQG
LVDIYIFSED TTFKWDSCAA HAILRAMGGG IVDLKECLER NPETGLDLPQ LVYHVENEGA
AGVDRWANKG GLIAYRSRKR LETFLSLLVQ NLAPAETHT
