VIP2_HUMAN
ID VIP2_HUMAN Reviewed; 1243 AA.
AC O43314; A1NI53; A6NGS8; Q8TB50;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 {ECO:0000305};
DE EC=2.7.4.24 {ECO:0000269|PubMed:21222653};
DE AltName: Full=Diphosphoinositol pentakisphosphate kinase 2;
DE AltName: Full=Histidine acid phosphatase domain-containing protein 1;
DE AltName: Full=InsP6 and PP-IP5 kinase 2;
DE AltName: Full=VIP1 homolog 2;
DE Short=hsVIP2;
GN Name=PPIP5K2 {ECO:0000303|PubMed:29590114, ECO:0000312|HGNC:HGNC:29035};
GN Synonyms=HISPPD1, KIAA0433, VIP2;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
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 [6]
RP FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17690096; DOI=10.1074/jbc.m704656200;
RA Fridy P.C., Otto J.C., Dollins D.E., York J.D.;
RT "Cloning and characterization of two human VIP1-like inositol
RT hexakisphosphate and diphosphoinositol pentakisphosphate kinases.";
RL J. Biol. Chem. 282:30754-30762(2007).
RN [7]
RP FUNCTION, AND ENZYME ACTIVITY.
RX PubMed=17702752; DOI=10.1074/jbc.m704655200;
RA Choi J.H., Williams J., Cho J., Falck J.R., Shears S.B.;
RT "Purification, sequencing, and molecular identification of a mammalian PP-
RT InsP5 kinase that is activated when cells are exposed to hyperosmotic
RT stress.";
RL J. Biol. Chem. 282:30763-30775(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1006; SER-1016 AND SER-1172,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND POLYPHOSPHOINOSITIDE-BINDING DOMAIN.
RX PubMed=21222653; DOI=10.1042/bj20101437;
RA Gokhale N.A., Zaremba A., Shears S.B.;
RT "Receptor-dependent compartmentalization of PPIP5K1, a kinase with a
RT cryptic polyphosphoinositide binding domain.";
RL Biochem. J. 434:415-426(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38; SER-223; SER-1006;
RP SER-1016; SER-1074; SER-1091; SER-1165; SER-1172; SER-1180; SER-1220 AND
RP SER-1221, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38; SER-1006 AND SER-1091,
RP AND 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 [14]
RP INVOLVEMENT IN DFNB100, VARIANT DFNB100 HIS-837, CHARACTERIZATION OF
RP VARIANT DFNB100 HIS-837, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29590114; DOI=10.1371/journal.pgen.1007297;
RA Yousaf R., Gu C., Ahmed Z.M., Khan S.N., Friedman T.B., Riazuddin S.,
RA Shears S.B., Riazuddin S.;
RT "Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are
RT associated with hearing loss in human and mouse.";
RL PLoS Genet. 14:E1007297-E1007297(2018).
RN [15] {ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A, ECO:0007744|PDB:3T99, ECO:0007744|PDB:3T9A, ECO:0007744|PDB:3T9B, ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9D, ECO:0007744|PDB:3T9E, ECO:0007744|PDB:3T9F}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 41-366 IN COMPLEXES WITH ATP;
RP SUBSTRATE AND TRANSITION STATE ANALOG, MUTAGENESIS OF ARG-213; LYS-248 AND
RP ARG-262, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22119861; DOI=10.1038/nchembio.733;
RA Wang H., Falck J.R., Hall T.M., Shears S.B.;
RT "Structural basis for an inositol pyrophosphate kinase surmounting
RT phosphate crowding.";
RL Nat. Chem. Biol. 8:111-116(2012).
CC -!- FUNCTION: Bifunctional inositol kinase that acts in concert with the
CC IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate
CC group-containing inositol pyrophosphates diphosphoinositol
CC pentakisphosphate, PP-InsP5, and bis-diphosphoinositol
CC tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752,
CC PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also
CC respectively called InsP7 and InsP8, regulate a variety of cellular
CC processes, including apoptosis, vesicle trafficking, cytoskeletal
CC dynamics, exocytosis, insulin signaling and neutrophil activation
CC (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114).
CC Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to
CC produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce
CC (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively,
CC phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to
CC produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for
CC normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096,
CC ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653,
CC ECO:0000269|PubMed:29590114}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol hexakisphosphate + ATP = 1-diphospho-myo-
CC inositol 2,3,4,5,6-pentakisphosphate + ADP; Xref=Rhea:RHEA:37459,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58130, ChEBI:CHEBI:74946,
CC ChEBI:CHEBI:456216; EC=2.7.4.24;
CC Evidence={ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37460;
CC Evidence={ECO:0000305|PubMed:29590114};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ATP
CC + H(+) = 1,5-bis(diphospho)-1D-myo-inositol 2,3,4,6-tetrakisphosphate
CC + ADP; Xref=Rhea:RHEA:10276, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:58628, ChEBI:CHEBI:77983, ChEBI:CHEBI:456216;
CC EC=2.7.4.24; Evidence={ECO:0000269|PubMed:21222653,
CC ECO:0000269|PubMed:22119861, ECO:0000269|PubMed:29590114};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10277;
CC Evidence={ECO:0000269|PubMed:22119861};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.13 uM for InsP6 {ECO:0000269|PubMed:17690096};
CC KM=0.19 uM for InsP7 {ECO:0000269|PubMed:17690096};
CC Vmax=0.39 nmol/min/mg enzyme with InsP6 as substrate
CC {ECO:0000269|PubMed:17690096};
CC Vmax=1.38 nmol/min/mg enzyme with InsP7 as substrate
CC {ECO:0000269|PubMed:17690096};
CC -!- INTERACTION:
CC O43314-2; P14859-6: POU2F1; NbExp=3; IntAct=EBI-12906508, EBI-11526590;
CC O43314-2; P78424: POU6F2; NbExp=3; IntAct=EBI-12906508, EBI-12029004;
CC O43314-2; Q92922: SMARCC1; NbExp=3; IntAct=EBI-12906508, EBI-355653;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17690096}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43314-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43314-2; Sequence=VSP_030636;
CC -!- DOMAIN: The C-terminal acid phosphatase-like domain binds
CC PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase
CC domain of histidine acid phosphatases, it has no phosphatase activity.
CC {ECO:0000305|PubMed:21222653}.
CC -!- DISEASE: Deafness, autosomal recessive, 100 (DFNB100) [MIM:618422]: A
CC form of non-syndromic, sensorineural deafness characterized by
CC prelingual hearing impairment. Sensorineural deafness results from
CC damage to the neural receptors of the inner ear, the nerve pathways to
CC the brain, or the area of the brain that receives sound information.
CC {ECO:0000269|PubMed:29590114}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the histidine acid phosphatase family. VIP1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA24863.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW49076.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AB007893; BAA24863.2; ALT_INIT; mRNA.
DR EMBL; AC011362; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW49076.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC024591; AAH24591.1; -; mRNA.
DR CCDS; CCDS34207.1; -. [O43314-2]
DR CCDS; CCDS64212.1; -. [O43314-1]
DR RefSeq; NP_001263206.1; NM_001276277.2. [O43314-1]
DR RefSeq; NP_001268400.1; NM_001281471.2.
DR RefSeq; NP_056031.2; NM_015216.4. [O43314-2]
DR PDB; 3T54; X-ray; 1.90 A; A=37-366.
DR PDB; 3T7A; X-ray; 1.70 A; A=41-366.
DR PDB; 3T99; X-ray; 2.10 A; A=37-366.
DR PDB; 3T9A; X-ray; 1.80 A; A=41-366.
DR PDB; 3T9B; X-ray; 1.85 A; A=41-366.
DR PDB; 3T9C; X-ray; 1.90 A; A=41-366.
DR PDB; 3T9D; X-ray; 1.85 A; A=41-366.
DR PDB; 3T9E; X-ray; 1.90 A; A=41-366.
DR PDB; 3T9F; X-ray; 2.00 A; A=41-366.
DR PDB; 4HN2; X-ray; 1.90 A; A=41-366.
DR PDB; 4NZM; X-ray; 2.00 A; A=41-366.
DR PDB; 4NZN; X-ray; 1.75 A; A=41-366.
DR PDB; 4NZO; X-ray; 1.90 A; A=41-366.
DR PDB; 4Q4C; X-ray; 1.90 A; A=41-366.
DR PDB; 4Q4D; X-ray; 1.85 A; A=41-366.
DR PDB; 5BYA; X-ray; 1.90 A; A=41-366.
DR PDB; 5BYB; X-ray; 2.30 A; A=41-366.
DR PDB; 5DGH; X-ray; 2.10 A; A=41-366.
DR PDB; 5DGI; X-ray; 1.85 A; A=41-366.
DR PDB; 6N5C; X-ray; 1.95 A; A=41-366.
DR PDBsum; 3T54; -.
DR PDBsum; 3T7A; -.
DR PDBsum; 3T99; -.
DR PDBsum; 3T9A; -.
DR PDBsum; 3T9B; -.
DR PDBsum; 3T9C; -.
DR PDBsum; 3T9D; -.
DR PDBsum; 3T9E; -.
DR PDBsum; 3T9F; -.
DR PDBsum; 4HN2; -.
DR PDBsum; 4NZM; -.
DR PDBsum; 4NZN; -.
DR PDBsum; 4NZO; -.
DR PDBsum; 4Q4C; -.
DR PDBsum; 4Q4D; -.
DR PDBsum; 5BYA; -.
DR PDBsum; 5BYB; -.
DR PDBsum; 5DGH; -.
DR PDBsum; 5DGI; -.
DR PDBsum; 6N5C; -.
DR AlphaFoldDB; O43314; -.
DR SMR; O43314; -.
DR BioGRID; 116864; 51.
DR IntAct; O43314; 17.
DR STRING; 9606.ENSP00000482907; -.
DR ChEMBL; CHEMBL4523135; -.
DR DEPOD; PPIP5K2; -.
DR iPTMnet; O43314; -.
DR PhosphoSitePlus; O43314; -.
DR BioMuta; PPIP5K2; -.
DR EPD; O43314; -.
DR jPOST; O43314; -.
DR MassIVE; O43314; -.
DR MaxQB; O43314; -.
DR PaxDb; O43314; -.
DR PeptideAtlas; O43314; -.
DR PRIDE; O43314; -.
DR ProteomicsDB; 48892; -. [O43314-1]
DR ProteomicsDB; 48893; -. [O43314-2]
DR Antibodypedia; 44750; 78 antibodies from 20 providers.
DR DNASU; 23262; -.
DR Ensembl; ENST00000321521.13; ENSP00000313070.8; ENSG00000145725.20. [O43314-2]
DR Ensembl; ENST00000358359.8; ENSP00000351126.3; ENSG00000145725.20. [O43314-1]
DR Ensembl; ENST00000414217.5; ENSP00000416016.1; ENSG00000145725.20. [O43314-2]
DR GeneID; 23262; -.
DR KEGG; hsa:23262; -.
DR MANE-Select; ENST00000358359.8; ENSP00000351126.3; NM_001276277.3; NP_001263206.1.
DR UCSC; uc003kod.6; human. [O43314-1]
DR CTD; 23262; -.
DR DisGeNET; 23262; -.
DR GeneCards; PPIP5K2; -.
DR HGNC; HGNC:29035; PPIP5K2.
DR HPA; ENSG00000145725; Low tissue specificity.
DR MalaCards; PPIP5K2; -.
DR MIM; 611648; gene.
DR MIM; 618422; phenotype.
DR neXtProt; NX_O43314; -.
DR OpenTargets; ENSG00000145725; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA165660454; -.
DR VEuPathDB; HostDB:ENSG00000145725; -.
DR eggNOG; KOG1057; Eukaryota.
DR GeneTree; ENSGT00390000009048; -.
DR HOGENOM; CLU_000914_0_0_1; -.
DR InParanoid; O43314; -.
DR OrthoDB; 93740at2759; -.
DR PhylomeDB; O43314; -.
DR TreeFam; TF313594; -.
DR BRENDA; 2.7.4.21; 2681.
DR BRENDA; 2.7.4.24; 2681.
DR PathwayCommons; O43314; -.
DR Reactome; R-HSA-1855167; Synthesis of pyrophosphates in the cytosol.
DR SABIO-RK; O43314; -.
DR SignaLink; O43314; -.
DR BioGRID-ORCS; 23262; 20 hits in 1066 CRISPR screens.
DR ChiTaRS; PPIP5K2; human.
DR GenomeRNAi; 23262; -.
DR Pharos; O43314; Tchem.
DR PRO; PR:O43314; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O43314; protein.
DR Bgee; ENSG00000145725; Expressed in adrenal tissue and 194 other tissues.
DR ExpressionAtlas; O43314; baseline and differential.
DR Genevisible; O43314; HS.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0102092; F:5-diphosphoinositol pentakisphosphate 3-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0033857; F:diphosphoinositol-pentakisphosphate kinase activity; IDA:MGI.
DR GO; GO:0000829; F:inositol heptakisphosphate kinase activity; IBA:GO_Central.
DR GO; GO:0052723; F:inositol hexakisphosphate 1-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0052724; F:inositol hexakisphosphate 3-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0000832; F:inositol hexakisphosphate 5-kinase activity; ISS:UniProtKB.
DR GO; GO:0000828; F:inositol hexakisphosphate kinase activity; IDA:MGI.
DR GO; GO:0000827; F:inositol-1,3,4,5,6-pentakisphosphate kinase activity; ISS:UniProtKB.
DR GO; GO:0006020; P:inositol metabolic process; ISS:UniProtKB.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW.
DR CDD; cd07061; HP_HAP_like; 1.
DR Gene3D; 3.40.50.1240; -; 1.
DR InterPro; IPR033379; Acid_Pase_AS.
DR InterPro; IPR000560; His_Pase_clade-2.
DR InterPro; IPR037446; His_Pase_VIP1.
DR InterPro; IPR029033; His_PPase_superfam.
DR InterPro; IPR040557; VIP1_N.
DR PANTHER; PTHR12750; PTHR12750; 1.
DR Pfam; PF00328; His_Phos_2; 1.
DR Pfam; PF18086; PPIP5K2_N; 1.
DR SUPFAM; SSF53254; SSF53254; 1.
DR PROSITE; PS00616; HIS_ACID_PHOSPHAT_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Deafness;
KW Disease variant; Hearing; Kinase; Non-syndromic deafness;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..1243
FT /note="Inositol hexakisphosphate and diphosphoinositol-
FT pentakisphosphate kinase 2"
FT /id="PRO_0000315692"
FT REGION 371..442
FT /note="Polyphosphoinositide-binding domain"
FT /evidence="ECO:0000269|PubMed:21222653"
FT REGION 898..941
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 957..1016
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1185..1243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 916..941
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 957..973
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 974..994
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1196..1225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 53..54
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9D,
FT ECO:0007744|PDB:3T9E, ECO:0007744|PDB:3T9F"
FT BINDING 134
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A,
FT ECO:0007744|PDB:3T99, ECO:0007744|PDB:3T9A,
FT ECO:0007744|PDB:3T9B, ECO:0007744|PDB:3T9C,
FT ECO:0007744|PDB:3T9D, ECO:0007744|PDB:3T9E,
FT ECO:0007744|PDB:3T9F"
FT BINDING 187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A,
FT ECO:0007744|PDB:3T99, ECO:0007744|PDB:3T9A,
FT ECO:0007744|PDB:3T9B, ECO:0007744|PDB:3T9C,
FT ECO:0007744|PDB:3T9D, ECO:0007744|PDB:3T9E,
FT ECO:0007744|PDB:3T9F"
FT BINDING 194
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A,
FT ECO:0007744|PDB:3T99, ECO:0007744|PDB:3T9A,
FT ECO:0007744|PDB:3T9B, ECO:0007744|PDB:3T9C,
FT ECO:0007744|PDB:3T9D, ECO:0007744|PDB:3T9E,
FT ECO:0007744|PDB:3T9F"
FT BINDING 213..214
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9D,
FT ECO:0007744|PDB:3T9E, ECO:0007744|PDB:3T9F"
FT BINDING 213
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T9A, ECO:0007744|PDB:3T9B,
FT ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9D"
FT BINDING 237..240
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A,
FT ECO:0007744|PDB:3T99, ECO:0007744|PDB:3T9A,
FT ECO:0007744|PDB:3T9B, ECO:0007744|PDB:3T9C,
FT ECO:0007744|PDB:3T9D, ECO:0007744|PDB:3T9E,
FT ECO:0007744|PDB:3T9F"
FT BINDING 246..248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T9A,
FT ECO:0007744|PDB:3T9B, ECO:0007744|PDB:3T9C,
FT ECO:0007744|PDB:3T9D"
FT BINDING 248
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9D,
FT ECO:0007744|PDB:3T9E, ECO:0007744|PDB:3T9F"
FT BINDING 262
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9E,
FT ECO:0007744|PDB:3T9F"
FT BINDING 264
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A"
FT BINDING 309
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54, ECO:0007744|PDB:3T7A,
FT ECO:0007744|PDB:3T99, ECO:0007744|PDB:3T9B,
FT ECO:0007744|PDB:3T9C, ECO:0007744|PDB:3T9D,
FT ECO:0007744|PDB:3T9E, ECO:0007744|PDB:3T9F"
FT BINDING 321..323
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T54"
FT BINDING 326..329
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22119861,
FT ECO:0007744|PDB:3T9D, ECO:0007744|PDB:3T9E"
FT MOD_RES 38
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1006
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1016
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1074
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1091
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1220
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1221
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1097..1117
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030636"
FT VARIANT 837
FT /note="R -> H (in DFNB100; Impaired diphosphoinositol-
FT pentakisphosphate kinase activity; dbSNP:rs548137246)"
FT /evidence="ECO:0000269|PubMed:29590114"
FT /id="VAR_082201"
FT VARIANT 944
FT /note="A -> G (in dbSNP:rs17155115)"
FT /id="VAR_038276"
FT VARIANT 985
FT /note="E -> K (in dbSNP:rs12519525)"
FT /id="VAR_038277"
FT VARIANT 1003
FT /note="R -> K (in dbSNP:rs12520040)"
FT /id="VAR_038278"
FT VARIANT 1206
FT /note="P -> Q (in dbSNP:rs17155138)"
FT /id="VAR_038279"
FT VARIANT 1232
FT /note="T -> M (in dbSNP:rs17155147)"
FT /id="VAR_038280"
FT MUTAGEN 213
FT /note="R->A,K: Reduces enzyme activity by about 99%."
FT /evidence="ECO:0000269|PubMed:22119861"
FT MUTAGEN 248
FT /note="K->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:22119861"
FT MUTAGEN 262
FT /note="R->A: Reduces enzyme activity by about 99%."
FT /evidence="ECO:0000269|PubMed:22119861"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 58..67
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 80..85
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 95..99
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 107..117
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 127..131
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:4NZN"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 170..175
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 178..190
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 208..215
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 218..224
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 243..253
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 257..263
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:3T9A"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:3T9A"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 303..313
FT /evidence="ECO:0007829|PDB:3T7A"
FT STRAND 316..325
FT /evidence="ECO:0007829|PDB:3T7A"
FT HELIX 332..354
FT /evidence="ECO:0007829|PDB:3T7A"
SQ SEQUENCE 1243 AA; 140407 MW; A8831DDDAB9B2E6E CRC64;
MSEAPRFFVG PEDTEINPGN YRHFFHHADE DDEEEDDSPP ERQIVVGICS MAKKSKSKPM
KEILERISLF KYITVVVFEE EVILNEPVEN WPLCDCLISF HSKGFPLDKA VAYAKLRNPF
VINDLNMQYL IQDRREVYSI LQAEGILLPR YAILNRDPNN PKECNLIEGE DHVEVNGEVF
QKPFVEKPVS AEDHNVYIYY PTSAGGGSQR LFRKIGSRSS VYSPESNVRK TGSYIYEEFM
PTDGTDVKVY TVGPDYAHAE ARKSPALDGK VERDSEGKEV RYPVILNARE KLIAWKVCLA
FKQTVCGFDL LRANGQSYVC DVNGFSFVKN SMKYYDDCAK ILGNIVMREL APQFHIPWSI
PLEAEDIPIV PTTSGTMMEL RCVIAVIRHG DRTPKQKMKM EVRHQKFFDL FEKCDGYKSG
KLKLKKPKQL QEVLDIARQL LMELGQNNDS EIEENKPKLE QLKTVLEMYG HFSGINRKVQ
LTYLPHGCPK TSSEEEDSRR EEPSLLLVLK WGGELTPAGR VQAEELGRAF RCMYPGGQGD
YAGFPGCGLL RLHSTYRHDL KIYASDEGRV QMTAAAFAKG LLALEGELTP ILVQMVKSAN
MNGLLDSDSD SLSSCQQRVK ARLHEILQKD RDFTAEDYEK LTPSGSISLI KSMHLIKNPV
KTCDKVYSLI QSLTSQIRHR MEDPKSSDIQ LYHSETLELM LRRWSKLEKD FKTKNGRYDI
SKIPDIYDCI KYDVQHNGSL KLENTMELYR LSKALADIVI PQEYGITKAE KLEIAKGYCT
PLVRKIRSDL QRTQDDDTVN KLHPVYSRGV LSPERHVRTR LYFTSESHVH SLLSILRYGA
LCNESKDEQW KRAMDYLNVV NELNYMTQIV IMLYEDPNKD LSSEERFHVE LHFSPGAKGC
EEDKNLPSGY GYRPASRENE GRRPFKIDND DEPHTSKRDE VDRAVILFKP MVSEPIHIHR
KSPLPRSRKT ATNDEESPLS VSSPEGTGTW LHYTSGVGTG RRRRRSGEQI TSSPVSPKSL
AFTSSIFGSW QQVVSENANY LRTPRTLVEQ KQNPTVGSHC AGLFSTSVLG GSSSAPNLQD
YARTHRKKLT SSGCIDDATR GSAVKRFSIS FARHPTNGFE LYSMVPSICP LETLHNALSL
KQVDEFLASI ASPSSDVPRK TAEISSTALR SSPIMRKKVS LNTYTPAKIL PTPPATLKST
KASSKPATSG PSSAVVPNTS SRKKNITSKT ETHEHKKNTG KKK
