ID   IP6K3_HUMAN             Reviewed;         410 AA.
AC   Q96PC2; Q96MQ9;
DT   19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 2.
DT   24-JAN-2024, entry version 169.
DE   RecName: Full=Inositol hexakisphosphate kinase 3;
DE            Short=InsP6 kinase 3;
DE            EC=2.7.4.21;
DE   AltName: Full=Inositol hexaphosphate kinase 3;
GN   Name=IP6K3; Synonyms=IHPK3;
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], MUTAGENESIS OF LYS-217 AND SER-325, FUNCTION,
RP   AND SUBCELLULAR LOCATION.
RC   TISSUE=Brain;
RX   PubMed=11502751; DOI=10.1074/jbc.m106842200;
RA   Saiardi A., Nagata E., Luo H.R., Snowman A.M., Snyder S.H.;
RT   "Identification and characterization of a novel inositol hexakisphosphate
RT   kinase.";
RL   J. Biol. Chem. 276:39179-39185(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-312.
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
CC   -!- FUNCTION: Converts inositol hexakisphosphate (InsP6) to
CC       diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts
CC       1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
CC       {ECO:0000269|PubMed:11502751}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1D-myo-inositol hexakisphosphate + ATP = 5-diphospho-1D-myo-
CC         inositol 1,2,3,4,6-pentakisphosphate + ADP; Xref=Rhea:RHEA:12793,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:58130, ChEBI:CHEBI:58628,
CC         ChEBI:CHEBI:456216; EC=2.7.4.21;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate + ATP
CC         + H(+) = 1,5-bis(diphospho)-1D-myo-inositol 2,3,4,6-tetrakisphosphate
CC         + ADP; Xref=Rhea:RHEA:37467, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:74946, ChEBI:CHEBI:77983, ChEBI:CHEBI:456216;
CC         EC=2.7.4.21;
CC   -!- INTERACTION:
CC       Q96PC2; Q5TD97: FHL5; NbExp=3; IntAct=EBI-10990676, EBI-750641;
CC       Q96PC2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-10990676, EBI-10171774;
CC       Q96PC2; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-10990676, EBI-739832;
CC       Q96PC2; Q9NPJ6: MED4; NbExp=3; IntAct=EBI-10990676, EBI-394607;
CC       Q96PC2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-10990676, EBI-16439278;
CC       Q96PC2; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-10990676, EBI-740897;
CC       Q96PC2; A8MTQ0: NOTO; NbExp=3; IntAct=EBI-10990676, EBI-17490746;
CC       Q96PC2; P19388: POLR2E; NbExp=6; IntAct=EBI-10990676, EBI-395189;
CC       Q96PC2; Q12933: TRAF2; NbExp=3; IntAct=EBI-10990676, EBI-355744;
CC       Q96PC2; Q13114: TRAF3; NbExp=5; IntAct=EBI-10990676, EBI-357631;
CC       Q96PC2; P14373: TRIM27; NbExp=3; IntAct=EBI-10990676, EBI-719493;
CC       Q96PC2; Q15654: TRIP6; NbExp=3; IntAct=EBI-10990676, EBI-742327;
CC       Q96PC2; Q8N720: ZNF655; NbExp=3; IntAct=EBI-10990676, EBI-625509;
CC       Q96PC2; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-10990676, EBI-527853;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11502751}.
CC   -!- TISSUE SPECIFICITY: Detected in brain.
CC   -!- SIMILARITY: Belongs to the inositol phosphokinase (IPK) family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB71225.2; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF393812; AAL17053.1; -; mRNA.
DR   EMBL; AK056586; BAB71225.2; ALT_FRAME; mRNA.
DR   CCDS; CCDS34435.1; -.
DR   RefSeq; NP_001136355.1; NM_001142883.1.
DR   RefSeq; NP_473452.2; NM_054111.4.
DR   RefSeq; XP_005248899.1; XM_005248842.3.
DR   AlphaFoldDB; Q96PC2; -.
DR   BioGRID; 125584; 31.
DR   IntAct; Q96PC2; 31.
DR   STRING; 9606.ENSP00000293756; -.
DR   BindingDB; Q96PC2; -.
DR   ChEMBL; CHEMBL4523431; -.
DR   iPTMnet; Q96PC2; -.
DR   PhosphoSitePlus; Q96PC2; -.
DR   BioMuta; IP6K3; -.
DR   DMDM; 143811404; -.
DR   MassIVE; Q96PC2; -.
DR   PaxDb; 9606-ENSP00000398861; -.
DR   PeptideAtlas; Q96PC2; -.
DR   ProteomicsDB; 77659; -.
DR   Antibodypedia; 45687; 171 antibodies from 29 providers.
DR   DNASU; 117283; -.
DR   Ensembl; ENST00000293756.5; ENSP00000293756.4; ENSG00000161896.12.
DR   Ensembl; ENST00000451316.6; ENSP00000398861.1; ENSG00000161896.12.
DR   GeneID; 117283; -.
DR   KEGG; hsa:117283; -.
DR   MANE-Select; ENST00000293756.5; ENSP00000293756.4; NM_054111.5; NP_473452.2.
DR   UCSC; uc003ofb.3; human.
DR   AGR; HGNC:17269; -.
DR   CTD; 117283; -.
DR   DisGeNET; 117283; -.
DR   GeneCards; IP6K3; -.
DR   HGNC; HGNC:17269; IP6K3.
DR   HPA; ENSG00000161896; Group enriched (skeletal muscle, tongue).
DR   MIM; 606993; gene.
DR   neXtProt; NX_Q96PC2; -.
DR   OpenTargets; ENSG00000161896; -.
DR   PharmGKB; PA164721016; -.
DR   VEuPathDB; HostDB:ENSG00000161896; -.
DR   eggNOG; KOG1620; Eukaryota.
DR   GeneTree; ENSGT00940000160887; -.
DR   HOGENOM; CLU_014862_0_0_1; -.
DR   InParanoid; Q96PC2; -.
DR   OMA; VYQADTG; -.
DR   OrthoDB; 20436at2759; -.
DR   PhylomeDB; Q96PC2; -.
DR   TreeFam; TF314066; -.
DR   BioCyc; MetaCyc:HS08619-MONOMER; -.
DR   BRENDA; 2.7.4.21; 2681.
DR   PathwayCommons; Q96PC2; -.
DR   Reactome; R-HSA-1855167; Synthesis of pyrophosphates in the cytosol.
DR   SignaLink; Q96PC2; -.
DR   BioGRID-ORCS; 117283; 16 hits in 1161 CRISPR screens.
DR   GenomeRNAi; 117283; -.
DR   Pharos; Q96PC2; Tbio.
DR   PRO; PR:Q96PC2; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q96PC2; Protein.
DR   Bgee; ENSG00000161896; Expressed in gastrocnemius and 130 other cell types or tissues.
DR   ExpressionAtlas; Q96PC2; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0052836; F:inositol 5-diphosphate pentakisphosphate 5-kinase activity; TAS:Reactome.
DR   GO; GO:0052839; F:inositol diphosphate tetrakisphosphate kinase activity; TAS:Reactome.
DR   GO; GO:0000829; F:inositol heptakisphosphate kinase activity; TAS:Reactome.
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; IEA:UniProtKB-EC.
DR   GO; GO:0000831; F:inositol hexakisphosphate 6-kinase activity; IDA:MGI.
DR   GO; GO:0000828; F:inositol hexakisphosphate kinase activity; IDA:UniProtKB.
DR   GO; GO:0000827; F:inositol-1,3,4,5,6-pentakisphosphate kinase activity; TAS:Reactome.
DR   GO; GO:0032958; P:inositol phosphate biosynthetic process; IDA:MGI.
DR   GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR   GO; GO:0040011; P:locomotion; IEA:Ensembl.
DR   GO; GO:0046488; P:phosphatidylinositol metabolic process; IDA:UniProtKB.
DR   GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   Gene3D; 3.30.470.160; Inositol polyphosphate kinase; 1.
DR   InterPro; IPR005522; IPK.
DR   InterPro; IPR038286; IPK_sf.
DR   PANTHER; PTHR12400:SF40; INOSITOL HEXAKISPHOSPHATE KINASE 3; 1.
DR   PANTHER; PTHR12400; INOSITOL POLYPHOSPHATE KINASE; 1.
DR   Pfam; PF03770; IPK; 1.
DR   SUPFAM; SSF56104; SAICAR synthase-like; 1.
DR   Genevisible; Q96PC2; HS.
PE   1: Evidence at protein level;
KW   ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Reference proteome;
KW   Transferase.
FT   CHAIN           1..410
FT                   /note="Inositol hexakisphosphate kinase 3"
FT                   /id="PRO_0000066881"
FT   REGION          333..358
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         211..219
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   VARIANT         60
FT                   /note="R -> W (in dbSNP:rs34431226)"
FT                   /id="VAR_031590"
FT   VARIANT         308
FT                   /note="A -> V (in dbSNP:rs34573836)"
FT                   /id="VAR_031591"
FT   VARIANT         312
FT                   /note="V -> I (in dbSNP:rs4713668)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_031592"
FT   VARIANT         378
FT                   /note="Y -> S (in dbSNP:rs34343647)"
FT                   /id="VAR_031593"
FT   MUTAGEN         217
FT                   /note="K->A: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:11502751"
FT   MUTAGEN         325
FT                   /note="S->A: Strongly reduces activity."
FT                   /evidence="ECO:0000269|PubMed:11502751"
FT   CONFLICT        56
FT                   /note="L -> Q (in Ref. 1; AAL17053)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        304
FT                   /note="H -> L (in Ref. 2; BAB71225)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   410 AA;  46417 MW;  CA61C7D4FA70F7F3 CRC64;
     MVVQNSADAG DMRAGVQLEP FLHQVGGHMS VMKYDEHTVC KPLVSREQRF YESLPLAMKR
     FTPQYKGTVT VHLWKDSTGH LSLVANPVKE SQEPFKVSTE SAAVAIWQTL QQTTGSNGSD
     CTLAQWPHAQ LARSPKESPA KALLRSEPHL NTPAFSLVED TNGNQVERKS FNPWGLQCHQ
     AHLTRLCSEY PENKRHRFLL LENVVSQYTH PCVLDLKMGT RQHGDDASEE KKARHMRKCA
     QSTSACLGVR ICGMQVYQTD KKYFLCKDKY YGRKLSVEGF RQALYQFLHN GSHLRRELLE
     PILHQLRALL SVIRSQSSYR FYSSSLLVIY DGQEPPERAP GSPHPHEAPQ AAHGSSPGGL
     TKVDIRMIDF AHTTYKGYWN EHTTYDGPDP GYIFGLENLI RILQDIQEGE
//