IP6K3_HUMAN
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 03-AUG-2022, entry version 161.
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-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.ENSP00000398861; -.
DR BindingDB; Q96PC2; -.
DR ChEMBL; CHEMBL4523431; -.
DR iPTMnet; Q96PC2; -.
DR PhosphoSitePlus; Q96PC2; -.
DR BioMuta; IP6K3; -.
DR DMDM; 143811404; -.
DR PaxDb; Q96PC2; -.
DR PeptideAtlas; Q96PC2; -.
DR PRIDE; Q96PC2; -.
DR ProteomicsDB; 77659; -.
DR Antibodypedia; 45687; 146 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 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; YDGPDHG; -.
DR OrthoDB; 1102768at2759; -.
DR PhylomeDB; Q96PC2; -.
DR TreeFam; TF314066; -.
DR BioCyc; MetaCyc:HS08619-MON; -.
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 1083 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 129 other tissues.
DR ExpressionAtlas; Q96PC2; baseline and differential.
DR Genevisible; Q96PC2; HS.
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:0016301; F:kinase activity; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR005522; IPK.
DR InterPro; IPR038286; IPK_sf.
DR PANTHER; PTHR12400; PTHR12400; 1.
DR Pfam; PF03770; IPK; 1.
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