ID   IP3KC_HUMAN             Reviewed;         683 AA.
AC   Q96DU7; Q9UE25; Q9Y475;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 160.
DE   RecName: Full=Inositol-trisphosphate 3-kinase C {ECO:0000305};
DE            EC=2.7.1.127 {ECO:0000269|PubMed:11085927, ECO:0000269|PubMed:12747803};
DE   AltName: Full=Inositol 1,4,5-trisphosphate 3-kinase C;
DE            Short=IP3 3-kinase C;
DE            Short=IP3K C;
DE            Short=InsP 3-kinase C;
GN   Name=ITPKC {ECO:0000312|HGNC:HGNC:14897}; Synonyms=IP3KC;
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], ACTIVITY REGULATION, TISSUE SPECIFICITY,
RP   CATALYTIC ACTIVITY, AND FUNCTION.
RC   TISSUE=Thyroid;
RX   PubMed=11085927; DOI=10.1042/bj3520343;
RA   Dewaste V., Pouillon V., Moreau C., Shears S., Takazawa K., Erneux C.;
RT   "Cloning and expression of a cDNA encoding human inositol 1,4,5-
RT   trisphosphate 3-kinase C.";
RL   Biochem. J. 352:343-351(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 80-683.
RC   TISSUE=Thyroid;
RA   Takazawa K., Go M., Togashi S., Endo T., Erneux C., Onaya T.;
RL   Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 531-667.
RC   TISSUE=Placenta;
RA   Erneux C., Communi D.;
RL   Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   SUBCELLULAR LOCATION, ACTIVITY REGULATION, FUNCTION, MUTAGENESIS OF
RP   LYS-486, AND CATALYTIC ACTIVITY.
RX   PubMed=12747803; DOI=10.1042/bj20021963;
RA   Dewaste V., Moreau C., De Smedt F., Bex F., De Smedt H., Wuytack F.,
RA   Missiaen L., Erneux C.;
RT   "The three isoenzymes of human inositol-1,4,5-trisphosphate 3-kinase show
RT   specific intracellular localization but comparable Ca2+ responses on
RT   transfection in COS-7 cells.";
RL   Biochem. J. 374:41-49(2003).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-336 AND SER-404, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127, AND IDENTIFICATION BY
RP   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   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 425-683 IN COMPLEX WITH
RP   INOSITOL-1,4,5-TRIPHOSPHATE.
RG   Structural genomics consortium (SGC);
RT   "The crystal structure of the catalytic domain of human inositol 1,4,5-
RT   trisphosphate 3-kinase C.";
RL   Submitted (OCT-2005) to the PDB data bank.
CC   -!- FUNCTION: Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-
CC       trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate
CC       and participates to the regulation of calcium homeostasis
CC       (PubMed:11085927, PubMed:12747803). Can phosphorylate inositol 2,4,5-
CC       triphosphate to inositol 2,4,5,6-tetraphosphate (By similarity).
CC       {ECO:0000250|UniProtKB:Q80ZG2, ECO:0000269|PubMed:11085927,
CC       ECO:0000269|PubMed:12747803}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1D-myo-inositol 1,4,5-trisphosphate + ATP = 1D-myo-inositol
CC         1,3,4,5-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:11020,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57895,
CC         ChEBI:CHEBI:203600, ChEBI:CHEBI:456216; EC=2.7.1.127;
CC         Evidence={ECO:0000269|PubMed:11085927, ECO:0000269|PubMed:12747803};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11021;
CC         Evidence={ECO:0000269|PubMed:11085927, ECO:0000269|PubMed:12747803};
CC   -!- ACTIVITY REGULATION: Activated by calcium/calmodulin (PubMed:12747803).
CC       Inhibited by high concentrations of the substrate Ins(1,2,4)P3, and
CC       allosterically activated by the product Ins(1,3,4,5)P4.
CC       {ECO:0000269|PubMed:11085927, ECO:0000269|PubMed:12747803}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12747803}. Cytoplasm
CC       {ECO:0000269|PubMed:12747803}. Note=Shuttles actively between nucleus
CC       and cytoplasm with both nuclear import and nuclear export activity.
CC       {ECO:0000250|UniProtKB:Q80ZG2}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in pancreas, skeletal muscle,
CC       liver, placenta and weakly in kidney and brain.
CC       {ECO:0000269|PubMed:11085927}.
CC   -!- SIMILARITY: Belongs to the inositol phosphokinase (IPK) family.
CC       {ECO:0000305}.
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DR   EMBL; AJ290975; CAC40815.1; -; mRNA.
DR   EMBL; BC060788; AAH60788.1; -; mRNA.
DR   EMBL; D38169; BAA22524.1; -; mRNA.
DR   EMBL; Y11999; CAA72728.1; -; mRNA.
DR   CCDS; CCDS12563.1; -.
DR   RefSeq; NP_079470.1; NM_025194.2.
DR   PDB; 2A98; X-ray; 2.60 A; A=425-683.
DR   PDBsum; 2A98; -.
DR   AlphaFoldDB; Q96DU7; -.
DR   SMR; Q96DU7; -.
DR   BioGRID; 123209; 18.
DR   IntAct; Q96DU7; 4.
DR   STRING; 9606.ENSP00000263370; -.
DR   GuidetoPHARMACOLOGY; 1449; -.
DR   iPTMnet; Q96DU7; -.
DR   PhosphoSitePlus; Q96DU7; -.
DR   BioMuta; ITPKC; -.
DR   EPD; Q96DU7; -.
DR   jPOST; Q96DU7; -.
DR   MassIVE; Q96DU7; -.
DR   MaxQB; Q96DU7; -.
DR   PaxDb; 9606-ENSP00000263370; -.
DR   PeptideAtlas; Q96DU7; -.
DR   ProteomicsDB; 76328; -.
DR   Pumba; Q96DU7; -.
DR   Antibodypedia; 30626; 225 antibodies from 32 providers.
DR   DNASU; 80271; -.
DR   Ensembl; ENST00000263370.3; ENSP00000263370.1; ENSG00000086544.4.
DR   Ensembl; ENST00000699490.1; ENSP00000514401.1; ENSG00000086544.4.
DR   GeneID; 80271; -.
DR   KEGG; hsa:80271; -.
DR   MANE-Select; ENST00000263370.3; ENSP00000263370.1; NM_025194.3; NP_079470.1.
DR   UCSC; uc002oot.5; human.
DR   AGR; HGNC:14897; -.
DR   CTD; 80271; -.
DR   DisGeNET; 80271; -.
DR   GeneCards; ITPKC; -.
DR   HGNC; HGNC:14897; ITPKC.
DR   HPA; ENSG00000086544; Tissue enhanced (esophagus).
DR   MIM; 606476; gene.
DR   neXtProt; NX_Q96DU7; -.
DR   OpenTargets; ENSG00000086544; -.
DR   PharmGKB; PA29977; -.
DR   VEuPathDB; HostDB:ENSG00000086544; -.
DR   eggNOG; KOG1621; Eukaryota.
DR   GeneTree; ENSGT00940000160033; -.
DR   HOGENOM; CLU_017767_5_0_1; -.
DR   InParanoid; Q96DU7; -.
DR   OMA; WADNLWT; -.
DR   OrthoDB; 2898831at2759; -.
DR   PhylomeDB; Q96DU7; -.
DR   TreeFam; TF318394; -.
DR   BioCyc; MetaCyc:HS01533-MONOMER; -.
DR   BRENDA; 2.7.1.127; 2681.
DR   PathwayCommons; Q96DU7; -.
DR   Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR   SignaLink; Q96DU7; -.
DR   BioGRID-ORCS; 80271; 17 hits in 1169 CRISPR screens.
DR   ChiTaRS; ITPKC; human.
DR   EvolutionaryTrace; Q96DU7; -.
DR   GenomeRNAi; 80271; -.
DR   Pharos; Q96DU7; Tchem.
DR   PRO; PR:Q96DU7; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q96DU7; Protein.
DR   Bgee; ENSG00000086544; Expressed in lower esophagus mucosa and 170 other cell types or tissues.
DR   ExpressionAtlas; Q96DU7; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0051765; F:inositol tetrakisphosphate kinase activity; IBA:GO_Central.
DR   GO; GO:0008440; F:inositol-1,4,5-trisphosphate 3-kinase activity; IDA:UniProtKB.
DR   GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR   GO; GO:0032958; P:inositol phosphate biosynthetic process; IBA:GO_Central.
DR   GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.470.160; Inositol polyphosphate kinase; 1.
DR   InterPro; IPR005522; IPK.
DR   InterPro; IPR038286; IPK_sf.
DR   PANTHER; PTHR12400; INOSITOL POLYPHOSPHATE KINASE; 1.
DR   PANTHER; PTHR12400:SF104; INOSITOL-TRISPHOSPHATE 3-KINASE C; 1.
DR   Pfam; PF03770; IPK; 1.
DR   SUPFAM; SSF56104; SAICAR synthase-like; 1.
DR   Genevisible; Q96DU7; HS.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Calmodulin-binding; Cytoplasm; Kinase;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Transferase.
FT   CHAIN           1..683
FT                   /note="Inositol-trisphosphate 3-kinase C"
FT                   /id="PRO_0000234070"
FT   REGION          1..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          147..308
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          334..387
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          509..517
FT                   /note="Calmodulin-binding"
FT                   /evidence="ECO:0000250"
FT   MOTIF           324..332
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        107..123
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        176..209
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        264..289
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         431
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         471..473
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         484
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         486
FT                   /ligand="substrate"
FT   BINDING         507..513
FT                   /ligand="substrate"
FT   BINDING         534..541
FT                   /ligand="substrate"
FT   BINDING         558
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         638
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         641
FT                   /ligand="substrate"
FT   MOD_RES         127
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         162
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q7TS72"
FT   MOD_RES         336
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         404
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MUTAGEN         486
FT                   /note="K->A: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:12747803"
FT   CONFLICT        80..82
FT                   /note="PGT -> NSA (in Ref. 3; BAA22524)"
FT                   /evidence="ECO:0000305"
FT   STRAND          427..432
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           435..444
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           450..452
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          456..462
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          465..471
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   TURN            473..476
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          481..489
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           494..496
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   TURN            500..502
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           508..515
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           524..529
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           534..544
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           547..550
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          551..558
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           574..585
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           589..608
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           610..613
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          615..617
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          621..626
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          632..637
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          642..644
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   STRAND          653..655
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   TURN            659..661
FT                   /evidence="ECO:0007829|PDB:2A98"
FT   HELIX           666..681
FT                   /evidence="ECO:0007829|PDB:2A98"
SQ   SEQUENCE   683 AA;  75207 MW;  58093A2A8E046458 CRC64;
     MRRCPCRGSL NEAEAGALPA AARMGLEAPR GGRRRQPGQQ RPGPGAGAPA GRPEGGGPWA
     RTEGSSLHSE PERAGLGPAP GTESPQAEFW TDGQTEPAAA GLGVETERPK QKTEPDRSSL
     RTHLEWSWSE LETTCLWTET GTDGLWTDPH RSDLQFQPEE ASPWTQPGVH GPWTELETHG
     SQTQPERVKS WADNLWTHQN SSSLQTHPEG ACPSKEPSAD GSWKELYTDG SRTQQDIEGP
     WTEPYTDGSQ KKQDTEAARK QPGTGGFQIQ QDTDGSWTQP STDGSQTAPG TDCLLGEPED
     GPLEEPEPGE LLTHLYSHLK CSPLCPVPRL IITPETPEPE AQPVGPPSRV EGGSGGFSSA
     SSFDESEDDV VAGGGGASDP EDRSGSKPWK KLKTVLKYSP FVVSFRKHYP WVQLSGHAGN
     FQAGEDGRIL KRFCQCEQRS LEQLMKDPLR PFVPAYYGMV LQDGQTFNQM EDLLADFEGP
     SIMDCKMGSR TYLEEELVKA RERPRPRKDM YEKMVAVDPG APTPEEHAQG AVTKPRYMQW
     RETMSSTSTL GFRIEGIKKA DGTCNTNFKK TQALEQVTKV LEDFVDGDHV ILQKYVACLE
     ELREALEISP FFKTHEVVGS SLLFVHDHTG LAKVWMIDFG KTVALPDHQT LSHRLPWAEG
     NREDGYLWGL DNMICLLQGL AQS
//