IP3KC_HUMAN
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 03-AUG-2022, entry version 151.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 16.
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; Q96DU7; -.
DR PeptideAtlas; Q96DU7; -.
DR PRIDE; Q96DU7; -.
DR ProteomicsDB; 76328; -.
DR Antibodypedia; 30626; 190 antibodies from 31 providers.
DR DNASU; 80271; -.
DR Ensembl; ENST00000263370.3; ENSP00000263370.1; ENSG00000086544.3.
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 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; 966687at2759; -.
DR PhylomeDB; Q96DU7; -.
DR TreeFam; TF318394; -.
DR BioCyc; MetaCyc:HS01533-MON; -.
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; 12 hits in 1085 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 168 other tissues.
DR ExpressionAtlas; Q96DU7; baseline and differential.
DR Genevisible; Q96DU7; HS.
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:0000828; F:inositol hexakisphosphate kinase activity; IBA:GO_Central.
DR GO; GO:0008440; F:inositol-1,4,5-trisphosphate 3-kinase activity; IDA:UniProtKB.
DR GO; GO:0016301; F:kinase activity; IBA:GO_Central.
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; -; 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 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
