IP3KA_HUMAN
ID IP3KA_HUMAN Reviewed; 461 AA.
AC P23677; Q8TAN3;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Inositol-trisphosphate 3-kinase A {ECO:0000305};
DE EC=2.7.1.127 {ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:15350214, ECO:0000269|PubMed:1847047};
DE AltName: Full=Inositol 1,4,5-trisphosphate 3-kinase A;
DE Short=IP3 3-kinase A;
DE Short=IP3K A;
DE Short=InsP 3-kinase A;
GN Name=ITPKA {ECO:0000312|HGNC:HGNC:6178};
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], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND ACTIVITY REGULATION.
RC TISSUE=Brain;
RX PubMed=1847047; DOI=10.1016/0006-291x(91)91449-m;
RA Takazawa K., Perret J., Dumont J.E., Erneux C.;
RT "Molecular cloning and expression of a human brain inositol 1,4,5-
RT trisphosphate 3-kinase.";
RL Biochem. Biophys. Res. Commun. 174:529-535(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=2175886; DOI=10.1093/nar/18.23.7141;
RA Takazawa K., Perret J., Dumont J.E., Erneux C.;
RT "Human brain inositol 1,4,5-trisphosphate 3-kinase cDNA sequence.";
RL Nucleic Acids Res. 18:7141-7141(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, FUNCTION, MUTAGENESIS OF LYS-264
RP AND 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197, AND IDENTIFICATION BY
RP 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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 197-461 IN COMPLEX WITH SUBSTRATE
RP AND ADP, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF TRP-188; LYS-199; ASP-262; ARG-319 AND ASP-416.
RX PubMed=15350214; DOI=10.1016/j.molcel.2004.08.004;
RA Gonzalez B., Schell M.J., Letcher A.J., Veprintsev D.B., Irvine R.F.,
RA Williams R.L.;
RT "Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate
RT binding reveals why it is not a phosphoinositide 3-kinase.";
RL Mol. Cell 15:689-701(2004).
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 {ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:15350214,
CC ECO:0000269|PubMed:1847047}.
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:12747803, ECO:0000269|PubMed:15350214,
CC ECO:0000269|PubMed:1847047};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11021;
CC Evidence={ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:15350214,
CC ECO:0000269|PubMed:1847047};
CC -!- ACTIVITY REGULATION: Activated by calcium/calmodulin.
CC {ECO:0000269|PubMed:12747803, ECO:0000269|PubMed:1847047}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 uM for 1D-myo-inositol 1,4,5-trisphosphate
CC {ECO:0000269|PubMed:15350214};
CC Vmax=30 umol/min/mg enzyme {ECO:0000269|PubMed:15350214};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12747803}.
CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:1847047}.
CC -!- SIMILARITY: Belongs to the inositol phosphokinase (IPK) family.
CC {ECO:0000305}.
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DR EMBL; X54938; CAA38700.1; -; mRNA.
DR EMBL; BC026331; AAH26331.1; -; mRNA.
DR CCDS; CCDS10076.1; -.
DR PIR; JN0129; JN0129.
DR RefSeq; NP_002211.1; NM_002220.2.
DR PDB; 1W2C; X-ray; 1.95 A; A/B=197-461.
DR PDB; 1W2D; X-ray; 1.94 A; A/B=197-461.
DR PDB; 1W2F; X-ray; 1.80 A; A/B=188-461.
DR PDB; 4UPU; X-ray; 2.34 A; B=158-183.
DR PDBsum; 1W2C; -.
DR PDBsum; 1W2D; -.
DR PDBsum; 1W2F; -.
DR PDBsum; 4UPU; -.
DR AlphaFoldDB; P23677; -.
DR SMR; P23677; -.
DR BioGRID; 109911; 6.
DR IntAct; P23677; 2.
DR STRING; 9606.ENSP00000260386; -.
DR BindingDB; P23677; -.
DR DrugBank; DB03401; 1D-myo-inositol 1,4,5-trisphosphate.
DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR GuidetoPHARMACOLOGY; 1447; -.
DR iPTMnet; P23677; -.
DR PhosphoSitePlus; P23677; -.
DR BioMuta; ITPKA; -.
DR DMDM; 124807; -.
DR EPD; P23677; -.
DR jPOST; P23677; -.
DR MassIVE; P23677; -.
DR MaxQB; P23677; -.
DR PaxDb; P23677; -.
DR PeptideAtlas; P23677; -.
DR PRIDE; P23677; -.
DR ProteomicsDB; 54145; -.
DR Antibodypedia; 23312; 203 antibodies from 28 providers.
DR DNASU; 3706; -.
DR Ensembl; ENST00000260386.7; ENSP00000260386.5; ENSG00000137825.11.
DR GeneID; 3706; -.
DR KEGG; hsa:3706; -.
DR MANE-Select; ENST00000260386.7; ENSP00000260386.5; NM_002220.3; NP_002211.1.
DR UCSC; uc001znz.4; human.
DR CTD; 3706; -.
DR DisGeNET; 3706; -.
DR GeneCards; ITPKA; -.
DR HGNC; HGNC:6178; ITPKA.
DR HPA; ENSG00000137825; Tissue enhanced (brain, intestine).
DR MIM; 147521; gene.
DR neXtProt; NX_P23677; -.
DR OpenTargets; ENSG00000137825; -.
DR PharmGKB; PA29975; -.
DR VEuPathDB; HostDB:ENSG00000137825; -.
DR eggNOG; KOG1621; Eukaryota.
DR GeneTree; ENSGT00940000161350; -.
DR HOGENOM; CLU_017767_1_1_1; -.
DR InParanoid; P23677; -.
DR OMA; HIILESS; -.
DR OrthoDB; 966687at2759; -.
DR PhylomeDB; P23677; -.
DR TreeFam; TF318394; -.
DR BioCyc; MetaCyc:HS06405-MON; -.
DR BRENDA; 2.7.1.127; 2681.
DR PathwayCommons; P23677; -.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR SignaLink; P23677; -.
DR SIGNOR; P23677; -.
DR BioGRID-ORCS; 3706; 18 hits in 1084 CRISPR screens.
DR ChiTaRS; ITPKA; human.
DR EvolutionaryTrace; P23677; -.
DR GeneWiki; ITPKA; -.
DR GenomeRNAi; 3706; -.
DR Pharos; P23677; Tchem.
DR PRO; PR:P23677; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P23677; protein.
DR Bgee; ENSG00000137825; Expressed in mucosa of transverse colon and 107 other tissues.
DR ExpressionAtlas; P23677; baseline and differential.
DR Genevisible; P23677; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:Ensembl.
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:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0097062; P:dendritic spine maintenance; IEA:Ensembl.
DR GO; GO:0006020; P:inositol metabolic process; IEA:Ensembl.
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 GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IEA:Ensembl.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; Cytoskeleton;
KW Kinase; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..461
FT /note="Inositol-trisphosphate 3-kinase A"
FT /id="PRO_0000066865"
FT REGION 1..133
FT /note="Required for cytoskeleton location"
FT /evidence="ECO:0000269|PubMed:12747803"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 49..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..295
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 114..136
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 197
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2D"
FT BINDING 209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 249..251
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 262
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 264
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 285
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 312..319
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15350214"
FT BINDING 336
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 416
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT BINDING 419
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15350214,
FT ECO:0007744|PDB:1W2C"
FT MOD_RES 35
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8R071"
FT MOD_RES 55
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8R071"
FT MOD_RES 62
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q8R071"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8R071"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MUTAGEN 188
FT /note="W->A: Decreases to 44% of kinase activity."
FT /evidence="ECO:0000269|PubMed:15350214"
FT MUTAGEN 199
FT /note="K->A: Decreases to 80% of kinase activity."
FT /evidence="ECO:0000269|PubMed:15350214"
FT MUTAGEN 262
FT /note="D->A,N: Decreases to 12% of kinase activity."
FT /evidence="ECO:0000269|PubMed:15350214"
FT MUTAGEN 264
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12747803"
FT MUTAGEN 319
FT /note="R->D,A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15350214"
FT MUTAGEN 416
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15350214"
FT CONFLICT 71
FT /note="P -> Q (in Ref. 3; AAH26331)"
FT /evidence="ECO:0000305"
FT HELIX 166..174
FT /evidence="ECO:0007829|PDB:4UPU"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:4UPU"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:1W2D"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 213..223
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 226..230
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 234..240
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:1W2F"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 259..267
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 272..280
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 286..295
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 302..307
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 312..322
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 329..336
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:1W2D"
FT HELIX 352..363
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 367..384
FT /evidence="ECO:0007829|PDB:1W2F"
FT HELIX 388..391
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 393..397
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 399..404
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 410..415
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 419..422
FT /evidence="ECO:0007829|PDB:1W2F"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:1W2D"
FT HELIX 444..459
FT /evidence="ECO:0007829|PDB:1W2F"
SQ SEQUENCE 461 AA; 51009 MW; 18CA214A091F5B19 CRC64;
MTLPGGPTGM ARPGGARPCS PGLERAPRRS VGELRLLFEA RCAAVAAAAA AGEPRARGAK
RRGGQVPNGL PRAPPAPVIP QLTVTAEEPD VPPTSPGPPE RERDCLPAAG SSHLQQPRRL
STSSVSSTGS SSLLEDSEDD LLSDSESRSR GNVQLEAGED VGQKNHWQKI RTMVNLPVIS
PFKKRYAWVQ LAGHTGSFKA AGTSGLILKR CSEPERYCLA RLMADALRGC VPAFHGVVER
DGESYLQLQD LLDGFDGPCV LDCKMGVRTY LEEELTKARE RPKLRKDMYK KMLAVDPEAP
TEEEHAQRAV TKPRYMQWRE GISSSTTLGF RIEGIKKADG SCSTDFKTTR SREQVLRVFE
EFVQGDEEVL RRYLNRLQQI RDTLEVSEFF RRHEVIGSSL LFVHDHCHRA GVWLIDFGKT
TPLPDGQILD HRRPWEEGNR EDGYLLGLDN LIGILASLAE R
