ITPK1_HUMAN
ID ITPK1_HUMAN Reviewed; 414 AA.
AC Q13572; Q9BTL6; Q9H2E7;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Inositol-tetrakisphosphate 1-kinase {ECO:0000305};
DE EC=2.7.1.134 {ECO:0000269|PubMed:11042108, ECO:0000269|PubMed:15762844, ECO:0000269|PubMed:17616525};
DE AltName: Full=Inositol 1,3,4-trisphosphate 5/6-kinase;
DE Short=Inositol-triphosphate 5/6-kinase;
DE Short=Ins(1,3,4)P(3) 5/6-kinase;
DE EC=2.7.1.159 {ECO:0000269|PubMed:11042108, ECO:0000269|PubMed:17616525, ECO:0000269|PubMed:8662638};
GN Name=ITPK1 {ECO:0000312|HGNC:HGNC:6177};
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] (ISOFORM 1), COFACTOR, TISSUE SPECIFICITY,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=8662638; DOI=10.1074/jbc.271.20.11904;
RA Wilson M.P., Majerus P.W.;
RT "Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and
RT expression of the recombinant enzyme.";
RL J. Biol. Chem. 271:11904-11910(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11042108; DOI=10.1042/bj3510551;
RA Yang X., Shears S.B.;
RT "Multitasking in signal transduction by a promiscuous human
RT Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase.";
RL Biochem. J. 351:551-555(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye, and Muscle;
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 PUTATIVE FUNCTION AS PROTEIN KINASE.
RX PubMed=11533064; DOI=10.1074/jbc.m106605200;
RA Wilson M.P., Sun Y., Cao L., Majerus P.W.;
RT "Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that
RT phosphorylates the transcription factors c-Jun and ATF-2.";
RL J. Biol. Chem. 276:40998-41004(2001).
RN [5]
RP FUNCTION.
RX PubMed=11909533; DOI=10.1016/s0960-9822(02)00713-3;
RA Ho M.W.Y., Yang X., Carew M.A., Zhang T., Hua L., Kwon Y.-U., Chung S.-K.,
RA Adelt S., Vogel G., Riley A.M., Potter B.V.L., Shears S.B.;
RT "Regulation of Ins(3,4,5,6)P(4) signaling by a reversible
RT kinase/phosphatase.";
RL Curr. Biol. 12:477-482(2002).
RN [6]
RP INTERACTION WITH GPS1.
RX PubMed=12324474; DOI=10.1074/jbc.m208709200;
RA Sun Y., Wilson M.P., Majerus P.W.;
RT "Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9
RT signalosome by binding to CSN1.";
RL J. Biol. Chem. 277:45759-45764(2002).
RN [7]
RP FUNCTION.
RX PubMed=12925536; DOI=10.1074/jbc.m300674200;
RA Sun Y., Mochizuki Y., Majerus P.W.;
RT "Inositol 1,3,4-trisphosphate 5/6-kinase inhibits tumor necrosis factor-
RT induced apoptosis.";
RL J. Biol. Chem. 278:43645-43653(2003).
RN [8]
RP MUTAGENESIS OF ARG-106; LYS-157; GLY-163; ASP-281; ASP-295 AND ASN-297,
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15762844; DOI=10.1042/bj20050297;
RA Qian X., Mitchell J., Wei S.J., Williams J., Petrovich R.M., Shears S.B.;
RT "The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein
RT kinase.";
RL Biochem. J. 389:389-395(2005).
RN [9]
RP MUTAGENESIS OF LYS-18; HIS-58; LYS-59; ARG-106; HIS-162; GLY-163; HIS-167;
RP GLN-188; HIS-193; LYS-199; ARG-212; SER-214; LEU-215; ASN-297 AND GLY-301.
RX PubMed=15837423; DOI=10.1016/j.molcel.2005.03.016;
RA Miller G.J., Wilson M.P., Majerus P.W., Hurley J.H.;
RT "Specificity determinants in inositol polyphosphate synthesis: crystal
RT structure of inositol 1,3,4-trisphosphate 5/6-kinase.";
RL Mol. Cell 18:201-212(2005).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP ACETYLATION AT LYS-340; LYS-383 AND LYS-410.
RX PubMed=22308441; DOI=10.1073/pnas.1119740109;
RA Zhang C., Majerus P.W., Wilson M.P.;
RT "Regulation of inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) by
RT reversible lysine acetylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:2290-2295(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-396, 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 [14]
RP FUNCTION.
RX PubMed=29883610; DOI=10.1016/j.molcel.2018.05.010;
RA Dovey C.M., Diep J., Clarke B.P., Hale A.T., McNamara D.E., Guo H.,
RA Brown N.W. Jr., Cao J.Y., Grace C.R., Gough P.J., Bertin J., Dixon S.J.,
RA Fiedler D., Mocarski E.S., Kaiser W.J., Moldoveanu T., York J.D.,
RA Carette J.E.;
RT "MLKL requires the inositol phosphate code to execute necroptosis.";
RL Mol. Cell 70:936-948(2018).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-335 IN COMPLEXES WITH MANGANESE;
RP ATP ANALOG AND ADP, FUNCTION, SUBUNIT, AND CATALYTIC ACTIVITY.
RX PubMed=17616525; DOI=10.1074/jbc.m703121200;
RA Chamberlain P.P., Qian X., Stiles A.R., Cho J., Jones D.H., Lesley S.A.,
RA Grabau E.A., Shears S.B., Spraggon G.;
RT "Integration of inositol phosphate signaling pathways via human ITPK1.";
RL J. Biol. Chem. 282:28117-28125(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 1-327.
RG Structural genomics consortium (SGC);
RT "Structure of human inositol 1,3,4-trisphosphate 5/6-kinase.";
RL Submitted (FEB-2007) to the PDB data bank.
CC -!- FUNCTION: Kinase that can phosphorylate various inositol polyphosphate
CC such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3 (PubMed:11042108,
CC PubMed:8662638). Phosphorylates Ins(3,4,5,6)P4 at position 1 to form
CC Ins(1,3,4,5,6)P5 (PubMed:11042108). This reaction is thought to have
CC regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma
CC membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is
CC not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form
CC Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6)
CC pathway (PubMed:11042108, PubMed:8662638). Also acts as an inositol
CC polyphosphate phosphatase that dephosphorylates Ins(1,3,4,5)P4 and
CC Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4
CC (PubMed:17616525, PubMed:11909533). May also act as an isomerase that
CC interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and
CC Ins(1,3,4,6)P4 in the presence of ADP and magnesium (PubMed:11909533).
CC Probably acts as the rate-limiting enzyme of the InsP6 pathway.
CC Modifies TNF-alpha-induced apoptosis by interfering with the activation
CC of TNFRSF1A-associated death domain (PubMed:11909533, PubMed:12925536,
CC PubMed:17616525). Plays an important role in MLKL-mediated necroptosis.
CC Produces highly phosphorylated inositol phosphates such as
CC inositolhexakisphosphate (InsP6) which bind to MLKL mediating the
CC release of an N-terminal auto-inhibitory region leading to its
CC activation. Essential for activated phospho-MLKL to oligomerize and
CC localize to the cell membrane during necroptosis (PubMed:17616525).
CC {ECO:0000269|PubMed:11042108, ECO:0000269|PubMed:11909533,
CC ECO:0000269|PubMed:12925536, ECO:0000269|PubMed:17616525,
CC ECO:0000269|PubMed:8662638}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3,4,5,6-tetrakisphosphate + ATP = 1D-myo-
CC inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+);
CC Xref=Rhea:RHEA:12452, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57539, ChEBI:CHEBI:57733, ChEBI:CHEBI:456216;
CC EC=2.7.1.134; Evidence={ECO:0000269|PubMed:11042108,
CC ECO:0000269|PubMed:15762844, ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12453;
CC Evidence={ECO:0000269|PubMed:11042108, ECO:0000269|PubMed:15762844};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12454;
CC Evidence={ECO:0000269|PubMed:15762844, ECO:0000269|PubMed:17616525};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol
CC 1,3,4,5-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:13253,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;
CC Evidence={ECO:0000269|PubMed:11042108, ECO:0000269|PubMed:17616525,
CC ECO:0000269|PubMed:8662638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13254;
CC Evidence={ECO:0000269|PubMed:17616525, ECO:0000269|PubMed:8662638};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13255;
CC Evidence={ECO:0000269|PubMed:17616525};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol
CC 1,3,4,6-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:20940,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57660,
CC ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;
CC Evidence={ECO:0000269|PubMed:11042108, ECO:0000269|PubMed:17616525,
CC ECO:0000269|PubMed:8662638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20941;
CC Evidence={ECO:0000269|PubMed:17616525, ECO:0000269|PubMed:8662638};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20942;
CC Evidence={ECO:0000269|PubMed:17616525};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3,4,6-trisphosphate + ATP = 1D-myo-inositol
CC 1,3,4,6-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:70287,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57660,
CC ChEBI:CHEBI:189099, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70288;
CC Evidence={ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70289;
CC Evidence={ECO:0000269|PubMed:17616525};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 1D-myo-inositol
CC 1,3,4-trisphosphate = 1D-myo-inositol 1,3,4,6-tetrakisphosphate + 1D-
CC myo-inositol 3,4,5,6-tetrakisphosphate; Xref=Rhea:RHEA:70263,
CC ChEBI:CHEBI:57539, ChEBI:CHEBI:57660, ChEBI:CHEBI:57733,
CC ChEBI:CHEBI:58414; Evidence={ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70264;
CC Evidence={ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70265;
CC Evidence={ECO:0000269|PubMed:17616525};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 1D-myo-inositol
CC 1,3,4-trisphosphate = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + 1D-
CC myo-inositol 3,4,5,6-tetrakisphosphate; Xref=Rhea:RHEA:70271,
CC ChEBI:CHEBI:57539, ChEBI:CHEBI:57733, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414; Evidence={ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70272;
CC Evidence={ECO:0000269|PubMed:17616525};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70273;
CC Evidence={ECO:0000269|PubMed:17616525};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8662638};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:8662638};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 uM for Ins(1,3,4)P3 {ECO:0000269|PubMed:11042108};
CC KM=0.1 uM for Ins(3,4,5,6)P4 {ECO:0000269|PubMed:11042108};
CC KM=0.05 uM for Ins(3,4,5,6)P4 {ECO:0000269|PubMed:15762844};
CC KM=0.03 uM for Ins(1,3,4,5,6)P5 {ECO:0000269|PubMed:15762844};
CC Vmax=320 pmol/min/ug enzyme with Ins(1,3,4)P3 as substrate
CC {ECO:0000269|PubMed:11042108};
CC Vmax=780 pmol/min/ug enzyme with Ins(3,4,5,6)P4 as substrate
CC {ECO:0000269|PubMed:11042108};
CC Vmax=220 nmol/min/mg enzyme with Ins(3,4,5,6)P4 as substrate
CC {ECO:0000269|PubMed:15762844};
CC Vmax=16 nmol/min/mg enzyme with Ins(1,3,4,5,6)P5 as substrate
CC {ECO:0000269|PubMed:15762844};
CC -!- SUBUNIT: Monomer. Interacts with GPS1/COPS1.
CC {ECO:0000269|PubMed:12324474, ECO:0000269|PubMed:17616525}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13572-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13572-2; Sequence=VSP_016478, VSP_016479;
CC -!- TISSUE SPECIFICITY: Expressed in brain > heart > skeletal muscle =
CC kidney = pancreas = liver = placenta > lung. In brain, it is expressed
CC in cerebellum, cerebral cortex, medulla, spinal cord, occipital lobe,
CC frontal lobe, temporal lobe and putamen. {ECO:0000269|PubMed:8662638}.
CC -!- PTM: Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-
CC regulates enzymatic activity. Deacetylated by SIRT1.
CC {ECO:0000269|PubMed:22308441}.
CC -!- SIMILARITY: Belongs to the ITPK1 family. {ECO:0000305}.
CC -!- CAUTION: PubMed:11533064 detected some protein kinase activity and
CC ability to phosphorylate transcription factors c-jun/JUN and ATF2.
CC However, PubMed:15762844 showed that it does not have protein kinase
CC activity. {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; U51336; AAC50483.1; -; mRNA.
DR EMBL; AF279372; AAG44835.1; -; mRNA.
DR EMBL; BC003622; AAH03622.1; -; mRNA.
DR EMBL; BC007428; AAH07428.1; -; mRNA.
DR EMBL; BC018192; AAH18192.1; -; mRNA.
DR CCDS; CCDS45157.1; -. [Q13572-2]
DR CCDS; CCDS9907.1; -. [Q13572-1]
DR RefSeq; NP_001136065.1; NM_001142593.2. [Q13572-1]
DR RefSeq; NP_001136066.1; NM_001142594.2. [Q13572-2]
DR RefSeq; NP_055031.2; NM_014216.5. [Q13572-1]
DR PDB; 2ODT; X-ray; 2.01 A; X=1-327.
DR PDB; 2Q7D; X-ray; 1.60 A; A/B=1-335.
DR PDB; 2QB5; X-ray; 1.80 A; A/B=1-335.
DR PDBsum; 2ODT; -.
DR PDBsum; 2Q7D; -.
DR PDBsum; 2QB5; -.
DR AlphaFoldDB; Q13572; -.
DR SMR; Q13572; -.
DR BioGRID; 109910; 25.
DR DIP; DIP-60016N; -.
DR IntAct; Q13572; 10.
DR MINT; Q13572; -.
DR STRING; 9606.ENSP00000267615; -.
DR BindingDB; Q13572; -.
DR ChEMBL; CHEMBL1938220; -.
DR iPTMnet; Q13572; -.
DR PhosphoSitePlus; Q13572; -.
DR BioMuta; ITPK1; -.
DR DMDM; 83288249; -.
DR EPD; Q13572; -.
DR jPOST; Q13572; -.
DR MassIVE; Q13572; -.
DR MaxQB; Q13572; -.
DR PaxDb; Q13572; -.
DR PeptideAtlas; Q13572; -.
DR PRIDE; Q13572; -.
DR ProteomicsDB; 59575; -. [Q13572-1]
DR ProteomicsDB; 59576; -. [Q13572-2]
DR Antibodypedia; 26868; 305 antibodies from 31 providers.
DR DNASU; 3705; -.
DR Ensembl; ENST00000267615.11; ENSP00000267615.5; ENSG00000100605.17. [Q13572-1]
DR Ensembl; ENST00000354313.7; ENSP00000346272.3; ENSG00000100605.17. [Q13572-2]
DR Ensembl; ENST00000556603.6; ENSP00000451091.1; ENSG00000100605.17. [Q13572-1]
DR Ensembl; ENST00000614271.3; ENSP00000483767.1; ENSG00000274958.4. [Q13572-1]
DR Ensembl; ENST00000617836.4; ENSP00000480918.1; ENSG00000274958.4. [Q13572-2]
DR Ensembl; ENST00000626153.2; ENSP00000486991.1; ENSG00000274958.4. [Q13572-1]
DR GeneID; 3705; -.
DR KEGG; hsa:3705; -.
DR MANE-Select; ENST00000267615.11; ENSP00000267615.5; NM_014216.6; NP_055031.2.
DR UCSC; uc001ybe.2; human. [Q13572-1]
DR CTD; 3705; -.
DR DisGeNET; 3705; -.
DR GeneCards; ITPK1; -.
DR HGNC; HGNC:6177; ITPK1.
DR HPA; ENSG00000100605; Low tissue specificity.
DR MIM; 601838; gene.
DR neXtProt; NX_Q13572; -.
DR OpenTargets; ENSG00000100605; -.
DR PharmGKB; PA29974; -.
DR VEuPathDB; HostDB:ENSG00000100605; -.
DR eggNOG; ENOG502QQS1; Eukaryota.
DR GeneTree; ENSGT00390000001278; -.
DR HOGENOM; CLU_041857_1_1_1; -.
DR InParanoid; Q13572; -.
DR OMA; CKPLIAY; -.
DR OrthoDB; 1116241at2759; -.
DR PhylomeDB; Q13572; -.
DR TreeFam; TF329288; -.
DR BioCyc; MetaCyc:HS02123-MON; -.
DR BRENDA; 2.7.1.134; 2681.
DR BRENDA; 2.7.1.159; 2681.
DR PathwayCommons; Q13572; -.
DR Reactome; R-HSA-1855167; Synthesis of pyrophosphates in the cytosol.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SABIO-RK; Q13572; -.
DR SignaLink; Q13572; -.
DR BioGRID-ORCS; 3705; 98 hits in 1083 CRISPR screens.
DR ChiTaRS; ITPK1; human.
DR EvolutionaryTrace; Q13572; -.
DR GeneWiki; ITPK1; -.
DR GenomeRNAi; 3705; -.
DR Pharos; Q13572; Tbio.
DR PRO; PR:Q13572; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q13572; protein.
DR Bgee; ENSG00000100605; Expressed in C1 segment of cervical spinal cord and 102 other tissues.
DR ExpressionAtlas; Q13572; baseline and differential.
DR Genevisible; Q13572; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0047325; F:inositol tetrakisphosphate 1-kinase activity; EXP:Reactome.
DR GO; GO:0000825; F:inositol tetrakisphosphate 6-kinase activity; IMP:UniProtKB.
DR GO; GO:0052726; F:inositol-1,3,4-trisphosphate 5-kinase activity; EXP:Reactome.
DR GO; GO:0052725; F:inositol-1,3,4-trisphosphate 6-kinase activity; EXP:Reactome.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0052746; P:inositol phosphorylation; IBA:GO_Central.
DR GO; GO:0032957; P:inositol trisphosphate metabolic process; IEA:InterPro.
DR GO; GO:0070266; P:necroptotic process; IMP:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR008656; Inositol_tetrakis-P_1-kinase.
DR InterPro; IPR040464; InsP(3)kin_ATP-grasp.
DR InterPro; IPR041429; ITPK1_N.
DR PANTHER; PTHR14217; PTHR14217; 1.
DR Pfam; PF05770; Ins134_P3_kin; 1.
DR Pfam; PF17927; Ins134_P3_kin_N; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Hydrolase;
KW Isomerase; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..414
FT /note="Inositol-tetrakisphosphate 1-kinase"
FT /id="PRO_0000220833"
FT DOMAIN 117..325
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 18
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 167
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 188..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 199
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 281
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT BINDING 297
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT MOD_RES 340
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000269|PubMed:22308441"
FT MOD_RES 383
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000269|PubMed:22308441"
FT MOD_RES 396
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 410
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000269|PubMed:22308441"
FT VAR_SEQ 302..314
FT /note="YEGVSEFFTDLLN -> DCQVCFIEGWKTD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016478"
FT VAR_SEQ 315..414
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016479"
FT MUTAGEN 18
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 58
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 59
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 106
FT /note="R->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15762844,
FT ECO:0000269|PubMed:15837423"
FT MUTAGEN 157
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15762844"
FT MUTAGEN 162
FT /note="H->Q: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 163
FT /note="G->A,P: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15762844,
FT ECO:0000269|PubMed:15837423"
FT MUTAGEN 163
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:15762844,
FT ECO:0000269|PubMed:15837423"
FT MUTAGEN 167
FT /note="H->A,Q: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 188
FT /note="Q->A: No effect."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 193
FT /note="H->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 199
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 212
FT /note="R->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 214
FT /note="S->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 215
FT /note="L->A: No effect."
FT /evidence="ECO:0000269|PubMed:15837423"
FT MUTAGEN 281
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15762844"
FT MUTAGEN 295
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15762844"
FT MUTAGEN 297
FT /note="N->A,L: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15762844,
FT ECO:0000269|PubMed:15837423"
FT MUTAGEN 297
FT /note="N->D: Induces a strong reduction in kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:15762844,
FT ECO:0000269|PubMed:15837423"
FT MUTAGEN 301
FT /note="G->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15837423"
FT CONFLICT 356
FT /note="S -> N (in Ref. 1; AAC50483)"
FT /evidence="ECO:0000305"
FT HELIX 1..5
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 16..22
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 24..32
FT /evidence="ECO:0007829|PDB:2Q7D"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 97..102
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 106..120
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 130..133
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2ODT"
FT HELIX 141..147
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 152..157
FT /evidence="ECO:0007829|PDB:2Q7D"
FT TURN 164..167
FT /evidence="ECO:0007829|PDB:2QB5"
FT STRAND 168..172
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 196..203
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 206..213
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 259..273
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 277..284
FT /evidence="ECO:0007829|PDB:2Q7D"
FT TURN 286..288
FT /evidence="ECO:0007829|PDB:2Q7D"
FT STRAND 291..299
FT /evidence="ECO:0007829|PDB:2Q7D"
FT HELIX 308..324
FT /evidence="ECO:0007829|PDB:2Q7D"
SQ SEQUENCE 414 AA; 45621 MW; E89E2EE11971278E CRC64;
MQTFLKGKRV GYWLSEKKIK KLNFQAFAEL CRKRGMEVVQ LNLSRPIEEQ GPLDVIIHKL
TDVILEADQN DSQSLELVHR FQEYIDAHPE TIVLDPLPAI RTLLDRSKSY ELIRKIEAYM
EDDRICSPPF MELTSLCGDD TMRLLEKNGL TFPFICKTRV AHGTNSHEMA IVFNQEGLNA
IQPPCVVQNF INHNAVLYKV FVVGESYTVV QRPSLKNFSA GTSDRESIFF NSHNVSKPES
SSVLTELDKI EGVFERPSDE VIRELSRALR QALGVSLFGI DIIINNQTGQ HAVIDINAFP
GYEGVSEFFT DLLNHIATVL QGQSTAMAAT GDVALLRHSK LLAEPAGGLV GERTCSASPG
CCGSMMGQDA PWKAEADAGG TAKLPHQRLG CNAGVSPSFQ QHCVASLATK ASSQ
