ITPK1_BOVIN
ID ITPK1_BOVIN Reviewed; 419 AA.
AC P0C0T1;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Inositol-tetrakisphosphate 1-kinase;
DE EC=2.7.1.134 {ECO:0000269|PubMed:8662638};
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:8662638};
GN Name=ITPK1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP PROTEIN SEQUENCE OF 1-17; 200-211 AND 338-359, ENZYME ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, 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 [LARGE SCALE MRNA] OF 1-245.
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 203-419.
RA Prather R.S., Antoniou E., Garverick H.A., Green J.A., Lucy M.C.,
RA Roberts R.M., Smith M.F., Youngquist R.S.;
RT "Bovine ESTs: focus on female reproduction.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Kinase that can phosphorylate various inositol polyphosphate
CC such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4
CC at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to
CC have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of
CC plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5
CC is 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:8662638). Also acts as an inositol polyphosphate
CC phosphatase that dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to
CC Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as
CC an isomerase that interconverts the inositol tetrakisphosphate isomers
CC Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium.
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. Plays an important role in MLKL-
CC mediated necroptosis. Produces highly phosphorylated inositol
CC phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL
CC mediating the release of an N-terminal auto-inhibitory region leading
CC to its activation. Essential for activated phospho-MLKL to oligomerize
CC and localize to the cell membrane during necroptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q13572, 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:8662638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12453;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12454;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
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:8662638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13254;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13255;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
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:8662638};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20941;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20942;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
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:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70288;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70289;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
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:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70264;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70265;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
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:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70272;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70273;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC Note=Binds 2 magnesium ions per subunit.
CC {ECO:0000250|UniProtKB:Q13572};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=80 nM for Ins(1,3,4)P3 {ECO:0000269|PubMed:8662638};
CC Vmax=60 nmol/min/mg enzyme with Ins(1,3,4)P3 as substrate
CC {ECO:0000269|PubMed:8662638};
CC -!- SUBUNIT: Monomer. Interacts with GPS1/COPS1.
CC {ECO:0000250|UniProtKB:Q13572}.
CC -!- PTM: Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-
CC regulates enzymatic activity. Deacetylated by SIRT1.
CC {ECO:0000250|UniProtKB:Q13572}.
CC -!- SIMILARITY: Belongs to the ITPK1 family. {ECO:0000305}.
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DR EMBL; DT820636; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CV982275; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001179418.1; NM_001192489.1.
DR RefSeq; XP_015314814.1; XM_015459328.1.
DR AlphaFoldDB; P0C0T1; -.
DR SMR; P0C0T1; -.
DR STRING; 9913.ENSBTAP00000042643; -.
DR PaxDb; P0C0T1; -.
DR PRIDE; P0C0T1; -.
DR Ensembl; ENSBTAT00000072598; ENSBTAP00000066033; ENSBTAG00000009845.
DR GeneID; 518488; -.
DR KEGG; bta:518488; -.
DR CTD; 3705; -.
DR VEuPathDB; HostDB:ENSBTAG00000009845; -.
DR VGNC; VGNC:30343; ITPK1.
DR eggNOG; ENOG502QQS1; Eukaryota.
DR GeneTree; ENSGT00390000001278; -.
DR HOGENOM; CLU_041857_1_1_1; -.
DR InParanoid; P0C0T1; -.
DR OMA; CKPLIAY; -.
DR OrthoDB; 1116241at2759; -.
DR TreeFam; TF329288; -.
DR SABIO-RK; P0C0T1; -.
DR Proteomes; UP000009136; Chromosome 21.
DR Bgee; ENSBTAG00000009845; Expressed in diaphragm and 103 other tissues.
DR ExpressionAtlas; P0C0T1; baseline and differential.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0047325; F:inositol tetrakisphosphate 1-kinase activity; IBA:GO_Central.
DR GO; GO:0000825; F:inositol tetrakisphosphate 6-kinase activity; ISS:UniProtKB.
DR GO; GO:0052726; F:inositol-1,3,4-trisphosphate 5-kinase activity; IBA:GO_Central.
DR GO; GO:0052725; F:inositol-1,3,4-trisphosphate 6-kinase activity; IBA:GO_Central.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
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; ISS:UniProtKB.
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 Acetylation; ATP-binding; Direct protein sequencing; Hydrolase; Isomerase;
KW Kinase; Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..419
FT /note="Inositol-tetrakisphosphate 1-kinase"
FT /id="PRO_0000220832"
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 /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
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 /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 281
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000250"
FT MOD_RES 388
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q13572"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13572"
FT MOD_RES 415
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q13572"
SQ SEQUENCE 419 AA; 45842 MW; FD4560C869A1A917 CRC64;
MQTFLKGKRV GYWLSEKKIK KLNFQAFAEL CRKRGIEVVQ LNLSRPIEEQ GPLDVIIHKL
TDVILEADQN DSQALELVHR FQEYIDAHPE TIVLDPLPAI RTLLDRSKSY ELIRKIEAYM
KDDRICSPPF MELTSLCGDD TMRLLEENGL AFPFICKTRV AHGTNSHEMA IVFNQEGLSA
IQPPCVVQNF INHNAVLYKV FVVGESYTVV QRPSLKNFSA GTSDRESIFF NSHNVSKPES
SSVLTALDKI EGVFERPSDE VIRELSRALR QALGVSLFGI DIIINNQTGQ HAVIDINAFP
GYEGVSEFFT DLLNHIASVL QGQSSGVAGA GDVAPLKHSR LLAEQAGGLA AERTCSASPG
CCSSMMGQEP PWTPEADMGG VGAGSTAKLP HQRLGCTAGV SPSFQQHCVA SLATKASSQ
