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Database: UniProt
Entry: P0C0T1
LinkDB: P0C0T1
Original site: P0C0T1 
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   16-JAN-2019, entry version 92.
DE   RecName: Full=Inositol-tetrakisphosphate 1-kinase;
DE            EC=2.7.1.134;
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;
GN   Name=ITPK1;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC   Pecora; Bovidae; Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   PROTEIN SEQUENCE OF 1-17; 200-211 AND 338-359, ENZYME ACTIVITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
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
RT   and 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
CC       polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3.
CC       Phosphorylates Ins(3,4,5,6)P4 at position 1 to form
CC       Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory
CC       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
CC       is not. Also acts as an inositol polyphosphate phosphatase that
CC       dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3,
CC       and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an
CC       isomerase that interconverts the inositol tetrakisphosphate
CC       isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP
CC       and magnesium. Probably acts as the rate-limiting enzyme of the
CC       InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering
CC       with the activation of TNFRSF1A-associated death domain (By
CC       similarity). Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to
CC       form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate
CC       (InsP6) pathway. Plays an important role in MLKL-mediated
CC       necroptosis. Produces highly phosphorylated inositol phosphates
CC       such as inositolhexakisphosphate (InsP6) which bind to MLKL
CC       mediating the release of an N-terminal auto-inhibitory region
CC       leading to its activation. Essential for activated phospho-MLKL to
CC       oligomerize and localize to the cell membrane during necroptosis
CC       (By similarity). {ECO:0000250|UniProtKB:Q13572}.
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-
CC         inositol 1,3,4,5-tetrakisphosphate + ADP + H(+);
CC         Xref=Rhea:RHEA:13253, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:57895, ChEBI:CHEBI:58414, ChEBI:CHEBI:456216;
CC         EC=2.7.1.159; Evidence={ECO:0000269|PubMed:8662638};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-
CC         inositol 1,3,4,6-tetrakisphosphate + ADP + H(+);
CC         Xref=Rhea:RHEA:20940, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:57660, ChEBI:CHEBI:58414, ChEBI:CHEBI:456216;
CC         EC=2.7.1.159; Evidence={ECO:0000269|PubMed:8662638};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC       Note=Binds 2 magnesium ions per subunit. {ECO:0000250};
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 (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-
CC       regulates enzymatic activity. Deacetylated by SIRT1 (By
CC       similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ITPK1 family. {ECO:0000305}.
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   ProteinModelPortal; P0C0T1; -.
DR   SMR; P0C0T1; -.
DR   STRING; 9913.ENSBTAP00000042643; -.
DR   PaxDb; P0C0T1; -.
DR   PRIDE; P0C0T1; -.
DR   Ensembl; ENSBTAT00000045234; ENSBTAP00000042643; ENSBTAG00000009845.
DR   GeneID; 518488; -.
DR   KEGG; bta:518488; -.
DR   CTD; 3705; -.
DR   VGNC; VGNC:30343; ITPK1.
DR   eggNOG; ENOG410IHA6; Eukaryota.
DR   eggNOG; ENOG4110KIK; LUCA.
DR   GeneTree; ENSGT00390000001278; -.
DR   HOGENOM; HOG000007762; -.
DR   HOVERGEN; HBG079462; -.
DR   InParanoid; P0C0T1; -.
DR   KO; K00913; -.
DR   OMA; MQDERIC; -.
DR   OrthoDB; 1116241at2759; -.
DR   TreeFam; TF329288; -.
DR   Reactome; R-BTA-1855167; Synthesis of pyrophosphates in the cytosol.
DR   Reactome; R-BTA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR   Reactome; R-BTA-983231; Factors involved in megakaryocyte development and platelet production.
DR   SABIO-RK; P0C0T1; -.
DR   Proteomes; UP000009136; Chromosome 21.
DR   Bgee; ENSBTAG00000009845; Expressed in 9 organ(s), highest expression level in prefrontal cortex.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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   GO; GO:0021915; P:neural tube development; IEA:Ensembl.
DR   InterPro; IPR011761; ATP-grasp.
DR   InterPro; IPR008656; Inositol_tetrakis-P_1-kinase.
DR   InterPro; IPR040464; InsP(3)kin_ATP-grasp.
DR   PANTHER; PTHR14217; PTHR14217; 1.
DR   Pfam; PF05770; Ins134_P3_kin; 1.
DR   PROSITE; PS50975; ATP_GRASP; 1.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Complete proteome;
KW   Direct protein sequencing; Hydrolase; Isomerase; Kinase; Magnesium;
KW   Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Transferase.
FT   CHAIN         1    419       Inositol-tetrakisphosphate 1-kinase.
FT                                /FTId=PRO_0000220832.
FT   DOMAIN      117    325       ATP-grasp. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00409}.
FT   NP_BIND     188    199       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00409}.
FT   METAL       281    281       Magnesium 1. {ECO:0000250}.
FT   METAL       295    295       Magnesium 1. {ECO:0000250}.
FT   METAL       295    295       Magnesium 2. {ECO:0000250}.
FT   METAL       297    297       Magnesium 2. {ECO:0000250}.
FT   BINDING      18     18       1D-myo-inositol 1,3,4-trisphosphate.
FT                                {ECO:0000250}.
FT   BINDING     106    106       ATP. {ECO:0000250}.
FT   BINDING     157    157       ATP. {ECO:0000250}.
FT   BINDING     167    167       1D-myo-inositol 1,3,4-trisphosphate.
FT                                {ECO:0000250}.
FT   BINDING     199    199       1D-myo-inositol 1,3,4-trisphosphate.
FT                                {ECO:0000250}.
FT   BINDING     214    214       ATP. {ECO:0000250}.
FT   BINDING     232    232       ATP. {ECO:0000250}.
FT   BINDING     236    236       ATP. {ECO:0000250}.
FT   BINDING     297    297       1D-myo-inositol 1,3,4-trisphosphate.
FT                                {ECO:0000250}.
FT   MOD_RES     388    388       N6-acetyllysine; by EP300 and CREBBP.
FT                                {ECO:0000250|UniProtKB:Q13572}.
FT   MOD_RES     401    401       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q13572}.
FT   MOD_RES     415    415       N6-acetyllysine; by EP300 and CREBBP.
FT                                {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
//
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