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Protein

Inositol-tetrakisphosphate 1-kinase

Gene

ITPK1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca2+-activated Cl- channels, while Ins(1,3,4,5,6)P5 is not. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and 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. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain (By similarity). Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway.By similarity

Catalytic activityi

ATP + 1D-myo-inositol 3,4,5,6-tetrakisphosphate = ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate.1 Publication
ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate.1 Publication
ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,6-tetrakisphosphate.1 Publication

Cofactori

Mg2+By similarityNote: Binds 2 magnesium ions per subunit.By similarity

Kineticsi

  1. KM=80 nM for Ins(1,3,4)P31 Publication
  1. Vmax=60 nmol/min/mg enzyme with Ins(1,3,4)P3 as substrate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei18 – 1811D-myo-inositol 1,3,4-trisphosphateBy similarity
Binding sitei106 – 1061ATPBy similarity
Binding sitei157 – 1571ATPBy similarity
Binding sitei167 – 16711D-myo-inositol 1,3,4-trisphosphateBy similarity
Binding sitei199 – 19911D-myo-inositol 1,3,4-trisphosphateBy similarity
Binding sitei214 – 2141ATPBy similarity
Binding sitei232 – 2321ATPBy similarity
Binding sitei236 – 2361ATPBy similarity
Metal bindingi281 – 2811Magnesium 1By similarity
Metal bindingi295 – 2951Magnesium 1By similarity
Metal bindingi295 – 2951Magnesium 2By similarity
Metal bindingi297 – 2971Magnesium 2By similarity
Binding sitei297 – 29711D-myo-inositol 1,3,4-trisphosphateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi188 – 19912ATPPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Isomerase, Kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-BTA-1855167. Synthesis of pyrophosphates in the cytosol.
R-BTA-1855204. Synthesis of IP3 and IP4 in the cytosol.
R-BTA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKP0C0T1.

Names & Taxonomyi

Protein namesi
Recommended name:
Inositol-tetrakisphosphate 1-kinase (EC:2.7.1.134)
Alternative name(s):
Inositol 1,3,4-trisphosphate 5/6-kinase (EC:2.7.1.159)
Short name:
Inositol-triphosphate 5/6-kinase
Short name:
Ins(1,3,4)P(3) 5/6-kinase
Gene namesi
Name:ITPK1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 21

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 419419Inositol-tetrakisphosphate 1-kinasePRO_0000220832Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei388 – 3881N6-acetyllysine; by EP300 and CREBBPBy similarity
Modified residuei415 – 4151N6-acetyllysine; by EP300 and CREBBPBy similarity

Post-translational modificationi

Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-regulates enzymatic activity. Deacetylated by SIRT1 (By similarity).By similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiP0C0T1.
PRIDEiP0C0T1.

Interactioni

Subunit structurei

Monomer. Interacts with GPS1/COPS1 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000042643.

Structurei

3D structure databases

ProteinModelPortaliP0C0T1.
SMRiP0C0T1. Positions 6-322.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini117 – 325209ATP-graspPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the ITPK1 family.Curated
Contains 1 ATP-grasp domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IHA6. Eukaryota.
ENOG4110KIK. LUCA.
GeneTreeiENSGT00390000001278.
HOGENOMiHOG000007762.
HOVERGENiHBG079462.
InParanoidiP0C0T1.
KOiK00913.
OMAiERPNDDV.
OrthoDBiEOG70GMG7.
TreeFamiTF329288.

Family and domain databases

InterProiIPR011761. ATP-grasp.
IPR008656. Inositol_tetrakis-P_1-kinase.
[Graphical view]
PfamiPF05770. Ins134_P3_kin. 1 hit.
[Graphical view]
PROSITEiPS50975. ATP_GRASP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0C0T1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQTFLKGKRV GYWLSEKKIK KLNFQAFAEL CRKRGIEVVQ LNLSRPIEEQ
60 70 80 90 100
GPLDVIIHKL TDVILEADQN DSQALELVHR FQEYIDAHPE TIVLDPLPAI
110 120 130 140 150
RTLLDRSKSY ELIRKIEAYM KDDRICSPPF MELTSLCGDD TMRLLEENGL
160 170 180 190 200
AFPFICKTRV AHGTNSHEMA IVFNQEGLSA IQPPCVVQNF INHNAVLYKV
210 220 230 240 250
FVVGESYTVV QRPSLKNFSA GTSDRESIFF NSHNVSKPES SSVLTALDKI
260 270 280 290 300
EGVFERPSDE VIRELSRALR QALGVSLFGI DIIINNQTGQ HAVIDINAFP
310 320 330 340 350
GYEGVSEFFT DLLNHIASVL QGQSSGVAGA GDVAPLKHSR LLAEQAGGLA
360 370 380 390 400
AERTCSASPG CCSSMMGQEP PWTPEADMGG VGAGSTAKLP HQRLGCTAGV
410
SPSFQQHCVA SLATKASSQ
Length:419
Mass (Da):45,842
Last modified:December 6, 2005 - v1
Checksum:iFD4560C869A1A917
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DT820636 mRNA. No translation available.
CV982275 mRNA. No translation available.
RefSeqiNP_001179418.1. NM_001192489.1.
XP_015314814.1. XM_015459328.1.
UniGeneiBt.62530.

Genome annotation databases

EnsembliENSBTAT00000045234; ENSBTAP00000042643; ENSBTAG00000009845.
GeneIDi518488.
KEGGibta:518488.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DT820636 mRNA. No translation available.
CV982275 mRNA. No translation available.
RefSeqiNP_001179418.1. NM_001192489.1.
XP_015314814.1. XM_015459328.1.
UniGeneiBt.62530.

3D structure databases

ProteinModelPortaliP0C0T1.
SMRiP0C0T1. Positions 6-322.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000042643.

Proteomic databases

PaxDbiP0C0T1.
PRIDEiP0C0T1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000045234; ENSBTAP00000042643; ENSBTAG00000009845.
GeneIDi518488.
KEGGibta:518488.

Organism-specific databases

CTDi3705.

Phylogenomic databases

eggNOGiENOG410IHA6. Eukaryota.
ENOG4110KIK. LUCA.
GeneTreeiENSGT00390000001278.
HOGENOMiHOG000007762.
HOVERGENiHBG079462.
InParanoidiP0C0T1.
KOiK00913.
OMAiERPNDDV.
OrthoDBiEOG70GMG7.
TreeFamiTF329288.

Enzyme and pathway databases

ReactomeiR-BTA-1855167. Synthesis of pyrophosphates in the cytosol.
R-BTA-1855204. Synthesis of IP3 and IP4 in the cytosol.
R-BTA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKP0C0T1.

Miscellaneous databases

NextBioi20872664.

Family and domain databases

InterProiIPR011761. ATP-grasp.
IPR008656. Inositol_tetrakis-P_1-kinase.
[Graphical view]
PfamiPF05770. Ins134_P3_kin. 1 hit.
[Graphical view]
PROSITEiPS50975. ATP_GRASP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation of inositol 1,3,4-trisphosphate 5/6-kinase, cDNA cloning and expression of the recombinant enzyme."
    Wilson M.P., Majerus P.W.
    J. Biol. Chem. 271:11904-11910(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-17; 200-211 AND 338-359, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    Tissue: Brain.
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-245.
    Strain: Crossbred X Angus.
    Tissue: Ileum.
  3. "Bovine ESTs: focus on female reproduction."
    Prather R.S., Antoniou E., Garverick H.A., Green J.A., Lucy M.C., Roberts R.M., Smith M.F., Youngquist R.S.
    Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 203-419.

Entry informationi

Entry nameiITPK1_BOVIN
AccessioniPrimary (citable) accession number: P0C0T1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: May 11, 2016
This is version 74 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.