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Q13572 (ITPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inositol-tetrakisphosphate 1-kinase

EC=2.7.1.134
Alternative name(s):
Inositol 1,3,4-trisphosphate 5/6-kinase
Short name=Inositol-triphosphate 5/6-kinase
Short name=Ins(1,3,4)P(3) 5/6-kinase
EC=2.7.1.159
Gene names
Name:ITPK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length414 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 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. 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. Ref.4 Ref.5 Ref.7 Ref.13

Catalytic activity

ATP + 1D-myo-inositol 3,4,5,6-tetrakisphosphate = ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate. Ref.1 Ref.2

ATP + 1D-myo-inositol 1,3,4-trisphosphate = ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate. Ref.1 Ref.2

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

Cofactor

Binds 2 magnesium ions per subunit. Ref.1

Subunit structure

Monomer. Interacts with GPS1/COPS1. Ref.6 Ref.13

Tissue specificity

Expressed in brain > heart > skeletal muscle = kidney = pancreas = liver = placenta > lung. In brain, it is expressed in cerebellum, cerebral cortex, medulla, spinal cord, occipital lobe, frontal lobe, temporal lobe and putamen. Ref.1

Post-translational modification

Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-regulates enzymatic activity. Deacetylated by SIRT1. Ref.12

Sequence similarities

Belongs to the ITPK1 family.

Contains 1 ATP-grasp domain.

Caution

Ref.4 detected some protein kinase activity and ability to phosphorylate transcription factors c-jun/JUN and ATF2. However, Ref.8 showed that it does not have protein kinase activity.

Biophysicochemical properties

Kinetic parameters:

KM=0.3 µM for Ins(1,3,4)P3 Ref.2

KM=0.1 µM for Ins(3,4,5,6)P4

Vmax=320 pmol/min/µg enzyme with Ins(1,3,4)P3 as substrate

Vmax=780 pmol/min/µg enzyme enzyme with Ins(3,4,5,6)P4 as substrate

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionHydrolase
Isomerase
Kinase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

dephosphorylation

Traceable author statement. Source: GOC

inositol phosphate metabolic process

Traceable author statement. Source: Reactome

inositol trisphosphate metabolic process

Inferred from electronic annotation. Source: InterPro

signal transduction

Traceable author statement Ref.1. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

catalytic activity

Traceable author statement Ref.1. Source: ProtInc

inositol tetrakisphosphate 1-kinase activity

Traceable author statement. Source: Reactome

inositol-1,3,4,5,6-pentakisphosphate 1-phosphatase activity

Traceable author statement. Source: Reactome

inositol-1,3,4,6-tetrakisphosphate 1-phosphatase activity

Traceable author statement. Source: Reactome

inositol-1,3,4,6-tetrakisphosphate 6-phosphatase activity

Traceable author statement. Source: Reactome

inositol-1,3,4-trisphosphate 5-kinase activity

Traceable author statement. Source: Reactome

inositol-1,3,4-trisphosphate 6-kinase activity

Traceable author statement. Source: Reactome

inositol-3,4,6-trisphosphate 1-kinase activity

Traceable author statement. Source: Reactome

isomerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13572-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q13572-2)

The sequence of this isoform differs from the canonical sequence as follows:
     302-314: YEGVSEFFTDLLN → DCQVCFIEGWKTD
     315-414: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 414414Inositol-tetrakisphosphate 1-kinase
PRO_0000220833

Regions

Domain117 – 325209ATP-grasp
Nucleotide binding188 – 19912ATP

Sites

Metal binding2811Magnesium 1
Metal binding2951Magnesium 1
Metal binding2951Magnesium 2
Metal binding2971Magnesium 2
Binding site1811D-myo-inositol 1,3,4-trisphosphate By similarity
Binding site1061ATP
Binding site1571ATP
Binding site16711D-myo-inositol 1,3,4-trisphosphate By similarity
Binding site19911D-myo-inositol 1,3,4-trisphosphate By similarity
Binding site2141ATP
Binding site2321ATP
Binding site2361ATP
Binding site29711D-myo-inositol 1,3,4-trisphosphate By similarity

Amino acid modifications

Modified residue3401N6-acetyllysine; by EP300 and CREBBP Ref.12
Modified residue3831N6-acetyllysine; by EP300 and CREBBP Ref.12
Modified residue4101N6-acetyllysine; by EP300 and CREBBP Ref.12

Natural variations

Alternative sequence302 – 31413YEGVS…TDLLN → DCQVCFIEGWKTD in isoform 2.
VSP_016478
Alternative sequence315 – 414100Missing in isoform 2.
VSP_016479

Experimental info

Mutagenesis181K → A: Loss of kinase activity. Ref.9
Mutagenesis581H → A: No effect. Ref.9
Mutagenesis591K → A: Loss of kinase activity. Ref.9
Mutagenesis1061R → A: Loss of kinase activity. Ref.8 Ref.9
Mutagenesis1571K → A: Loss of kinase activity. Ref.8
Mutagenesis1621H → Q: Loss of kinase activity. Ref.9
Mutagenesis1631G → A or P: Loss of kinase activity. Ref.8 Ref.9
Mutagenesis1631G → A: No effect. Ref.8 Ref.9
Mutagenesis1671H → A or Q: Loss of kinase activity. Ref.9
Mutagenesis1881Q → A: No effect. Ref.9
Mutagenesis1931H → A: Loss of kinase activity. Ref.9
Mutagenesis1991K → A: Loss of kinase activity. Ref.9
Mutagenesis2121R → A: Loss of kinase activity. Ref.9
Mutagenesis2141S → A: Loss of kinase activity. Ref.9
Mutagenesis2151L → A: No effect. Ref.9
Mutagenesis2811D → A: Loss of kinase activity. Ref.8
Mutagenesis2951D → A: Loss of kinase activity. Ref.8
Mutagenesis2971N → A or L: Loss of kinase activity. Ref.8 Ref.9
Mutagenesis2971N → D: Induces a strong reduction in kinase activity. Ref.8 Ref.9
Mutagenesis3011G → A: Loss of kinase activity. Ref.9
Sequence conflict3561S → N in AAC50483. Ref.1

Secondary structure

.......................................................... 414
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 6, 2005. Version 2.
Checksum: E89E2EE11971278E

FASTA41445,621
        10         20         30         40         50         60 
MQTFLKGKRV GYWLSEKKIK KLNFQAFAEL CRKRGMEVVQ LNLSRPIEEQ GPLDVIIHKL 

        70         80         90        100        110        120 
TDVILEADQN DSQSLELVHR FQEYIDAHPE TIVLDPLPAI RTLLDRSKSY ELIRKIEAYM 

       130        140        150        160        170        180 
EDDRICSPPF MELTSLCGDD TMRLLEKNGL TFPFICKTRV AHGTNSHEMA IVFNQEGLNA 

       190        200        210        220        230        240 
IQPPCVVQNF INHNAVLYKV FVVGESYTVV QRPSLKNFSA GTSDRESIFF NSHNVSKPES 

       250        260        270        280        290        300 
SSVLTELDKI EGVFERPSDE VIRELSRALR QALGVSLFGI DIIINNQTGQ HAVIDINAFP 

       310        320        330        340        350        360 
GYEGVSEFFT DLLNHIATVL QGQSTAMAAT GDVALLRHSK LLAEPAGGLV GERTCSASPG 

       370        380        390        400        410 
CCGSMMGQDA PWKAEADAGG TAKLPHQRLG CNAGVSPSFQ QHCVASLATK ASSQ 

« Hide

Isoform 2 [UniParc].

Checksum: DD10427FADBBB3E0
Show »

FASTA31435,632

References

« Hide 'large scale' references
[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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, COFACTOR, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Multitasking in signal transduction by a promiscuous human Ins(3,4,5,6)P(4) 1-kinase/Ins(1,3,4)P(3) 5/6-kinase."
Yang X., Shears S.B.
Biochem. J. 351:551-555(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Eye and Muscle.
[4]"Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates the transcription factors c-Jun and ATF-2."
Wilson M.P., Sun Y., Cao L., Majerus P.W.
J. Biol. Chem. 276:40998-41004(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PUTATIVE FUNCTION AS PROTEIN KINASE.
[5]"Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase."
Ho M.W.Y., Yang X., Carew M.A., Zhang T., Hua L., Kwon Y.-U., Chung S.-K., Adelt S., Vogel G., Riley A.M., Potter B.V.L., Shears S.B.
Curr. Biol. 12:477-482(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1."
Sun Y., Wilson M.P., Majerus P.W.
J. Biol. Chem. 277:45759-45764(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GPS1.
[7]"Inositol 1,3,4-trisphosphate 5/6-kinase inhibits tumor necrosis factor-induced apoptosis."
Sun Y., Mochizuki Y., Majerus P.W.
J. Biol. Chem. 278:43645-43653(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein kinase."
Qian X., Mitchell J., Wei S.J., Williams J., Petrovich R.M., Shears S.B.
Biochem. J. 389:389-395(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-106; LYS-157; GLY-163; ASP-281; ASP-295 AND ASN-297.
[9]"Specificity determinants in inositol polyphosphate synthesis: crystal structure of inositol 1,3,4-trisphosphate 5/6-kinase."
Miller G.J., Wilson M.P., Majerus P.W., Hurley J.H.
Mol. Cell 18:201-212(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LYS-18; HIS-58; LYS-59; ARG-106; HIS-162; GLY-163; HIS-167; GLN-188; HIS-193; LYS-199; ARG-212; SER-214; LEU-215; ASN-297 AND GLY-301.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Regulation of inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) by reversible lysine acetylation."
Zhang C., Majerus P.W., Wilson M.P.
Proc. Natl. Acad. Sci. U.S.A. 109:2290-2295(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-340; LYS-383 AND LYS-410.
[13]"Integration of inositol phosphate signaling pathways via human ITPK1."
Chamberlain P.P., Qian X., Stiles A.R., Cho J., Jones D.H., Lesley S.A., Grabau E.A., Shears S.B., Spraggon G.
J. Biol. Chem. 282:28117-28125(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-335 IN COMPLEXES WITH MANGANESE; ATP ANALOG AND ADP, FUNCTION, SUBUNIT.
[14]"Structure of human inositol 1,3,4-trisphosphate 5/6-kinase."
Structural genomics consortium (SGC)
Submitted (FEB-2007) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 1-327.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U51336 mRNA. Translation: AAC50483.1.
AF279372 mRNA. Translation: AAG44835.1.
BC003622 mRNA. Translation: AAH03622.1.
BC007428 mRNA. Translation: AAH07428.1.
BC018192 mRNA. Translation: AAH18192.1.
CCDSCCDS45157.1. [Q13572-2]
CCDS9907.1. [Q13572-1]
RefSeqNP_001136065.1. NM_001142593.1. [Q13572-1]
NP_001136066.1. NM_001142594.1. [Q13572-2]
NP_055031.2. NM_014216.4. [Q13572-1]
UniGeneHs.308122.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ODTX-ray2.01X1-327[»]
2Q7DX-ray1.60A/B1-335[»]
2QB5X-ray1.80A/B1-335[»]
ProteinModelPortalQ13572.
SMRQ13572. Positions 6-322.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109910. 6 interactions.
DIPDIP-60016N.
IntActQ13572. 2 interactions.
MINTMINT-1463374.
STRING9606.ENSP00000267615.

Chemistry

ChEMBLCHEMBL1938220.

PTM databases

PhosphoSiteQ13572.

Polymorphism databases

DMDM83288249.

Proteomic databases

MaxQBQ13572.
PaxDbQ13572.
PRIDEQ13572.

Protocols and materials databases

DNASU3705.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000267615; ENSP00000267615; ENSG00000100605. [Q13572-1]
ENST00000354313; ENSP00000346272; ENSG00000100605. [Q13572-2]
ENST00000556603; ENSP00000451091; ENSG00000100605. [Q13572-1]
GeneID3705.
KEGGhsa:3705.
UCSCuc001ybe.2. human. [Q13572-2]
uc001ybf.3. human. [Q13572-1]

Organism-specific databases

CTD3705.
GeneCardsGC14M093403.
H-InvDBHIX0037938.
HGNCHGNC:6177. ITPK1.
HPAHPA055230.
MIM601838. gene.
neXtProtNX_Q13572.
PharmGKBPA29974.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG85132.
HOVERGENHBG079462.
KOK00913.
OMACSASPGC.
OrthoDBEOG70GMG7.
PhylomeDBQ13572.
TreeFamTF329288.

Enzyme and pathway databases

BioCycMetaCyc:HS02123-MONOMER.
BRENDA2.7.1.134. 2681.
ReactomeREACT_111217. Metabolism.
REACT_604. Hemostasis.
SABIO-RKQ13572.

Gene expression databases

ArrayExpressQ13572.
BgeeQ13572.
GenevestigatorQ13572.

Family and domain databases

InterProIPR011761. ATP-grasp.
IPR008656. Inositol_tetrakis-P_1-kinase.
[Graphical view]
PfamPF05770. Ins134_P3_kin. 1 hit.
[Graphical view]
PROSITEPS50975. ATP_GRASP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSITPK1. human.
EvolutionaryTraceQ13572.
GeneWikiITPK1.
GenomeRNAi3705.
NextBio14521.
PROQ13572.
SOURCESearch...

Entry information

Entry nameITPK1_HUMAN
AccessionPrimary (citable) accession number: Q13572
Secondary accession number(s): Q9BTL6, Q9H2E7
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: July 9, 2014
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM