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Protein

Inositol-tetrakisphosphate 1-kinase

Gene

ITPK1

Organism
Homo sapiens (Human)
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 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.3 Publications

Catalytic activityi

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

Cofactori

Mg2+1 PublicationNote: Binds 2 magnesium ions per subunit.1 Publication

Kineticsi

  1. KM=0.3 µM for Ins(1,3,4)P31 Publication
  2. KM=0.1 µM for Ins(3,4,5,6)P41 Publication
  1. Vmax=320 pmol/min/µg enzyme with Ins(1,3,4)P3 as substrate1 Publication
  2. Vmax=780 pmol/min/µg enzyme enzyme with Ins(3,4,5,6)P4 as substrate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei181D-myo-inositol 1,3,4-trisphosphateBy similarity1
Binding sitei106ATP1
Binding sitei157ATP1
Binding sitei1671D-myo-inositol 1,3,4-trisphosphateBy similarity1
Binding sitei1991D-myo-inositol 1,3,4-trisphosphateBy similarity1
Binding sitei214ATP1
Binding sitei232ATP1
Binding sitei236ATP1
Metal bindingi281Magnesium 11
Metal bindingi295Magnesium 11
Metal bindingi295Magnesium 21
Metal bindingi297Magnesium 21
Binding sitei2971D-myo-inositol 1,3,4-trisphosphateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi188 – 199ATPAdd BLAST12

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

BioCyciMetaCyc:HS02123-MONOMER.
ZFISH:HS02123-MONOMER.
BRENDAi2.7.1.134. 2681.
2.7.1.159. 2681.
ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.
R-HSA-1855204. Synthesis of IP3 and IP4 in the cytosol.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKQ13572.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:6177. ITPK1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi58H → A: No effect. 1 Publication1
Mutagenesisi59K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi106R → A: Loss of kinase activity. 2 Publications1
Mutagenesisi157K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi162H → Q: Loss of kinase activity. 1 Publication1
Mutagenesisi163G → A or P: Loss of kinase activity. 2 Publications1
Mutagenesisi163G → A: No effect. 2 Publications1
Mutagenesisi167H → A or Q: Loss of kinase activity. 1 Publication1
Mutagenesisi188Q → A: No effect. 1 Publication1
Mutagenesisi193H → A: Loss of kinase activity. 1 Publication1
Mutagenesisi199K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi212R → A: Loss of kinase activity. 1 Publication1
Mutagenesisi214S → A: Loss of kinase activity. 1 Publication1
Mutagenesisi215L → A: No effect. 1 Publication1
Mutagenesisi281D → A: Loss of kinase activity. 1 Publication1
Mutagenesisi295D → A: Loss of kinase activity. 1 Publication1
Mutagenesisi297N → A or L: Loss of kinase activity. 2 Publications1
Mutagenesisi297N → D: Induces a strong reduction in kinase activity. 2 Publications1
Mutagenesisi301G → A: Loss of kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi3705.
OpenTargetsiENSG00000100605.
ENSG00000274958.
PharmGKBiPA29974.

Chemistry databases

ChEMBLiCHEMBL1938220.

Polymorphism and mutation databases

BioMutaiITPK1.
DMDMi83288249.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002208331 – 414Inositol-tetrakisphosphate 1-kinaseAdd BLAST414

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei340N6-acetyllysine; by EP300 and CREBBP1 Publication1
Modified residuei383N6-acetyllysine; by EP300 and CREBBP1 Publication1
Modified residuei396PhosphoserineCombined sources1
Modified residuei410N6-acetyllysine; by EP300 and CREBBP1 Publication1

Post-translational modificationi

Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-regulates enzymatic activity. Deacetylated by SIRT1.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13572.
MaxQBiQ13572.
PaxDbiQ13572.
PeptideAtlasiQ13572.
PRIDEiQ13572.

PTM databases

iPTMnetiQ13572.
PhosphoSitePlusiQ13572.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSG00000100605.
ExpressionAtlasiQ13572. baseline and differential.
GenevisibleiQ13572. HS.

Organism-specific databases

HPAiHPA055230.

Interactioni

Subunit structurei

Monomer. Interacts with GPS1/COPS1.2 Publications

Protein-protein interaction databases

BioGridi109910. 13 interactors.
DIPiDIP-60016N.
IntActiQ13572. 2 interactors.
MINTiMINT-1463374.
STRINGi9606.ENSP00000267615.

Chemistry databases

BindingDBiQ13572.

Structurei

Secondary structure

1414
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1 – 5Combined sources5
Beta strandi9 – 13Combined sources5
Helixi16 – 22Combined sources7
Helixi24 – 32Combined sources9
Turni33 – 35Combined sources3
Beta strandi37 – 40Combined sources4
Helixi48 – 50Combined sources3
Beta strandi54 – 58Combined sources5
Helixi61 – 68Combined sources8
Helixi72 – 87Combined sources16
Beta strandi91 – 95Combined sources5
Helixi97 – 102Combined sources6
Helixi106 – 120Combined sources15
Beta strandi130 – 133Combined sources4
Helixi138 – 140Combined sources3
Helixi141 – 147Combined sources7
Beta strandi152 – 157Combined sources6
Turni164 – 167Combined sources4
Beta strandi168 – 172Combined sources5
Helixi175 – 177Combined sources3
Beta strandi185 – 189Combined sources5
Beta strandi196 – 203Combined sources8
Beta strandi206 – 213Combined sources8
Beta strandi228 – 231Combined sources4
Helixi232 – 234Combined sources3
Helixi243 – 245Combined sources3
Helixi259 – 273Combined sources15
Beta strandi277 – 284Combined sources8
Turni286 – 288Combined sources3
Beta strandi291 – 299Combined sources9
Helixi308 – 324Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ODTX-ray2.01X1-327[»]
2Q7DX-ray1.60A/B1-335[»]
2QB5X-ray1.80A/B1-335[»]
ProteinModelPortaliQ13572.
SMRiQ13572.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13572.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini117 – 325ATP-graspPROSITE-ProRule annotationAdd BLAST209

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IHA6. Eukaryota.
ENOG4110KIK. LUCA.
GeneTreeiENSGT00390000001278.
HOVERGENiHBG079462.
InParanoidiQ13572.
KOiK00913.
OMAiLFVAIDH.
OrthoDBiEOG091G08J8.
PhylomeDBiQ13572.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13572-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MQTFLKGKRV GYWLSEKKIK KLNFQAFAEL CRKRGMEVVQ LNLSRPIEEQ
60 70 80 90 100
GPLDVIIHKL TDVILEADQN DSQSLELVHR FQEYIDAHPE TIVLDPLPAI
110 120 130 140 150
RTLLDRSKSY ELIRKIEAYM EDDRICSPPF MELTSLCGDD TMRLLEKNGL
160 170 180 190 200
TFPFICKTRV AHGTNSHEMA IVFNQEGLNA IQPPCVVQNF INHNAVLYKV
210 220 230 240 250
FVVGESYTVV QRPSLKNFSA GTSDRESIFF NSHNVSKPES SSVLTELDKI
260 270 280 290 300
EGVFERPSDE VIRELSRALR QALGVSLFGI DIIINNQTGQ HAVIDINAFP
310 320 330 340 350
GYEGVSEFFT DLLNHIATVL QGQSTAMAAT GDVALLRHSK LLAEPAGGLV
360 370 380 390 400
GERTCSASPG CCGSMMGQDA PWKAEADAGG TAKLPHQRLG CNAGVSPSFQ
410
QHCVASLATK ASSQ
Length:414
Mass (Da):45,621
Last modified:December 6, 2005 - v2
Checksum:iE89E2EE11971278E
GO
Isoform 2 (identifier: Q13572-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     302-314: YEGVSEFFTDLLN → DCQVCFIEGWKTD
     315-414: Missing.

Note: No experimental confirmation available.
Show »
Length:314
Mass (Da):35,632
Checksum:iDD10427FADBBB3E0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti356S → N in AAC50483 (PubMed:8662638).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016478302 – 314YEGVS…TDLLN → DCQVCFIEGWKTD in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_016479315 – 414Missing in isoform 2. 1 PublicationAdd BLAST100

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS45157.1. [Q13572-2]
CCDS9907.1. [Q13572-1]
RefSeqiNP_001136065.1. NM_001142593.2. [Q13572-1]
NP_001136066.1. NM_001142594.2. [Q13572-2]
NP_055031.2. NM_014216.5. [Q13572-1]
UniGeneiHs.308122.

Genome annotation databases

EnsembliENST00000267615; ENSP00000267615; ENSG00000100605. [Q13572-1]
ENST00000354313; ENSP00000346272; ENSG00000100605. [Q13572-2]
ENST00000556603; ENSP00000451091; ENSG00000100605. [Q13572-1]
ENST00000614271; ENSP00000483767; ENSG00000274958. [Q13572-1]
ENST00000617836; ENSP00000480918; ENSG00000274958. [Q13572-2]
ENST00000626153; ENSP00000486991; ENSG00000274958. [Q13572-1]
GeneIDi3705.
KEGGihsa:3705.
UCSCiuc001ybe.2. human. [Q13572-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS45157.1. [Q13572-2]
CCDS9907.1. [Q13572-1]
RefSeqiNP_001136065.1. NM_001142593.2. [Q13572-1]
NP_001136066.1. NM_001142594.2. [Q13572-2]
NP_055031.2. NM_014216.5. [Q13572-1]
UniGeneiHs.308122.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ODTX-ray2.01X1-327[»]
2Q7DX-ray1.60A/B1-335[»]
2QB5X-ray1.80A/B1-335[»]
ProteinModelPortaliQ13572.
SMRiQ13572.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109910. 13 interactors.
DIPiDIP-60016N.
IntActiQ13572. 2 interactors.
MINTiMINT-1463374.
STRINGi9606.ENSP00000267615.

Chemistry databases

BindingDBiQ13572.
ChEMBLiCHEMBL1938220.

PTM databases

iPTMnetiQ13572.
PhosphoSitePlusiQ13572.

Polymorphism and mutation databases

BioMutaiITPK1.
DMDMi83288249.

Proteomic databases

EPDiQ13572.
MaxQBiQ13572.
PaxDbiQ13572.
PeptideAtlasiQ13572.
PRIDEiQ13572.

Protocols and materials databases

DNASUi3705.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267615; ENSP00000267615; ENSG00000100605. [Q13572-1]
ENST00000354313; ENSP00000346272; ENSG00000100605. [Q13572-2]
ENST00000556603; ENSP00000451091; ENSG00000100605. [Q13572-1]
ENST00000614271; ENSP00000483767; ENSG00000274958. [Q13572-1]
ENST00000617836; ENSP00000480918; ENSG00000274958. [Q13572-2]
ENST00000626153; ENSP00000486991; ENSG00000274958. [Q13572-1]
GeneIDi3705.
KEGGihsa:3705.
UCSCiuc001ybe.2. human. [Q13572-1]

Organism-specific databases

CTDi3705.
DisGeNETi3705.
GeneCardsiITPK1.
H-InvDBHIX0037938.
HGNCiHGNC:6177. ITPK1.
HPAiHPA055230.
MIMi601838. gene.
neXtProtiNX_Q13572.
OpenTargetsiENSG00000100605.
ENSG00000274958.
PharmGKBiPA29974.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHA6. Eukaryota.
ENOG4110KIK. LUCA.
GeneTreeiENSGT00390000001278.
HOVERGENiHBG079462.
InParanoidiQ13572.
KOiK00913.
OMAiLFVAIDH.
OrthoDBiEOG091G08J8.
PhylomeDBiQ13572.
TreeFamiTF329288.

Enzyme and pathway databases

BioCyciMetaCyc:HS02123-MONOMER.
ZFISH:HS02123-MONOMER.
BRENDAi2.7.1.134. 2681.
2.7.1.159. 2681.
ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.
R-HSA-1855204. Synthesis of IP3 and IP4 in the cytosol.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKQ13572.

Miscellaneous databases

ChiTaRSiITPK1. human.
EvolutionaryTraceiQ13572.
GeneWikiiITPK1.
GenomeRNAii3705.
PROiQ13572.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100605.
ExpressionAtlasiQ13572. baseline and differential.
GenevisibleiQ13572. HS.

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...

Entry informationi

Entry nameiITPK1_HUMAN
AccessioniPrimary (citable) accession number: Q13572
Secondary accession number(s): Q9BTL6, Q9H2E7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: November 2, 2016
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

PubMed:11533064 detected some protein kinase activity and ability to phosphorylate transcription factors c-jun/JUN and ATF2. However, PubMed:15762844 showed that it does not have protein kinase activity.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.