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Protein

Inositol-tetrakisphosphate 1-kinase

Gene

ITPK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:11909533, PubMed:12925536, PubMed:17616525). Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:17616525).3 Publications

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

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

Keywordsi

Molecular functionHydrolase, Isomerase, Kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc: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-RKiQ13572

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

EuPathDBiHostDB:ENSG00000100605.16
HGNCiHGNC:6177 ITPK1
MIMi601838 gene
neXtProtiNX_Q13572

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
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
ProteomicsDBi59575
59576 [Q13572-2]

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 Expressed in 235 organ(s), highest expression level in medial globus pallidus
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, 15 interactors
DIPiDIP-60016N
IntActiQ13572, 5 interactors
MINTiQ13572
STRINGi9606.ENSP00000267615

Chemistry databases

BindingDBiQ13572

Structurei

Secondary structure

1414
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiENOG410IHA6 Eukaryota
ENOG4110KIK LUCA
GeneTreeiENSGT00390000001278
HOVERGENiHBG079462
InParanoidiQ13572
KOiK00913
OMAiMQDERIC
OrthoDBiEOG091G08J8
PhylomeDBiQ13572
TreeFamiTF329288

Family and domain databases

InterProiView protein in InterPro
IPR011761 ATP-grasp
IPR008656 Inositol_tetrakis-P_1-kinase
PANTHERiPTHR14217 PTHR14217, 1 hit
PfamiView protein in Pfam
PF05770 Ins134_P3_kin, 1 hit
PROSITEiView protein in PROSITE
PS50975 ATP_GRASP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V4M9G3V4M9_HUMAN
Inositol 1,3,4-triphosphate 5/6 kin...
ITPK1 hCG_20056
295Annotation score:
G3V588G3V588_HUMAN
Inositol-tetrakisphosphate 1-kinase
ITPK1
168Annotation score:
G3V5A3G3V5A3_HUMAN
Inositol-tetrakisphosphate 1-kinase
ITPK1
206Annotation score:
G3V3C0G3V3C0_HUMAN
Inositol-tetrakisphosphate 1-kinase
ITPK1
181Annotation score:

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

Similar proteinsi

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, 15 interactors
DIPiDIP-60016N
IntActiQ13572, 5 interactors
MINTiQ13572
STRINGi9606.ENSP00000267615

Chemistry databases

BindingDBiQ13572
ChEMBLiCHEMBL1938220

PTM databases

iPTMnetiQ13572
PhosphoSitePlusiQ13572

Polymorphism and mutation databases

BioMutaiITPK1
DMDMi83288249

Proteomic databases

EPDiQ13572
MaxQBiQ13572
PaxDbiQ13572
PeptideAtlasiQ13572
PRIDEiQ13572
ProteomicsDBi59575
59576 [Q13572-2]

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
EuPathDBiHostDB:ENSG00000100605.16
GeneCardsiITPK1
H-InvDBiHIX0037938
HGNCiHGNC:6177 ITPK1
HPAiHPA055230
MIMi601838 gene
neXtProtiNX_Q13572
OpenTargetsiENSG00000100605
PharmGKBiPA29974
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHA6 Eukaryota
ENOG4110KIK LUCA
GeneTreeiENSGT00390000001278
HOVERGENiHBG079462
InParanoidiQ13572
KOiK00913
OMAiMQDERIC
OrthoDBiEOG091G08J8
PhylomeDBiQ13572
TreeFamiTF329288

Enzyme and pathway databases

BioCyciMetaCyc: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-RKiQ13572

Miscellaneous databases

ChiTaRSiITPK1 human
EvolutionaryTraceiQ13572
GeneWikiiITPK1
GenomeRNAii3705
PROiPR:Q13572
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100605 Expressed in 235 organ(s), highest expression level in medial globus pallidus
ExpressionAtlasiQ13572 baseline and differential
GenevisibleiQ13572 HS

Family and domain databases

InterProiView protein in InterPro
IPR011761 ATP-grasp
IPR008656 Inositol_tetrakis-P_1-kinase
PANTHERiPTHR14217 PTHR14217, 1 hit
PfamiView protein in Pfam
PF05770 Ins134_P3_kin, 1 hit
PROSITEiView protein in PROSITE
PS50975 ATP_GRASP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiITPK1_HUMAN
AccessioniPrimary (citable) accession number: Q13572
Secondary accession number(s): Q9BTL6, Q9H2E7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: October 10, 2018
This is version 154 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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