UniProtKB - Q13572 (ITPK1_HUMAN)
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Protein
Inositol-tetrakisphosphate 1-kinase
Gene
ITPK1
Organism
Homo sapiens (Human)
Status
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
- KM=0.3 µM for Ins(1,3,4)P31 Publication
- KM=0.1 µM for Ins(3,4,5,6)P41 Publication
- Vmax=320 pmol/min/µg enzyme with Ins(1,3,4)P3 as substrate1 Publication
- Vmax=780 pmol/min/µg enzyme enzyme with Ins(3,4,5,6)P4 as substrate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 18 | 1D-myo-inositol 1,3,4-trisphosphateBy similarity | 1 | |
Binding sitei | 106 | ATP | 1 | |
Binding sitei | 157 | ATP | 1 | |
Binding sitei | 167 | 1D-myo-inositol 1,3,4-trisphosphateBy similarity | 1 | |
Binding sitei | 199 | 1D-myo-inositol 1,3,4-trisphosphateBy similarity | 1 | |
Binding sitei | 214 | ATP | 1 | |
Binding sitei | 232 | ATP | 1 | |
Binding sitei | 236 | ATP | 1 | |
Metal bindingi | 281 | Magnesium 1 | 1 | |
Metal bindingi | 295 | Magnesium 1 | 1 | |
Metal bindingi | 295 | Magnesium 2 | 1 | |
Metal bindingi | 297 | Magnesium 2 | 1 | |
Binding sitei | 297 | 1D-myo-inositol 1,3,4-trisphosphateBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 188 – 199 | ATPAdd BLAST | 12 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- catalytic activity Source: ProtInc
- inositol-1,3,4,5,6-pentakisphosphate 1-phosphatase activity Source: Reactome
- inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity Source: Reactome
- inositol-1,3,4,6-tetrakisphosphate 1-phosphatase activity Source: Reactome
- inositol-1,3,4,6-tetrakisphosphate 6-phosphatase activity Source: Reactome
- inositol-1,3,4-trisphosphate 5-kinase activity Source: Reactome
- inositol-1,3,4-trisphosphate 6-kinase activity Source: Reactome
- inositol-3,4,6-trisphosphate 1-kinase activity Source: Reactome
- inositol tetrakisphosphate 1-kinase activity Source: Reactome
- isomerase activity Source: UniProtKB-KW
- magnesium ion binding Source: InterPro
GO - Biological processi
- blood coagulation Source: Reactome
- inositol phosphate metabolic process Source: Reactome
- inositol trisphosphate metabolic process Source: InterPro
- neural tube development Source: Ensembl
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Hydrolase, Isomerase, Kinase, Transferase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS02123-MONOMER. |
BRENDAi | 2.7.1.134. 2681. 2.7.1.159. 2681. |
Reactomei | R-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-RKi | Q13572. |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:ITPK1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100605.16. |
HGNCi | HGNC:6177. ITPK1. |
MIMi | 601838. gene. |
neXtProti | NX_Q13572. |
Subcellular locationi
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 18 | K → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 58 | H → A: No effect. 1 Publication | 1 | |
Mutagenesisi | 59 | K → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 106 | R → A: Loss of kinase activity. 2 Publications | 1 | |
Mutagenesisi | 157 | K → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 162 | H → Q: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 163 | G → A or P: Loss of kinase activity. 2 Publications | 1 | |
Mutagenesisi | 163 | G → A: No effect. 2 Publications | 1 | |
Mutagenesisi | 167 | H → A or Q: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 188 | Q → A: No effect. 1 Publication | 1 | |
Mutagenesisi | 193 | H → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 199 | K → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 212 | R → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 214 | S → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 215 | L → A: No effect. 1 Publication | 1 | |
Mutagenesisi | 281 | D → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 295 | D → A: Loss of kinase activity. 1 Publication | 1 | |
Mutagenesisi | 297 | N → A or L: Loss of kinase activity. 2 Publications | 1 | |
Mutagenesisi | 297 | N → D: Induces a strong reduction in kinase activity. 2 Publications | 1 | |
Mutagenesisi | 301 | G → A: Loss of kinase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3705. |
OpenTargetsi | ENSG00000100605. |
PharmGKBi | PA29974. |
Chemistry databases
ChEMBLi | CHEMBL1938220. |
Polymorphism and mutation databases
BioMutai | ITPK1. |
DMDMi | 83288249. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220833 | 1 – 414 | Inositol-tetrakisphosphate 1-kinaseAdd BLAST | 414 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 340 | N6-acetyllysine; by EP300 and CREBBP1 Publication | 1 | |
Modified residuei | 383 | N6-acetyllysine; by EP300 and CREBBP1 Publication | 1 | |
Modified residuei | 396 | PhosphoserineCombined sources | 1 | |
Modified residuei | 410 | N6-acetyllysine; by EP300 and CREBBP1 Publication | 1 |
Post-translational modificationi
Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-regulates enzymatic activity. Deacetylated by SIRT1.1 Publication
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q13572. |
MaxQBi | Q13572. |
PaxDbi | Q13572. |
PeptideAtlasi | Q13572. |
PRIDEi | Q13572. |
PTM databases
iPTMneti | Q13572. |
PhosphoSitePlusi | Q13572. |
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
Bgeei | ENSG00000100605. |
ExpressionAtlasi | Q13572. baseline and differential. |
Genevisiblei | Q13572. HS. |
Organism-specific databases
HPAi | HPA055230. |
Interactioni
Subunit structurei
Monomer. Interacts with GPS1/COPS1.2 Publications
Protein-protein interaction databases
BioGridi | 109910. 14 interactors. |
DIPi | DIP-60016N. |
IntActi | Q13572. 5 interactors. |
MINTi | Q13572. |
STRINGi | 9606.ENSP00000267615. |
Chemistry databases
BindingDBi | Q13572. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 1 – 5 | Combined sources | 5 | |
Beta strandi | 9 – 13 | Combined sources | 5 | |
Helixi | 16 – 22 | Combined sources | 7 | |
Helixi | 24 – 32 | Combined sources | 9 | |
Turni | 33 – 35 | Combined sources | 3 | |
Beta strandi | 37 – 40 | Combined sources | 4 | |
Helixi | 48 – 50 | Combined sources | 3 | |
Beta strandi | 54 – 58 | Combined sources | 5 | |
Helixi | 61 – 68 | Combined sources | 8 | |
Helixi | 72 – 87 | Combined sources | 16 | |
Beta strandi | 91 – 95 | Combined sources | 5 | |
Helixi | 97 – 102 | Combined sources | 6 | |
Helixi | 106 – 120 | Combined sources | 15 | |
Beta strandi | 130 – 133 | Combined sources | 4 | |
Helixi | 138 – 140 | Combined sources | 3 | |
Helixi | 141 – 147 | Combined sources | 7 | |
Beta strandi | 152 – 157 | Combined sources | 6 | |
Turni | 164 – 167 | Combined sources | 4 | |
Beta strandi | 168 – 172 | Combined sources | 5 | |
Helixi | 175 – 177 | Combined sources | 3 | |
Beta strandi | 185 – 189 | Combined sources | 5 | |
Beta strandi | 196 – 203 | Combined sources | 8 | |
Beta strandi | 206 – 213 | Combined sources | 8 | |
Beta strandi | 228 – 231 | Combined sources | 4 | |
Helixi | 232 – 234 | Combined sources | 3 | |
Helixi | 243 – 245 | Combined sources | 3 | |
Helixi | 259 – 273 | Combined sources | 15 | |
Beta strandi | 277 – 284 | Combined sources | 8 | |
Turni | 286 – 288 | Combined sources | 3 | |
Beta strandi | 291 – 299 | Combined sources | 9 | |
Helixi | 308 – 324 | Combined sources | 17 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2ODT | X-ray | 2.01 | X | 1-327 | [»] | |
2Q7D | X-ray | 1.60 | A/B | 1-335 | [»] | |
2QB5 | X-ray | 1.80 | A/B | 1-335 | [»] | |
ProteinModelPortali | Q13572. | |||||
SMRi | Q13572. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13572. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 117 – 325 | ATP-graspPROSITE-ProRule annotationAdd BLAST | 209 |
Sequence similaritiesi
Belongs to the ITPK1 family.Curated
Phylogenomic databases
eggNOGi | ENOG410IHA6. Eukaryota. ENOG4110KIK. LUCA. |
GeneTreei | ENSGT00390000001278. |
HOVERGENi | HBG079462. |
InParanoidi | Q13572. |
KOi | K00913. |
OMAi | MQDERIC. |
OrthoDBi | EOG091G08J8. |
PhylomeDBi | Q13572. |
TreeFami | TF329288. |
Family and domain databases
InterProi | View protein in InterPro IPR011761. ATP-grasp. IPR008656. Inositol_tetrakis-P_1-kinase. |
PANTHERi | PTHR14217. PTHR14217. 1 hit. |
Pfami | View protein in Pfam PF05770. Ins134_P3_kin. 1 hit. |
PROSITEi | View protein in PROSITE PS50975. ATP_GRASP. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative 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.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 356 | S → N in AAC50483 (PubMed:8662638).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016478 | 302 – 314 | YEGVS…TDLLN → DCQVCFIEGWKTD in isoform 2. 1 PublicationAdd BLAST | 13 | |
Alternative sequenceiVSP_016479 | 315 – 414 | Missing in isoform 2. 1 PublicationAdd BLAST | 100 |
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. |
CCDSi | CCDS45157.1. [Q13572-2] CCDS9907.1. [Q13572-1] |
RefSeqi | NP_001136065.1. NM_001142593.2. [Q13572-1] NP_001136066.1. NM_001142594.2. [Q13572-2] NP_055031.2. NM_014216.5. [Q13572-1] |
UniGenei | Hs.308122. |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | ITPK1_HUMAN | |
Accessioni | Q13572Primary (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: | March 28, 2018 | |
This is version 150 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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