Search Results

Overview

Uniprot IDQ13572
Protein NameInositol-tetrakisphosphate 1-kinase
Gene NameITPK1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
340 VALLRHSKLLAEPAG

Function

Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3 (PubMed:11042108, PubMed:8662638). Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5 (PubMed:11042108). This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-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 (PubMed:11042108, PubMed:8662638). Also acts as an inositol polyphosphate phosphatase that dephosphorylates 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 (PubMed:11909533, PubMed:17616525). 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 (PubMed:11909533). Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-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)

Protein Sequence

10 MQTFLKGKRV 20 GYWLSEKKIK 30 KLNFQAFAEL 40 CRKRGMEVVQ 50 LNLSRPIEEQ 60 GPLDVIIHKL 70 TDVILEADQN 80 DSQSLELVHR 90 FQEYIDAHPE 100 TIVLDPLPAI 110 RTLLDRSKSY 120 ELIRKIEAYM 130 EDDRICSPPF 140 MELTSLCGDD 150 TMRLLEKNGL 160 TFPFICKTRV 170 AHGTNSHEMA 180 IVFNQEGLNA 190 IQPPCVVQNF 200 INHNAVLYKV 210 FVVGESYTVV 220 QRPSLKNFSA 230 GTSDRESIFF 240 NSHNVSKPES 250 SSVLTELDKI 260 EGVFERPSDE 270 VIRELSRALR 280 QALGVSLFGI 290 DIIINNQTGQ 300 HAVIDINAFP 310 GYEGVSEFFT 320 DLLNHIATVL 330 QGQSTAMAAT 340 GDVALLRHSK 350 LLAEPAGGLV 360 GERTCSASPG 370 CCGSMMGQDA 380 PWKAEADAGG 390 TAKLPHQRLG 400 CNAGVSPSFQ 410 QHCVASLATK ASSQ

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016324 apical plasma membrane
Cellular Component GO:0005829 cytosol
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0003824 catalytic activity
Molecular Function GO:0016787 hydrolase activity
Molecular Function GO:0000825 inositol-1,3,4,5-tetrakisphosphate 6-kinase activity
Molecular Function GO:0052726 inositol-1,3,4-trisphosphate 5-kinase activity
Molecular Function GO:0052725 inositol-1,3,4-trisphosphate 6-kinase activity
Molecular Function GO:0047325 inositol-3,4,5,6-tetrakisphosphate 1-kinase activity
Molecular Function GO:0052835 inositol-3,4,6-trisphosphate 1-kinase activity
Molecular Function GO:0016853 isomerase activity
Molecular Function GO:0000287 magnesium ion binding
Biological Process GO:0007596 blood coagulation
Biological Process GO:0032957 inositol trisphosphate metabolic process
Biological Process GO:0070266 necroptotic process
Biological Process GO:0007165 signal transduction

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.