ITPK1_MOUSE
ID ITPK1_MOUSE Reviewed; 419 AA.
AC Q8BYN3; Q8K0J6; Q8R0Z0;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Inositol-tetrakisphosphate 1-kinase;
DE EC=2.7.1.134 {ECO:0000250|UniProtKB:Q13572};
DE AltName: Full=Inositol 1,3,4-trisphosphate 5/6-kinase;
DE Short=Inositol-triphosphate 5/6-kinase;
DE Short=Ins(1,3,4)P(3) 5/6-kinase;
DE EC=2.7.1.159 {ECO:0000250|UniProtKB:Q13572};
GN Name=Itpk1 {ECO:0000312|MGI:MGI:2446159};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, Colon, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Kinase that can phosphorylate various inositol polyphosphate
CC such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4
CC at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to
CC have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of
CC plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5
CC is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form
CC Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6)
CC pathway. Also acts as an inositol polyphosphate phosphatase that
CC dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and
CC Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that
CC interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and
CC Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as
CC the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-
CC induced apoptosis by interfering with the activation of TNFRSF1A-
CC associated death domain. Plays an important role in MLKL-mediated
CC necroptosis. Produces highly phosphorylated inositol phosphates such as
CC inositolhexakisphosphate (InsP6) which bind to MLKL mediating the
CC release of an N-terminal auto-inhibitory region leading to its
CC activation. Essential for activated phospho-MLKL to oligomerize and
CC localize to the cell membrane during necroptosis.
CC {ECO:0000250|UniProtKB:Q13572}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3,4,5,6-tetrakisphosphate + ATP = 1D-myo-
CC inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+);
CC Xref=Rhea:RHEA:12452, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57539, ChEBI:CHEBI:57733, ChEBI:CHEBI:456216;
CC EC=2.7.1.134; Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12453;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12454;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol
CC 1,3,4,5-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:13253,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13254;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13255;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol
CC 1,3,4,6-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:20940,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57660,
CC ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20941;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20942;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 3,4,6-trisphosphate + ATP = 1D-myo-inositol
CC 1,3,4,6-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:70287,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57660,
CC ChEBI:CHEBI:189099, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70288;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70289;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 1D-myo-inositol
CC 1,3,4-trisphosphate = 1D-myo-inositol 1,3,4,6-tetrakisphosphate + 1D-
CC myo-inositol 3,4,5,6-tetrakisphosphate; Xref=Rhea:RHEA:70263,
CC ChEBI:CHEBI:57539, ChEBI:CHEBI:57660, ChEBI:CHEBI:57733,
CC ChEBI:CHEBI:58414; Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70264;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70265;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 1D-myo-inositol
CC 1,3,4-trisphosphate = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + 1D-
CC myo-inositol 3,4,5,6-tetrakisphosphate; Xref=Rhea:RHEA:70271,
CC ChEBI:CHEBI:57539, ChEBI:CHEBI:57733, ChEBI:CHEBI:57895,
CC ChEBI:CHEBI:58414; Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70272;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70273;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q13572};
CC Note=Binds 2 magnesium ions per subunit.
CC {ECO:0000250|UniProtKB:Q13572};
CC -!- SUBUNIT: Monomer. Interacts with GPS1/COPS1.
CC {ECO:0000250|UniProtKB:Q13572}.
CC -!- PTM: Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-
CC regulates enzymatic activity. Deacetylated by SIRT1.
CC {ECO:0000250|UniProtKB:Q13572}.
CC -!- SIMILARITY: Belongs to the ITPK1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK038913; BAC30166.1; -; mRNA.
DR EMBL; BC025917; AAH25917.1; -; mRNA.
DR EMBL; BC031182; AAH31182.1; -; mRNA.
DR EMBL; BC056464; AAH56464.1; -; mRNA.
DR CCDS; CCDS26121.1; -.
DR RefSeq; NP_766172.1; NM_172584.3.
DR AlphaFoldDB; Q8BYN3; -.
DR SMR; Q8BYN3; -.
DR STRING; 10090.ENSMUSP00000046027; -.
DR PhosphoSitePlus; Q8BYN3; -.
DR EPD; Q8BYN3; -.
DR MaxQB; Q8BYN3; -.
DR PaxDb; Q8BYN3; -.
DR PeptideAtlas; Q8BYN3; -.
DR PRIDE; Q8BYN3; -.
DR ProteomicsDB; 269111; -.
DR Antibodypedia; 26868; 305 antibodies from 31 providers.
DR DNASU; 217837; -.
DR Ensembl; ENSMUST00000046518; ENSMUSP00000046027; ENSMUSG00000057963.
DR GeneID; 217837; -.
DR KEGG; mmu:217837; -.
DR UCSC; uc007ouj.1; mouse.
DR CTD; 3705; -.
DR MGI; MGI:2446159; Itpk1.
DR VEuPathDB; HostDB:ENSMUSG00000057963; -.
DR eggNOG; ENOG502QQS1; Eukaryota.
DR GeneTree; ENSGT00390000001278; -.
DR HOGENOM; CLU_041857_1_1_1; -.
DR InParanoid; Q8BYN3; -.
DR OMA; CKPLIAY; -.
DR OrthoDB; 1116241at2759; -.
DR PhylomeDB; Q8BYN3; -.
DR TreeFam; TF329288; -.
DR Reactome; R-MMU-1855167; Synthesis of pyrophosphates in the cytosol.
DR Reactome; R-MMU-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR Reactome; R-MMU-983231; Factors involved in megakaryocyte development and platelet production.
DR BioGRID-ORCS; 217837; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Itpk1; mouse.
DR PRO; PR:Q8BYN3; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BYN3; protein.
DR Bgee; ENSMUSG00000057963; Expressed in gastrula and 270 other tissues.
DR ExpressionAtlas; Q8BYN3; baseline and differential.
DR Genevisible; Q8BYN3; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0047325; F:inositol tetrakisphosphate 1-kinase activity; ISO:MGI.
DR GO; GO:0000825; F:inositol tetrakisphosphate 6-kinase activity; ISS:UniProtKB.
DR GO; GO:0052726; F:inositol-1,3,4-trisphosphate 5-kinase activity; ISO:MGI.
DR GO; GO:0052725; F:inositol-1,3,4-trisphosphate 6-kinase activity; ISO:MGI.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0052746; P:inositol phosphorylation; IBA:GO_Central.
DR GO; GO:0032957; P:inositol trisphosphate metabolic process; IEA:InterPro.
DR GO; GO:0070266; P:necroptotic process; ISS:UniProtKB.
DR GO; GO:0021915; P:neural tube development; IMP:MGI.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR008656; Inositol_tetrakis-P_1-kinase.
DR InterPro; IPR040464; InsP(3)kin_ATP-grasp.
DR InterPro; IPR041429; ITPK1_N.
DR PANTHER; PTHR14217; PTHR14217; 1.
DR Pfam; PF05770; Ins134_P3_kin; 1.
DR Pfam; PF17927; Ins134_P3_kin_N; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Hydrolase; Isomerase; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..419
FT /note="Inositol-tetrakisphosphate 1-kinase"
FT /id="PRO_0000220834"
FT DOMAIN 117..334
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 18
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 188..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 199
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 214
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 281
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="1D-myo-inositol 1,3,4-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:58414"
FT /evidence="ECO:0000250"
FT BINDING 297
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 388
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q13572"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13572"
FT MOD_RES 415
FT /note="N6-acetyllysine; by EP300 and CREBBP"
FT /evidence="ECO:0000250|UniProtKB:Q13572"
SQ SEQUENCE 419 AA; 46145 MW; 99C315EB5E513CE8 CRC64;
MQTFLKGKRV GYWLSEKKVK KLNFQAFAEL CRKRGIEVVQ LNLSRPIEEQ GPLDVIIHKL
TDVILEADQN DSQSLELVHR FQEYIDAHPE TIVLDPLPAI RTLLDRSKSY ELIRKIEAYM
KDDRICSPPF MELTSLCGED TMRLLEQNGL AFPFICKTRV AHGTNSHEMA IVFNQEGLNA
IQPPCVVQNF INHNAVLYKV FVVGESYTVV QRPSLKNFSA GTSDRESIFF NSHNVSKPES
SSVLTELDKI EGVFERPSDE VIRELSRALR QALGVSLFGI DIIINNQTGQ HAVIDVNAFP
GYEGVSEFFT DLLNHIATVL QGQSTGGAAT EEVAPLRHNR LLAEPAGSLA GERTCSASPG
CCGSMKGQDT PWKTETEAGN MGAGASAKLP HQRLGCTTGV SPSFQQHCVA SLATKASSQ
