ITPK1_DANRE
ID ITPK1_DANRE Reviewed; 396 AA.
AC Q7ZU91; Q5RIJ9;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 121.
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; ORFNames=zgc:56075;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=SJD;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
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. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ITPK1 family. {ECO:0000305}.
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DR EMBL; BX248515; CAI20735.1; -; Genomic_DNA.
DR EMBL; BC050497; AAH50497.1; -; mRNA.
DR RefSeq; NP_998182.1; NM_213017.1.
DR RefSeq; XP_009298398.1; XM_009300123.2.
DR AlphaFoldDB; Q7ZU91; -.
DR SMR; Q7ZU91; -.
DR STRING; 7955.ENSDARP00000009878; -.
DR PaxDb; Q7ZU91; -.
DR Ensembl; ENSDART00000008590; ENSDARP00000009878; ENSDARG00000013056.
DR GeneID; 406290; -.
DR KEGG; dre:406290; -.
DR CTD; 406290; -.
DR ZFIN; ZDB-GENE-040426-1953; itpk1a.
DR eggNOG; ENOG502QQS1; Eukaryota.
DR GeneTree; ENSGT00390000001278; -.
DR HOGENOM; CLU_041857_1_1_1; -.
DR InParanoid; Q7ZU91; -.
DR OMA; QHLYNRQ; -.
DR OrthoDB; 1116241at2759; -.
DR PhylomeDB; Q7ZU91; -.
DR TreeFam; TF329288; -.
DR PRO; PR:Q7ZU91; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000013056; Expressed in intestine and 17 other tissues.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047325; F:inositol tetrakisphosphate 1-kinase activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0052725; F:inositol-1,3,4-trisphosphate 6-kinase activity; IBA:GO_Central.
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 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 ATP-binding; Isomerase; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..396
FT /note="Inositol-tetrakisphosphate 1-kinase"
FT /id="PRO_0000220836"
FT DOMAIN 117..325
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 CONFLICT 91
FT /note="T -> A (in Ref. 2; AAH50497)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="H -> R (in Ref. 2; AAH50497)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 396 AA; 44193 MW; 40745589F8D7D5DB CRC64;
MQTFVKGKRV GYWLSEKKIK KLNFQTFVDL CRKQGIEMIQ LDLSQPIESQ GPFDVIIHKL
TDHIVDADQN VTESLLLVQG VQDYIDAHPE TVILDPLPAI RTLLDRCKSY KLIHKLEHSM
EDDRICSPPF MVLKTECGFE TLEQLHKHGI TFPFICKPQV AHGTNSHEMA IIFSEEDLKD
IKPPCVLQSF INHNAVLYKV FVVGEAYSVV QRPSIRNFPS GPTDRRAISF NSHHVSKPES
SSHLTCRDNM VGQSWKPSNE VIQKISRKLH QALGISLFGI DIIINNQTGQ HAVIDINAFP
GYEGVPEFFD DLLSHISSVL QGQVCNGVAC GHLRVNGTAQ SQTVHCGMLG NDSSWLMDSE
GIKKGPHQGL SCCGGCMTPN FHQHTRSSLT AETSSQ
