IPMK_MOUSE
ID IPMK_MOUSE Reviewed; 396 AA.
AC Q7TT16; Q8BZ11; Q8BZA8; Q9CWM9;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Inositol polyphosphate multikinase {ECO:0000303|PubMed:15939867};
DE EC=2.7.1.140 {ECO:0000250|UniProtKB:Q8NFU5};
DE EC=2.7.1.151 {ECO:0000269|PubMed:15939867};
DE EC=2.7.1.153 {ECO:0000250|UniProtKB:Q99NI4};
DE AltName: Full=Inositol 1,3,4,6-tetrakisphosphate 5-kinase;
GN Name=Ipmk; Synonyms=Impk, Ipk2 {ECO:0000303|PubMed:15939867};
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Embryonic stem cell, and Vagina;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=15939867; DOI=10.1073/pnas.0503706102;
RA Frederick J.P., Mattiske D., Wofford J.A., Megosh L.C., Drake L.Y.,
RA Chiou S.T., Hogan B.L., York J.D.;
RT "An essential role for an inositol polyphosphate multikinase, Ipk2, in
RT mouse embryogenesis and second messenger production.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8454-8459(2005).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Inositol phosphate kinase with a broad substrate specificity.
CC Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to
CC inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-
CC pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:15939867). Phosphorylates
CC inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4). Phosphorylates
CC glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-
CC phospho-1D-myo-inositol 3,4,5-trisphosphate (By similarity). Plays an
CC important role in MLKL-mediated necroptosis via its role in the
CC biosynthesis of inositol pentakisphosphate (InsP5) and inositol
CC hexakisphosphate (InsP6). Binding of these highly phosphorylated
CC inositol phosphates to MLKL mediates the release of an N-terminal auto-
CC inhibitory region, leading to activation of the kinase. Essential for
CC activated phospho-MLKL to oligomerize and localize to the cell membrane
CC during necroptosis (By similarity). Required for normal embryonic
CC development, probably via its role in the biosynthesis of inositol
CC 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol
CC hexakisphosphate (InsP6) (PubMed:15939867).
CC {ECO:0000250|UniProtKB:Q8NFU5, ECO:0000250|UniProtKB:Q99NI4,
CC ECO:0000269|PubMed:15939867}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,4,5-trisphosphate + 2 ATP = 1D-myo-inositol
CC 1,3,4,5,6-pentakisphosphate + 2 ADP + 2 H(+); Xref=Rhea:RHEA:32359,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57733,
CC ChEBI:CHEBI:203600, ChEBI:CHEBI:456216; EC=2.7.1.151;
CC Evidence={ECO:0000269|PubMed:15939867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1D-myo-inositol 1,3,4,6-tetrakisphosphate + ATP = 1D-myo-
CC inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+);
CC Xref=Rhea:RHEA:12717, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57660, ChEBI:CHEBI:57733, ChEBI:CHEBI:456216;
CC EC=2.7.1.140; Evidence={ECO:0000250|UniProtKB:Q8NFU5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137,
CC ChEBI:CHEBI:83243, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q8NFU5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153;
CC Evidence={ECO:0000250|UniProtKB:Q99NI4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000250|UniProtKB:Q99NI4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8NFU5};
CC Note=Binds two Mg(2+), but the interaction with the protein is mostly
CC indirect. {ECO:0000250|UniProtKB:Q8NFU5};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol metabolism.
CC {ECO:0000269|PubMed:15939867}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8NFU5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7TT16-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TT16-2; Sequence=VSP_010923, VSP_010924;
CC -!- SIMILARITY: Belongs to the inositol phosphokinase (IPK) family.
CC {ECO:0000305}.
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DR EMBL; AK010523; BAB27004.1; -; mRNA.
DR EMBL; AK036084; BAC29300.1; -; mRNA.
DR EMBL; AK036978; BAC29655.1; -; mRNA.
DR EMBL; BC052463; AAH52463.1; -; mRNA.
DR CCDS; CCDS23918.1; -. [Q7TT16-1]
DR RefSeq; NP_001334120.1; NM_001347191.1.
DR RefSeq; NP_081460.1; NM_027184.2. [Q7TT16-1]
DR AlphaFoldDB; Q7TT16; -.
DR SMR; Q7TT16; -.
DR STRING; 10090.ENSMUSP00000078240; -.
DR iPTMnet; Q7TT16; -.
DR PhosphoSitePlus; Q7TT16; -.
DR MaxQB; Q7TT16; -.
DR PaxDb; Q7TT16; -.
DR PRIDE; Q7TT16; -.
DR ProteomicsDB; 301657; -. [Q7TT16-1]
DR ProteomicsDB; 301658; -. [Q7TT16-2]
DR Antibodypedia; 28039; 195 antibodies from 27 providers.
DR DNASU; 69718; -.
DR Ensembl; ENSMUST00000079252; ENSMUSP00000078240; ENSMUSG00000060733. [Q7TT16-1]
DR Ensembl; ENSMUST00000118381; ENSMUSP00000113083; ENSMUSG00000060733. [Q7TT16-2]
DR Ensembl; ENSMUST00000147277; ENSMUSP00000120073; ENSMUSG00000060733. [Q7TT16-2]
DR GeneID; 69718; -.
DR KEGG; mmu:69718; -.
DR UCSC; uc007for.1; mouse. [Q7TT16-2]
DR UCSC; uc007fos.1; mouse. [Q7TT16-1]
DR CTD; 253430; -.
DR MGI; MGI:1916968; Ipmk.
DR VEuPathDB; HostDB:ENSMUSG00000060733; -.
DR eggNOG; KOG1620; Eukaryota.
DR GeneTree; ENSGT00940000155309; -.
DR HOGENOM; CLU_042569_0_0_1; -.
DR InParanoid; Q7TT16; -.
DR PhylomeDB; Q7TT16; -.
DR TreeFam; TF321442; -.
DR BRENDA; 2.7.1.151; 3474.
DR Reactome; R-MMU-1855191; Synthesis of IPs in the nucleus.
DR UniPathway; UPA00949; -.
DR BioGRID-ORCS; 69718; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Ipmk; mouse.
DR PRO; PR:Q7TT16; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q7TT16; protein.
DR Bgee; ENSMUSG00000060733; Expressed in animal zygote and 226 other tissues.
DR ExpressionAtlas; Q7TT16; baseline and differential.
DR Genevisible; Q7TT16; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0097243; F:flavonoid binding; ISO:MGI.
DR GO; GO:0000824; F:inositol tetrakisphosphate 3-kinase activity; IMP:MGI.
DR GO; GO:0047326; F:inositol tetrakisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0000825; F:inositol tetrakisphosphate 6-kinase activity; ISS:UniProtKB.
DR GO; GO:0051765; F:inositol tetrakisphosphate kinase activity; IBA:GO_Central.
DR GO; GO:0008440; F:inositol-1,4,5-trisphosphate 3-kinase activity; IMP:MGI.
DR GO; GO:0000823; F:inositol-1,4,5-trisphosphate 6-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0016301; F:kinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0102732; F:myo-inositol-1,2,3,4,6-heptakisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; IMP:MGI.
DR GO; GO:0032957; P:inositol trisphosphate metabolic process; ISO:MGI.
DR GO; GO:0070266; P:necroptotic process; ISS:UniProtKB.
DR GO; GO:0001841; P:neural tube formation; IMP:MGI.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.470.160; -; 1.
DR InterPro; IPR005522; IPK.
DR InterPro; IPR038286; IPK_sf.
DR PANTHER; PTHR12400; PTHR12400; 1.
DR Pfam; PF03770; IPK; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Kinase; Lipid metabolism;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phospholipid metabolism; Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT CHAIN 2..396
FT /note="Inositol polyphosphate multikinase"
FT /id="PRO_0000066871"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 300..310
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 65
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 114..116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 143..150
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT BINDING 365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFU5"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 194..216
FT /note="VSKFFHNGFCLRKDAIAASIQKV -> EPWSGAAAAVSKMALTRFSSPLE
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010923"
FT VAR_SEQ 217..396
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010924"
FT CONFLICT 56
FT /note="V -> D (in Ref. 1; BAC29655)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="N -> I (in Ref. 1; BAC29655)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="L -> I (in Ref. 1; BAC29655)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="D -> G (in Ref. 1; BAC29655)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 396 AA; 44453 MW; 5A91EED2E601E977 CRC64;
MAAEPPALRL RPPGSTGDSP PVPRLLGGCV PLSHQVAGHM YGKDKVGILQ HPDGTVLKQL
QPPPRGPREL EFYTMVYAAD CADAVLLELR KHLPKYYGVW SPPTAPNDVY LKLEDVTHKF
NKPCIMDVKI GRKSYDPFAS SEKIQQQVSK YPLMEEIGFL VLGMRVYHLH SDSYETQNQH
YGRGLTKETL KEGVSKFFHN GFCLRKDAIA ASIQKVEKIL QWFENQKQLN FYASSLLFVY
EGSSQPATTK ANDRTLAGRF LSKGPLTDAD GLECNNNFHL FGAPPNGMSV GKSLSKAYSR
HRKLYAKKHQ SQTSLKVETL EQDNGWRSMS QEHLNGNVLA QLEKVFYHLP AGRPEIPEAE
VRMIDFAHVF PSNTVDEGYV YGLKHLIAVL RSILDS
