IPMK_RAT
ID IPMK_RAT Reviewed; 396 AA.
AC Q99NI4;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Inositol polyphosphate multikinase {ECO:0000303|PubMed:11226235};
DE EC=2.7.1.140 {ECO:0000250|UniProtKB:Q8NFU5};
DE EC=2.7.1.151 {ECO:0000269|PubMed:11226235};
DE EC=2.7.1.153 {ECO:0000269|PubMed:16123124};
DE AltName: Full=Inositol 1,3,4,6-tetrakisphosphate 5-kinase;
GN Name=Ipmk; Synonyms=Impk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, PATHWAY, TISSUE
RP SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=11226235; DOI=10.1073/pnas.041614598;
RA Saiardi A., Nagata E., Luo H.R., Sawa A., Luo X., Snowman A.M.,
RA Snyder S.H.;
RT "Mammalian inositol polyphosphate multikinase synthesizes inositol 1,4,5-
RT trisphosphate and an inositol pyrophosphate.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2306-2311(2001).
RN [2]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, FUNCTION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=16123124; DOI=10.1073/pnas.0506184102;
RA Resnick A.C., Snowman A.M., Kang B.N., Hurt K.J., Snyder S.H., Saiardi A.;
RT "Inositol polyphosphate multikinase is a nuclear PI3-kinase with
RT transcriptional regulatory activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:12783-12788(2005).
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:11226235). Phosphorylates
CC inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (By similarity).
CC Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to
CC glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate
CC (PubMed:16123124). Plays an important role in MLKL-mediated necroptosis
CC via its role in the biosynthesis of inositol pentakisphosphate (InsP5)
CC and inositol hexakisphosphate (InsP6). Binding of these highly
CC phosphorylated inositol phosphates to MLKL mediates the release of an
CC N-terminal auto-inhibitory region, leading to activation of the kinase.
CC Essential for activated phospho-MLKL to oligomerize and localize to the
CC cell membrane during necroptosis (By similarity). Required for normal
CC embryonic development, probably via its role in the biosynthesis of
CC inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol
CC hexakisphosphate (InsP6) (By similarity).
CC {ECO:0000250|UniProtKB:Q7TT16, ECO:0000250|UniProtKB:Q8NFU5,
CC ECO:0000269|PubMed:11226235, ECO:0000269|PubMed:16123124}.
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:11226235};
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:0000269|PubMed:16123124};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000305|PubMed:16123124};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:11226235};
CC Note=Binds two Mg(2+), but the interaction with the protein is mostly
CC indirect. {ECO:0000250|UniProtKB:Q8NFU5};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6 uM for 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) {ECO:0000269|PubMed:16123124};
CC Vmax=0.7 umol/min/mg enzyme for 1,2-diacyl-sn-glycero-3-phospho-(1D-
CC myo-inositol-4,5-bisphosphate) {ECO:0000269|PubMed:16123124};
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol metabolism.
CC {ECO:0000269|PubMed:11226235}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16123124}.
CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, and at lower levels in
CC hippocampus, brain cortex, cerebellum, heart and lung.
CC {ECO:0000269|PubMed:11226235}.
CC -!- SIMILARITY: Belongs to the inositol phosphokinase (IPK) family.
CC {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; AY014898; AAG42923.1; -; mRNA.
DR RefSeq; NP_599244.1; NM_134417.1.
DR AlphaFoldDB; Q99NI4; -.
DR SMR; Q99NI4; -.
DR STRING; 10116.ENSRNOP00000000748; -.
DR SwissLipids; SLP:000000959; -.
DR iPTMnet; Q99NI4; -.
DR PhosphoSitePlus; Q99NI4; -.
DR PaxDb; Q99NI4; -.
DR PRIDE; Q99NI4; -.
DR GeneID; 171458; -.
DR KEGG; rno:171458; -.
DR UCSC; RGD:620954; rat.
DR CTD; 253430; -.
DR RGD; 620954; Ipmk.
DR VEuPathDB; HostDB:ENSRNOG00000000609; -.
DR eggNOG; KOG1620; Eukaryota.
DR HOGENOM; CLU_042569_0_0_1; -.
DR InParanoid; Q99NI4; -.
DR OMA; YGFCITG; -.
DR OrthoDB; 902814at2759; -.
DR PhylomeDB; Q99NI4; -.
DR TreeFam; TF321442; -.
DR BRENDA; 2.7.1.151; 5301.
DR Reactome; R-RNO-1855191; Synthesis of IPs in the nucleus.
DR SABIO-RK; Q99NI4; -.
DR UniPathway; UPA00949; -.
DR PRO; PR:Q99NI4; -.
DR Proteomes; UP000002494; Chromosome 20.
DR Bgee; ENSRNOG00000000609; Expressed in kidney and 20 other tissues.
DR Genevisible; Q99NI4; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0097243; F:flavonoid binding; ISO:RGD.
DR GO; GO:0000824; F:inositol tetrakisphosphate 3-kinase activity; ISO:RGD.
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; ISO:RGD.
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; IDA:UniProtKB.
DR GO; GO:0032958; P:inositol phosphate biosynthetic process; ISO:RGD.
DR GO; GO:0032957; P:inositol trisphosphate metabolic process; ISO:RGD.
DR GO; GO:0070266; P:necroptotic process; ISS:UniProtKB.
DR GO; GO:0001841; P:neural tube formation; ISO:RGD.
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; ATP-binding; Kinase; Lipid metabolism; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phospholipid metabolism;
KW 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_0000066872"
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:0000250|UniProtKB:Q7TT16"
SQ SEQUENCE 396 AA; 44410 MW; 781BF569245FFA02 CRC64;
MAAEPPALRL RPPGSTGDSP PVPRLLGGCV PLSHQVAGHM YGKDKVGILQ HPDGTVLKQL
QPPPRGPREL EFYTMVYAAD CADAVLLELR KHLPKYYGVW SPPSAPNDVY LKLEDVTHKF
NKPCIMDVKI GRKSYDPFAS AEKIQQQVSK YPLMEEIGFL VLGMRVYHLH SDSYETQNQH
YGRGLTKETL KEGVSKFFHN GFCLRKDAVA ASIQKVEKIL QWFENQKQLN FYASSLLFVY
EGSSQPATTK SNDRTLAGRF LSKGALSDAD VLECNNNFHL FSSPANGTSV GKSLSKAYSR
HRKLYAKKHQ SQTSLKVETL EQDNGWKSMS QEHLNGNVLS QLEKVFYHLP AGRQEIAEAE
VRMIDFAHVF PSNTVDEGYV YGLKHLIAVL RSILDS
