UniProtKB - Q99NI4 (IPMK_RAT)
Protein
Inositol polyphosphate multikinase
Gene
Ipmk
Organism
Rattus norvegicus (Rat)
Status
Functioni
Inositol phosphate kinase with a broad substrate specificity. Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:11226235). Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (By similarity). Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate (PubMed:16123124). Plays an important role in MLKL-mediated necroptosis via its role in the biosynthesis of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Binding of these highly phosphorylated inositol phosphates to MLKL mediates the release of an N-terminal auto-inhibitory region, leading to activation of the kinase. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (By similarity). Required for normal embryonic development, probably via its role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6) (By similarity).By similarity2 Publications
Catalytic activityi
- 1D-myo-inositol 1,4,5-trisphosphate + 2 ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 2 ADP + 2 H+1 PublicationEC:2.7.1.1511 Publication
- 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H+By similarityEC:2.7.1.140By similarity
- a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H+1 PublicationEC:2.7.1.1531 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Mg2+1 PublicationNote: Binds two Mg2+, but the interaction with the protein is mostly indirect.By similarity
Kineticsi
- KM=6 µM for 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)1 Publication
- Vmax=0.7 µmol/min/mg enzyme for 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)1 Publication
: phosphatidylinositol metabolism Pathwayi
This protein is involved in the pathway phosphatidylinositol metabolism, which is part of Phospholipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway phosphatidylinositol metabolism and in Phospholipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 58 | ATPBy similarity | 1 | |
Binding sitei | 65 | SubstrateBy similarity | 1 | |
Binding sitei | 127 | ATPBy similarity | 1 | |
Binding sitei | 129 | SubstrateBy similarity | 1 | |
Binding sitei | 179 | SubstrateBy similarity | 1 | |
Binding sitei | 365 | ATPBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 114 – 116 | ATPBy similarity | 3 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- flavonoid binding Source: RGD
- inositol-1,4,5-trisphosphate 3-kinase activity Source: RGD
- inositol-1,4,5-trisphosphate 6-kinase activity Source: UniProtKB-EC
- inositol tetrakisphosphate 3-kinase activity Source: RGD
- inositol tetrakisphosphate 5-kinase activity Source: UniProtKB-EC
- inositol tetrakisphosphate 6-kinase activity Source: UniProtKB
- inositol tetrakisphosphate kinase activity Source: GO_Central
- kinase activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- myo-inositol-1,2,3,4,6-heptakisphosphate 5-kinase activity Source: UniProtKB-EC
- phosphatidylinositol-3,4-bisphosphate 5-kinase activity Source: UniProtKB-EC
- phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: UniProtKB
GO - Biological processi
- inositol phosphate biosynthetic process Source: RGD
- inositol trisphosphate metabolic process Source: RGD
- necroptotic process Source: UniProtKB
- neural tube formation Source: RGD
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Lipid metabolism, Phospholipid metabolism |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.1.151, 5301 |
Reactomei | R-RNO-1855191, Synthesis of IPs in the nucleus |
SABIO-RKi | Q99NI4 |
UniPathwayi | UPA00949 |
Chemistry databases
SwissLipidsi | SLP:000000959 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Ipmk Synonyms:Impk |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 620954, Ipmk |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nucleoplasm Source: Ensembl
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000066872 | 2 – 396 | Inositol polyphosphate multikinaseAdd BLAST | 395 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 19 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
PaxDbi | Q99NI4 |
PRIDEi | Q99NI4 |
PTM databases
iPTMneti | Q99NI4 |
PhosphoSitePlusi | Q99NI4 |
Expressioni
Tissue specificityi
Highly expressed in kidney, and at lower levels in hippocampus, brain cortex, cerebellum, heart and lung.1 Publication
Gene expression databases
Bgeei | ENSRNOG00000000609, Expressed in kidney and 22 other tissues |
Genevisiblei | Q99NI4, RN |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 143 – 150 | Substrate bindingBy similarity | 8 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 300 – 310 | Nuclear localization signalBy similarityAdd BLAST | 11 |
Sequence similaritiesi
Belongs to the inositol phosphokinase (IPK) family.Curated
Phylogenomic databases
eggNOGi | KOG1620, Eukaryota |
GeneTreei | ENSGT00940000155309 |
HOGENOMi | CLU_042569_0_0_1 |
InParanoidi | Q99NI4 |
OMAi | TGCQEVA |
OrthoDBi | 902814at2759 |
PhylomeDBi | Q99NI4 |
TreeFami | TF321442 |
Family and domain databases
Gene3Di | 1.10.510.50, 2 hits |
InterProi | View protein in InterPro IPR005522, IPK IPR038286, IPK_sf |
PANTHERi | PTHR12400, PTHR12400, 1 hit |
Pfami | View protein in Pfam PF03770, IPK, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q99NI4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAAEPPALRL RPPGSTGDSP PVPRLLGGCV PLSHQVAGHM YGKDKVGILQ
60 70 80 90 100
HPDGTVLKQL QPPPRGPREL EFYTMVYAAD CADAVLLELR KHLPKYYGVW
110 120 130 140 150
SPPSAPNDVY LKLEDVTHKF NKPCIMDVKI GRKSYDPFAS AEKIQQQVSK
160 170 180 190 200
YPLMEEIGFL VLGMRVYHLH SDSYETQNQH YGRGLTKETL KEGVSKFFHN
210 220 230 240 250
GFCLRKDAVA ASIQKVEKIL QWFENQKQLN FYASSLLFVY EGSSQPATTK
260 270 280 290 300
SNDRTLAGRF LSKGALSDAD VLECNNNFHL FSSPANGTSV GKSLSKAYSR
310 320 330 340 350
HRKLYAKKHQ SQTSLKVETL EQDNGWKSMS QEHLNGNVLS QLEKVFYHLP
360 370 380 390
AGRQEIAEAE VRMIDFAHVF PSNTVDEGYV YGLKHLIAVL RSILDS
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY014898 mRNA Translation: AAG42923.1 |
RefSeqi | NP_599244.1, NM_134417.1 |
Genome annotation databases
Ensembli | ENSRNOT00000000748; ENSRNOP00000000748; ENSRNOG00000000609 |
GeneIDi | 171458 |
KEGGi | rno:171458 |
UCSCi | RGD:620954, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY014898 mRNA Translation: AAG42923.1 |
RefSeqi | NP_599244.1, NM_134417.1 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000000748 |
Chemistry databases
SwissLipidsi | SLP:000000959 |
PTM databases
iPTMneti | Q99NI4 |
PhosphoSitePlusi | Q99NI4 |
Proteomic databases
PaxDbi | Q99NI4 |
PRIDEi | Q99NI4 |
Genome annotation databases
Ensembli | ENSRNOT00000000748; ENSRNOP00000000748; ENSRNOG00000000609 |
GeneIDi | 171458 |
KEGGi | rno:171458 |
UCSCi | RGD:620954, rat |
Organism-specific databases
CTDi | 253430 |
RGDi | 620954, Ipmk |
Phylogenomic databases
eggNOGi | KOG1620, Eukaryota |
GeneTreei | ENSGT00940000155309 |
HOGENOMi | CLU_042569_0_0_1 |
InParanoidi | Q99NI4 |
OMAi | TGCQEVA |
OrthoDBi | 902814at2759 |
PhylomeDBi | Q99NI4 |
TreeFami | TF321442 |
Enzyme and pathway databases
UniPathwayi | UPA00949 |
BRENDAi | 2.7.1.151, 5301 |
Reactomei | R-RNO-1855191, Synthesis of IPs in the nucleus |
SABIO-RKi | Q99NI4 |
Miscellaneous databases
PROi | PR:Q99NI4 |
Gene expression databases
Bgeei | ENSRNOG00000000609, Expressed in kidney and 22 other tissues |
Genevisiblei | Q99NI4, RN |
Family and domain databases
Gene3Di | 1.10.510.50, 2 hits |
InterProi | View protein in InterPro IPR005522, IPK IPR038286, IPK_sf |
PANTHERi | PTHR12400, PTHR12400, 1 hit |
Pfami | View protein in Pfam PF03770, IPK, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IPMK_RAT | |
Accessioni | Q99NI4Primary (citable) accession number: Q99NI4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | June 1, 2001 | |
Last modified: | February 10, 2021 | |
This is version 114 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families