UniProtKB - Q8NFU5 (IPMK_HUMAN)
Inositol polyphosphate multikinase
IPMK
Functioni
Inositol phosphate kinase with a broad substrate specificity (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30420721, PubMed:30624931).
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:12027805, PubMed:12223481, PubMed:28882892, PubMed:30624931).
Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (PubMed:12223481).
Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate (PubMed:30420721, PubMed:28882892).
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 (PubMed:29883610).
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 similarity6 PublicationsCatalytic activityi
- 1D-myo-inositol 1,4,5-trisphosphate + 2 ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 2 ADP + 2 H+4 PublicationsEC:2.7.1.1514 Publications
- 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H+1 PublicationEC:2.7.1.1401 Publication
- 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+By similarityEC:2.7.1.153By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Activity regulationi
Kineticsi
- KM=112 nM for myo-inositol-1,4,5-trisphosphate1 Publication
- KM=295 nM for myo-inositol-1,3,4,6-tetrakisphosphate1 Publication
- KM=129 nM for myo-inositol-1,3,4,5-tetrakisphosphate1 Publication
- KM=61 µM for ATP1 Publication
- KM=39 µM for phosphatidylinositol 4,5-bisphosphate1 Publication
- Vmax=27 nmol/min/mg enzyme with myo-inositol-1,4,5-trisphosphate as substrate1 Publication
- Vmax=114 nmol/min/mg enzyme with myo-inositol-1,3,4,6-tetrakisphosphate as substrate1 Publication
- Vmax=1.1 nmol/min/mg enzyme with myo-inositol-1,3,4,5-tetrakisphosphate as substrate1 Publication
: phosphatidylinositol metabolism Pathwayi
This protein is involved in the pathway phosphatidylinositol metabolism, which is part of Phospholipid metabolism.4 PublicationsView 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 | 75 | ATPCombined sources1 Publication | 1 | |
Binding sitei | 82 | SubstrateCombined sources1 Publication | 1 | |
Binding sitei | 144 | ATPCombined sources1 Publication | 1 | |
Binding sitei | 146 | SubstrateCombined sources1 Publication | 1 | |
Binding sitei | 196 | SubstrateCombined sources1 Publication | 1 | |
Binding sitei | 385 | ATPCombined sources1 Publication | 1 | |
Binding sitei | 388 | SubstrateCombined sources1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 131 – 133 | ATPCombined sources1 Publication | 3 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- flavonoid binding Source: UniProtKB
- inositol-1,4,5-trisphosphate 3-kinase activity Source: UniProtKB
- inositol-1,4,5-trisphosphate 6-kinase activity Source: UniProtKB-EC
- inositol tetrakisphosphate 3-kinase activity Source: Reactome
- inositol tetrakisphosphate 5-kinase activity Source: Reactome
- 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: GO_Central
- inositol phosphate metabolic process Source: Reactome
- inositol trisphosphate metabolic process Source: UniProtKB
- necroptotic process Source: UniProtKB
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, 2681 |
PathwayCommonsi | Q8NFU5 |
Reactomei | R-HSA-1855191, Synthesis of IPs in the nucleus |
SABIO-RKi | Q8NFU5 |
SignaLinki | Q8NFU5 |
UniPathwayi | UPA00949 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:IPMK Synonyms:IMPK1 Publication |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20739, IPMK |
MIMi | 609851, gene |
neXtProti | NX_Q8NFU5 |
VEuPathDBi | HostDB:ENSG00000151151 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 – 69 | Missing : No effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated with 279-S--V-365 DEL and 366-G--S-373. 1 PublicationAdd BLAST | 68 | |
Mutagenesisi | 78 | Q → A: Strongly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 82 | R → A: Strongly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 144 | D → N: Loss of kinase activity and ability to execute necroptosis; when associated with A-146. 1 Publication | 1 | |
Mutagenesisi | 146 | K → A: Loss of kinase activity and ability to execute necroptosis; when associated with N-144. 1 Publication | 1 | |
Mutagenesisi | 160 | K → A: Strongly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 163 | Q → A: Moderately decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 163 | Q → R: Decreased activity with inositol 1,4,5-trisphosphate. No effect on phosphorylation of inositol 1,3,4,5-tetrakisphosphate. 1 Publication | 1 | |
Mutagenesisi | 164 | Q → A: Strongly decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 164 | Q → R: Decreased activity with inositol 1,4,5-trisphosphate. Increased phosphorylation of inositol 1,3,4,5-tetrakisphosphate. 1 Publication | 1 | |
Mutagenesisi | 167 | K → A: Decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 196 | Q → A: Decreased enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 196 | Q → R: Decreased activity with inositol 1,4,5-trisphosphate. Increased phosphorylation of inositol 1,3,4,5-tetrakisphosphate. 1 Publication | 1 | |
Mutagenesisi | 279 – 365 | Missing : No effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated with 2-A--P-69 DEL and 366-G--S-373 DEL. 1 PublicationAdd BLAST | 87 | |
Mutagenesisi | 322 – 323 | RK → QQ: Interferes with nuclear localization. 1 Publication | 2 | |
Mutagenesisi | 327 – 328 | KK → QQ: Interferes with nuclear localization. 1 Publication | 2 | |
Mutagenesisi | 366 – 373 | FYHLPTGC → GGGGSGGGGS: No effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated with 2-A--P-69 DEL and 279-S--V-365 DEL. 1 Publication | 8 | |
Mutagenesisi | 388 | H → A: Loss of enzyme activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 253430 |
MalaCardsi | IPMK |
OpenTargetsi | ENSG00000151151 |
Orphaneti | 456333, Hereditary neuroendocrine tumor of small intestine |
PharmGKBi | PA134903369 |
Miscellaneous databases
Pharosi | Q8NFU5, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4523401 |
Genetic variation databases
BioMutai | IPMK |
DMDMi | 50401072 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000066870 | 2 – 416 | Inositol polyphosphate multikinaseAdd BLAST | 415 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 7 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q8NFU5 |
jPOSTi | Q8NFU5 |
MassIVEi | Q8NFU5 |
MaxQBi | Q8NFU5 |
PaxDbi | Q8NFU5 |
PeptideAtlasi | Q8NFU5 |
PRIDEi | Q8NFU5 |
ProteomicsDBi | 73362 |
PTM databases
iPTMneti | Q8NFU5 |
PhosphoSitePlusi | Q8NFU5 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000151151, Expressed in epithelium of mammary gland and 212 other tissues |
Genevisiblei | Q8NFU5, HS |
Organism-specific databases
HPAi | ENSG00000151151, Low tissue specificity |
Interactioni
Binary interactionsi
Q8NFU5
With | #Exp. | IntAct |
---|---|---|
HSF2BP [O75031] | 3 | EBI-11347579,EBI-7116203 |
Protein-protein interaction databases
BioGRIDi | 128968, 7 interactors |
IntActi | Q8NFU5, 4 interactors |
STRINGi | 9606.ENSP00000363046 |
Chemistry databases
BindingDBi | Q8NFU5 |
Miscellaneous databases
RNActi | Q8NFU5, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q8NFU5 |
SMRi | Q8NFU5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 38 | DisorderedSequence analysisAdd BLAST | 38 | |
Regioni | 160 – 167 | Substrate bindingCombined sources1 Publication | 8 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 320 – 330 | Nuclear localization signal1 PublicationAdd BLAST | 11 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1620, Eukaryota |
GeneTreei | ENSGT00940000155309 |
HOGENOMi | CLU_042569_0_0_1 |
InParanoidi | Q8NFU5 |
OMAi | YGFCITG |
OrthoDBi | 902814at2759 |
PhylomeDBi | Q8NFU5 |
TreeFami | TF321442 |
Family and domain databases
Gene3Di | 3.30.470.160, 1 hit |
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
10 20 30 40 50
MATEPPSPLR VEAPGPPEMR TSPAIESTPE GTPQPAGGRL RFLNGCVPLS
60 70 80 90 100
HQVAGHMYGK DKVGILQHPD GTVLKQLQPP PRGPRELEFY NMVYAADCFD
110 120 130 140 150
GVLLELRKYL PKYYGIWSPP TAPNDLYLKL EDVTHKFNKP CIMDVKIGQK
160 170 180 190 200
SYDPFASSEK IQQQVSKYPL MEEIGFLVLG MRVYHVHSDS YETENQHYGR
210 220 230 240 250
SLTKETIKDG VSRFFHNGYC LRKDAVAASI QKIEKILQWF ENQKQLNFYA
260 270 280 290 300
SSLLFVYEGS SQPTTTKLND RTLAEKFLSK GQLSDTEVLE YNNNFHVLSS
310 320 330 340 350
TANGKIESSV GKSLSKMYAR HRKIYTKKHH SQTSLKVENL EQDNGWKSMS
360 370 380 390 400
QEHLNGNVLS QLEKVFYHLP TGCQEIAEVE VRMIDFAHVF PSNTIDEGYV
410
YGLKHLISVL RSILDN
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022112 | 349 | M → I. Corresponds to variant dbSNP:rs2275443Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF432853 mRNA Translation: AAM97838.1 BK000580 mRNA Translation: DAA01362.1 BC065709 mRNA Translation: AAH65709.1 |
CCDSi | CCDS7250.1 |
RefSeqi | NP_689416.1, NM_152230.4 |
Genome annotation databases
Ensembli | ENST00000373935.4; ENSP00000363046.3; ENSG00000151151.6 |
GeneIDi | 253430 |
KEGGi | hsa:253430 |
MANE-Selecti | ENST00000373935.4; ENSP00000363046.3; NM_152230.5; NP_689416.1 |
UCSCi | uc001jkb.3, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF432853 mRNA Translation: AAM97838.1 BK000580 mRNA Translation: DAA01362.1 BC065709 mRNA Translation: AAH65709.1 |
CCDSi | CCDS7250.1 |
RefSeqi | NP_689416.1, NM_152230.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5W2G | X-ray | 1.80 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
5W2H | X-ray | 1.90 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
5W2I | X-ray | 1.60 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6E7F | X-ray | 2.50 | A/B | 70-279 | [»] | |
A/B | 374-416 | [»] | ||||
6M88 | X-ray | 1.90 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6M89 | X-ray | 1.85 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6M8A | X-ray | 1.75 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6M8B | X-ray | 1.80 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6M8C | X-ray | 1.80 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6M8D | X-ray | 2.00 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
6M8E | X-ray | 2.00 | A | 50-262 | [»] | |
A | 378-416 | [»] | ||||
AlphaFoldDBi | Q8NFU5 | |||||
SMRi | Q8NFU5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 128968, 7 interactors |
IntActi | Q8NFU5, 4 interactors |
STRINGi | 9606.ENSP00000363046 |
Chemistry databases
BindingDBi | Q8NFU5 |
ChEMBLi | CHEMBL4523401 |
PTM databases
iPTMneti | Q8NFU5 |
PhosphoSitePlusi | Q8NFU5 |
Genetic variation databases
BioMutai | IPMK |
DMDMi | 50401072 |
Proteomic databases
EPDi | Q8NFU5 |
jPOSTi | Q8NFU5 |
MassIVEi | Q8NFU5 |
MaxQBi | Q8NFU5 |
PaxDbi | Q8NFU5 |
PeptideAtlasi | Q8NFU5 |
PRIDEi | Q8NFU5 |
ProteomicsDBi | 73362 |
Protocols and materials databases
Antibodypediai | 28039, 194 antibodies from 27 providers |
DNASUi | 253430 |
Genome annotation databases
Ensembli | ENST00000373935.4; ENSP00000363046.3; ENSG00000151151.6 |
GeneIDi | 253430 |
KEGGi | hsa:253430 |
MANE-Selecti | ENST00000373935.4; ENSP00000363046.3; NM_152230.5; NP_689416.1 |
UCSCi | uc001jkb.3, human |
Organism-specific databases
CTDi | 253430 |
DisGeNETi | 253430 |
GeneCardsi | IPMK |
HGNCi | HGNC:20739, IPMK |
HPAi | ENSG00000151151, Low tissue specificity |
MalaCardsi | IPMK |
MIMi | 609851, gene |
neXtProti | NX_Q8NFU5 |
OpenTargetsi | ENSG00000151151 |
Orphaneti | 456333, Hereditary neuroendocrine tumor of small intestine |
PharmGKBi | PA134903369 |
VEuPathDBi | HostDB:ENSG00000151151 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1620, Eukaryota |
GeneTreei | ENSGT00940000155309 |
HOGENOMi | CLU_042569_0_0_1 |
InParanoidi | Q8NFU5 |
OMAi | YGFCITG |
OrthoDBi | 902814at2759 |
PhylomeDBi | Q8NFU5 |
TreeFami | TF321442 |
Enzyme and pathway databases
UniPathwayi | UPA00949 |
BRENDAi | 2.7.1.151, 2681 |
PathwayCommonsi | Q8NFU5 |
Reactomei | R-HSA-1855191, Synthesis of IPs in the nucleus |
SABIO-RKi | Q8NFU5 |
SignaLinki | Q8NFU5 |
Miscellaneous databases
BioGRID-ORCSi | 253430, 38 hits in 1069 CRISPR screens |
ChiTaRSi | IPMK, human |
GenomeRNAii | 253430 |
Pharosi | Q8NFU5, Tbio |
PROi | PR:Q8NFU5 |
RNActi | Q8NFU5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000151151, Expressed in epithelium of mammary gland and 212 other tissues |
Genevisiblei | Q8NFU5, HS |
Family and domain databases
Gene3Di | 3.30.470.160, 1 hit |
InterProi | View protein in InterPro IPR005522, IPK IPR038286, IPK_sf |
PANTHERi | PTHR12400, PTHR12400, 1 hit |
Pfami | View protein in Pfam PF03770, IPK, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IPMK_HUMAN | |
Accessioni | Q8NFU5Primary (citable) accession number: Q8NFU5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | October 1, 2002 | |
Last modified: | May 25, 2022 | |
This is version 158 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families