P07250 · IPMK_YEAST
- ProteinInositol polyphosphate multikinase
- GeneARG82
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids355 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Inositol phosphate kinase with both monophosphoinositol and diphosphoinositol polyphosphate synthase activities. Able to phosphorylate inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) on both the carbon-3 and carbon-6 positions to synthesize inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) and inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4), and then to subsequently phosphorylate and convert either isomer of InsP4 to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:10574768, PubMed:10683435, PubMed:11311242).
Its predominant in vivo catalytic function is to convert Ins(1,4,5)P3 to Ins(1,4,5,6)P4 to Ins(1,3,4,5,6)P5 via 6- and 3-kinase activities (PubMed:15944147).
It can also use Ins(1,3,4,5,6)P5 as a substrate and act as a diphosphoinositol polyphosphate synthase to generate two different isomers of PP-InsP4 (PubMed:11311242).
Has also a role in transcription regulation. Forms a complex with ARG80, ARG81 and MCM1 (ArgR-MCM1), which coordinates the expression of arginine anabolic and catabolic genes in response to arginine. Recruits ARG80 and MCM21 to stabilize them (PubMed:10632874, PubMed:3298999, PubMed:8043104).
Neither the kinase activity nor inositol phosphates are required for the formation of ArgR-MCM1 transcriptional complexes on DNA promoter elements and the control of arginine metabolism (PubMed:10720331, PubMed:11119723, PubMed:12828642, PubMed:22992733).
In contrast, only the catalytic activity is required for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability, indicating a role for inositol pyrophosphates in these controls (PubMed:12828642).
Inositol polyphosphates may be involved in the regulation of chromatin remodeling of transcription (PubMed:12434012).
Regulates nuclear mRNA export via inositol phosphate metabolism (PubMed:10390371, PubMed:10683435).
Also has lipid kinase activity, transforming the lipid inositol phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) into phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) in the nucleus (PubMed:16123124).
Its kinase activity is necessary for the propagation of most [PSI+] prion variants (PubMed:28923943).
Its predominant in vivo catalytic function is to convert Ins(1,4,5)P3 to Ins(1,4,5,6)P4 to Ins(1,3,4,5,6)P5 via 6- and 3-kinase activities (PubMed:15944147).
It can also use Ins(1,3,4,5,6)P5 as a substrate and act as a diphosphoinositol polyphosphate synthase to generate two different isomers of PP-InsP4 (PubMed:11311242).
Has also a role in transcription regulation. Forms a complex with ARG80, ARG81 and MCM1 (ArgR-MCM1), which coordinates the expression of arginine anabolic and catabolic genes in response to arginine. Recruits ARG80 and MCM21 to stabilize them (PubMed:10632874, PubMed:3298999, PubMed:8043104).
Neither the kinase activity nor inositol phosphates are required for the formation of ArgR-MCM1 transcriptional complexes on DNA promoter elements and the control of arginine metabolism (PubMed:10720331, PubMed:11119723, PubMed:12828642, PubMed:22992733).
In contrast, only the catalytic activity is required for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability, indicating a role for inositol pyrophosphates in these controls (PubMed:12828642).
Inositol polyphosphates may be involved in the regulation of chromatin remodeling of transcription (PubMed:12434012).
Regulates nuclear mRNA export via inositol phosphate metabolism (PubMed:10390371, PubMed:10683435).
Also has lipid kinase activity, transforming the lipid inositol phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) into phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) in the nucleus (PubMed:16123124).
Its kinase activity is necessary for the propagation of most [PSI+] prion variants (PubMed:28923943).
Miscellaneous
The expression of this protein is not effected by the presence of arginine.
Present with 2720 molecules/cell in log phase SD medium.
Catalytic activity
- 1D-myo-inositol 1,4,5-trisphosphate + 2 ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 2 ADP + 2 H+
- 1D-myo-inositol 1,4,5-trisphosphate + ATP = 1D-myo-inositol 1,4,5,6-tetrakisphosphate + ADP + H+This reaction proceeds in the forward direction.
- 1D-myo-inositol 1,4,5,6-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H+This reaction proceeds in the forward direction.
- 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+This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
15.3 μM | 1D-myo-inositol 1,4,5-trisphosphate | |||||
7.1 μM | 1D-myo-inositol 1,4,5-trisphosphate | |||||
62 μM | 1D-myo-inositol 1,3,4,5,6-pentakisphosphate | |||||
30 μM | phosphatidylinositol 4,5-bisphosphate | |||||
2.1 mM | ATP |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
6272 nmol/min/mg | for 1D-myo-inositol 1,4,5-trisphosphate | ||||
4.9 nmol/min/mg | for 1D-myo-inositol 1,3,4,5,6-pentakisphosphate |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 31 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 118-120 | ATP (UniProtKB | ChEBI) | ||||
Sequence: ENL | ||||||
Binding site | 127-135 | substrate | ||||
Sequence: PNILDIKLG | ||||||
Binding site | 131 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 271 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 274 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 325 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 334 | Ca2+ (UniProtKB | ChEBI) | ||||
Sequence: G |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameInositol polyphosphate multikinase
- EC number
- Short namesIPMK
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Saccharomycotina > Saccharomycetes > Saccharomycetales > Saccharomycetaceae > Saccharomyces
Accessions
- Primary accessionP07250
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Impairs nuclear mRNA export, slows cell growth, increases cellular InsP3 170-fold and decreases InsP6 100-fold.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 131 | Abolishes catalytic activity, but preserves its nonkinase transcription regulation functions. | ||||
Sequence: D → A | ||||||
Mutagenesis | 133 | Abolishes catalytic activity, but preserves its nonkinase transcription regulation functions. | ||||
Sequence: K → A | ||||||
Mutagenesis | 257-260 | Abolishes catalytic activity. | ||||
Sequence: SSLL → AAAA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 6 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000066873 | 1-355 | Inositol polyphosphate multikinase | |||
Sequence: MDTVNNYRVLEHKAAGHDGTLTDGDGLLIFKPAFPQELEFYKAIQVRDVSRRKSSADGDAPLCSWMPTYLGVLNEGAKIEQSGDAALLKIDERLSDSTDNLDSIPVKSEKSKQYLVLENLLYGFSKPNILDIKLGKTLYDSKASLEKRERMKRVSETTTSGSLGFRICGMKIQKNPSVLNQLSLEYYEEEADSDYIFINKLYGRSRTDQNVSDAIELYFNNPHLSDARKHQLKKTFLKRLQLFYNTMLEEEVRMISSSLLFIYEGDPERWELLNDVDKLMRDDFIDDDDDDDDNDDDDDDDAEGSSEGPKDKKTTGSLSSMSLIDFAHSEITPGKGYDENVIEGVETLLDIFMKF | ||||||
Modified residue | 97 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with ARG80 and MCM1.
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 284-304 | Acidic residues | ||||
Sequence: FIDDDDDDDDNDDDDDDDAEG | ||||||
Region | 284-317 | Disordered | ||||
Sequence: FIDDDDDDDDNDDDDDDDAEGSSEGPKDKKTTGS |
Sequence similarities
Belongs to the inositol phosphokinase (IPK) family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length355
- Mass (Da)40,353
- Last updated1988-04-01 v1
- ChecksumF858B39E3C54E6BF
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 109 | in Ref. 4; AAS56022 | ||||
Sequence: E → K | ||||||
Compositional bias | 284-304 | Acidic residues | ||||
Sequence: FIDDDDDDDDNDDDDDDDAEG |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X05328 EMBL· GenBank· DDBJ | CAA28945.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Z46727 EMBL· GenBank· DDBJ | CAA86678.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY557696 EMBL· GenBank· DDBJ | AAS56022.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BK006938 EMBL· GenBank· DDBJ | DAA12015.1 EMBL· GenBank· DDBJ | Genomic DNA |