PMVK

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004631 phosphomevalonate kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the defining molecular function. This is the correct, experimentally corroborated core catalytic activity of PMVK. Reason: PMVK is the human phosphomevalonate kinase; the activity is directly demonstrated for the recombinant human enzyme and encoded by UniProt EC 2.7.4.2. Supporting Evidence: PMID:16519518 Phosphomevalonate kinase (PMK) catalyzes a key step in isoprenoid/sterol
GO:0006695 cholesterol biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic assignment placing PMVK in cholesterol biosynthesis. This is correct but represents a downstream branch of the pathway; the enzymatic step feeds the whole isoprenoid program, of which cholesterol is one output. Reason: Cholesterol is a downstream product of the mevalonate pathway; the more precise pathway role of PMVK is IPP biosynthesis (GO:0019287, step 2/3 to IPP), from which the sterol and nonsterol isoprenoid branches diverge. Keep as a valid but non-core (broader downstream) process annotation. Supporting Evidence: PMID:27052676 PMVK catalyzes the fifth reaction of the cholesterol/isoprenoid biosynthetic pathway
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment to IPP biosynthesis via the mevalonate pathway. This is the most precise biological-process term for PMVK and matches the UniProt PATHWAY statement (IPP from (R)-mevalonate, step 2/3). Reason: PMVK catalyses the direct precursor step to IPP; the UniProt PATHWAY line places it at "isopentenyl diphosphate from (R)-mevalonate, step 2/3", making this the core process annotation. Supporting Evidence: file:human/PMVK/PMVK-uniprot.txt isopentenyl diphosphate from (R)-mevalonate:
GO:0004631 phosphomevalonate kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the phosphomevalonate kinase activity via ARBA/InterPro (IPR005919, RHEA:16341, EC 2.7.4.2). Correct and consistent with the experimental evidence. Reason: Correctly captures the core molecular function (duplicate of the EXP/IDA/IBA GO:0004631 annotations); the electronic mapping is accurate. Supporting Evidence: file:human/PMVK/PMVK-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
GO:0005737 cytoplasm	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO electronic mapping to cytoplasm. Consistent with the established cytosolic localization, but less precise than the cytosol (GO:0005829) IDA/TAS terms. Reason: Cytoplasm is a broader parent of the more precise, experimentally supported cytosol term; correct but non-core given the specific cytosol annotations. Supporting Evidence: file:human/PMVK/PMVK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: UniProt Subcellular-Location keyword mapping to cytosol. Correct; matches the experimental IDA cytosol annotations. Reason: Correctly captures the core cytosolic location (duplicate of the experimental IDA GO:0005829 annotations). Supporting Evidence: file:human/PMVK/PMVK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0006695 cholesterol biosynthetic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic (ARBA/InterPro) assignment to cholesterol biosynthesis. Correct but a downstream branch rather than the most precise pathway role. Reason: Duplicate of the cholesterol biosynthetic process annotation; correct but downstream/broad relative to the core IPP biosynthesis role (GO:0019287). Supporting Evidence: PMID:27052676 PMVK catalyzes the fifth reaction of the cholesterol/isoprenoid biosynthetic pathway
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the HuRI high-throughput yeast-two-hybrid binary interactome map (interactors ZNF177 Q13360-2 and DDIT4L Q96D03). Uninformative and not connected to a characterised biological function of PMVK. Reason: GO:0005515 (protein binding) is uninformative and per curation guidelines should not be used as a stand-in for a specific molecular function. The interactors (a zinc-finger protein and a DDIT4-like protein) come from a proteome-wide binary screen with no follow-up establishing a physiological complex or function for PMVK. Marked as over-annotated rather than removed (experimental IPI, full text not read). Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'.
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (ARBA/UniPathway UPA00057) assignment to IPP biosynthesis via the mevalonate pathway. Correct and matches the core pathway role. Reason: Correctly captures the core pathway role (duplicate of the IBA GO:0019287 annotation); matches the UniProt PATHWAY statement (IPP from (R)-mevalonate, step 2/3). Supporting Evidence: file:human/PMVK/PMVK-uniprot.txt isopentenyl diphosphate from (R)-mevalonate:
GO:0006695 cholesterol biosynthetic process	TAS Reactome:R-HSA-9969896	KEEP AS NON CORE	Summary: Reactome (Lanosterol biosynthesis) traceable-author annotation to cholesterol biosynthesis. Correct but a downstream branch relative to the core IPP-precursor role. Reason: Correct pathway membership but downstream/broad; duplicate of the cholesterol biosynthetic process annotations kept as non-core (core process is GO:0019287). Supporting Evidence: PMID:27052676 PMVK catalyzes the fifth reaction of the cholesterol/isoprenoid biosynthetic pathway
GO:0004631 phosphomevalonate kinase activity	TAS Reactome:R-HSA-191422	ACCEPT	Summary: Reactome reaction "Mevalonate-5-phosphate is further phosphorylated" attributes the phosphomevalonate kinase activity to PMVK. Correct core molecular function. Reason: Correctly captures the core molecular function (duplicate of the experimental GO:0004631 annotations). Supporting Evidence: PMID:16519518 Phosphomevalonate kinase (PMK) catalyzes a key step in isoprenoid/sterol
GO:0005829 cytosol	TAS Reactome:R-HSA-1655839	ACCEPT	Summary: Reactome (Expression of PMVK) traceable-author cytosol location. Consistent with the experimental IDA cytosol annotations. Reason: Correctly captures the core cytosolic location (duplicate of the experimental IDA GO:0005829 annotations). Supporting Evidence: PMID:14729858 exclusive cytosolic localization of both endogenously expressed human
GO:0005829 cytosol	TAS Reactome:R-HSA-191422	ACCEPT	Summary: Reactome (mevalonate-5-phosphate phosphorylation reaction) traceable-author cytosol location. Consistent with the established cytosolic localization. Reason: Correctly captures the core cytosolic location (duplicate of the experimental IDA GO:0005829 annotations). Supporting Evidence: PMID:14729858 exclusive cytosolic localization of both endogenously expressed human
GO:0004631 phosphomevalonate kinase activity	EXP PMID:17902708 Functional evaluation of conserved basic residues in human p...	ACCEPT	Summary: Experimental demonstration of phosphomevalonate kinase activity for human PMVK via kinetic and mutagenesis analysis of conserved active-site basic residues. Reason: Direct experimental evidence for the core catalytic activity; identifies catalytic (R110, K48, R73) and substrate/ATP-binding (R111, R84, R141) residues. Supporting Evidence: PMID:17902708 Phosphomevalonate kinase (PMK) catalyzes the cation-dependent reaction of
GO:0004631 phosphomevalonate kinase activity	EXP PMID:9392419 Post-translational regulation of mevalonate kinase by interm...	ACCEPT	Summary: Experimental study expressing and assaying recombinant human PMKase (alongside MKase and MDDase); confirms phosphomevalonate kinase activity for PMVK. Reason: Direct experimental evidence for the core catalytic activity (the enzyme was purified and assayed spectrophotometrically); underpins UniProt EC 2.7.4.2. Supporting Evidence: PMID:9392419 phosphomevalonate kinase (PMKase), and
GO:0005777 peroxisome	IDA NOT PMID:14729858 Phosphomevalonate kinase is a cytosolic protein in humans.	ACCEPT	Summary: Correct NOT annotation. Multiple techniques (subcellular fractionation, digitonin permeabilization, immunofluorescence, immunoelectron microscopy) found no peroxisomal PMVK, overturning the earlier peroxisomal claim. Reason: This negated annotation captures the definitive finding that human PMVK is not peroxisomal; it is corroborated by PMID:27052676 (no co-localization with PEX14) and by the UniProt CAUTION note. Supporting Evidence: PMID:14729858 No indication of a peroxisomal localization was obtained.
GO:0005829 cytosol	IDA PMID:27052676 Loss-of-function Mutation in PMVK Causes Autosomal Dominant ...	ACCEPT	Summary: Direct assay (immunofluorescence in HaCaT/ARPE-19 cells) showing wild-type PMVK has a dispersed cytoplasmic (cytosolic) distribution that does not co-localize with the peroxisomal marker PEX14. Reason: Experimental confirmation of the core cytosolic localization of PMVK. Supporting Evidence: PMID:27052676 The wild-type PMVK exhibited dispersed cytoplasmic localization and showed little co-localization with the peroxisomal marker PEX14
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput detection of PMVK in an NK-cell "membrane proteome" preparation. This is a soluble cytosolic kinase; membrane co-purification in a large-scale MS dataset is not a functional membrane localization. Reason: PMVK is an established soluble, cytosolic enzyme with no transmembrane domain or lipid anchor (UniProt). Its appearance in a bulk membrane-enriched MS dataset most likely reflects incomplete fractionation/contamination rather than a physiological membrane location. Supporting Evidence: PMID:19946888 define the composition of the membrane file:human/PMVK/PMVK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: High-throughput MS identification of PMVK in a urinary-exosome proteome. This is a bulk proteomic catalogue rather than evidence of a functional exosomal role for this cytosolic kinase. Reason: Detection in a large-scale exosome proteomics survey is a common finding for abundant cytosolic proteins and does not indicate a biological function of PMVK in exosomes; the enzyme's characterised location is the cytosol. Supporting Evidence: PMID:19056867 LC-MS/MS to profile the proteome of human urinary exosomes file:human/PMVK/PMVK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0005777 peroxisome	IDA PMID:17180682 Localization of the pre-squalene segment of the isoprenoid b...	MARK AS OVER ANNOTATED	Summary: Minority-view IDA reporting peroxisomal localization of presqualene enzymes (including PMVK) using isotopomer and immunofluorescence methods. This conclusion has been rejected by the field; the consensus (and UniProt) is that human PMVK is cytosolic. Reason: Directly contradicted by PMID:14729858 (exclusive cytosolic localization; NOT peroxisome) and PMID:27052676 (no PEX14 co-localization), and by the UniProt CAUTION note stating PMVK "was later shown to be cytosolic". Retained rather than removed because it is an experimental IDA whose full text was not read, but flagged as an over-annotation superseded by stronger, concordant evidence. Supporting Evidence: PMID:17180682 segment of the cholesterol biosynthetic pathway is localized to peroxisomes file:human/PMVK/PMVK-uniprot.txt Was originally thought to be located in the peroxisome
GO:0005829 cytosol	IDA PMID:14729858 Phosphomevalonate kinase is a cytosolic protein in humans.	ACCEPT	Summary: Direct experimental determination (subcellular fractionation, digitonin permeabilization, immunofluorescence, immunoelectron microscopy) that endogenous and overexpressed human PMVK localize exclusively to the cytosol. Reason: Definitive experimental evidence for the core cytosolic localization; this is the study that established PMVK as cytosolic and underlies the UniProt annotation. Supporting Evidence: PMID:14729858 exclusive cytosolic localization of both endogenously expressed human
GO:0004631 phosphomevalonate kinase activity	IDA PMID:16519518 Phosphomevalonate kinase: functional investigation of the re...	ACCEPT	Summary: Direct assay of recombinant His-tagged human PMVK confirming phosphomevalonate kinase activity; kinetic constants determined for both forward and reverse reactions. Reason: Primary experimental evidence for the core catalytic activity of the human enzyme, with determined KM and Vmax values. Supporting Evidence: PMID:16519518 Phosphomevalonate kinase (PMK) catalyzes a key step in isoprenoid/sterol
GO:0005524 ATP binding	IDA PMID:16519518 Phosphomevalonate kinase: functional investigation of the re...	ACCEPT	Summary: ATP is the phosphoryl donor for the kinase reaction; the study identifies an N-terminal Walker-A-like basic-residue motif and demonstrates ATP binding via mutagenesis (e.g. K22M abolishes activity). Reason: ATP binding is directly supported and mechanistically integral to the core phosphotransferase function (ATP + mevalonate-5-P -> mevalonate-5-PP + ADP). Supporting Evidence: PMID:16519518 an N-terminal basic file:human/PMVK/PMVK-uniprot.txt ligand="ATP"
GO:0016126 sterol biosynthetic process	IDA PMID:16519518 Phosphomevalonate kinase: functional investigation of the re...	KEEP AS NON CORE	Summary: Places PMVK in sterol biosynthesis. Correct at a broad level but downstream of the direct enzymatic step; the more precise process is IPP biosynthesis (GO:0019287). Reason: Sterol biosynthesis is a downstream/broad process relative to the direct IPP-precursor role; retained as a valid but non-core process annotation. Supporting Evidence: PMID:16519518 catalyzes a key step in isoprenoid/sterol
GO:0070723 response to cholesterol	IEP PMID:10191291 Characterization of phosphomevalonate kinase: chromosomal lo...	KEEP AS NON CORE	Summary: Expression-pattern evidence that PMVK message and activity are regulated in response to dietary/cellular sterol levels, coordinately with HMG-CoA reductase. This reflects transcriptional (SREBP-type) regulation of the gene, not a core enzymatic function. Reason: The sterol-responsive regulation of PMVK is a genuine, documented property but is a regulatory/response process distinct from the enzyme's molecular function; kept as a valid non-core annotation. Supporting Evidence: PMID:10191291 activity of rat liver phosphomevalonate kinase are regulated in response to
GO:0004631 phosphomevalonate kinase activity	IDA PMID:8663599 Molecular cloning of human phosphomevalonate kinase and iden...	ACCEPT	Summary: Original molecular cloning of human liver PMKase with expression of PMKase catalytic activity in bacteria from the cloned cDNA, establishing the enzyme's identity and activity. Reason: Foundational experimental evidence for the core phosphomevalonate kinase activity of human PMVK. Supporting Evidence: PMID:8663599 expression of PMKase activity in bacteria
GO:0006695 cholesterol biosynthetic process	IDA PMID:8663599 Molecular cloning of human phosphomevalonate kinase and iden...	KEEP AS NON CORE	Summary: Assigns PMVK to cholesterol biosynthesis. Correct membership but a downstream/broad process relative to the direct IPP-precursor step. Reason: Cholesterol biosynthesis is downstream of PMVK's direct reaction; duplicate of the cholesterol biosynthetic process annotations, kept as non-core (core process is GO:0019287 IPP biosynthesis). Supporting Evidence: PMID:8663599 cholesterol biosynthetic protein which contains a consensus PTS-1
GO:0004631 phosphomevalonate kinase activity	IDA PMID:14680974 Cholesterol biosynthesis is not defective in peroxisome biog...	ACCEPT	Summary: Directly measured phosphomevalonate kinase protein level and enzymatic activity in fibroblasts (among five presqualene-pathway enzymes) while assessing peroxisomal involvement in cholesterol biosynthesis. Reason: Provides direct experimental measurement of PMVK activity, supporting the core catalytic function; also shows the activity is retained in peroxisome-deficient cells. Supporting Evidence: PMID:14680974 determined the protein levels and activities of five different

Gene Description

Existing Annotations Review

Core Functions

Phosphomevalonate kinase activity - ATP-dependent phosphorylation of (R)-mevalonate 5-phosphate to (R)-mevalonate 5-diphosphate, the direct precursor step to isopentenyl diphosphate in the mevalonate pathway.

ATP binding required for phosphoryl transfer; ATP is the phosphate donor consumed in the phosphomevalonate kinase reaction, coordinated by an N-terminal Walker-A-like basic-residue motif.

References

📚 Additional Documentation

Notes

📄 View Raw YAML