id: P53602
gene_symbol: MVD
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MVD is human diphosphomevalonate decarboxylase (mevalonate-5-diphosphate
  decarboxylase; EC 4.1.1.33), the enzyme that catalyses the final step of the
  mevalonate pathway. It performs the ATP-dependent decarboxylation of
  (R)-5-diphosphomevalonate (mevalonate-5-diphosphate) to isopentenyl
  diphosphate (IPP), releasing CO2, ADP and inorganic phosphate. IPP is the
  fundamental five-carbon (C5) isoprenoid building block from which all
  downstream isoprenoids are assembled, so MVD sits at the point where the
  mevalonate pathway delivers activated isoprene units for sterol (cholesterol)
  biosynthesis and for the non-sterol isoprenoid branches (dolichol, ubiquinone,
  and the prenyl groups used in protein prenylation). The protein is a member of
  the GHMP kinase superfamily, binds ATP, and functions as a homodimer of
  ~43-kDa subunits. It is a soluble cytosolic enzyme. In humans, loss-of-function
  and missense variants in MVD (together with MVK, the two principal
  porokeratosis genes) cause porokeratosis (POROK7), a disorder of faulty
  epidermal keratinization characterised by the cornoid lamella.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/MVD/MVD-uniprot.txt
  title: UniProtKB entry P53602 (MVD1_HUMAN), Diphosphomevalonate decarboxylase
  findings: []
- id: PMID:11792727
  title: Absence of functional peroxisomes does not lead to deficiency of enzymes
    involved in cholesterol biosynthesis.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Shows MVD (and other MVA-pathway enzymes) retain activity in
      peroxisome-deficient cells; supports cytosolic function, not a specific catalytic
      characterization of MVD.
- id: PMID:12646231
  title: Mortalin-MPD (mevalonate pyrophosphate decarboxylase) interactions and their
    role in control of cellular proliferation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Yeast two-hybrid / co-IP interaction between MPD (MVD) and mortalin
      (mot-2/GRP75, an HSP70-family protein). Supports the Hsp70-binding IPI but this
      is an interaction finding, not MVD's core molecular function.
- id: PMID:14680974
  title: Cholesterol biosynthesis is not defective in peroxisome biogenesis defective
    fibroblasts.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Measures MVD (MPD) activity among five presqualene MVA/isoprenoid
      enzymes in PBD fibroblasts; supports enzymatic activity and cytosolic function.
- id: PMID:14972328
  title: Human mevalonate pyrophosphate decarboxylase is localized in the cytosol.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive subcellular localization study; MVD is cytosolic with no
      peroxisomal localization. Directly supports the cytosol/NOT-peroxisome annotations.
- id: PMID:18823933
  title: 'Human mevalonate diphosphate decarboxylase: characterization, investigation
    of the mevalonate diphosphate binding site, and crystal structure.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available. Recombinant human MDD characterization, kinetics,
      active-site mutagenesis (R161, N17) and 2.4 A crystal structure (3D4J). Directly
      establishes the diphosphomevalonate decarboxylase activity and reaction.
- id: PMID:8626466
  title: Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate
    pyrophosphate decarboxylase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cloning and expression of human MVD; recombinant enzyme is a homodimer
      of 43-kDa subunits with measurable decarboxylase activity. Supports catalytic
      activity and homodimerization.
- id: PMID:9270019
  title: Regulation of proliferation and Ras localization in transformed cells by
    products of mevalonate metabolism.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Uses 6-fluoromevalonate (Fmev, an MVD inhibitor) to block downstream
      mevalonate products and Ras prenylation, suppressing proliferation. Supports a
      pathway-level role in proliferation but the effect is indirect (via prenylated
      products), not a direct MVD signalling function.
- id: PMID:9392419
  title: Post-translational regulation of mevalonate kinase by intermediates of the
    cholesterol and nonsterol isoprene biosynthetic pathways.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Expressed and assayed recombinant human MDDase (MVD) alongside MKase
      and PMKase; the focus is feedback inhibition of MKase, but MVD activity and
      kinetics (KM for mevalonate diphosphate) were determined. Supports catalytic
      activity.
- id: Reactome:R-HSA-1655836
  title: Expression of Diphosphomevalonate Decarboxylase (MVD)
  findings: []
- id: Reactome:R-HSA-191414
  title: MVD decarboxylates MVA5PP to IPPP
  findings: []
existing_annotations:
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Core catalytic molecular function of MVD, propagated by phylogenetic
      inference across the diphosphomevalonate decarboxylase family and strongly
      corroborated by direct human experimental evidence.
    action: ACCEPT
    reason: >-
      This is the defining molecular function of MVD (EC 4.1.1.33): ATP-dependent
      decarboxylation of (R)-5-diphosphomevalonate to isopentenyl diphosphate.
      The IBA is consistent with human biochemical and structural characterization.
    supported_by:
    - reference_id: PMID:18823933
      supporting_text: "Mevalonate diphosphate decarboxyase (MDD1; EC 4.1.1.33) catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate"
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "Catalyzes the ATP dependent decarboxylation of (R)-5-"
- term:
    id: GO:0019287
    label: isopentenyl diphosphate biosynthetic process, mevalonate pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Precise biological process for MVD: it produces isopentenyl diphosphate
      (IPP) as the final step of the mevalonate pathway.
    action: ACCEPT
    reason: >-
      MVD's product is IPP, and the enzyme catalyses the terminal mevalonate-pathway
      step that generates it. This term captures the direct biological process at
      the correct level of specificity and is the best core BP term.
    supported_by:
    - reference_id: PMID:18823933
      supporting_text: "catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate"
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "Functions in\nCC       the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP)"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      MVD is a soluble cytosolic enzyme; the phylogenetically inferred cytosolic
      localization matches direct human experimental evidence.
    action: ACCEPT
    reason: >-
      Direct subcellular fractionation, immunofluorescence and immunoelectron
      microscopy established a cytosolic localization for human MVD, with no
      peroxisomal signal.
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "We found a\ncytosolic localization for both endogenous human mevalonate pyrophosphate\ndecarboxylase"
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Automated (ARBA/InterPro/RHEA/EC) assignment of the core catalytic function,
      redundant with the experimental and IBA annotations.
    action: ACCEPT
    reason: >-
      Correctly maps the specific diphosphomevalonate decarboxylase activity
      (EC 4.1.1.33, RHEA:23732) to MVD; concordant with experimental evidence.
    supported_by:
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "EC=4.1.1.33"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Broader cytoplasmic localization from the UniProt subcellular-location
      mapping; correct but less specific than cytosol.
    action: ACCEPT
    reason: >-
      UniProt annotates MVD as cytoplasmic, consistent with its established
      cytosolic localization. This parent term is correct though the more specific
      GO:0005829 (cytosol) is preferred.
    supported_by:
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      Automated cytosol localization consistent with experimental evidence.
    action: ACCEPT
    reason: >-
      Correct; MVD is cytosolic (established experimentally in PMID:14972328).
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "but no indication for a peroxisomal localization"
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Broader isoprenoid biosynthesis framing; MVD produces IPP, the universal
      isoprenoid precursor.
    action: ACCEPT
    reason: >-
      True but general parent of the more precise GO:0019287. Retained as an
      accurate higher-level BP: MVD's product IPP is the substrate for all
      isoprenoid biosynthesis.
    supported_by:
    - reference_id: PMID:18823933
      supporting_text: "The reaction is required for production of polyisoprenoids and sterols from acetyl-CoA."
- term:
    id: GO:0016831
    label: carboxy-lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Broad InterPro2GO molecular-function parent of the specific
      diphosphomevalonate decarboxylase activity.
    action: MODIFY
    reason: >-
      MVD is a decarboxylase (carboxy-lyase), so this term is not wrong, but it is
      an uninformative parent of the specific GO:0004163 diphosphomevalonate
      decarboxylase activity which is experimentally established. Replace with the
      specific term.
    proposed_replacement_terms:
    - id: GO:0004163
      label: diphosphomevalonate decarboxylase activity
    supported_by:
    - reference_id: PMID:18823933
      supporting_text: "catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate"
- term:
    id: GO:0019287
    label: isopentenyl diphosphate biosynthetic process, mevalonate pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Automated (InterPro2GO) assignment of the precise mevalonate-pathway IPP
      biosynthesis process, redundant with the IBA.
    action: ACCEPT
    reason: >-
      Correct and specific; MVD produces IPP as the terminal mevalonate-pathway step.
    supported_by:
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "Functions in\nCC       the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP)"
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      UniPathway-derived link to cholesterol biosynthesis. MVD feeds the sterol
      branch but its direct product is IPP, upstream of the sterol/non-sterol
      branch point.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cholesterol biosynthesis is a downstream consequence of MVD activity rather
      than its direct process: MVD makes IPP, which supplies both sterol
      (cholesterol) and many non-sterol isoprenoid branches (dolichol, ubiquinone,
      prenyl groups). The accurate direct BP is the mevalonate-pathway IPP
      biosynthesis (GO:0019287). Retain as a valid non-core downstream pathway
      association.
    supported_by:
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "a key precursor for the biosynthesis of isoprenoids and sterol"
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "PATHWAY: Steroid biosynthesis; cholesterol biosynthesis."
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:14972328
  qualifier: is_active_in
  review:
    summary: >-
      Experimental cytoplasmic/cytosolic localization of human MVD.
    action: ACCEPT
    reason: >-
      Directly supported by the localization study; MVD is active in the cytosol
      (cytoplasm). GO:0005829 (cytosol) is the more specific form of the same
      finding.
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "We found a\ncytosolic localization for both endogenous human mevalonate pyrophosphate\ndecarboxylase"
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: EXP
  original_reference_id: PMID:18823933
  qualifier: enables
  review:
    summary: >-
      Direct experimental characterization of recombinant human MVD's
      diphosphomevalonate decarboxylase activity, including kinetics and active-site
      mutagenesis, backed by a crystal structure.
    action: ACCEPT
    reason: >-
      Gold-standard experimental support for the core catalytic function. Kinetic
      parameters were measured and active-site residues (R161, N17) validated; R161Q
      causes ~1000-fold loss of activity.
    supported_by:
    - reference_id: PMID:18823933
      supporting_text: "Mevalonate diphosphate decarboxyase (MDD1; EC 4.1.1.33) catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate"
    - reference_id: PMID:18823933
      supporting_text: "R161Q exhibits a approximately \n1000-fold diminution in specific activity"
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: EXP
  original_reference_id: PMID:8626466
  qualifier: enables
  review:
    summary: >-
      Cloning/expression paper showing recombinant human MVD has decarboxylase
      activity (2.4 units/mg).
    action: ACCEPT
    reason: >-
      Experimental confirmation of the core catalytic function; duplicate of the
      other GO:0004163 catalytic annotations.
    supported_by:
    - reference_id: PMID:8626466
      supporting_text: "The recombinant human enzyme is a \nhomodimer of 43-kDa subunits with a specific activity of 2.4 units/mg."
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: EXP
  original_reference_id: PMID:9392419
  qualifier: enables
  review:
    summary: >-
      Recombinant human MDDase (MVD) was expressed, purified and assayed as part of
      a mevalonate-pathway feedback-inhibition study.
    action: ACCEPT
    reason: >-
      Experimental support for the decarboxylase activity; MVD's KM for
      (R)-5-diphosphomevalonate was determined. Duplicate of the core catalytic
      annotation.
    supported_by:
    - reference_id: PMID:9392419
      supporting_text: "mevalonate diphosphate decarboxylase (MDDase)"
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "KM=7.4 uM for (R)-5-diphosphomevalonate {ECO:0000269|PubMed:9392419}"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1655836
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion placing MVD in the cytosol.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally established cytosolic localization of MVD.
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "Human mevalonate pyrophosphate decarboxylase is localized in the \ncytosol."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-191414
  qualifier: located_in
  review:
    summary: >-
      Reactome traceable assertion (MVD decarboxylates MVA5PP to IPPP reaction)
      placing MVD in the cytosol.
    action: ACCEPT
    reason: >-
      Consistent with the experimentally established cytosolic localization; the
      cited Reactome reaction is exactly the MVD decarboxylation of
      mevalonate-5-diphosphate to IPP.
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "Human mevalonate pyrophosphate decarboxylase is localized in the \ncytosol."
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:11792727
  qualifier: enables
  review:
    summary: >-
      MVD (MPD) decarboxylase activity measured directly in human/mouse tissue in a
      study of MVA-pathway enzyme activities.
    action: ACCEPT
    reason: >-
      Direct activity measurement of MVD supports the core catalytic function
      (duplicate of the other GO:0004163 annotations).
    supported_by:
    - reference_id: PMID:11792727
      supporting_text: "mislocalization of enzymes to the cytosol does not lead to decreased activity or"
- term:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  evidence_type: IDA
  original_reference_id: PMID:14680974
  qualifier: enables
  review:
    summary: >-
      MVD (mevalonate pyrophosphate decarboxylase) activity measured directly among
      presqualene MVA/isoprenoid enzymes in PBD fibroblasts.
    action: ACCEPT
    reason: >-
      Direct activity measurement supports the core catalytic function (duplicate
      of the other GO:0004163 annotations).
    supported_by:
    - reference_id: PMID:14680974
      supporting_text: "mevalonate pyrophosphate decarboxylase"
- term:
    id: GO:0006695
    label: cholesterol biosynthetic process
  evidence_type: NAS
  original_reference_id: PMID:14680974
  qualifier: involved_in
  review:
    summary: >-
      Author-stated (NAS) placement of MVD in the cholesterol/isoprenoid
      biosynthetic pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      MVD is one of the presqualene enzymes of the cholesterol/isoprenoid pathway,
      but cholesterol synthesis is downstream of MVD's direct product IPP (which
      also feeds non-sterol branches). Accurate as a non-core downstream pathway
      association; the precise direct BP is the mevalonate-pathway IPP biosynthesis.
    supported_by:
    - reference_id: PMID:14680974
      supporting_text: "five different \nenzymes of the presqualene segment of the cholesterol/isoprenoid biosynthetic \npathway"
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:9270019
  qualifier: involved_in
  review:
    summary: >-
      Inhibiting MVD with 6-fluoromevalonate (Fmev) blocks production of downstream
      mevalonate products, prevents Ras prenylation/membrane localization, and
      suppresses proliferation of transformed cells.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a pathway-level, indirect effect: MVD activity is required to make IPP
      and hence the prenyl groups that drive Ras-dependent proliferation. It reflects
      a physiological consequence of MVD's metabolic role rather than a distinct
      signalling function of the protein. Retain as a non-core process rather than a
      core molecular function. Per curation policy this experimental (IMP) annotation
      is not removed.
    supported_by:
    - reference_id: PMID:9270019
      supporting_text: "6-fluoromevalonate (Fmev), an inhibitor of diphosphomevalonate decarboxylase"
    - reference_id: PMID:9270019
      supporting_text: "completely \nprevented the proliferation of U-937 cells"
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:11792727
  qualifier: involved_in
  review:
    summary: >-
      Experimental support for MVD participation in isoprenoid/cholesterol
      biosynthesis (MVA-pathway enzyme activities measured).
    action: ACCEPT
    reason: >-
      Broad but accurate: MVD produces IPP, the universal isoprenoid precursor.
      GO:0019287 is the more precise BP; this parent is retained as correct.
    supported_by:
    - reference_id: PMID:11792727
      supporting_text: "enzymes \ninvolved in cholesterol biosynthesis"
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:14680974
  qualifier: involved_in
  review:
    summary: >-
      Experimental support for MVD participation in the cholesterol/isoprenoid
      biosynthetic pathway.
    action: ACCEPT
    reason: >-
      Accurate higher-level BP; MVD's product IPP is the isoprenoid building block.
      GO:0019287 is the precise process; this parent is retained as correct.
    supported_by:
    - reference_id: PMID:14680974
      supporting_text: "cholesterol/isoprenoid biosynthetic \npathway"
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IPI
  original_reference_id: PMID:12646231
  qualifier: enables
  review:
    summary: >-
      MVD (MPD) was identified in a yeast two-hybrid screen and co-IP as an
      interactor of mortalin (mot-2/GRP75), a member of the HSP70 family, in a study
      of proliferation control.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      A physical interaction with an HSP70-family chaperone (mortalin) is a
      protein-binding-type annotation that does not describe MVD's core catalytic
      molecular function; it is peripheral to why MVD exists (isoprenoid synthesis).
      Per curation policy this experimental (IPI) annotation is not removed but is
      flagged as an over-annotation relative to the enzyme's function.
    supported_by:
    - reference_id: PMID:12646231
      supporting_text: "Mevalonate pyrophosphate decarboxylase (MPD) was \nidentified as one of the mortalin binding partners"
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:8626466
  qualifier: enables
  review:
    summary: >-
      Recombinant human MVD is a homodimer of ~43-kDa subunits.
    action: KEEP_AS_NON_CORE
    reason: >-
      Homodimerization is an experimentally supported structural property of the
      enzyme (also stated as SUBUNIT: Homodimer in UniProt), but it is a quaternary
      structure feature rather than MVD's core catalytic function. Retain as non-core.
    supported_by:
    - reference_id: PMID:8626466
      supporting_text: "The recombinant human enzyme is a \nhomodimer of 43-kDa subunits"
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "SUBUNIT: Homodimer."
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:14972328
  qualifier: located_in
  negated: true
  review:
    summary: >-
      MVD is explicitly NOT located in the peroxisome; earlier peroxisomal claims
      were refuted by direct localization studies.
    action: ACCEPT
    reason: >-
      The negated annotation is correct and important: careful subcellular
      fractionation and microscopy found no peroxisomal MVD, overturning earlier
      reports of a peroxisomal targeting signal. UniProt records the same correction
      in its CAUTION note.
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "but no indication for a peroxisomal localization"
    - reference_id: file:human/MVD/MVD-uniprot.txt
      supporting_text: "However, was later shown to be cytosolic"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:14972328
  qualifier: located_in
  review:
    summary: >-
      Direct experimental evidence that human MVD is a cytosolic protein.
    action: ACCEPT
    reason: >-
      The definitive localization study; MVD is cytosolic in fibroblasts, liver,
      CV1 and HEK293 cells by fractionation, immunofluorescence and immunoelectron
      microscopy.
    supported_by:
    - reference_id: PMID:14972328
      supporting_text: "We found a\ncytosolic localization for both endogenous human mevalonate pyrophosphate\ndecarboxylase"
core_functions:
- description: >-
    ATP-dependent decarboxylation of (R)-5-diphosphomevalonate
    (mevalonate-5-diphosphate) to isopentenyl diphosphate (IPP), CO2, ADP and
    phosphate, the final step of the mevalonate pathway that generates the
    universal C5 isoprenoid unit.
  molecular_function:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  directly_involved_in:
  - id: GO:0019287
    label: isopentenyl diphosphate biosynthetic process, mevalonate pathway
  supported_by:
  - reference_id: PMID:18823933
    supporting_text: "Mevalonate diphosphate decarboxyase (MDD1; EC 4.1.1.33) catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate"
  - reference_id: file:human/MVD/MVD-uniprot.txt
    supporting_text: "Catalyzes the ATP dependent decarboxylation of (R)-5-"
- description: >-
    As the terminal mevalonate-pathway enzyme, MVD supplies IPP for the broader
    isoprenoid biosynthetic program (sterols and non-sterol isoprenoids), acting
    as a soluble cytosolic enzyme.
  molecular_function:
    id: GO:0004163
    label: diphosphomevalonate decarboxylase activity
  directly_involved_in:
  - id: GO:0008299
    label: isoprenoid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:18823933
    supporting_text: "The reaction is required for production of polyisoprenoids and sterols from acetyl-CoA."
  - reference_id: PMID:14972328
    supporting_text: "We found a\ncytosolic localization for both endogenous human mevalonate pyrophosphate\ndecarboxylase"
proposed_new_terms: []
suggested_questions:
- question: >-
    Beyond its metabolic role, does the MVD-mortalin (HSP70) interaction have a
    regulatory function on MVD stability or activity, or is it primarily relevant
    to mortalin-controlled proliferation?
suggested_experiments:
- description: >-
    Structure-guided kinetic characterization of the full panel of POROK7 missense
    variants to quantify how each affects diphosphomevalonate decarboxylase
    activity and homodimer stability, correlating biochemical severity with
    clinical presentation.