erg8

UniProt ID: Q4WV38
Organism: Aspergillus fumigatus Af293
Review Status: COMPLETE
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Gene Description

erg8 (AFUA_5G10680) encodes the fungal GHMP-type phosphomevalonate kinase that phosphorylates (R)-5-phosphomevalonate with ATP to form (R)-5-diphosphomevalonate. This is the second kinase step of isopentenyl diphosphate formation from mevalonate and supplies prenyl diphosphate precursors for ergosterol biosynthesis in Aspergillus fumigatus.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004631 phosphomevalonate kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN001274235, the fungal/plant GHMP phosphomevalonate kinase node seeded by Arabidopsis PMK and S. cerevisiae ERG8. Q4WV38 is in fungal PTHR31814:SF2, and the same phosphomevalonate kinase reaction is curated on the A. fumigatus Swiss-Prot record, so this is the core molecular function.
Supporting Evidence:
file:interpro/panther/PTHR31814/PTHR31814-paint.tsv
PTHR31814 PTN001274235 GO:0004631 F IBD false
file:ASPFU/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
GO:0004631 phosphomevalonate kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated annotation from the yeast ERG8 ortholog, Erg8 InterPro signature, RHEA:16341, and EC:2.7.4.2. These all match the curated Q4WV38 phosphomevalonate kinase reaction.
Supporting Evidence:
file:ASPFU/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
file:ASPFU/erg8/erg8-uniprot.txt
DR InterPro; IPR035102; Phosphomevalonate_kinase.
GO:0005524 ATP binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: InterPro2GO from the GHMP kinase N-terminal domain. ATP is the phosphoryl donor in the Erg8 phosphomevalonate kinase reaction, so the binding term is correct but subsidiary to the kinase molecular function.
Reason: ATP binding is substrate binding implied by the accepted phosphomevalonate kinase activity.
Supporting Evidence:
file:ASPFU/erg8/erg8-uniprot.txt
DR InterPro; IPR006204; GHMP_kinase_N_dom.
file:ASPFU/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
GO:0005777 peroxisome
IBA
GO_REF:0000033
REMOVE
Summary: IBA from PTN000781523, a plant peroxisomal PMK node seeded only by Arabidopsis AT1G31910. The PTHR31814 family review already marks this peroxisome node as needing pruning for the fungal PMK subfamily.
Reason: PTN000781523 propagates a plant-lineage compartment to fungal Erg8 proteins; this is a compartment and taxon mismatch, not evidence that A. fumigatus erg8 acts in peroxisomes.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH
Sources checked:
PANTHER:PTN000781523 Β· PTN000781523 SUPPORTS SOURCE BUT NOT TARGET
The Arabidopsis-seeded peroxisome node should not propagate to fungal PTHR31814:SF2 Erg8 proteins.
Supporting Evidence:
file:interpro/panther/PTHR31814/PTHR31814-paint.tsv
PTHR31814 PTN000781523 GO:0005777 C IBD false
file:interpro/panther/PTHR31814/PTHR31814-review.yaml
Peroxisome is removed by both the S. cerevisiae ERG8 and S. pombe erg8 reviews
GO:0006696 ergosterol biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from fungal node PTN001274236, seeded by yeast ERG8. A. fumigatus Erg8 produces the mevalonate-pathway intermediate that is converted to isopentenyl diphosphate and farnesyl diphosphate, a direct precursor route for fungal ergosterol.
Supporting Evidence:
file:interpro/panther/PTHR31814/PTHR31814-paint.tsv
PTHR31814 PTN001274236 GO:0006696 P IBD false
file:ASPFU/erg8/erg8-uniprot.txt
Phosphomevalonate kinase; part of the second module of ergosterol biosynthesis pathway
GO:0006696 ergosterol biosynthetic process
IEA
GO_REF:0000107
ACCEPT
Summary: Ensembl Compara transfer from yeast ERG8 to the A. fumigatus erg8 ortholog. The transferred ergosterol-biosynthesis process is consistent with the curated PMK reaction and fungal PAINT node.
Supporting Evidence:
file:interpro/panther/PTHR31814/PTHR31814-paint.tsv
PTHR31814 PTN001274236 GO:0006696 P IBD false
file:ASPFU/erg8/erg8-uniprot.txt
Phosphomevalonate kinase; part of the second module of ergosterol biosynthesis pathway
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN001274235. The phosphomevalonate kinase reaction is step 2/3 in the UniProt-curated isopentenyl diphosphate biosynthetic route from mevalonate, so this is a direct core biological process for Erg8.
Supporting Evidence:
file:interpro/panther/PTHR31814/PTHR31814-paint.tsv
PTHR31814 PTN001274235 GO:0019287 P IBD false
file:ASPFU/erg8/erg8-uniprot.txt
via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated annotation from the yeast ortholog and UniPathway UPA00057. This matches the Q4WV38 pathway statement that Erg8 catalyzes the second step of IPP biosynthesis from mevalonate.
Supporting Evidence:
file:ASPFU/erg8/erg8-uniprot.txt
via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
file:ASPFU/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +

Core Functions

ATP-dependent phosphorylation of (R)-5-phosphomevalonate to (R)-5-diphosphomevalonate, the second of three reactions that convert mevalonate to isopentenyl diphosphate and feed fungal ergosterol biosynthesis.

Supporting Evidence:
  • file:ASPFU/erg8/erg8-uniprot.txt
    Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate +
  • file:interpro/panther/PTHR31814/PTHR31814-review.yaml
    GHMP-kinase phosphomevalonate kinases phosphorylate mevalonate 5-phosphate to mevalonate 5-diphosphate

References

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Notes

(erg8-notes.md)

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