MRX20 (YFR045W / P43617) — curation notes

Journal for the AI GO-annotation review of Saccharomyces cerevisiae MRX20.
Provenance is recorded inline as [SOURCE "verbatim supporting text"] where possible.

Identity (resolved carefully — there is a genuine name/function tension)

• SGD standard name = MRX20; systematic name YFR045W; UniProt P43617
  (entry name YFL5_YEAST). SGD confirms MRX20 is the standard name and expands it
  as "Mitochondrial oRganization of gene eXpression"
  [https://www.yeastgenome.org/locus/YFR045W].
• Important: UniProt P43617 itself does NOT carry the MRX20 gene name; it lists
  only OrderedLocusNames=YFR045W and describes the protein as
  "Uncharacterized mitochondrial carrier YFR045W" (RecName)
  [genes/yeast/MRX20/MRX20-uniprot.txt line 6-7].
• The "Mrx" name series (Mrx1–Mrx21) was coined by the MIOREX study
  (Kehrein et al. 2015, Cell Reports, PMID:25683707): previously uncharacterized
  proteins that co-purified by quantitative mass spectrometry with native
  mitochondrial-ribosome ("MIOREX") complexes were given Mrx numbers. SGD's
  "name description" reference for MRX20 is this paper. Being pulled down with
  MIOREX complexes is a proteomic association, not a demonstrated molecular
  function. The abstract describes MIOREX as ribosome interactomes
  PMID:25683707.
  I could NOT obtain the full text (not open access; PubMed MCP unauthenticated),
  so I do not have a verbatim, MRX20-specific quote from this paper and treat its
  MRX20-specific content as an association only.

The core tension

The name "MRX20" suggests a role in mitochondrial gene expression, but every
structural/sequence line of evidence says this is a mitochondrial carrier
(SLC25 / MCF; TC 2.A.29) family inner-membrane transporter. These two facts are
not contradictory — an integral inner-membrane carrier could plausibly be found in
the vicinity of membrane-tethered translation machinery — but they mean the gene's
actual molecular function (what it transports, if anything) is unknown.

Domain / sequence analysis (done inline from the UniProt record)

Source: genes/yeast/MRX20/MRX20-uniprot.txt

• 309 aa, ~34.4 kDa. PE=3 (inferred from homology). No experimental structure; AlphaFold model exists.
• Mitochondrial carrier family (MCF/SLC25): SIMILARITY ... Belongs to the mitochondrial carrier (TC 2.A.29) family (line 73). Pfam PF00153 Mito_carr ×3;
  PROSITE PS50920 SOLCAR ×3; PRINTS MITOCARRIER; InterPro IPR002067 (MCP),
  IPR023395 (MCP_dom_sf), IPR018108 (MCP_transmembrane), IPR049563 (TXTP-like);
  Gene3D 1.50.40.10 mitochondrial carrier domain; SUPFAM SSF103506 (lines 116–126).
• Six TM helices (12–32, 47–67, 100–120, 184–204, 222–242, 285–305) and
  three tandem Solcar repeats (6–83, 97–211, 216–302) (lines 133–156) — the
  canonical MCF three-repeat / six-TM architecture (pseudo-3-fold symmetry).
• Subcellular location: Mitochondrion inner membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305} (lines 71–72). KW Mitochondrion,
  Mitochondrion inner membrane, Transmembrane, Transport (lines 128–129).
• PANTHER: family PTHR45788 "SUCCINATE/FUMARATE MITOCHONDRIAL
  TRANSPORTER-RELATED"; subfamily PTHR45788:SF5 "AFR253WP" (lines 121–122).

Subfamily context is decisive for judging the IBA "citrate" annotations

From interpro/panther/PTHR45788/PTHR45788-entries.csv (reviewed members):
- The broad family PTHR45788 contains the characterized tricarboxylate/citrate
carriers CTP1 (P38152, S. cerevisiae), SLC25A1 (human P53007, bovine P79110,
rat P32089, mouse), SFC1 succinate/fumarate carrier (P33303, S. cerevisiae),
plant SFC1 (Q9M038), Aspergillus ctpA/B/C, etc.
- But MRX20's own subfamily PTHR45788:SF5 ("AFR253WP") contains ONLY
Saccharomyces-lineage uncharacterized carriers: P43617 (YFR045W itself),
A7A285 (SCY_1795), B3LUQ6 (SCRG_05595), B5VI70 (AWRI1631_61110) — all annotated
"Uncharacterized mitochondrial carrier". No SF5 member has a demonstrated
substrate.
- => The GOA IBA annotations for citrate secondary active transmembrane
transporter activity (GO:0071913) and mitochondrial citrate transmembrane
transport (GO:0006843) are propagated from the family level (driven by the
CTP1/SLC25A1 clade), NOT from MRX20's own uncharacterized subfamily. This is a
classic over-specific IBA propagation: MRX20 is very likely a carrier, but the
citrate substrate assignment is not supported for it specifically.

Literature (sparse — this is a dark gene)

1. Belenkiy et al. 2000, Biochim Biophys Acta, PMID:10930523 (abstract only).
2. Systematic survey/resequencing of the 35 yeast mitochondrial transport
   proteins (MTPs); YFR045W is one of them.
   PMID:10930523
3. The five MTP consensus residues (present in MTPs with identified transport
   function) were confirmed present in YFR045W after resequencing
   PMID:10930523.
4. Expression of YFR045W is stress-inducible
   PMID:10930523.
5. This is the ISS source SGD used for the "mitochondrial inner membrane"
   and "mitochondrial transport" annotations (GOA original_reference_id
   PMID:10930523; note SGD's with/from points to paralogs SGD:S000003838 and
   SGD:S000005027).

6. NOTE: abstract reports YFR045W resequenced to 285 aa; current UniProt sequence
   is 309 aa (SEQUENCE CAUTION notes an earlier erroneous gene model / frameshift,
   lines 75–78) — the annotation predates the corrected model but the MCF family
   assignment is unaffected.

7. Kehrein et al. 2015, Cell Reports, PMID:25683707 (abstract only).

8. Source of the MRX20 name; MIOREX (mitochondrial ribosome) co-purification by
   quantitative MS. Provides only an association, no molecular function for
   MRX20. (See "Identity" above.)

9. SGD large-scale phenotype data (https://www.yeastgenome.org/locus/YFR045W):
   null mutant is viable; "decreased levels of chitin and normal resistance to
   calcofluor white"; high-throughput screens additionally report decreased chitin
   deposition, decreased competitive fitness, increased chronological lifespan, and
   abnormal vacuolar morphology. All non-specific/pleiotropic; none pins a molecular
   function. Protein abundance ~710 molecules/cell (low). Not recorded as a
   dedicated citable PMID here; treated as background, not used for a specific GO
   claim.

Assessment summary (what is KNOWN vs NOT known)

KNOWN (well supported):
- Integral mitochondrial inner-membrane protein, multi-pass (6 TM). [homology/ISS/subcell]
- Member of the mitochondrial carrier (SLC25/MCF) family with canonical
three-repeat architecture. [Pfam/PROSITE/PANTHER/InterPro]
- Almost certainly functions in transmembrane transport (family-level). [InterPro IEA + family]
- Stress-inducible expression; non-essential; low abundance. [PMID:10930523; SGD HTP]

NOT known (genuine knowledge gaps):
- Transported substrate / specific molecular function — SF5 subfamily is
entirely uncharacterized; citrate assignment is a family-level IBA over-propagation.
- Whether MRX20 has any direct role in mitochondrial gene expression (the "MRX"
name reflects only MIOREX proteomic co-purification, not a demonstrated function).
- Physiological process / pathway it serves; loss-of-function phenotypes are
weak and pleiotropic.
- Whether it is a genuine transporter or a pseudo-transporter (no substrate assay exists).

Curation decisions (rationale)

• C: mitochondrial inner membrane (ISS, PMID:10930523) → ACCEPT (core; strong homology + MCF membrane protein).
• C: mitochondrial inner membrane (IEA, GO_REF:0000044 SubCell) → ACCEPT (consistent, redundant with ISS).
• C: mitochondrion (IBA) → ACCEPT as non-core (correct but less specific than inner membrane).
• 2026-09-28 IBA re-review: the broad mitochondrion IBA at PTN002909487 was
  retained as a safe non-core mitochondrial-carrier localization, and the existing
  structured over-annotation calls for the PTN000640552 citrate rows were retained.
  A newer yeast SLC25 review, PMID:40836422, still lists Mrx20/YFR045W as unknown.
• 2026-09-30 IBA re-review: refreshed PTHR45788 PAINT and found the same three
  IBA-bearing nodes. The structured propagation reviews now keep the ancestral
  PAINT nodes and the curated seed donors that the transfer arguments rest on.
  The citrate rows remain over-specific because PTN000640552 spans the
  characterized PTHR45788:SF4 CTP1/SLC25A1 branch and the uncharacterized MRX20
  PTHR45788:SF5 branch.
• P: transmembrane transport (IEA InterPro) → ACCEPT (family-level; correct general process).
• P: mitochondrial transport (ISS, PMID:10930523) → ACCEPT/KEEP (general, defensible).
• F: citrate secondary active transmembrane transporter activity (IBA) → MARK_AS_OVER_ANNOTATED
  (family-level propagation; MRX20's SF5 subfamily has no citrate-transport member; substrate unknown).
• P: mitochondrial citrate transmembrane transport (IBA) → MARK_AS_OVER_ANNOTATED (same reason).
• F: molecular_function (ND) → ACCEPT (honestly records that MF is unknown; do not invent one).

core_functions: only the defensible general MF ("transmembrane transporter activity",
GO:0022857) with location mitochondrial inner membrane (GO:0005743). No specific
substrate claimed.