MCH2 (YKL221W) research notes

UniProt: P36032 (MCH2_YEAST) · Systematic name: YKL221W · SGD: S000001704
Standard name: MCH2 (Monocarboxylate transporter Homologue 2)

One-line summary

MCH2 is a dark Saccharomyces cerevisiae gene: a 473-aa polytopic membrane protein
of the Major Facilitator Superfamily (MFS), classified in the monocarboxylate porter
(MCT/TC 2.A.1.13) family by sequence homology, but with no demonstrated transport
substrate, no measured transport activity, and no defined physiological role. It is one
of five paralogous "monocarboxylate transporter homologues" (MCH1–MCH5) in budding yeast;
only Mch5p has an assigned substrate (riboflavin). MCH2's own substrate and direction are
unknown.

What is KNOWN (with provenance)

Sequence / domain architecture (high confidence)

Membrane topology (experimental, moderate confidence for the specific residue map)

Localization

Function — the negative result (this is the load-bearing experimental finding)

Paralog context (family-level)

What is NOT known (the gap)

  1. Transported substrate — undetermined. Ruled OUT: monocarboxylic acids (lactate,
    pyruvate, acetate). Not expected to be riboflavin (that is Mch5p; paralogs "unrelated").
  2. Transport direction / mechanism / driving force — unknown (uniport / symport /
    antiport; proton-coupled vs facilitated). The UniProt "Symport" keyword and the IEA
    symporter-activity term come from family/keyword mapping, not from an MCH2 assay.
  3. Physiological role / biological process — unknown. GOA carries ND for both MF and
    BP from SGD. No individual mch2Δ phenotype is established.
  4. Subcellular compartment of action — the plasma-membrane IBA call is a phylogenetic
    inference; direct MCH2 localization (plasma membrane vs endomembrane) is not firmly
    established in the files available here.
  5. Paralog redundancy — the only functional phenotype (reduced chemostat biomass) is
    from the mch1-5Δ quintuple mutant; whether MCH2 contributes, and whether the paralogs
    are redundant, is unresolved.

Existing GOA annotations (7) and disposition (planned)

  1. GO:0005886 plasma membrane — IBA (GO_REF:0000033) — KEEP_AS_NON_CORE (phylogenetic
    inference; MFS transporters are typically PM, but MCH2's own localization is not directly
    demonstrated; keep but do not treat as a solved core fact).
  2. GO:0022857 transmembrane transporter activity — IBA (GO_REF:0000033) — ACCEPT
    (generic; well supported by 12-TMS MFS fold; the ONLY defensible MF given no substrate).
  3. GO:0016020 membrane — IEA (GO_REF:0000044, SubCell) — ACCEPT (broad, correct).
  4. GO:0022857 transmembrane transporter activity — IEA (GO_REF:0000002, InterPro) — ACCEPT
    (same generic MF, InterPro route; correct at this generality).
  5. GO:0055085 transmembrane transport — IEA (GO_REF:0000002, InterPro) — ACCEPT
    (generic BP consistent with the fold; substrate/direction unknown so keep generic).
  6. GO:0003674 molecular_function — ND (GO_REF:0000015, SGD) — REMOVE (superseded by the
    generic transmembrane transporter activity terms already present; ND root is now
    redundant and less informative).
  7. GO:0008150 biological_process — ND (GO_REF:0000015, SGD) — REMOVE (superseded by the
    generic transmembrane transport BP term already present).

Note on the UniProt keyword block: the refreshed flatfile still carries the "Symport"
keyword, but no GO:0015293 DR line and no current QuickGO GOA row for GO:0015293 are
present. The "Symport" keyword is a family-level inference; there is no MCH2 symport
assay.

Sources consulted

Review completion (annotation dispositions, final)

All 7 GOA annotations reviewed (no monocarboxylate-specific term was actually present in GOA;
the two transporter-activity rows are already generic GO:0022857, which is the defensible level):

  1. GO:0005886 plasma membrane (IBA) — KEEP_AS_NON_CORE (phylogenetic inference; PM not directly
    demonstrated for MCH2; family study places some Mch proteins in intracellular membranes;
    propagation_review: NO_FAILURE_NON_CORE, traced to PAINT node PTN002260587).
  2. GO:0022857 transmembrane transporter activity (IBA) — ACCEPT (generic MF; the only defensible
    MF given no substrate; explicitly NOT specialized to a monocarboxylate term — no TM1 Lys, no
    motif A, experimental negative).
  3. GO:0016020 membrane (IEA/SubCell) — ACCEPT (correct; confirmed 12-TMS integral membrane protein).
  4. GO:0022857 transmembrane transporter activity (IEA/InterPro) — ACCEPT (same generic MF, InterPro route).
  5. GO:0055085 transmembrane transport (IEA/InterPro) — ACCEPT (generic BP; substrate/direction unknown).
  6. GO:0003674 molecular_function (ND/SGD) — REMOVE (root placeholder superseded by GO:0022857).
  7. GO:0008150 biological_process (ND/SGD) — REMOVE (root placeholder superseded by GO:0055085).

core_functions: single generic transmembrane transporter (GO:0022857) in membrane (GO:0016020);
substrate deliberately left open. knowledge_gaps: unknown substrate/direction/mechanism/biological
role (WHOLLY_DARK), substrate-level BP_DARK on the core function, and paralog-redundancy residual
sub-gap (mch1-5 quintuple-only phenotype). Validation clean: schema, references, terms all pass.

2026-09-28 spot re-review

Searched for newer MCH2/Mch2/YKL221W publications and did not find a 2024-2026 paper
that directly identifies MCH2's substrate, localization, or biological role. Re-checked the
two IBA rows against PANTHER PTHR11360: both GO:0022857 and GO:0005886 are placed at
PTN002260587, while the monocarboxylate, riboflavin, thyroid-hormone, lactate, creatine,
carboxylic-acid, and basolateral-plasma-membrane assertions sit on narrower descendant
nodes and do not propagate to MCH2.
The generic transporter IBA is still supported; the plasma-membrane IBA remains a plausible
but not directly demonstrated localization and was aligned with the IBA project by tracing
propagation_review.source_entities to the PAINT ancestral node rather than to the extant
MCH5 donor list.

2026-10-01 current-GOA refresh

Forced a current GOA/UniProt refresh and re-fetched the four cached PMIDs. Current GOA
still has the same seven exact rows and no retired assertions are needed: the two live
IBA rows, three live IEA rows, and two SGD ND placeholders all remain represented in
the review. The refresh backfilled current supporting_entities for the two
PTN002260587 IBA rows plus the SubCell and InterPro IEA rows; those source sets match
the current GOA WITH/FROM values.

Re-checked PANTHER PTHR11360 after the refresh. PTN002260587 still carries only the
broad GO:0022857 transmembrane transporter activity and GO:0005886 plasma membrane
IBDs inherited by MCH2, while the substrate-specific riboflavin (GO:0032218 on
PTN000888807), thyroid-hormone (GO:0015349/GO:0070327 on PTN002603511), lactate
(GO:0015129/GO:0035879 on PTN002603597 and GO:0015650/GO:0035879 on
PTN002603626), and creatine (GO:0015881 on PTN008516712) transport functions are
assigned on narrower descendant nodes outside the MCH2 branch. No new literature from
the MCH2/Mch2/YKL221W search identified a substrate, localization, or single-mutant
process for MCH2, so the action set remains unchanged: generic transport ACCEPT,
plasma membrane KEEP_AS_NON_CORE, and ND roots REMOVE.