LYRM7 (Q5U5X0) review notes
Identity
- Human LYRM7 = LYR motif-containing protein 7; synonyms C5orf31, MZM1L. HGNC:28072. 104 aa.
- Ortholog of S. cerevisiae Mzm1 (SGD:S000002901; PANTHER PTN005318945). Complex I LYR family / MZM1-LYRM7 InterPro family (IPR045298, IPR050435; Pfam PF05347 Complex1_LYR).
Core function (verified)
- Mitochondrial-matrix assembly chaperone for respiratory Complex III (cytochrome bc1 / ubiquinol-cytochrome c reductase). Non-catalytic.
- Specifically a UQCRFS1 (Rieske Fe-S protein) chaperone: binds and stabilises UQCRFS1 in the mitochondrial matrix prior to its [2Fe-2S] cluster insertion, translocation and incorporation into the late CIII dimeric intermediate in the inner membrane.
- PMID:23168492
- PMID:23168492
- LYR motif engages the Fe-S transfer cochaperone HSC20/HSCB (Q8IWL3): the UQCRFS1-LYRM7 intermediate recruits HSC20-HSPA9-ISCU to deliver the [2Fe-2S] cluster to UQCRFS1.
- PMID:28380382
- PMID:24606901
Localisation (verified)
- Mitochondrial matrix (IDA, PMID:23168492; UniProt SUBCELLULAR LOCATION: Mitochondrion matrix). Also mitochondrial membrane (IDA, PMID:23168492 — consistent with association with the inner-membrane CIII intermediate). HTP mito proteome PMID:34800366.
Disease (context, not a GO annotation here)
- Mitochondrial complex III deficiency, nuclear type 8 (MC3DN8; MIM:615838). Homozygous D25N impairs Rieske Fe-S incorporation into CIII; early-onset encephalopathy/leukoencephalopathy, lactic acidosis, severe CIII activity reduction. PMID:24014394.
GOA interactors (IPI WITH/FROM accessions)
- P47985 = UQCRFS1 (Rieske) — the physiological client. Cited by PMID:23168492, 27499296, 28380382, 33961781, 40205054.
- Q8IWL3 = HSCB/HSC20 — the Fe-S cochaperone. Cited by PMID:24606901, 28380382.
- P21673 = SAT1 (diamine acetyltransferase) — from HuRI binary interactome (PMID:32296183); no known mitochondrial/CIII role; likely non-physiological Y2H hit.
GO term decisions
- MF: GO:0044183 protein folding chaperone (IBA + Reactome TAS) is the correct non-catalytic MF. Keep as core. Do NOT invent a catalytic MF.
- BP core: GO:0034551 mitochondrial respiratory chain complex III assembly (IDA/IBA/IEA/TAS) — accept as core.
- CC: GO:0005759 mitochondrial matrix (IDA + IBA + IEA + TAS) core; GO:0005739 mitochondrion (IEA/HTP) broader-accept; GO:0031966 mitochondrial membrane (IDA) accept as non-core (association with membrane CIII intermediate).
- GO:0006457 protein folding (IEA, inferred from the chaperone MF) — accept, general but sound.
- GO:0045333 cellular respiration (IDA) — LYRM7 is an assembly factor, not itself part of respiration; the phenotype of its loss is impaired respiration. Mark as over-annotated (indirect; complex III assembly is the precise BP).
- GO:0005515 protein binding IPIs — bare, uninformative MF; per policy MARK_AS_OVER_ANNOTATED (do not REMOVE). SAT1 hit noted as likely non-physiological but not removed.
- Note: current CIII complex term is GO:0045275 (GO:0005750 obsolete); no complex-membership annotation is present in this GOA, and LYRM7 is a transient assembly factor, not a stable CIII subunit, so no in_complex is asserted.