ATP5MC1

Overview
ATP5MC1 (ATP synthase membrane subunit C locus 1) is a protein-coding gene in the species Homo sapiens. The gene encodes one of the three human paralogous proteins that form the c subunit of the membrane-embedded component (F₀) of mitochondrial ATP synthase, the enzyme complex responsible for the synthesis of adenosine triphosphate (ATP) during oxidative phosphorylation.

Gene and protein

• Location: Chromosome 17q24.2.
• Gene ID: 516 (Entrez Gene).
• Transcript variants: Multiple alternatively spliced transcripts have been reported, all of which encode the same mature protein.
• Protein: The ATP5MC1 protein is a small, highly hydrophobic proteolipid that integrates into the inner mitochondrial membrane as part of the proton channel of the F₀ complex. The mature protein is identical to the mature forms produced by its two paralogs, ATP5MC2 and ATP5MC3, differing only in their N‑terminal mitochondrial targeting sequences.

Function
Mitochondrial ATP synthase (Complex V) synthesizes ATP from ADP and inorganic phosphate, using the electrochemical gradient of protons generated by the electron transport chain across the inner mitochondrial membrane. The enzyme consists of two linked multi‑subunit sectors: the soluble catalytic domain (F₁) and the membrane‑spanning proton channel (F₀). ATP5MC1 contributes the c subunit to the F₀ sector, which assembles as a ring of nine c subunits forming the core of the proton‑conducting pathway. By rotating within the membrane, the c‑ring transduces proton flow into mechanical torque that drives conformational changes in the F₁ sector, leading to ATP synthesis.

Paralogs and isoforms
Humans possess three genes—ATP5MC1, ATP5MC2, and ATP5MC3—that encode the identical mature c subunit. Each gene contains a distinct mitochondrial targeting peptide, allowing differential regulation of import into mitochondria, but the final protein product incorporated into the ATP synthase complex is the same across the three loci.

Expression
ATP5MC1 is ubiquitously expressed in human tissues, reflecting the universal requirement for oxidative phosphorylation in most cell types. Data from the Human Protein Atlas indicate moderate to high protein levels in metabolically active tissues such as heart, skeletal muscle, and brain.

Clinical significance
To date, no pathogenic variants in ATP5MC1 have been definitively linked to human disease. Mutations affecting the c subunit of ATP synthase are rare, and most reported mitochondrial disorders involve other subunits or assembly factors. Consequently, accurate information on disease associations for ATP5MC1 is not confirmed.

References

1. Dyer MR, Walker JE. “Sequences of members of the human gene family for the c subunit of mitochondrial ATP synthase.” The Biochemical Journal 293 (1993): 51–64. PMID: 8328972.
2. Entrez Gene: ATP5MC1 ATP synthase membrane subunit c locus 1. National Center for Biotechnology Information.
3. UniProtKB: P05496 – ATP synthase F₀ complex subunit C1, mitochondrial.
4. The Human Protein Atlas – ATP5MC1 expression data.

This entry summarizes established scientific knowledge about the ATP5MC1 gene and its protein product, without speculation beyond the cited literature.