Affinage

COA1

Cytochrome c oxidase assembly factor 1 homolog · UniProt Q9GZY4

Length
146 aa
Mass
16.7 kDa
Annotated
2026-04-28
27 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COA1 is a mitochondrial assembly factor that functions at the interface of respiratory complex biogenesis and mitochondrial translation regulation. In yeast, Coa1 is essential for early Cox1 maturation during cytochrome c oxidase (complex IV) assembly: it cooperates with Shy1 and associates with Cox14, Coa3, and newly synthesized Cox1 to sequester the translational activator Mss51, thereby coupling COX1 translation to downstream assembly and preventing Cox1 degradation (PMID:17882259, PMID:20876281, PMID:18541668). In human cells, the ortholog MITRAC15/COA1 has been repurposed as a component of the MCIA complex (with NDUFAF1, ECSIT, ACAD9, TMEM126B), where it associates with the ribosome-nascent chain complex during ND2 translation and is required for ND2 module assembly into complex I, with ACAD9 binding the ND2 polypeptide downstream of COA1 (PMID:31721420, PMID:32320651). Genetic epistasis in yeast places Coa1 upstream of Cox1 hemylation by Cox10, establishing its role at one of the earliest committed steps in Cox1 biogenesis (PMID:19841065).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2007 High

    Identification of Coa1 as a novel complex IV assembly factor resolved how Shy1-dependent assembly intermediates form, establishing that a previously uncharacterized mitochondrial protein is required for early subcomplexes of cytochrome c oxidase.

    Evidence Gene deletion, co-immunoprecipitation, and BN-PAGE of assembly intermediates in yeast

    PMID:17882259

    Open questions at the time
    • Molecular mechanism by which Coa1 promotes subcomplex formation was unknown
    • Whether Coa1 had a role in translational regulation was not addressed
    • No structural information on Coa1 or its complexes
  2. 2008 High

    Demonstrating that absence of Coa1 leads to rapid Cox1 degradation and that Coa2 acts downstream established Coa1 as a guardian of newly synthesized Cox1 at an early maturation step, ordering the assembly pathway.

    Evidence Genetic suppressor analysis and pulse-chase analysis of Cox1 stability in yeast deletion strains

    PMID:18541668

    Open questions at the time
    • Whether Coa1 directly contacts Cox1 or acts indirectly was not determined
    • Relationship to Mss51 translational feedback was not yet established
  3. 2010 High

    Two contemporaneous studies placed Coa1 upstream of Cox1 hemylation and within the Mss51-containing translational feedback complex, revealing that Coa1 couples COX1 translation to assembly by sequestering the translational activator Mss51 together with Cox14 and Coa3.

    Evidence Co-IP of Mss51–Coa1–Cox14–Coa3–Cox1 complexes, pulse-chase radiolabeling, and genetic epistasis with Cox10 gain-of-function alleles in yeast

    PMID:19841065 PMID:20876281

    Open questions at the time
    • Stoichiometry and direct binding interfaces within the Mss51-sequestering complex were not resolved
    • Whether Coa1's role extended beyond complex IV was unknown
  4. 2019 High

    Showing that human MITRAC15/COA1 is required for ND2 translation and resides on the ribosome-nascent chain complex revealed a striking functional divergence from yeast — the mammalian ortholog participates in complex I rather than complex IV biogenesis.

    Evidence MITRAC15 knockout human cell line, ribosome-nascent chain isolation, chemical crosslinking, and metabolic labeling of mitochondrial translation products

    PMID:31721420

    Open questions at the time
    • Structural basis for COA1 recognition of the ND2 nascent chain was unknown
    • Whether COA1 also retains any complex IV function in human cells was not resolved
  5. 2020 High

    Establishing COA1 as a bona fide MCIA complex subunit (alongside NDUFAF1, ECSIT, ACAD9, TMEM126B) unified its translational role with the known complex I assembly machinery, showing that loss of COA1 destabilizes the entire MCIA complex.

    Evidence CRISPR knockout, BN-PAGE, co-IP/mass spectrometry, and metabolic labeling in human cells

    PMID:32320651

    Open questions at the time
    • How COA1 is recruited to the mitoribosome during ND2 translation is not structurally resolved
    • Whether COA1 loss causes disease in humans has not been demonstrated
    • The precise handoff mechanism from COA1 to ACAD9 on the ND2 polypeptide is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for COA1's chaperone-like activity on nascent mitochondrial subunits, the molecular determinants of its evolutionary switch from complex IV to complex I assembly between yeast and mammals, and whether COA1 mutations cause human mitochondrial disease remain unresolved.
  • No high-resolution structure of COA1 alone or in the MCIA complex
  • No Mendelian disease association established for COA1
  • Mechanism of functional divergence between yeast Coa1 (complex IV) and human COA1 (complex I) is unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 3
Localization
GO:0005739 mitochondrion 5
Partners
ACAD9COA3COX14ECSITMSS51NDUFAF1SHY1TMEM126B
Complex memberships
MCIA complexMss51-Cox14-Coa3-Cox1 complex

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Coa1 (YIL157c) is a novel assembly factor for cytochrome c oxidase (complex IV) in yeast that cooperates with Shy1; formation of complex IV subcomplexes (assembly intermediates) depends on Coa1, and Shy1 associates with these Coa1-dependent intermediates. Genetic deletion, co-immunoprecipitation, blue-native PAGE analysis of assembly intermediates The EMBO journal High 17882259
2010 Coa1 binding to Mss51 in complex with Cox14, Coa3, and newly synthesized Cox1 is essential for full inactivation of Mss51 (translational regulator), placing Coa1 as a key component of the negative feedback loop that couples COX1 translation to cytochrome c oxidase assembly. Co-immunoprecipitation, pulse-chase radiolabeling of newly synthesized Cox1, analysis of Mss51 complex equilibrium in deletion mutants The Journal of cell biology High 20876281
2008 Coa2 suppresses respiratory deficiency of coa1Δ cells and functions downstream of the Mss51-Coa1 step in Cox1 maturation; Coa1 and Shy1 function at an early step in Cox1 maturation, and absence of Coa1 leads to rapid degradation of newly synthesized Cox1. Genetic suppressor analysis, respiratory growth assays, pulse-chase analysis of Cox1 stability in deletion strains Molecular and cellular biology High 18541668
2010 The Cox10 N196K gain-of-function suppressor allele (which enhances heme a addition to Cox1) rescues coa2Δ cells but lacks suppressor activity for coa1Δ and shy1Δ cells, indicating that Coa1 acts at an earlier step than Cox1 hemylation. Genetic epistasis, suppressor analysis with Cox10 alleles, respiratory growth assays Molecular and cellular biology Medium 19841065
2016 The I101F Cox1 gain-of-function suppressor mutation restores respiration in cox23Δ cells but fails to rescue respiratory growth in cells lacking Coa1 (or Coa2, Cox14, Shy1, Cox17, Cox19), demonstrating the specificity and essential nature of Coa1 in cytochrome c oxidase biogenesis. Genetic epistasis, suppressor mutation mapping, deletion of assembly factor genes in suppressor background Microbial cell Medium 28357365
2019 Human MITRAC15/COA1 is required for translation of the mitochondrial-encoded complex I subunit ND2; MITRAC15 is a constituent of a ribosome-nascent chain complex during ND2 translation, and ACAD9 binds the ND2 polypeptide at its C-terminus downstream of MITRAC15 binding. MITRAC15 knockout cell line, ribosome-nascent chain complex isolation, chemical crosslinking analysis, metabolic labeling of mitochondrial translation products EMBO reports High 31721420
2020 Human COA1/MITRAC15 is a bona fide component of the mitochondrial complex I intermediate assembly (MCIA) complex (with NDUFAF1, ECSIT, ACAD9, TMEM126B); loss of COA1 causes MCIA complex defects and reduced complex I assembly, and COA1 specifically enriches with newly translated ND2. CRISPR knockout, blue-native PAGE, co-immunoprecipitation/mass spectrometry, metabolic labeling of mitochondrial translation products Cell reports High 32320651
2003 The COA-1 (colorectal tumor-associated antigen-1) gene product, whose transcript is nearly identical to Socius (a protein binding members of the Rnd family of GTPases), is recognized by CD4+ T-cell clones in an HLA-DRβ1-restricted manner; the tumor-derived COA-1 contains a single nucleotide substitution near the C-terminus relative to normal cell types, which may affect localization or processing of the protein. cDNA library screening with T-cell clone, T-cell recognition assays, sequence analysis of tumor vs. normal COA-1 transcripts Cancer research Medium 14583468
2021 COA1/MITRAC15 promotes mitochondrial translation (chaperone-like role) and its gene has been recurrently lost in lineages relying heavily on glycolytic muscle fibers (cheetah, galliform birds, certain rodents), demonstrating conditional dispensability linked to skeletal muscle fiber composition. Comparative genomics, genome re-sequencing, evolutionary analysis of gene-disrupting mutations across species Scientific reports Low 34952909

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Shy1 couples Cox1 translational regulation to cytochrome c oxidase assembly. The EMBO journal 113 17882259
2010 Coa3 and Cox14 are essential for negative feedback regulation of COX1 translation in mitochondria. The Journal of cell biology 102 20876281
2013 Cancer-initiating cells from colorectal cancer patients escape from T cell-mediated immunosurveillance in vitro through membrane-bound IL-4. Journal of immunology (Baltimore, Md. : 1950) 94 24277698
2020 Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly Complex Factors in the Biogenesis of Complex I. Cell reports 82 32320651
2008 Coa2 is an assembly factor for yeast cytochrome c oxidase biogenesis that facilitates the maturation of Cox1. Molecular and cellular biology 41 18541668
2019 CD4 T cells target colorectal cancer antigens upregulated by oxaliplatin. International journal of cancer 39 31396953
2019 MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome-nascent chain complex. EMBO reports 36 31721420
2010 The role of Coa2 in hemylation of yeast Cox1 revealed by its genetic interaction with Cox10. Molecular and cellular biology 35 19841065
2006 Structural and functional studies suggest a catalytic mechanism for the phosphotransacetylase from Methanosarcina thermophila. Journal of bacteriology 33 16428418
2017 MiR-127 and miR-376a act as tumor suppressors by in vivo targeting of COA1 and PDIA6 in giant cell tumor of bone. Cancer letters 32 28866093
2015 Restoration of miR-127-3p and miR-376a-3p counteracts the neoplastic phenotype of giant cell tumor of bone derived stromal cells by targeting COA1, GLE1 and PDIA6. Cancer letters 26 26655997
2004 FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors. The Journal of steroid biochemistry and molecular biology 26 15698540
2003 Identification of a colorectal tumor-associated antigen (COA-1) recognized by CD4(+) T lymphocytes. Cancer research 26 14583468
2012 The mutation in Chd7 causes misexpression of Bmp4 and developmental defects in telencephalic midline. The American journal of pathology 24 22658483
2003 Cochlioquinone A1, a new anti-angiogenic agent from Bipolaris zeicola. Bioorganic & medicinal chemistry 19 14556789
1991 Enzyme-linked immunosorbent assay for detection of antibodies against Mycobacterium paratuberculosis in goats. American journal of veterinary research 19 1883088
2016 Whole Genome Re-Sequencing Identifies a Quantitative Trait Locus Repressing Carbon Reserve Accumulation during Optimal Growth in Chlamydomonas reinhardtii. Scientific reports 12 27141848
2021 Recurrent erosion of COA1/MITRAC15 exemplifies conditional gene dispensability in oxidative phosphorylation. Scientific reports 11 34952909
2008 Induction of both CD8+ and CD4+ T-cell-mediated responses in colorectal cancer patients by colon antigen-1. Clinical cancer research : an official journal of the American Association for Cancer Research 10 18974390
2016 Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis. Microbial cell (Graz, Austria) 8 28357365
2011 Metabolic engineering of soybean affords improved phytosterol seed traits. Plant biotechnology journal 8 21554529
2021 Association of COA1 with Patellar Tendonitis: A Genome-wide Association Analysis. Medicine and science in sports and exercise 5 34081057
2024 The secretory protein COA1 enables Metarhizium robertsii to evade insect immune recognition during cuticle penetration. Communications biology 4 39349686
2023 Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model. International journal of molecular sciences 4 37047078
2019 Coagulase gene polymorphisms of Staphylococcus aureus isolates from patients at Kosti Teaching Hospital, Sudan. Access microbiology 2 32974518
1992 Evaluation of an enzyme immunoassay and a modified coagglutination assay for typing gonococcal isolates with monoclonal antibodies. Sexually transmitted diseases 2 1411837
2024 [Effects of PIM1 Gene on Proliferation, Apoptosis and JAK2/STAT3 Signaling Pathway of Acute Myeloid Leukemia U937 Cells]. Zhongguo shi yan xue ye xue za zhi 0 38926951