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Showing COA1 — MITRAC15 is a alias.

COA1

Cytochrome c oxidase assembly factor 1 homolog · UniProt Q9GZY4

Length
146 aa
Mass
16.7 kDa
Annotated
2026-06-09
28 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COA1 (MITRAC15) is a mitochondrial respiratory-chain assembly factor with conserved but functionally divergent roles in the biogenesis of cytochrome c oxidase (complex IV) in yeast and complex I in humans (PMID:17882259, PMID:32320651). In yeast, Coa1 cooperates with Shy1 at an early step of Cox1 maturation, where it is required for the formation of early complex IV subcomplexes and acts upstream of the Coa2-dependent, Cox10-mediated heme a insertion step (PMID:17882259, PMID:18541668, PMID:19841065). Mechanistically, Coa1 binding to the Mss51–Cox14–Coa3–Cox1 intermediate is essential for trapping the translational activator Mss51 in its latent, translation-resting state, thereby coupling Cox1 translation to downstream cytochrome c oxidase assembly through a negative feedback loop (PMID:20876281). Genetic epistasis with gain-of-function Cox1 alleles confirms that Coa1 is specifically and non-bypassably required for Cox1 maturation (PMID:28357365). In human cells, COA1/MITRAC15 acts co-translationally at the mitochondrial ribosome exit tunnel as a component of a ribosome–nascent chain complex during translation of the complex I subunit ND2, handing the nascent chain to the ND2-specific assembly factor ACAD9 (PMID:31721420). COA1 is a bona fide subunit of the mitochondrial complex I intermediate assembly (MCIA) complex with NDUFAF1, ECSIT, ACAD9, and TMEM126B, and its loss destabilizes the MCIA complex and impairs complex I assembly (PMID:32320651).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2007 Medium

    Established COA1 as a novel complex IV assembly factor, defining where it acts: an early step required for formation of Shy1-associated Cox1 assembly intermediates.

    Evidence coa1∆ deletion with co-immunoprecipitation and blue-native PAGE detection of assembly intermediates in yeast

    PMID:17882259

    Open questions at the time
    • Molecular mechanism by which Coa1 promotes subcomplex formation not defined
    • Direct binding partners within the intermediate not resolved
  2. 2008 Medium

    Ordered Coa1 within the Cox1 maturation pathway by genetic epistasis, placing it upstream of Coa2 and the heme a3 insertion step.

    Evidence overexpression suppressor screen (COA2 suppresses coa1∆), respiratory growth and epistasis analysis in yeast

    PMID:18541668

    Open questions at the time
    • Biochemical step catalyzed or facilitated by Coa1 unknown
    • Whether Coa1 and Shy1 act in the same or parallel substeps unresolved
  3. 2010 Medium

    Defined Coa1's regulatory function in coupling Cox1 translation to assembly by showing it traps the translational activator Mss51 in a latent state.

    Evidence co-IP of assembly intermediates, pulse-labeling of mitochondrial translation, and COA1/COA3/COX14 deletions in yeast

    PMID:20876281

    Open questions at the time
    • Structural basis of Mss51 sequestration not determined
    • Stoichiometry and dynamics of the Mss51–Cox14–Coa3–Cox1 intermediate not defined
  4. 2010 Medium

    Distinguished Coa1's step from the Cox10 heme a addition step using allele-specific suppression, confirming Coa1 acts upstream and independently.

    Evidence allele-specific epistasis with gain-of-function Cox10 N196K in coa1∆, coa2∆, shy1∆ backgrounds

    PMID:19841065

    Open questions at the time
    • Direct molecular interaction of Coa1 with Cox1 not shown
    • Mechanism remains genetically rather than biochemically defined
  5. 2016 Medium

    Reinforced that Coa1 is a specific, non-bypassable requirement for Cox1 maturation distinct from other assembly factors.

    Evidence mitochondrial Cox1 I101F suppressor tested against a panel of CcO assembly factor deletions in yeast

    PMID:28357365

    Open questions at the time
    • Why the Cox1 allele cannot bypass Coa1 loss not mechanistically explained
  6. 2019 High

    Revealed the human function: MITRAC15/COA1 acts co-translationally at the ribosome exit tunnel during ND2 (complex I) synthesis, handing the nascent chain to ACAD9.

    Evidence MITRAC15 knockout cells, mitochondrial translation pulse-labeling, ribosome co-fractionation, and chemical crosslinking mass spectrometry

    PMID:31721420

    Open questions at the time
    • Direct structural contact of MITRAC15 with the ribosome or nascent ND2 not visualized
    • How MITRAC15 recognizes the ND2 nascent chain unknown
  7. 2020 High

    Established COA1 as a stable subunit of the MCIA complex whose loss destabilizes the complex and impairs complex I assembly.

    Evidence CRISPR/Cas9 COA1 knockout in human cells, blue-native PAGE, co-IP/MS of MCIA components, and translation assays

    PMID:32320651

    Open questions at the time
    • Structural arrangement of COA1 within MCIA not resolved
    • Whether the yeast Cox1 and human ND2 roles share a conserved biochemical mechanism unaddressed
  8. 2021 Low

    Comparative genomics linked COA1 function to OXPHOS demand, showing it is conditionally dispensable in glycolysis-reliant lineages.

    Evidence comparative genomics and genome re-sequencing across cheetah, galliform birds, and rodents

    PMID:34952909

    Open questions at the time
    • Computational/evolutionary inference only, no direct biochemical experiment on the protein
    • Physiological consequences of COA1 loss in these lineages not experimentally tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether the yeast Cox1/complex IV role and the human ND2/complex I role of COA1 reflect a single conserved biochemical mechanism or lineage-specific repurposing remains unresolved.
  • No structural model of COA1 in either complex
  • No cross-species functional complementation reported
  • Direct substrate-recognition mechanism undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 2
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-392499 Metabolism of proteins 1
Partners
ACAD9COA3COX14ECSITMSS51NDUFAF1SHY1TMEM126B
Complex memberships
MCIA complexMss51–Cox14–Coa3–Cox1 intermediate

Evidence

Reading pass · 8 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; Coa1 is required for formation of early complex IV subcomplexes that serve as assembly intermediates, and its loss prevents Shy1-associated subcomplexes from forming. Genetic analysis (coa1∆ deletion), co-immunoprecipitation, blue-native PAGE to detect assembly intermediates The EMBO journal Medium 17882259
2010 Coa1 binding to the Mss51–Cox14–Coa3–Cox1 complex is essential for full inactivation of Mss51 (trapping it in the latent, translation-resting state), thereby coupling Cox1 translational regulation to cytochrome c oxidase assembly in a negative feedback loop. Co-immunoprecipitation of assembly intermediates, pulse-labeling of mitochondrial translation products, genetic deletion of COA1/COA3/COX14 The Journal of cell biology Medium 20876281
2008 Coa2 was identified as a suppressor of coa1∆ respiratory deficiency, placing Coa1 upstream of Coa2 in Cox1 maturation; Coa1 and Shy1 function at an early step in Cox1 maturation, while Coa2 acts downstream at the Shy1-related heme a3 insertion step. Genetic suppressor screen (overexpression of COA2 suppresses coa1∆), respiratory growth assays, epistasis analysis Molecular and cellular biology Medium 18541668
2010 The gain-of-function Cox10 N196K suppressor allele restores respiration in coa2∆ cells but lacks suppressor activity for coa1∆ and shy1∆ cells, demonstrating that Coa1's role in Cox1 maturation is distinct from and upstream of the Cox10-mediated heme a addition step. Genetic epistasis — allele-specific suppression analysis using mutant Cox10 in coa1∆, coa2∆, shy1∆ backgrounds Molecular and cellular biology Medium 19841065
2016 The I101F Cox1 gain-of-function suppressor mutation restores respiration in cox23∆ cells but fails to suppress respiratory deficiency in cells lacking Coa1, Cox14, Coa2, Shy1, Cox17, or Cox19, demonstrating that Coa1 is specifically required for Cox1 maturation and cannot be bypassed by this Cox1 allele. Genetic epistasis — mitochondrial Cox1 suppressor mutation tested against panel of CcO assembly factor deletions including coa1∆ Microbial cell Medium 28357365
2019 MITRAC15/COA1 is required for translation of the mitochondrial complex I subunit ND2; MITRAC15 is a constituent of a ribosome–nascent chain complex during ND2 translation, and chemical crosslinking shows that the ND2-specific assembly factor ACAD9 binds the ND2 C-terminus downstream of MITRAC15, placing MITRAC15 co-translationally at the ribosome exit tunnel. MITRAC15 knockout cell lines, mitochondrial translation pulse-labeling, ribosome sedimentation/co-fractionation, chemical crosslinking mass spectrometry EMBO reports High 31721420
2020 COA1/MITRAC15 is a bona fide component of the mitochondrial complex I intermediate assembly (MCIA) complex (alongside NDUFAF1, ECSIT, ACAD9, and TMEM126B); COA1 loss causes MCIA complex instability and reduced complex I assembly, and COA1 enriches with newly translated ND2. CRISPR/Cas9 knockout of COA1 in human cells, blue-native PAGE, co-immunoprecipitation/mass spectrometry of MCIA complex components, mitochondrial translation assays Cell reports High 32320651
2021 COA1/MITRAC15 promotes mitochondrial translation (chaperone-like role in OXPHOS biogenesis) and is conditionally dispensable in species/lineages that predominantly rely on glycolytic rather than oxidative muscle fibers; gene-disrupting mutations have independently accumulated in cheetah, galliform birds, and rodents. Comparative genomics, genome re-sequencing of multiple species, evolutionary analysis of COA1 gene structure Scientific reports Low 34952909

Source papers

Stage 0 corpus · 28 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 114 17882259
2010 Coa3 and Cox14 are essential for negative feedback regulation of COX1 translation in mitochondria. The Journal of cell biology 104 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) 97 24277698
2020 Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly Complex Factors in the Biogenesis of Complex I. Cell reports 85 32320651
2008 Coa2 is an assembly factor for yeast cytochrome c oxidase biogenesis that facilitates the maturation of Cox1. Molecular and cellular biology 42 18541668
2019 CD4 T cells target colorectal cancer antigens upregulated by oxaliplatin. International journal of cancer 40 31396953
2019 MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome-nascent chain complex. EMBO reports 38 31721420
2010 The role of Coa2 in hemylation of yeast Cox1 revealed by its genetic interaction with Cox10. Molecular and cellular biology 36 19841065
2006 Structural and functional studies suggest a catalytic mechanism for the phosphotransacetylase from Methanosarcina thermophila. Journal of bacteriology 34 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
2003 Identification of a colorectal tumor-associated antigen (COA-1) recognized by CD4(+) T lymphocytes. Cancer research 27 14583468
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
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
2024 The secretory protein COA1 enables Metarhizium robertsii to evade insect immune recognition during cuticle penetration. Communications biology 5 39349686
2023 Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model. International journal of molecular sciences 5 37047078
2021 Association of COA1 with Patellar Tendonitis: A Genome-wide Association Analysis. Medicine and science in sports and exercise 5 34081057
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
2026 Large-scale meta- and cross-trait analyses uncover shared genetic risk factors for IBS and psychiatric disorders. Frontiers in psychiatry 0 42221328
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

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