Mitochondrial respiratory Complex IV (cytochrome c oxidase) — nuclear subunits and MT-CO1/CO2 assembly; COX5A/COX6A2/COX7B/COX8A + COX14/COX20

Respiratory Complex IV (cytochrome c oxidase, COX) is the terminal enzyme of the mitochondrial electron transport chain: it accepts electrons from reduced cytochrome c and uses them to reduce molecular oxygen to water, coupling this to proton pumping across the inner membrane. The three catalytic core subunits — MT-CO1 (the heme a/a3-CuB binuclear centre), MT-CO2 (the CuA centre) and MT-CO3 — are encoded by mitochondrial DNA; around ten nuclear-encoded structural subunits (COX4, COX5A, COX5B, COX6A/B/C, COX7A/B/C, COX8) surround and stabilise this core and modulate activity. Because the catalytic subunits are mtDNA-encoded and membrane-embedded, COX assembly is a highly ordered process guided by dedicated inner-membrane factors: COX14 (with COA3/MITRAC) couples MT-CO1 translation to its stepwise assembly, and COX20 chaperones the newly-made MT-CO2 through membrane insertion (with COX18) and copper (CuA) metallation by SCO1/SCO2, before the nuclear subunits are added. Inherited defects in the nuclear subunits or the assembly factors cause mitochondrial complex IV (cytochrome c oxidase) deficiency — a clinically heterogeneous group including Leigh syndrome, cardiomyopathy (COX6A2), X-linked linear skin defects with multiple congenital anomalies (COX7B) and encephalopathy/ataxia.

MODULE:mitochondrial_complex_ivDRAFTProtein Complexmodules/mitochondrial_complex_iv.yaml
mitochondrial electron transport, cytochrome c to oxygenGO:0006123 mitochondrial respiratory chain complex IV assemblyGO:0033617
GO:0006123
mitochondrial electron transport, cytochrome c to oxygen
The module is grounded in mitochondrial electron transport, cytochrome c to oxygen (GO:0006123) — the reaction catalysed by Complex IV.
GO:0033617
mitochondrial respiratory chain complex IV assembly
The dedicated factors (COX14, COX20) mediate mitochondrial respiratory chain complex IV assembly (GO:0033617).
Reactome:R-HSA-163214
Electron transfer from reduced cytochrome c to molecular oxygen
The catalytic reaction and the ordered subunit/MT-CO1/MT-CO2 assembly follow the human Reactome cytochrome-c-oxidase reactions R-HSA-163214, R-HSA-9865412 and R-HSA-9902096.
file:human/COX4I1/COX4I1-ai-review.yaml
COX4I1 gene review (human)
The COX4 nuclear structural subunit (UniProtKB:P13073) matches the previously completed human COX4I1 review (on main).
file:human/COX6A1/COX6A1-ai-review.yaml
COX6A1 gene review (human)
The ubiquitous COX6A structural subunit (UniProtKB:P12074) matches the previously completed human COX6A1 review (on main).
file:human/COX6B1/COX6B1-ai-review.yaml
COX6B1 gene review (human)
The COX6B structural subunit (UniProtKB:P14854) matches the previously completed human COX6B1 review (on main).
file:human/SCO1/SCO1-ai-review.yaml
SCO1 gene review (human)
The SCO1 copper metallochaperone (UniProtKB:O75880, GO:0016531) matches the previously completed human SCO1 review (on main).
file:human/SCO2/SCO2-ai-review.yaml
SCO2 gene review (human)
The SCO2 copper metallochaperone (UniProtKB:O43819, GO:0016531) matches the previously completed human SCO2 review (on main).
file:human/SURF1/SURF1-ai-review.yaml
SURF1 gene review (human)
The SURF1 assembly factor (UniProtKB:Q15526) matches the previously completed human SURF1 review (on main).
file:human/COX5A/COX5A-ai-review.yaml
COX5A gene review (human)
The COX5A structural subunit (UniProtKB:P20674, GO:0005198) matches the completed human COX5A review.
file:human/COX6A2/COX6A2-ai-review.yaml
COX6A2 gene review (human)
The heart/muscle COX6A2 structural subunit (UniProtKB:Q02221, GO:0005198) matches the completed human COX6A2 review.
file:human/COX7B/COX7B-ai-review.yaml
COX7B gene review (human)
The COX7B structural subunit (UniProtKB:P24311, GO:0005198) matches the completed human COX7B review.
file:human/COX8A/COX8A-ai-review.yaml
COX8A gene review (human)
The COX8A structural subunit (UniProtKB:P10176, GO:0005198) matches the completed human COX8A review.
file:human/COX14/COX14-ai-review.yaml
COX14 gene review (human)
The COX14 MT-CO1 assembly factor (UniProtKB:Q96I36, GO:0033617) matches the completed human COX14 review.
file:human/COX20/COX20-ai-review.yaml
COX20 gene review (human)
The COX20 MT-CO2 assembly chaperone (UniProtKB:Q5RI15, GO:0033617) matches the completed human COX20 review.
3Nodes
2Parts
0Variant Sets
0Variants
6Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:mitochondrial_complex_iv deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 0 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
COX14 Q96I36 ✓ ✓ ✗
COX20 Q5RI15 ✓ ✓ ✗
COX5A P20674 ✓ ✓ ✗
COX6A2 Q02221 ✓ ✓ ✗
COX7B P24311 ✓ ✓ ✗
COX8A P10176 ✓ ✓ ✗

Details

Context
mitochondrial inner membraneGO:0005743
Mitochondrial respiratory Complex IV (cytochrome c oxidase)Protein Complexmitochondrial_complex_iv
mitochondrial electron transport, cytochrome c to oxygenGO:0006123 mitochondrial respiratory chain complex IV assemblyGO:0033617
Context
mitochondrial inner membraneGO:0005743

Mitochondrial respiratory Complex IV (cytochrome c oxidase), grounded to the human nuclear-encoded structural subunits COX5A (UniProtKB:P20674), COX6A2 (Q02221), COX7B (P24311) and COX8A (P10176) — all GO:0005198 structural molecule activity — and the assembly factors COX14 (Q96I36) and COX20 (Q5RI15) — both GO:0033617. GO molecular-function/BP/location terms were taken from the completed human gene reviews and verified against the local go.db; Reactome reaction ids/titles were verified against the local reactome cache. The holoenzyme is a PROTEIN_COMPLEX node; the catalytic core (MT-CO1 heme a/a3-CuB, MT-CO2 CuA, MT-CO3) is mtDNA-encoded and therefore not represented as nuclear dismech genes. Other nuclear subunits and factors are already reviewed on main and cited via file: — structural subunits COX4I1/COX6A1/ COX6B1, and the maturation factors SCO1/SCO2 (copper metallochaperones, GO:0016531), COX15 (heme a synthesis), COX10 (heme O farnesyltransferase) and SURF1 (assembly). The current Complex IV membership term is GO:0045277 "respiratory chain complex IV" (GO:0005751 is obsolete); the assembly BP is GO:0033617. Complex IV accepts electrons from Complex III via cytochrome c and is the terminal oxidase of the chain, feeding the proton gradient used by Complex V (ATP synthase). Disorders: mitochondrial complex IV (cytochrome c oxidase) deficiency — Leigh syndrome, cardio- myopathy (COX6A2), X-linked linear skin defects with multiple congenital anomalies (COX7B) and encephalopathy/ataxia; the remaining Complex IV assembly factors (COX11/16/18, COA3/5/6/7/8, PET100/117, TACO1) are a further module.

Connections

complex_iv_assembly -> complex_iv_holo Positively Regulates
The assembly factors (COX14 for MT-CO1, COX20 for MT-CO2, with SCO1/SCO2 copper delivery and SURF1) build the MT-CO1/CO2/CO3 catalytic core into which the nuclear subunits assemble.
Part 1: holoenzyme (electron transfer, cytochrome c to oxygen)
Complex IV (cytochrome c oxidase) — nuclear structural subunitsProtein Complexcomplex_iv_holo

Annotons

COX5A: structural subunit 5A
cox5a_activity
Participant: Family: Cytochrome c oxidase subunit 5A family (COX5A)
Family:
Cytochrome c oxidase subunit 5A family (COX5A)PANTHER:PTHR14200
Representative Members: COX5A (human)UniProtKB:P20674

Function

structural molecule activityGO:0005198
Substrates: (structural scaffold)
Products: assembled/stable Complex IV

Locations

mitochondrial inner membraneGO:0005743

Structural subunit 5A.

COX6A2: structural subunit 6A2 (heart/muscle)
cox6a2_activity
Participant: Family: Cytochrome c oxidase subunit 6A family (COX6A)
Family:
Cytochrome c oxidase subunit 6A family (COX6A)PANTHER:PTHR11504
Representative Members: COX6A2 (human)UniProtKB:Q02221

Function

structural molecule activityGO:0005198
Substrates: (monomer-interface / dimerisation)
Products: assembled/stable Complex IV

Locations

mitochondrial inner membraneGO:0005743

Structural subunit 6A2 (tissue-specific isoform).

COX7B: structural subunit 7B
cox7b_activity
Participant: Family: Cytochrome c oxidase subunit 7B family (COX7B)
Family:
Cytochrome c oxidase subunit 7B family (COX7B)PANTHER:PTHR16716
Representative Members: COX7B (human)UniProtKB:P24311

Function

structural molecule activityGO:0005198
Substrates: (structural scaffold)
Products: assembled/stable Complex IV

Locations

mitochondrial inner membraneGO:0005743

Structural subunit 7B.

COX8A: structural subunit 8A
cox8a_activity
Participant: Family: Cytochrome c oxidase subunit 8 family (COX8A)
Family:
Cytochrome c oxidase subunit 8 family (COX8A)PANTHER:PTHR16717
Representative Members: COX8A (human)UniProtKB:P10176

Function

structural molecule activityGO:0005198
Substrates: (structural scaffold)
Products: assembled/stable Complex IV

Locations

mitochondrial inner membraneGO:0005743

Structural subunit 8A.

Part 2: MT-CO1 / MT-CO2 assembly factors
Complex IV assembly (MT-CO1/MT-CO2 maturation)Reactioncomplex_iv_assembly

Annotons

COX14: MT-CO1 assembly factor (MITRAC)
cox14_activity
Participant: Family: COX14 assembly-factor family
Family:
COX14 assembly-factor familyPANTHER:PTHR36684
Representative Members: COX14 (human)UniProtKB:Q96I36

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial inner membraneGO:0005743

Couples MT-CO1 translation to its stepwise assembly.

Reactome:R-HSA-9865412
TIMM21 carries COX4, COX5A, COX6C to MT-CO1:MITRAC (human Reactome reaction)
file:human/COX14/COX14-ai-review.yaml
couples MT-CO1 translation with COX assembly via the MITRAC/COA3 module; non-catalytic; deficiency = MC4DN10
COX20: MT-CO2 assembly chaperone
cox20_activity
Participant: Family: COX20/FAM36A assembly-chaperone family
Family:
COX20/FAM36A assembly-chaperone familyPANTHER:PTHR31586
Representative Members: COX20 (human)UniProtKB:Q5RI15

Processes

mitochondrial respiratory chain complex IV assemblyGO:0033617

Locations

mitochondrial inner membraneGO:0005743

Chaperones MT-CO2 through insertion and CuA metallation.

Reactome:R-HSA-9902096
COX18 inserts nascent MT-CO2 in COX20:TMEM77 (human Reactome reaction)
file:human/COX20/COX20-ai-review.yaml
MT-CO2-specific chaperone; stabilises newly-made MT-CO2 for membrane insertion and SCO1/SCO2 copper metallation; non-catalytic; deficiency = MC4DN