UniProtKB - Q96IL0 (COA8_HUMAN)
Protein
Cytochrome c oxidase assembly factor 8
Gene
COA8
Organism
Homo sapiens (Human)
Status
Functioni
Required for cytochrome c complex (COX) IV assembly and function Protects COX assembly from oxidation-induced degradation, COX being the terminal component of the mitochondrial respiratory chain.2 Publications
Caution
It is uncertain whether Met-1 or Met-14 is the initiator. However, according to some experiments, Met-14 seems to be the initiator.2 Publications
First thought to play a role in the regulation of apoptosis, mediating mitochondria-induced cell death in vascular smooth muscle cells through the release of cytochrome c (COX) from mitochondria and the activation of the caspase cascade (By similarity). However, recent studies show that it is not directly involved in apoptosis regulation but in the protection of COX from oxidatively induced degradation (PubMed:30552096, PubMed:25175347).By similarity2 Publications
GO - Biological processi
- intrinsic apoptotic signaling pathway Source: InterPro
- mitochondrial cytochrome c oxidase assembly Source: UniProtKB
- negative regulation of reactive oxygen species biosynthetic process Source: UniProtKB
- positive regulation of cytochrome-c oxidase activity Source: UniProtKB
- protein stabilization Source: UniProtKB
- response to reactive oxygen species Source: UniProtKB
Keywordsi
Biological process | Apoptosis |
Enzyme and pathway databases
PathwayCommonsi | Q96IL0 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytochrome c oxidase assembly factor 8CuratedShort name: COA8Curated Alternative name(s): Apoptogenic protein 1, mitochondrial Short name: APOP-1 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20492, COA8 |
MIMi | 616003, gene |
neXtProti | NX_Q96IL0 |
VEuPathDBi | HostDB:ENSG00000256053.7 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 2 Publications; Peripheral membrane protein 1 Publication; Matrix side 1 Publication
Mitochondrion
- matrix side of mitochondrial inner membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Involvement in diseasei
Mitochondrial complex IV deficiency (MT-C4D)3 Publications
The disease is caused by variants affecting the gene represented in this entry. Patients present in late infancy or early childhood with evidence of complex IV deficiency, but the phenotype varies widely. Some patients have episodes of neurologic regression manifest as gait difficulties and spastic tetraparesis, sensorimotor polyneuropathy, and dysarthria that in some cases improved over time. Some never develop neurologic signs. Brain imaging show a cavitating leukodystrophy, predominantly affecting the posterior cerebral white matter and corpus callosum, that stabilizes or even improves over time.1 Publication
Disease descriptionA disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_082029 | 79 – 206 | Missing in MT-C4D; low steady-state levels of COX subunits, reduced levels of fully assembled COX; highly decreased COX complex IV activity and decreased COX complex II activity in muscle. 2 PublicationsAdd BLAST | 128 | |
Natural variantiVAR_082030 | 118 | F → S in MT-C4D; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777786Ensembl. | 1 | |
Natural variantiVAR_082031 | 124 | Missing in MT-C4D. 1 PublicationCorresponds to variant dbSNP:rs587777787Ensembl. | 1 |
Keywords - Diseasei
Primary mitochondrial diseaseOrganism-specific databases
DisGeNETi | 84334 |
MalaCardsi | COA8 |
MIMi | 220110, phenotype |
OpenTargetsi | ENSG00000256053 |
Orphaneti | 436271, Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy |
PharmGKBi | PA134961925 |
Miscellaneous databases
Pharosi | Q96IL0, Tdark |
Genetic variation databases
BioMutai | APOPT1 |
DMDMi | 363548522 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 39 | Mitochondrion1 PublicationAdd BLAST | 39 | |
ChainiPRO_0000019559 | 40 – 206 | Cytochrome c oxidase assembly factor 8Add BLAST | 167 |
Post-translational modificationi
N-terminal mitochondrial targeting sequence is cleaved from the mature protein once in the mitochondrion.2 Publications
In normal conditions, the cytoplasmic precursor protein is rapidly degraded by the ubiquitination-proteasome system (UPS). Oxidative stress induces protein stabilization and import into mitochondria where it protects COX from degradation.2 Publications
Keywords - PTMi
Ubl conjugationProteomic databases
EPDi | Q96IL0 |
jPOSTi | Q96IL0 |
MassIVEi | Q96IL0 |
MaxQBi | Q96IL0 |
PaxDbi | Q96IL0 |
PeptideAtlasi | Q96IL0 |
PRIDEi | Q96IL0 |
ProteomicsDBi | 45152 76839 |
PTM databases
iPTMneti | Q96IL0 |
PhosphoSitePlusi | Q96IL0 |
Expressioni
Tissue specificityi
Expressed in fibroblasts.1 Publication
Inductioni
In conditions of increased oxidative stress, the protein is stabilized, increasing its mature intramitochondrial form and thereby protecting COX from oxidatively induced degradation.2 Publications
Gene expression databases
Bgeei | ENSG00000256053, Expressed in right testis and 212 other tissues |
ExpressionAtlasi | Q96IL0, baseline and differential |
Genevisiblei | Q96IL0, HS |
Organism-specific databases
HPAi | ENSG00000256053, Low tissue specificity |
Interactioni
Protein-protein interaction databases
BioGRIDi | 124058, 4 interactors |
IntActi | Q96IL0, 1 interactor |
STRINGi | 9606.ENSP00000386485 |
Miscellaneous databases
RNActi | Q96IL0, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the COA8 family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG4094, Eukaryota |
GeneTreei | ENSGT00390000008212 |
HOGENOMi | CLU_118274_0_0_1 |
InParanoidi | Q96IL0 |
OMAi | HIPENET |
OrthoDBi | 1410150at2759 |
PhylomeDBi | Q96IL0 |
TreeFami | TF315168 |
Family and domain databases
InterProi | View protein in InterPro IPR018796, COA8 |
PANTHERi | PTHR31107, PTHR31107, 1 hit |
Pfami | View protein in Pfam PF10231, DUF2315, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96IL0-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLPCAAGARG RGAMVVLRAG KKTFLPPLCR AFACRGCQLA PERGAERRDT
60 70 80 90 100
APSGVSRFCP PRKSCHDWIG PPDKYSNLRP VHFYIPENES PLEQKLRKLR
110 120 130 140 150
QETQEWNQQF WANQNLTFSK EKEEFIHSRL KTKGLGLRTE SGQKATLNAE
160 170 180 190 200
EMADFYKEFL SKNFQKHMYY NRDWYKRNFA ITFFMGKVAL ERIWNKLKQK
QKKRSN
Computationally mapped potential isoform sequencesi
There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH0YJK3 | H0YJK3_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 108 | Annotation score: | ||
H0YJ38 | H0YJ38_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 57 | Annotation score: | ||
G3V4L6 | G3V4L6_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 177 | Annotation score: | ||
A0A0U1RR29 | A0A0U1RR29_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 132 | Annotation score: | ||
A0A0U1RQS9 | A0A0U1RQS9_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 55 | Annotation score: | ||
A0A0U1RQK3 | A0A0U1RQK3_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 76 | Annotation score: | ||
A0A5H1ZRQ9 | A0A5H1ZRQ9_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 112 | Annotation score: | ||
H0YJM4 | H0YJM4_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 72 | Annotation score: | ||
A0A6Q8JUI0 | A0A6Q8JUI0_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 193 | Annotation score: | ||
H7BZ67 | H7BZ67_HUMAN | Cytochrome c oxidase assembly facto... | COA8 | 46 | Annotation score: |
Sequence cautioni
The sequence AAH07412 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAD96812 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence BAD96823 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 191 | E → G in CB136383 (PubMed:16712791).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023000 | 27 | P → A1 PublicationCorresponds to variant dbSNP:rs2274268Ensembl. | 1 | |
Natural variantiVAR_082029 | 79 – 206 | Missing in MT-C4D; low steady-state levels of COX subunits, reduced levels of fully assembled COX; highly decreased COX complex IV activity and decreased COX complex II activity in muscle. 2 PublicationsAdd BLAST | 128 | |
Natural variantiVAR_033745 | 88 | N → S. Corresponds to variant dbSNP:rs35960830Ensembl. | 1 | |
Natural variantiVAR_082030 | 118 | F → S in MT-C4D; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777786Ensembl. | 1 | |
Natural variantiVAR_082031 | 124 | Missing in MT-C4D. 1 PublicationCorresponds to variant dbSNP:rs587777787Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_060246 | 121 – 125 | EKEEF → VRKQH in isoform 2. | 5 | |
Alternative sequenceiVSP_060247 | 126 – 206 | Missing in isoform 2. Add BLAST | 81 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL139300 Genomic DNA No translation available. CB136383 mRNA No translation available. AK223092 mRNA Translation: BAD96812.1 Different initiation. AK223103 mRNA Translation: BAD96823.1 Different initiation. BC007412 mRNA Translation: AAH07412.1 Different initiation. |
RefSeqi | NP_001289581.1, NM_001302652.1 NP_001289582.1, NM_001302653.1 NP_115750.2, NM_032374.4 |
Genome annotation databases
Ensembli | ENST00000674165; ENSP00000501341; ENSG00000256053 [Q96IL0-1] |
GeneIDi | 84334 |
KEGGi | hsa:84334 |
UCSCi | uc010tyc.3, human [Q96IL0-1] uc059frt.1, human |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL139300 Genomic DNA No translation available. CB136383 mRNA No translation available. AK223092 mRNA Translation: BAD96812.1 Different initiation. AK223103 mRNA Translation: BAD96823.1 Different initiation. BC007412 mRNA Translation: AAH07412.1 Different initiation. |
RefSeqi | NP_001289581.1, NM_001302652.1 NP_001289582.1, NM_001302653.1 NP_115750.2, NM_032374.4 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 124058, 4 interactors |
IntActi | Q96IL0, 1 interactor |
STRINGi | 9606.ENSP00000386485 |
PTM databases
iPTMneti | Q96IL0 |
PhosphoSitePlusi | Q96IL0 |
Genetic variation databases
BioMutai | APOPT1 |
DMDMi | 363548522 |
Proteomic databases
EPDi | Q96IL0 |
jPOSTi | Q96IL0 |
MassIVEi | Q96IL0 |
MaxQBi | Q96IL0 |
PaxDbi | Q96IL0 |
PeptideAtlasi | Q96IL0 |
PRIDEi | Q96IL0 |
ProteomicsDBi | 45152 76839 |
Protocols and materials databases
Antibodypediai | 66570, 34 antibodies |
Genome annotation databases
Ensembli | ENST00000674165; ENSP00000501341; ENSG00000256053 [Q96IL0-1] |
GeneIDi | 84334 |
KEGGi | hsa:84334 |
UCSCi | uc010tyc.3, human [Q96IL0-1] uc059frt.1, human |
Organism-specific databases
CTDi | 84334 |
DisGeNETi | 84334 |
GeneCardsi | COA8 |
HGNCi | HGNC:20492, COA8 |
HPAi | ENSG00000256053, Low tissue specificity |
MalaCardsi | COA8 |
MIMi | 220110, phenotype 616003, gene |
neXtProti | NX_Q96IL0 |
OpenTargetsi | ENSG00000256053 |
Orphaneti | 436271, Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy |
PharmGKBi | PA134961925 |
VEuPathDBi | HostDB:ENSG00000256053.7 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4094, Eukaryota |
GeneTreei | ENSGT00390000008212 |
HOGENOMi | CLU_118274_0_0_1 |
InParanoidi | Q96IL0 |
OMAi | HIPENET |
OrthoDBi | 1410150at2759 |
PhylomeDBi | Q96IL0 |
TreeFami | TF315168 |
Enzyme and pathway databases
PathwayCommonsi | Q96IL0 |
Miscellaneous databases
BioGRID-ORCSi | 84334, 6 hits in 876 CRISPR screens |
ChiTaRSi | APOPT1, human |
GenomeRNAii | 84334 |
Pharosi | Q96IL0, Tdark |
PROi | PR:Q96IL0 |
RNActi | Q96IL0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000256053, Expressed in right testis and 212 other tissues |
ExpressionAtlasi | Q96IL0, baseline and differential |
Genevisiblei | Q96IL0, HS |
Family and domain databases
InterProi | View protein in InterPro IPR018796, COA8 |
PANTHERi | PTHR31107, PTHR31107, 1 hit |
Pfami | View protein in Pfam PF10231, DUF2315, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | COA8_HUMAN | |
Accessioni | Q96IL0Primary (citable) accession number: Q96IL0 Secondary accession number(s): H7C2Z1, Q53G28 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2005 |
Last sequence update: | December 14, 2011 | |
Last modified: | February 10, 2021 | |
This is version 130 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families