COA8_HUMAN
ID COA8_HUMAN Reviewed; 206 AA.
AC Q96IL0; H7C2Z1; Q53G28;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Cytochrome c oxidase assembly factor 8 {ECO:0000305};
DE Short=COA8 {ECO:0000305};
DE AltName: Full=Apoptogenic protein 1, mitochondrial;
DE Short=APOP-1;
DE Flags: Precursor;
GN Name=COA8 {ECO:0000312|HGNC:HGNC:20492};
GN Synonyms=APOP1, APOPT1 {ECO:0000312|HGNC:HGNC:20492}, C14orf153;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-197.
RC TISSUE=Ovary;
RX PubMed=16712791; DOI=10.1016/j.bbrc.2006.04.175;
RA Wang A.G., Yoon S.Y., Oh J.H., Jeon Y.J., Kim M., Kim J.M., Byun S.S.,
RA Yang J.O., Kim J.H., Kim D.G., Yeom Y.I., Yoo H.S., Kim Y.S., Kim N.S.;
RT "Identification of intrahepatic cholangiocarcinoma related genes by
RT comparison with normal liver tissues using expressed sequence tags.";
RL Biochem. Biophys. Res. Commun. 345:1022-1032(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-206.
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-206, AND VARIANT ALA-27.
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, CHARACTERIZATION OF
RP VARIANT MC4DN17 79-ARG--ASN-206 DEL, AND PROTEASOMAL DEGRADATION.
RX PubMed=30552096; DOI=10.15252/emmm.201809582;
RA Signes A., Cerutti R., Dickson A.S., Beninca C., Hinchy E.C., Ghezzi D.,
RA Carrozzo R., Bertini E., Murphy M.P., Nathan J.A., Viscomi C.,
RA Fernandez-Vizarra E., Zeviani M.;
RT "APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and
RT ROS.";
RL EMBO Mol. Med. 11:0-0(2019).
RN [6]
RP VARIANTS MC4DN17 79-ARG--ASN-206 DEL; SER-118 AND GLU-124 DEL,
RP CHARACTERIZATION OF VARIANT MC4DN17 79-ARG--ASN-206 DEL, INVOLVEMENT IN
RP MC4DN17, SUBCELLULAR LOCATION, CLEAVAGE, FUNCTION, INDUCTION BY OXIDATIVE
RP STRESS, AND TISSUE SPECIFICITY.
RX PubMed=25175347; DOI=10.1016/j.ajhg.2014.08.003;
RA Melchionda L., Haack T.B., Hardy S., Abbink T.E., Fernandez-Vizarra E.,
RA Lamantea E., Marchet S., Morandi L., Moggio M., Carrozzo R., Torraco A.,
RA Diodato D., Strom T.M., Meitinger T., Tekturk P., Yapici Z.,
RA Al-Murshedi F., Stevens R., Rodenburg R.J., Lamperti C., Ardissone A.,
RA Moroni I., Uziel G., Prokisch H., Taylor R.W., Bertini E.,
RA van der Knaap M.S., Ghezzi D., Zeviani M.;
RT "Mutations in APOPT1, encoding a mitochondrial protein, cause cavitating
RT leukoencephalopathy with cytochrome c oxidase deficiency.";
RL Am. J. Hum. Genet. 95:315-325(2014).
RN [7]
RP INVOLVEMENT IN MC4DN17.
RX PubMed=29577824; DOI=10.1177/0883073818760875;
RA Sharma S., Singh P., Fernandez-Vizarra E., Zeviani M., Van der Knaap M.S.,
RA Saran R.K.;
RT "Cavitating Leukoencephalopathy With Posterior Predominance Caused by a
RT Deletion in the APOPT1 Gene in an Indian Boy.";
RL J. Child Neurol. 33:428-431(2018).
CC -!- FUNCTION: Required for cytochrome c complex (COX) IV assembly and
CC function Protects COX assembly from oxidation-induced degradation, COX
CC being the terminal component of the mitochondrial respiratory chain.
CC {ECO:0000269|PubMed:25175347, ECO:0000269|PubMed:30552096}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:25175347, ECO:0000269|PubMed:30552096}; Peripheral
CC membrane protein {ECO:0000305|PubMed:30552096}; Matrix side
CC {ECO:0000269|PubMed:30552096}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96IL0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96IL0-2; Sequence=VSP_060246, VSP_060247;
CC -!- TISSUE SPECIFICITY: Expressed in fibroblasts.
CC {ECO:0000269|PubMed:25175347}.
CC -!- INDUCTION: In conditions of increased oxidative stress, the protein is
CC stabilized, increasing its mature intramitochondrial form and thereby
CC protecting COX from oxidatively induced degradation.
CC {ECO:0000269|PubMed:25175347, ECO:0000269|PubMed:30552096}.
CC -!- PTM: N-terminal mitochondrial targeting sequence is cleaved from the
CC mature protein once in the mitochondrion. {ECO:0000269|PubMed:25175347,
CC ECO:0000269|PubMed:30552096}.
CC -!- PTM: In normal conditions, the cytoplasmic precursor protein is rapidly
CC degraded by the ubiquitination-proteasome system (UPS). Oxidative
CC stress induces protein stabilization and import into mitochondria where
CC it protects COX from degradation. {ECO:0000269|PubMed:25175347,
CC ECO:0000269|PubMed:30552096}.
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 17 (MC4DN17)
CC [MIM:619061]: An autosomal recessive mitochondrial disorder with highly
CC variable clinical manifestations and severity. Clinical features vary
CC from acute neurometabolic decompensation in late infancy to subtle
CC neurological signs presenting in adolescence. Encephalopathic episodes
CC are characterized by acute loss of developmental milestones including
CC ability to walk or sit, loss of speech, episodes with somnolence and
CC seizure, and pyramidal signs rapidly evolving into spastic
CC tetraparesis. The clinical course subsequently tends to stabilize and
CC in several subjects marked recovery of neurological milestones is
CC observed over time. Brain imaging shows a cavitating leukodystrophy,
CC predominantly involving the posterior cerebral white matter and the
CC corpus callosum in the acute stage, after which the abnormalities
CC partially improve and then stabilize. Patient tissues show variably
CC decreased levels and activity of mitochondrial respiratory complex IV.
CC {ECO:0000269|PubMed:25175347, ECO:0000269|PubMed:29577824,
CC ECO:0000269|PubMed:30552096}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Protein may not fold correctly and may be
CC rapidly degraded. {ECO:0000303|PubMed:30552096}.
CC -!- SIMILARITY: Belongs to the COA8 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-14 is the initiator.
CC However, according to some experiments, Met-14 seems to be the
CC initiator. {ECO:0000305|PubMed:25175347, ECO:0000305|PubMed:30552096}.
CC -!- CAUTION: First thought to play a role in the regulation of apoptosis,
CC mediating mitochondria-induced cell death in vascular smooth muscle
CC cells through the release of cytochrome c (COX) from mitochondria and
CC the activation of the caspase cascade (By similarity). However, recent
CC studies show that it is not directly involved in apoptosis regulation
CC but in the protection of COX from oxidatively induced degradation
CC (PubMed:30552096, PubMed:25175347). {ECO:0000250|UniProtKB:Q9CQW7,
CC ECO:0000269|PubMed:25175347, ECO:0000269|PubMed:30552096}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH07412.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96812.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96823.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL139300; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CB136383; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK223092; BAD96812.1; ALT_INIT; mRNA.
DR EMBL; AK223103; BAD96823.1; ALT_INIT; mRNA.
DR EMBL; BC007412; AAH07412.1; ALT_INIT; mRNA.
DR RefSeq; NP_001289581.1; NM_001302652.1.
DR RefSeq; NP_001289582.1; NM_001302653.1.
DR RefSeq; NP_115750.2; NM_032374.4.
DR AlphaFoldDB; Q96IL0; -.
DR BioGRID; 124058; 12.
DR IntAct; Q96IL0; 1.
DR STRING; 9606.ENSP00000386485; -.
DR iPTMnet; Q96IL0; -.
DR PhosphoSitePlus; Q96IL0; -.
DR BioMuta; APOPT1; -.
DR DMDM; 363548522; -.
DR EPD; Q96IL0; -.
DR jPOST; Q96IL0; -.
DR MassIVE; Q96IL0; -.
DR MaxQB; Q96IL0; -.
DR PaxDb; Q96IL0; -.
DR PeptideAtlas; Q96IL0; -.
DR PRIDE; Q96IL0; -.
DR ProteomicsDB; 76839; -.
DR Antibodypedia; 66570; 40 antibodies from 12 providers.
DR DNASU; 84334; -.
DR Ensembl; ENST00000674165.1; ENSP00000501341.1; ENSG00000256053.9. [Q96IL0-1]
DR GeneID; 84334; -.
DR KEGG; hsa:84334; -.
DR UCSC; uc010tyc.3; human. [Q96IL0-1]
DR UCSC; uc059frt.1; human.
DR CTD; 84334; -.
DR DisGeNET; 84334; -.
DR GeneCards; COA8; -.
DR HGNC; HGNC:20492; COA8.
DR HPA; ENSG00000256053; Tissue enhanced (skeletal).
DR MalaCards; COA8; -.
DR MIM; 616003; gene.
DR MIM; 619061; phenotype.
DR neXtProt; NX_Q96IL0; -.
DR OpenTargets; ENSG00000256053; -.
DR Orphanet; 436271; Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy.
DR PharmGKB; PA134961925; -.
DR VEuPathDB; HostDB:ENSG00000256053; -.
DR eggNOG; KOG4094; Eukaryota.
DR GeneTree; ENSGT00390000008212; -.
DR HOGENOM; CLU_118274_0_0_1; -.
DR InParanoid; Q96IL0; -.
DR OrthoDB; 1410150at2759; -.
DR PhylomeDB; Q96IL0; -.
DR TreeFam; TF315168; -.
DR PathwayCommons; Q96IL0; -.
DR SignaLink; Q96IL0; -.
DR BioGRID-ORCS; 84334; 11 hits in 1035 CRISPR screens.
DR ChiTaRS; APOPT1; human.
DR GenomeRNAi; 84334; -.
DR Pharos; Q96IL0; Tdark.
DR PRO; PR:Q96IL0; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96IL0; protein.
DR Bgee; ENSG00000256053; Expressed in left testis and 178 other tissues.
DR ExpressionAtlas; Q96IL0; baseline and differential.
DR Genevisible; Q96IL0; HS.
DR GO; GO:0099617; C:matrix side of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IEA:InterPro.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IDA:UniProtKB.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:1904960; P:positive regulation of cytochrome-c oxidase activity; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0000302; P:response to reactive oxygen species; IDA:UniProtKB.
DR InterPro; IPR018796; COA8.
DR PANTHER; PTHR31107; PTHR31107; 1.
DR Pfam; PF10231; DUF2315; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Disease variant; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transit peptide; Ubl conjugation.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:25175347"
FT CHAIN 40..206
FT /note="Cytochrome c oxidase assembly factor 8"
FT /id="PRO_0000019559"
FT VAR_SEQ 121..125
FT /note="EKEEF -> VRKQH (in isoform 2)"
FT /id="VSP_060246"
FT VAR_SEQ 126..206
FT /note="Missing (in isoform 2)"
FT /id="VSP_060247"
FT VARIANT 27
FT /note="P -> A (in dbSNP:rs2274268)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_023000"
FT VARIANT 79..206
FT /note="Missing (in MC4DN17; low steady-state levels of COX
FT subunits and reduced levels of fully assembled COX; highly
FT decreased COX complex IV activity and decreased COX complex
FT II activity in muscle)"
FT /evidence="ECO:0000269|PubMed:25175347,
FT ECO:0000269|PubMed:30552096"
FT /id="VAR_082029"
FT VARIANT 88
FT /note="N -> S (in dbSNP:rs35960830)"
FT /id="VAR_033745"
FT VARIANT 118
FT /note="F -> S (in MC4DN17; unknown pathological
FT significance; dbSNP:rs587777786)"
FT /evidence="ECO:0000269|PubMed:25175347"
FT /id="VAR_082030"
FT VARIANT 124
FT /note="Missing (in MC4DN17; dbSNP:rs587777787)"
FT /evidence="ECO:0000269|PubMed:25175347"
FT /id="VAR_082031"
FT CONFLICT 191
FT /note="E -> G (in Ref. 2; CB136383)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 206 AA; 24153 MW; 7ABC3470215F2244 CRC64;
MLPCAAGARG RGAMVVLRAG KKTFLPPLCR AFACRGCQLA PERGAERRDT APSGVSRFCP
PRKSCHDWIG PPDKYSNLRP VHFYIPENES PLEQKLRKLR QETQEWNQQF WANQNLTFSK
EKEEFIHSRL KTKGLGLRTE SGQKATLNAE EMADFYKEFL SKNFQKHMYY NRDWYKRNFA
ITFFMGKVAL ERIWNKLKQK QKKRSN
