COA8_MOUSE
ID COA8_MOUSE Reviewed; 192 AA.
AC Q9CQW7;
DT 04-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 123.
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; Synonyms=Apop1, Apopt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Limb;
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 [3]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=16782708; DOI=10.1074/jbc.m512610200;
RA Yasuda O., Fukuo K., Sun X., Nishitani M., Yotsui T., Higuchi M.,
RA Suzuki T., Rakugi H., Smithies O., Maeda N., Ogihara T.;
RT "Apop-1, a novel protein inducing cyclophilin D-dependent but Bax/Bak-
RT related channel-independent apoptosis.";
RL J. Biol. Chem. 281:23899-23907(2006).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18977203; DOI=10.1016/j.bbrc.2008.10.109;
RA Sun X., Yasuda O., Takemura Y., Kawamoto H., Higuchi M., Baba Y.,
RA Katsuya T., Fukuo K., Ogihara T., Rakugi H.;
RT "Akt activation prevents Apop-1-induced death of cells.";
RL Biochem. Biophys. Res. Commun. 377:1097-1101(2008).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION BY OXIDATIVE STRESS.
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).
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:30552096}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000305|PubMed:16782708, ECO:0000305|PubMed:18977203}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:Q96IL0}; Matrix side
CC {ECO:0000250|UniProtKB:Q96IL0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Apop-2;
CC IsoId=Q9CQW7-1; Sequence=Displayed;
CC Name=2; Synonyms=Apop-1;
CC IsoId=Q9CQW7-2; Sequence=VSP_041973;
CC -!- TISSUE SPECIFICITY: Expressed in atherosclerotic smooth muscle cells
CC (at protein level). Expressed in aorta, brain, heart, kidney, liver,
CC lung and spleen. Isoform 1 is strongly expressed in Kidney. Isoform 2
CC is strongly expressed in brain. {ECO:0000269|PubMed:16782708}.
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:30552096}.
CC -!- PTM: N-terminal mitochondrial targeting sequence is cleaved from the
CC mature protein once in the mitochondrion.
CC {ECO:0000250|UniProtKB:Q96IL0}.
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:0000250|UniProtKB:Q96IL0}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice generated by CRISPR-Cas9-mediated
CC gene editing are born at the expected Mendelian rate. They show
CC impaired motor skills, with decreased motor coordination and endurance.
CC Mutant show global COX deficiency with reduced enzymatic activity, low
CC steady-state levels of structural subunits and defective assembly in
CC all the tested tissues. {ECO:0000269|PubMed:30552096}.
CC -!- SIMILARITY: Belongs to the COA8 family. {ECO:0000305}.
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 (PubMed:16782708,
CC PubMed:18977203). However, recent studies show that it is not directly
CC involved in apoptosis regulation but in the protection of COX from
CC oxidatively induced degradation (PubMed:30552096).
CC {ECO:0000269|PubMed:16782708, ECO:0000269|PubMed:18977203,
CC ECO:0000269|PubMed:30552096}.
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DR EMBL; AK002873; BAB22421.1; -; mRNA.
DR EMBL; AK005403; BAB24003.1; -; mRNA.
DR EMBL; AK010493; BAB26983.1; -; mRNA.
DR EMBL; AK012648; BAB28380.1; -; mRNA.
DR EMBL; BC071262; AAH71262.1; -; mRNA.
DR CCDS; CCDS26186.1; -. [Q9CQW7-1]
DR CCDS; CCDS49181.1; -. [Q9CQW7-2]
DR RefSeq; NP_001156860.1; NM_001163388.1. [Q9CQW7-2]
DR RefSeq; NP_080787.1; NM_026511.2. [Q9CQW7-1]
DR AlphaFoldDB; Q9CQW7; -.
DR STRING; 10090.ENSMUSP00000038865; -.
DR iPTMnet; Q9CQW7; -.
DR PhosphoSitePlus; Q9CQW7; -.
DR MaxQB; Q9CQW7; -.
DR PaxDb; Q9CQW7; -.
DR PRIDE; Q9CQW7; -.
DR ProteomicsDB; 296270; -. [Q9CQW7-1]
DR ProteomicsDB; 296271; -. [Q9CQW7-2]
DR Antibodypedia; 66570; 40 antibodies from 12 providers.
DR DNASU; 68020; -.
DR Ensembl; ENSMUST00000040519; ENSMUSP00000038865; ENSMUSG00000037787. [Q9CQW7-1]
DR Ensembl; ENSMUST00000163220; ENSMUSP00000131169; ENSMUSG00000037787. [Q9CQW7-2]
DR GeneID; 68020; -.
DR KEGG; mmu:68020; -.
DR UCSC; uc007pdt.2; mouse. [Q9CQW7-1]
DR UCSC; uc011yuy.1; mouse. [Q9CQW7-2]
DR CTD; 84334; -.
DR MGI; MGI:1915270; Coa8.
DR VEuPathDB; HostDB:ENSMUSG00000037787; -.
DR eggNOG; KOG4094; Eukaryota.
DR GeneTree; ENSGT00390000008212; -.
DR HOGENOM; CLU_118274_0_0_1; -.
DR InParanoid; Q9CQW7; -.
DR OMA; TRHNKRF; -.
DR OrthoDB; 1410150at2759; -.
DR PhylomeDB; Q9CQW7; -.
DR TreeFam; TF315168; -.
DR BioGRID-ORCS; 68020; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Apopt1; mouse.
DR PRO; PR:Q9CQW7; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q9CQW7; protein.
DR Bgee; ENSMUSG00000037787; Expressed in interventricular septum and 231 other tissues.
DR ExpressionAtlas; Q9CQW7; baseline and differential.
DR Genevisible; Q9CQW7; MM.
DR GO; GO:0099617; C:matrix side of mitochondrial inner membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IDA:MGI.
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; ISS: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; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Reference proteome; Transit peptide;
KW Ubl conjugation.
FT TRANSIT 1..26
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 27..192
FT /note="Cytochrome c oxidase assembly factor 8"
FT /id="PRO_0000353108"
FT VAR_SEQ 161..192
FT /note="DWYKRNFAITFFMGKVVLERMWSKLRQKKTSS -> AGPGSQDVGCVGKCSF
FT AELHPYLTVSALQGSCPA (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041973"
SQ SEQUENCE 192 AA; 22715 MW; 4DAC16ADC70CFC90 CRC64;
MAALRPGSRA LRRLLCRSFS GGGGVRLARE RPTDHRDAAS SRVSRFCPPR QSCHDWIGPP
DKCSNLRPVH FHIPENESPL EQRLRELRQE TQEWNQQFWA KQNLSFNKEK EEFIYSRLQA
KGAGLRTESG QRATLDAEEM ADFYKDFLSK NFQKHMRYNR DWYKRNFAIT FFMGKVVLER
MWSKLRQKKT SS
