COX16_HUMAN
ID COX16_HUMAN Reviewed; 106 AA.
AC Q9P0S2; A6NDT5; A8K3X8; B8XYC5;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Cytochrome c oxidase assembly protein COX16 homolog, mitochondrial {ECO:0000305};
DE Short=hCOX16 {ECO:0000303|PubMed:29355485};
GN Name=COX16 {ECO:0000303|PubMed:29355485, ECO:0000303|PubMed:29381136,
GN ECO:0000312|HGNC:HGNC:20213};
GN Synonyms=C14orf112 {ECO:0000312|HGNC:HGNC:20213};
GN ORFNames=HSPC203 {ECO:0000303|PubMed:11042152}, PTD019 {ECO:0000303|Ref.2};
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY,
RP TISSUE SPECIFICITY, AND SUBUNIT.
RX PubMed=29355485; DOI=10.1016/j.bbabio.2018.01.004;
RA Cerqua C., Morbidoni V., Desbats M.A., Doimo M., Frasson C., Sacconi S.,
RA Baldoin M.C., Sartori G., Basso G., Salviati L., Trevisson E.;
RT "COX16 is required for assembly of cytochrome c oxidase in human cells and
RT is involved in copper delivery to COX2.";
RL Biochim. Biophys. Acta 1859:244-252(2018).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary tumor;
RA Xiao H., Song H., Gao G., Ren S., Chen Z., Han Z.;
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [9]
RP IDENTIFICATION.
RX PubMed=12446688; DOI=10.1074/jbc.m209893200;
RA Carlson C.G., Barrientos A., Tzagoloff A., Glerum D.M.;
RT "COX16 encodes a novel protein required for the assembly of cytochrome
RT oxidase in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 278:3770-3775(2003).
RN [10]
RP LACK OF INVOLVEMENT IN COX DEFICIENCY.
RX PubMed=15596615; DOI=10.1001/archneur.61.12.1935;
RA Tay S.K.H., Nesti C., Mancuso M., Schon E.A., Shanske S., Bonilla E.,
RA Davidson M.M., Dimauro S.;
RT "Studies of COX16, COX19, and PET191 in human cytochrome-c oxidase
RT deficiency.";
RL Arch. Neurol. 61:1935-1937(2004).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND SUBUNIT.
RX PubMed=29381136; DOI=10.7554/elife.32572;
RA Aich A., Wang C., Chowdhury A., Ronsoer C., Pacheu-Grau D.,
RA Richter-Dennerlein R., Dennerlein S., Rehling P.;
RT "COX16 promotes COX2 metallation and assembly during respiratory complex IV
RT biogenesis.";
RL Elife 7:0-0(2018).
RN [12]
RP INVOLVEMENT IN MC4DN22, VARIANT MC4DN22 82-ARG--THR-106 DEL,
RP CHARACTERIZATION OF VARIANT MC4DN22 82-ARG--THR-106 DEL, AND FUNCTION.
RX PubMed=33169484; DOI=10.1002/humu.24137;
RA Wintjes L.T.M., Kava M., van den Brandt F.A., van den Brand M.A.M.,
RA Lapina O., Bliksrud Y.T., Kulseth M.A., Amundsen S.S., Selberg T.R.,
RA Ybema-Antoine M., Tutakhel O.A.Z., Greed L., Thorburn D.R., Tangeraas T.,
RA Balasubramaniam S., Rodenburg R.J.T.;
RT "A novel variant in COX16 causes cytochrome c oxidase deficiency, severe
RT fatal neonatal lactic acidosis, encephalopathy, cardiomyopathy, and liver
RT dysfunction.";
RL Hum. Mutat. 42:135-141(2021).
CC -!- FUNCTION: Required for the assembly of the mitochondrial respiratory
CC chain complex IV (CIV), also known as cytochrome c oxidase
CC (PubMed:29355485, PubMed:29381136, PubMed:33169484). Promotes the
CC insertion of copper into the active site of cytochrome c oxidase
CC subunit II (MT-CO2/COX2) (PubMed:29355485, PubMed:29381136). Interacts
CC specifically with newly synthesized MT-CO2/COX and its copper center-
CC forming metallochaperones SCO1, SCO2 and COA6 (PubMed:29381136).
CC Probably facilitates MT-CO2/COX2 association with the MITRAC assembly
CC intermediate containing MT-CO1/COX1, thereby participating in merging
CC the MT-CO1/COX1 and MT-CO2/COX2 assembly lines (PubMed:29381136).
CC {ECO:0000269|PubMed:29355485, ECO:0000269|PubMed:29381136,
CC ECO:0000269|PubMed:33169484}.
CC -!- SUBUNIT: Associates with the MITRAC complex (PubMed:29381136).
CC Interacts with MT-CO2/COX; specifically interacts with newly
CC synthesized MT-CO2/COX (PubMed:29355485, PubMed:29381136). Interacts
CC with SCO1, SCO2 and COA6 (PubMed:29381136).
CC {ECO:0000269|PubMed:29355485, ECO:0000269|PubMed:29381136}.
CC -!- INTERACTION:
CC Q9P0S2; B3EWG5: FAM25C; NbExp=3; IntAct=EBI-6570716, EBI-14240149;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:29355485, ECO:0000269|PubMed:29381136}; Single-pass
CC membrane protein {ECO:0000305|PubMed:29381136}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC skeletal muscle, heart and liver. {ECO:0000269|PubMed:29355485}.
CC -!- DISEASE: Mitochondrial complex IV deficiency, nuclear type 22 (MC4DN22)
CC [MIM:619355]: An autosomal recessive mitochondrial disorder
CC characterized by hypertrophic cardiomyopathy, encephalopathy, fatal
CC lactic acidosis, and isolated complex IV deficiency.
CC {ECO:0000269|PubMed:33169484}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: No COX16 mutations have been detected in patients with
CC cytochrome c oxidase (COX) deficiency. {ECO:0000269|PubMed:15596615}.
CC -!- SIMILARITY: Belongs to the COX16 family. {ECO:0000305}.
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DR EMBL; FJ460510; ACJ76681.1; -; mRNA.
DR EMBL; FJ460511; ACJ76682.1; -; mRNA.
DR EMBL; AF226729; AAG09730.1; -; mRNA.
DR EMBL; AF151037; AAF36123.1; -; mRNA.
DR EMBL; AK290743; BAF83432.1; -; mRNA.
DR EMBL; CR457199; CAG33480.1; -; mRNA.
DR EMBL; AL160191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81031.1; -; Genomic_DNA.
DR EMBL; BC001702; AAH01702.1; -; mRNA.
DR CCDS; CCDS9802.1; -.
DR RefSeq; NP_001191019.1; NM_001204090.1.
DR RefSeq; NP_057552.1; NM_016468.6.
DR AlphaFoldDB; Q9P0S2; -.
DR BioGRID; 119401; 49.
DR CORUM; Q9P0S2; -.
DR IntAct; Q9P0S2; 7.
DR STRING; 9606.ENSP00000374562; -.
DR TCDB; 3.D.4.11.1; the proton-translocating cytochrome oxidase (cox) superfamily.
DR iPTMnet; Q9P0S2; -.
DR PhosphoSitePlus; Q9P0S2; -.
DR BioMuta; COX16; -.
DR DMDM; 68565330; -.
DR EPD; Q9P0S2; -.
DR jPOST; Q9P0S2; -.
DR MassIVE; Q9P0S2; -.
DR MaxQB; Q9P0S2; -.
DR PaxDb; Q9P0S2; -.
DR PeptideAtlas; Q9P0S2; -.
DR PRIDE; Q9P0S2; -.
DR ProteomicsDB; 83592; -.
DR TopDownProteomics; Q9P0S2; -.
DR Antibodypedia; 25128; 57 antibodies from 16 providers.
DR DNASU; 51241; -.
DR Ensembl; ENST00000389912.7; ENSP00000374562.5; ENSG00000133983.16.
DR GeneID; 51241; -.
DR KEGG; hsa:51241; -.
DR MANE-Select; ENST00000389912.7; ENSP00000374562.5; NM_016468.7; NP_057552.1.
DR UCSC; uc001xmb.3; human.
DR CTD; 51241; -.
DR DisGeNET; 51241; -.
DR GeneCards; COX16; -.
DR HGNC; HGNC:20213; COX16.
DR HPA; ENSG00000133983; Low tissue specificity.
DR MIM; 618064; gene.
DR MIM; 619355; phenotype.
DR neXtProt; NX_Q9P0S2; -.
DR OpenTargets; ENSG00000133983; -.
DR PharmGKB; PA162382755; -.
DR VEuPathDB; HostDB:ENSG00000133983; -.
DR eggNOG; ENOG502S3RD; Eukaryota.
DR GeneTree; ENSGT00520000055955; -.
DR HOGENOM; CLU_163592_0_0_1; -.
DR InParanoid; Q9P0S2; -.
DR OMA; RTMTFGV; -.
DR OrthoDB; 1333715at2759; -.
DR PhylomeDB; Q9P0S2; -.
DR TreeFam; TF324420; -.
DR PathwayCommons; Q9P0S2; -.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-611105; Respiratory electron transport.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR SignaLink; Q9P0S2; -.
DR BioGRID-ORCS; 51241; 101 hits in 1084 CRISPR screens.
DR GenomeRNAi; 51241; -.
DR Pharos; Q9P0S2; Tbio.
DR PRO; PR:Q9P0S2; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9P0S2; protein.
DR Bgee; ENSG00000133983; Expressed in ganglionic eminence and 179 other tissues.
DR ExpressionAtlas; Q9P0S2; baseline and differential.
DR Genevisible; Q9P0S2; HS.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0033617; P:mitochondrial cytochrome c oxidase assembly; IDA:UniProtKB.
DR InterPro; IPR020164; Cyt_c_Oxase_assmbl_COX16.
DR Pfam; PF14138; COX16; 1.
PE 1: Evidence at protein level;
KW Disease variant; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Primary mitochondrial disease; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..106
FT /note="Cytochrome c oxidase assembly protein COX16 homolog,
FT mitochondrial"
FT /id="PRO_0000019556"
FT TOPO_DOM 1..14
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000305|PubMed:29355485,
FT ECO:0000305|PubMed:29381136"
FT TRANSMEM 15..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..106
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:29355485,
FT ECO:0000305|PubMed:29381136"
FT REGION 77..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 82..106
FT /note="Missing (in MC4DN22; isolated complex IV deficiency
FT in homozygous patient cells)"
FT /evidence="ECO:0000269|PubMed:33169484"
FT /id="VAR_085648"
SQ SEQUENCE 106 AA; 12293 MW; EB84EE268DF62B07 CRC64;
MFAPAVMRAF RKNKTLGYGV PMLLLIVGGS FGLREFSQIR YDAVKSKMDP ELEKKLKENK
ISLESEYEKI KDSKFDDWKN IRGPRPWEDP DLLQGRNPES LKTKTT
