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Protoheme IX farnesyltransferase, mitochondrial (EC 2.5.1.-) (Heme O synthase)

 COX10_HUMAN             Reviewed;         443 AA.
Q12887; B2R6U5; B4DJ50; O15334; Q969F7;
15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
23-MAR-2010, sequence version 3.
27-SEP-2017, entry version 161.
RecName: Full=Protoheme IX farnesyltransferase, mitochondrial;
EC=2.5.1.-;
AltName: Full=Heme O synthase;
Flags: Precursor;
Name=COX10;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS GLN-159 AND
ASP-340.
PubMed=8078902; DOI=10.1073/pnas.91.18.8452;
Glerum M.D., Tzagoloff A.;
"Isolation of a human cDNA for heme A:farnesyltransferase by
functional complementation of a yeast cox10 mutant.";
Proc. Natl. Acad. Sci. U.S.A. 91:8452-8456(1994).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-159.
PubMed=9177788; DOI=10.1006/geno.1997.4711;
Murakami T., Reiter L.T., Lupski J.R.;
"Genomic structure and expression of the human heme
A:farnesyltransferase (COX10) gene.";
Genomics 42:161-164(1997).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
GLN-159.
TISSUE=Brain, and Substantia nigra;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
GLN-159.
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor
vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16625196; DOI=10.1038/nature04689;
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
"DNA sequence of human chromosome 17 and analysis of rearrangement in
the human lineage.";
Nature 440:1045-1049(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
GLN-159.
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
VARIANT MT-C4D LYS-204.
PubMed=10767350; DOI=10.1093/hmg/9.8.1245;
Valnot I., von Kleist-Retzow J.C., Barrientos A., Gorbatyuk M.,
Taanman J.W., Mehaye B., Rustin P., Tzagoloff A., Munnich A.,
Rotig A.;
"A mutation in the human heme A:farnesyltransferase gene (COX10)
causes cytochrome c oxidase deficiency.";
Hum. Mol. Genet. 9:1245-1249(2000).
[8]
VARIANTS MT-C4D LYS-196; LEU-225; GLY-336 AND VAL-336.
PubMed=12928484; DOI=10.1093/hmg/ddg284;
Antonicka H., Leary S.C., Guercin G.-H., Agar J.N., Horvath R.,
Kennaway N.G., Harding C.O., Jaksch M., Shoubridge E.A.;
"Mutations in COX10 result in a defect in mitochondrial heme A
biosynthesis and account for multiple, early-onset clinical phenotypes
associated with isolated COX deficiency.";
Hum. Mol. Genet. 12:2693-2702(2003).
[9]
VARIANT HIS-258.
PubMed=21248752; DOI=10.1038/nature09639;
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P.,
Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A.,
Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C.,
Jia M., Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A.,
Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S.,
Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A.,
Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C.,
Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R.,
Futreal P.A.;
"Exome sequencing identifies frequent mutation of the SWI/SNF complex
gene PBRM1 in renal carcinoma.";
Nature 469:539-542(2011).
[10]
VARIANTS MT-C4D ARG-288 AND LEU-420.
PubMed=26741492; DOI=10.1371/journal.pgen.1005679;
Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y.,
Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H.,
Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T.,
Sato-Miyata Y., Ohnuma K., Suzuki T., Nagao A., Maehata H.,
Matsuda F., Higasa K., Nagasaki M., Yasuda J., Yamamoto M.,
Fushimi T., Shimura M., Kaiho-Ichimoto K., Harashima H., Yamazaki T.,
Mori M., Murayama K., Ohtake A., Okazaki Y.;
"A comprehensive genomic analysis reveals the genetic landscape of
mitochondrial respiratory chain complex deficiencies.";
PLoS Genet. 12:E1005679-E1005679(2016).
-!- FUNCTION: Converts protoheme IX and farnesyl diphosphate to heme
O. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane
protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q12887-1; Sequence=Displayed;
Name=2;
IsoId=Q12887-2; Sequence=VSP_056867, VSP_056868;
Note=No experimental confirmation available.;
-!- DISEASE: Mitochondrial complex IV deficiency (MT-C4D)
[MIM:220110]: A 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.
{ECO:0000269|PubMed:10767350, ECO:0000269|PubMed:12928484,
ECO:0000269|PubMed:26741492}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset
progressive neurodegenerative disorder characterized by the
presence of focal, bilateral lesions in one or more areas of the
central nervous system including the brainstem, thalamus, basal
ganglia, cerebellum and spinal cord. Clinical features depend on
which areas of the central nervous system are involved and include
subacute onset of psychomotor retardation, hypotonia, ataxia,
weakness, vision loss, eye movement abnormalities, seizures, and
dysphagia. Note=The disease is caused by mutations affecting the
gene represented in this entry.
-!- SIMILARITY: Belongs to the UbiA prenyltransferase family.
{ECO:0000305}.
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EMBL; U09466; AAA21148.1; -; mRNA.
EMBL; U82010; AAC51330.1; -; Genomic_DNA.
EMBL; U82004; AAC51330.1; JOINED; Genomic_DNA.
EMBL; U82005; AAC51330.1; JOINED; Genomic_DNA.
EMBL; U82006; AAC51330.1; JOINED; Genomic_DNA.
EMBL; U82007; AAC51330.1; JOINED; Genomic_DNA.
EMBL; U82008; AAC51330.1; JOINED; Genomic_DNA.
EMBL; U82009; AAC51330.1; JOINED; Genomic_DNA.
EMBL; AK295925; BAG58712.1; -; mRNA.
EMBL; AK312718; BAG35592.1; -; mRNA.
EMBL; BT006985; AAP35631.1; -; mRNA.
EMBL; AC005224; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC005389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC000060; AAH00060.1; -; mRNA.
EMBL; BC006394; AAH06394.1; -; mRNA.
CCDS; CCDS11166.1; -. [Q12887-1]
PIR; I38603; I38603.
RefSeq; NP_001294.2; NM_001303.3. [Q12887-1]
UniGene; Hs.462278; -.
UniGene; Hs.462281; -.
ProteinModelPortal; Q12887; -.
BioGrid; 107745; 1.
STRING; 9606.ENSP00000261643; -.
iPTMnet; Q12887; -.
PhosphoSitePlus; Q12887; -.
BioMuta; COX10; -.
DMDM; 292495084; -.
EPD; Q12887; -.
MaxQB; Q12887; -.
PaxDb; Q12887; -.
PeptideAtlas; Q12887; -.
PRIDE; Q12887; -.
DNASU; 1352; -.
Ensembl; ENST00000261643; ENSP00000261643; ENSG00000006695. [Q12887-1]
GeneID; 1352; -.
KEGG; hsa:1352; -.
UCSC; uc002gof.5; human. [Q12887-1]
CTD; 1352; -.
DisGeNET; 1352; -.
EuPathDB; HostDB:ENSG00000006695.10; -.
GeneCards; COX10; -.
H-InvDB; HIX0013550; -.
HGNC; HGNC:2260; COX10.
HPA; HPA032005; -.
HPA; HPA032006; -.
MalaCards; COX10; -.
MIM; 220110; phenotype.
MIM; 256000; phenotype.
MIM; 602125; gene.
neXtProt; NX_Q12887; -.
OpenTargets; ENSG00000006695; -.
Orphanet; 1561; Fatal infantile cytochrome C oxidase deficiency.
Orphanet; 70474; Leigh syndrome with cardiomyopathy.
Orphanet; 255241; Leigh syndrome with leukodystrophy.
PharmGKB; PA26776; -.
eggNOG; KOG1380; Eukaryota.
eggNOG; COG0109; LUCA.
GeneTree; ENSGT00390000008408; -.
HOGENOM; HOG000189335; -.
HOVERGEN; HBG051084; -.
InParanoid; Q12887; -.
KO; K02257; -.
OMA; WQFPHFW; -.
OrthoDB; EOG091G0F6B; -.
PhylomeDB; Q12887; -.
TreeFam; TF105071; -.
BRENDA; 2.5.1.B36; 2681.
Reactome; R-HSA-189451; Heme biosynthesis.
ChiTaRS; COX10; human.
GeneWiki; COX10; -.
GenomeRNAi; 1352; -.
PRO; PR:Q12887; -.
Proteomes; UP000005640; Chromosome 17.
Bgee; ENSG00000006695; -.
CleanEx; HS_COX10; -.
ExpressionAtlas; Q12887; baseline and differential.
Genevisible; Q12887; HS.
GO; GO:0070069; C:cytochrome complex; IMP:BHF-UCL.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
GO; GO:0005739; C:mitochondrion; IDA:HPA.
GO; GO:0005730; C:nucleolus; IDA:HPA.
GO; GO:0004311; F:farnesyltranstransferase activity; TAS:ProtInc.
GO; GO:0008495; F:protoheme IX farnesyltransferase activity; TAS:Reactome.
GO; GO:0009060; P:aerobic respiration; IEA:Ensembl.
GO; GO:0045333; P:cellular respiration; IGI:HGNC.
GO; GO:0006784; P:heme a biosynthetic process; IMP:HGNC.
GO; GO:0006783; P:heme biosynthetic process; TAS:Reactome.
GO; GO:0048034; P:heme O biosynthetic process; IEA:InterPro.
GO; GO:1902600; P:hydrogen ion transmembrane transport; IEA:GOC.
GO; GO:0006123; P:mitochondrial electron transport, cytochrome c to oxygen; IC:HGNC.
GO; GO:0000266; P:mitochondrial fission; IEA:Ensembl.
GO; GO:0008535; P:respiratory chain complex IV assembly; IMP:HGNC.
CDD; cd13957; PT_UbiA_Cox10; 1.
HAMAP; MF_00154; CyoE_CtaB; 1.
InterPro; IPR006369; Protohaem_IX_farnesylTrfase.
InterPro; IPR016315; Protohaem_IX_farnesylTrfase_mt.
InterPro; IPR000537; UbiA_prenyltransferase.
InterPro; IPR030470; UbiA_prenylTrfase_CS.
Pfam; PF01040; UbiA; 1.
PIRSF; PIRSF001773; COX10; 1.
TIGRFAMs; TIGR01473; cyoE_ctaB; 1.
PROSITE; PS00943; UBIA; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Disease mutation;
Heme biosynthesis; Leigh syndrome; Membrane; Mitochondrion;
Polymorphism; Primary mitochondrial disease; Reference proteome;
Transferase; Transit peptide; Transmembrane; Transmembrane helix.
TRANSIT 1 ? Mitochondrion. {ECO:0000255}.
CHAIN ? 443 Protoheme IX farnesyltransferase,
mitochondrial.
/FTId=PRO_0000035923.
TRANSMEM 174 194 Helical. {ECO:0000255}.
TRANSMEM 235 255 Helical. {ECO:0000255}.
TRANSMEM 257 277 Helical. {ECO:0000255}.
TRANSMEM 280 300 Helical. {ECO:0000255}.
TRANSMEM 309 329 Helical. {ECO:0000255}.
TRANSMEM 364 384 Helical. {ECO:0000255}.
TRANSMEM 411 431 Helical. {ECO:0000255}.
VAR_SEQ 1 15 MAASPHTLSSRLLTG -> MICQEFWLDYPKSNS (in
isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_056867.
VAR_SEQ 16 207 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_056868.
VARIANT 28 28 T -> I (in dbSNP:rs16948978).
/FTId=VAR_057371.
VARIANT 62 62 T -> S (in dbSNP:rs2230351).
/FTId=VAR_057372.
VARIANT 97 97 Y -> C (in dbSNP:rs16948986).
/FTId=VAR_057373.
VARIANT 159 159 R -> Q (in dbSNP:rs8077302).
{ECO:0000269|PubMed:14702039,
ECO:0000269|PubMed:15489334,
ECO:0000269|PubMed:8078902,
ECO:0000269|PubMed:9177788,
ECO:0000269|Ref.4}.
/FTId=VAR_060233.
VARIANT 196 196 T -> K (in MT-C4D; dbSNP:rs104894555).
{ECO:0000269|PubMed:12928484}.
/FTId=VAR_026562.
VARIANT 204 204 N -> K (in MT-C4D; dbSNP:rs104894560).
{ECO:0000269|PubMed:10767350}.
/FTId=VAR_026563.
VARIANT 225 225 P -> L (in MT-C4D; dbSNP:rs104894556).
{ECO:0000269|PubMed:12928484}.
/FTId=VAR_026564.
VARIANT 258 258 L -> H (in dbSNP:rs587780911).
{ECO:0000269|PubMed:21248752}.
/FTId=VAR_064768.
VARIANT 288 288 G -> R (in MT-C4D; dbSNP:rs753048807).
{ECO:0000269|PubMed:26741492}.
/FTId=VAR_076181.
VARIANT 336 336 D -> G (in MT-C4D; associated with Leigh
syndrome; dbSNP:rs104894557).
{ECO:0000269|PubMed:12928484}.
/FTId=VAR_026565.
VARIANT 336 336 D -> V (in MT-C4D; associated with Leigh
syndrome; dbSNP:rs104894557).
{ECO:0000269|PubMed:12928484}.
/FTId=VAR_026566.
VARIANT 340 340 G -> D (in dbSNP:rs1050214).
{ECO:0000269|PubMed:8078902}.
/FTId=VAR_060234.
VARIANT 420 420 P -> L (in MT-C4D; dbSNP:rs773079584).
{ECO:0000269|PubMed:26741492}.
/FTId=VAR_076182.
CONFLICT 303 303 A -> T (in Ref. 1; AAA21148).
{ECO:0000305}.
CONFLICT 394 394 Y -> H (in Ref. 1; AAA21148).
{ECO:0000305}.
SEQUENCE 443 AA; 48910 MW; EC39E8D8966F4094 CRC64;
MAASPHTLSS RLLTGCVGGS VWYLERRTIQ DSPHKFLHLL RNVNKQWITF QHFSFLKRMY
VTQLNRSHNQ QVRPKPEPVA SPFLEKTSSG QAKAEIYEMR PLSPPSLSLS RKPNEKELIE
LEPDSVIEDS IDVGKETKEE KRWKEMKLQV YDLPGILARL SKIKLTALVV STTAAGFALA
PGPFDWPCFL LTSVGTGLAS CAANSINQFF EVPFDSNMNR TKNRPLVRGQ ISPLLAVSFA
TCCAVPGVAI LTLGVNPLTG ALGLFNIFLY TCCYTPLKRI SIANTWVGAV VGAIPPVMGW
TAATGSLDAG AFLLGGILYS WQFPHFNALS WGLREDYSRG GYCMMSVTHP GLCRRVALRH
CLALLVLSAA APVLDITTWT FPIMALPINA YISYLGFRFY VDADRRSSRR LFFCSLWHLP
LLLLLMLTCK RPSGGGDAGP PPS


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