Q12887 (COX10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protoheme IX farnesyltransferase, mitochondrial
EC=2.5.1.-

Alternative name(s):
Heme O synthase

Gene names

Name:

COX10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	443 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts protoheme IX and farnesyl diphosphate to heme O By similarity.
Subcellular location	Mitochondrion membrane; Multi-pass membrane protein.
Involvement in disease	Defects in COX10 are a cause of mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]; also known as cytochrome c oxidase deficiency. 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, excercise intolerance, developmental delay, delayed motor development and mental retardation. A subset of patients manifest Leigh syndrome. Ref.7 Ref.8 Defects in COX10 are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.
Sequence similarities	Belongs to the UbiA prenyltransferase family.

Ontologies

Keywords
Biological process	Heme biosynthesis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leigh syndrome
Domain	Transit peptide Transmembrane Transmembrane helix
Molecular function	Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	heme O biosynthetic process Inferred from electronic annotation. Source: InterPro heme a biosynthetic process Inferred from mutant phenotype Ref.8. Source: HGNC mitochondrial electron transport, cytochrome c to oxygen Inferred by curator Ref.8. Source: HGNC respiratory chain complex IV assembly Inferred from mutant phenotype. Source: HGNC
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protoheme IX farnesyltransferase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – ?		Mitochondrion Potential
	Chain	? – 443		Protoheme IX farnesyltransferase, mitochondrial		PRO_0000035923
Regions
	Transmembrane	174 – 194	21	Helical; Potential
	Transmembrane	235 – 255	21	Helical; Potential
	Transmembrane	257 – 277	21	Helical; Potential
	Transmembrane	280 – 300	21	Helical; Potential
	Transmembrane	309 – 329	21	Helical; Potential
	Transmembrane	364 – 384	21	Helical; Potential
	Transmembrane	411 – 431	21	Helical; Potential
Natural variations
	Natural variant	28	1	T → I. Corresponds to variant rs16948978 [ dbSNP | Ensembl ].		VAR_057371
	Natural variant	62	1	T → S. Corresponds to variant rs2230351 [ dbSNP | Ensembl ].		VAR_057372
	Natural variant	97	1	Y → C. Corresponds to variant rs16948986 [ dbSNP | Ensembl ].		VAR_057373
	Natural variant	159	1	R → Q. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs8077302 [ dbSNP | Ensembl ].		VAR_060233
	Natural variant	196	1	T → K in MT-C4D. Ref.8		VAR_026562
	Natural variant	204	1	N → K in MT-C4D. Ref.7		VAR_026563
	Natural variant	225	1	P → L in MT-C4D. Ref.8		VAR_026564
	Natural variant	258	1	L → H. Ref.9		VAR_064768
	Natural variant	336	1	D → G in MT-C4D; associated with Leigh syndrome. Ref.8		VAR_026565
	Natural variant	336	1	D → V in MT-C4D; associated with Leigh syndrome. Ref.8		VAR_026566
	Natural variant	340	1	G → D. Ref.1 Corresponds to variant rs1050214 [ dbSNP | Ensembl ].		VAR_060234
Experimental info
	Sequence conflict	303	1	A → T in AAA21148. Ref.1
	Sequence conflict	394	1	Y → H in AAA21148. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q12887 [UniParc]. Last modified March 23, 2010. Version 3. Checksum: EC39E8D8966F4094	FASTA	443	48,910
	10 20 30 40 50 60 MAASPHTLSS RLLTGCVGGS VWYLERRTIQ DSPHKFLHLL RNVNKQWITF QHFSFLKRMY 70 80 90 100 110 120 VTQLNRSHNQ QVRPKPEPVA SPFLEKTSSG QAKAEIYEMR PLSPPSLSLS RKPNEKELIE 130 140 150 160 170 180 LEPDSVIEDS IDVGKETKEE KRWKEMKLQV YDLPGILARL SKIKLTALVV STTAAGFALA 190 200 210 220 230 240 PGPFDWPCFL LTSVGTGLAS CAANSINQFF EVPFDSNMNR TKNRPLVRGQ ISPLLAVSFA 250 260 270 280 290 300 TCCAVPGVAI LTLGVNPLTG ALGLFNIFLY TCCYTPLKRI SIANTWVGAV VGAIPPVMGW 310 320 330 340 350 360 TAATGSLDAG AFLLGGILYS WQFPHFNALS WGLREDYSRG GYCMMSVTHP GLCRRVALRH 370 380 390 400 410 420 CLALLVLSAA APVLDITTWT FPIMALPINA YISYLGFRFY VDADRRSSRR LFFCSLWHLP 430 440 LLLLLMLTCK RPSGGGDAGP PPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a human cDNA for heme A:farnesyltransferase by functional complementation of a yeast cox10 mutant." Glerum M.D., Tzagoloff A. Proc. Natl. Acad. Sci. U.S.A. 91:8452-8456(1994) [PubMed: 8078902] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLN-159 AND ASP-340.
[2]	"Genomic structure and expression of the human heme A:farnesyltransferase (COX10) gene." Murakami T., Reiter L.T., Lupski J.R. Genomics 42:161-164(1997) [PubMed: 9177788] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-159.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-159. Tissue: Brain.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." 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. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-159.
[5]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." 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. Nature 440:1045-1049(2006) [PubMed: 16625196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-159. Tissue: Brain.
[7]	"A mutation in the human heme A:farnesyltransferase gene (COX10) causes cytochrome c oxidase deficiency." Valnot I., von Kleist-Retzow J.C., Barrientos A., Gorbatyuk M., Taanman J.W., Mehaye B., Rustin P., Tzagoloff A., Munnich A., Rotig A. Hum. Mol. Genet. 9:1245-1249(2000) [PubMed: 10767350] [Abstract] Cited for: VARIANT MT-C4D LYS-204.
[8]	"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." Antonicka H., Leary S.C., Guercin G.-H., Agar J.N., Horvath R., Kennaway N.G., Harding C.O., Jaksch M., Shoubridge E.A. Hum. Mol. Genet. 12:2693-2702(2003) [PubMed: 12928484] [Abstract] Cited for: VARIANTS MT-C4D LYS-196; LEU-225; GLY-336 AND VAL-336.
[9]	"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma." 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. Nature 469:539-542(2011) [PubMed: 21248752] [Abstract] Cited for: VARIANT HIS-258.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U09466 mRNA. Translation: AAA21148.1. U82010 , U82004, U82005, U82006, U82007, U82008, U82009 Genomic DNA. Translation: AAC51330.1. AK312718 mRNA. Translation: BAG35592.1. BT006985 mRNA. Translation: AAP35631.1. AC005224 Genomic DNA. No translation available. AC005389 Genomic DNA. No translation available. BC000060 mRNA. Translation: AAH00060.1. BC006394 mRNA. Translation: AAH06394.1.
IPI	IPI00290099.
PIR	I38603.
RefSeq	NP_001294.2. NM_001303.3.
UniGene	Hs.462278.
3D structure databases
ProteinModelPortal	Q12887.
ModBase	Search...
Protein-protein interaction databases
STRING	Q12887.
Polymorphism databases
DMDM	292495084.
Proteomic databases
PRIDE	Q12887.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261643; ENSP00000261643; ENSG00000006695.
GeneID	1352.
KEGG	hsa:1352.
Organism-specific databases
CTD	1352.
GeneCards	GC17P013972.
H-InvDB	HIX0013550.
HGNC	HGNC:2260. COX10.
HPA	HPA032005. HPA032006.
MIM	220110. phenotype. 256000. phenotype. 602125. gene.
neXtProt	NX_Q12887.
Orphanet	1561. Fatal infantile cytochrome C oxidase deficiency. 255241. Leigh syndrome with leukodystrophy. 70474. Leigh syndrome with myopathy.
PharmGKB	PA26776.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18013.
GeneTree	ENSGT00390000008408.
HOGENOM	HBG397306.
HOVERGEN	HBG051084.
InParanoid	Q12887.
OMA	VPFDSQM.
OrthoDB	EOG49W2FQ.
PhylomeDB	Q12887.
Gene expression databases
ArrayExpress	Q12887.
Bgee	Q12887.
CleanEx	HS_COX10.
Genevestigator	Q12887.
GermOnline	ENSG00000006695. Homo sapiens.
Family and domain databases
InterPro	IPR006369. Protohaem_IX_farnesylTrfase. IPR016315. Protohaem_IX_farnesylTrfase_mt. IPR000537. UbiA_prenyltransferase. [Graphical view]
KO	K02257.
Pfam	PF01040. UbiA. 1 hit. [Graphical view]
PIRSF	PIRSF001773. COX10. 1 hit.
TIGRFAMs	TIGR01473. CyoE_ctaB. 1 hit.
PROSITE	PS00943. UBIA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

COX10_HUMAN

Accession

Primary (citable) accession number: Q12887
Secondary accession number(s): B2R6U5, O15334, Q969F7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	March 23, 2010
Last modified:	January 25, 2012
This is version 113 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.