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Q12887 (COX10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protoheme IX farnesyltransferase, mitochondrial

EC=2.5.1.-
Alternative name(s):
Heme O synthase
Gene names
Name:COX10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Converts protoheme IX and farnesyl diphosphate to heme O By similarity. HAMAP-Rule MF_00154

Subcellular location

Mitochondrion membrane; Multi-pass membrane protein HAMAP-Rule MF_00154.

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8

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.

Sequence similarities

Belongs to the UbiA prenyltransferase family.

Ontologies

Keywords
   Biological processHeme biosynthesis
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Leigh syndrome
   DomainTransit peptide
Transmembrane
Transmembrane helix
   Molecular functionTransferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaerobic respiration

Inferred from electronic annotation. Source: Ensembl

cellular respiration

Inferred from genetic interaction Ref.7. Source: HGNC

cytochrome complex assembly

Inferred from electronic annotation. Source: Ensembl

heme O biosynthetic process

Inferred from electronic annotation. Source: InterPro

heme a biosynthetic process

Inferred from mutant phenotype Ref.8. Source: HGNC

heme biosynthetic process

Traceable author statement. Source: Reactome

hydrogen ion transmembrane transport

Inferred from mutant phenotype Ref.8. Source: GOC

mitochondrial electron transport, cytochrome c to oxygen

Inferred by curator Ref.8. Source: HGNC

mitochondrial fission

Inferred from electronic annotation. Source: Ensembl

porphyrin-containing compound metabolic process

Traceable author statement. Source: Reactome

respiratory chain complex IV assembly

Inferred from mutant phenotype PubMed 14607829. Source: HGNC

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial inner membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred by curator PubMed 14607829. Source: HGNC

   Molecular_functionfarnesyltranstransferase activity

Traceable author statement Ref.1. Source: ProtInc

protoheme IX farnesyltransferase activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 443Protoheme IX farnesyltransferase, mitochondrial HAMAP-Rule MF_00154PRO_0000035923

Regions

Transmembrane174 – 19421Helical; Potential
Transmembrane235 – 25521Helical; Potential
Transmembrane257 – 27721Helical; Potential
Transmembrane280 – 30021Helical; Potential
Transmembrane309 – 32921Helical; Potential
Transmembrane364 – 38421Helical; Potential
Transmembrane411 – 43121Helical; Potential

Natural variations

Natural variant281T → I.
Corresponds to variant rs16948978 [ dbSNP | Ensembl ].
VAR_057371
Natural variant621T → S.
Corresponds to variant rs2230351 [ dbSNP | Ensembl ].
VAR_057372
Natural variant971Y → C.
Corresponds to variant rs16948986 [ dbSNP | Ensembl ].
VAR_057373
Natural variant1591R → Q. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs8077302 [ dbSNP | Ensembl ].
VAR_060233
Natural variant1961T → K in MT-C4D. Ref.8
VAR_026562
Natural variant2041N → K in MT-C4D. Ref.7
VAR_026563
Natural variant2251P → L in MT-C4D. Ref.8
Corresponds to variant rs104894556 [ dbSNP | Ensembl ].
VAR_026564
Natural variant2581L → H. Ref.9
VAR_064768
Natural variant3361D → G in MT-C4D; associated with Leigh syndrome. Ref.8
VAR_026565
Natural variant3361D → V in MT-C4D; associated with Leigh syndrome. Ref.8
VAR_026566
Natural variant3401G → D. Ref.1
Corresponds to variant rs1050214 [ dbSNP | Ensembl ].
VAR_060234

Experimental info

Sequence conflict3031A → T in AAA21148. Ref.1
Sequence conflict3941Y → H in AAA21148. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q12887 [UniParc].

Last modified March 23, 2010. Version 3.
Checksum: EC39E8D8966F4094

FASTA44348,910
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-258.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U09466 mRNA. Translation: AAA21148.1.
U82010 expand/collapse EMBL AC list , 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.
PIRI38603.
RefSeqNP_001294.2. NM_001303.3.
UniGeneHs.462278.

3D structure databases

ProteinModelPortalQ12887.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000261643.

PTM databases

PhosphoSiteQ12887.

Polymorphism databases

DMDM292495084.

Proteomic databases

PaxDbQ12887.
PRIDEQ12887.

Protocols and materials databases

DNASU1352.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261643; ENSP00000261643; ENSG00000006695.
GeneID1352.
KEGGhsa:1352.
UCSCuc002gof.4. human.

Organism-specific databases

CTD1352.
GeneCardsGC17P013972.
H-InvDBHIX0013550.
HGNCHGNC:2260. COX10.
HPAHPA032005.
HPA032006.
MIM220110. phenotype.
256000. phenotype.
602125. gene.
neXtProtNX_Q12887.
Orphanet1561. Fatal infantile cytochrome C oxidase deficiency.
70474. Leigh syndrome with cardiomyopathy.
255241. Leigh syndrome with leukodystrophy.
PharmGKBPA26776.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0109.
HOGENOMHOG000189335.
HOVERGENHBG051084.
InParanoidQ12887.
KOK02257.
OMAVPFDSQM.
PhylomeDBQ12887.
TreeFamTF105071.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ12887.
BgeeQ12887.
CleanExHS_COX10.
GenevestigatorQ12887.

Family and domain databases

HAMAPMF_00154. CyoE_CtaB.
InterProIPR006369. Protohaem_IX_farnesylTrfase.
IPR016315. Protohaem_IX_farnesylTrfase_mt.
IPR000537. UbiA_prenyltransferase.
[Graphical view]
PfamPF01040. UbiA. 1 hit.
[Graphical view]
PIRSFPIRSF001773. COX10. 1 hit.
TIGRFAMsTIGR01473. cyoE_ctaB. 1 hit.
PROSITEPS00943. UBIA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCOX10.
GenomeRNAi1352.
NextBio5479.
PROQ12887.
SOURCESearch...

Entry information

Entry nameCOX10_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 132 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM