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Q12887

- COX10_HUMAN

UniProt

Q12887 - COX10_HUMAN

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Protein

Protoheme IX farnesyltransferase, mitochondrial

Gene

COX10

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Converts protoheme IX and farnesyl diphosphate to heme O.By similarity

GO - Molecular functioni

  1. farnesyltranstransferase activity Source: ProtInc
  2. protoheme IX farnesyltransferase activity Source: InterPro

GO - Biological processi

  1. aerobic respiration Source: Ensembl
  2. cellular respiration Source: HGNC
  3. heme a biosynthetic process Source: HGNC
  4. heme biosynthetic process Source: Reactome
  5. heme O biosynthetic process Source: InterPro
  6. hydrogen ion transmembrane transport Source: GOC
  7. mitochondrial electron transport, cytochrome c to oxygen Source: HGNC
  8. mitochondrial fission Source: Ensembl
  9. porphyrin-containing compound metabolic process Source: Reactome
  10. respiratory chain complex IV assembly Source: HGNC
  11. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Heme biosynthesis

Enzyme and pathway databases

ReactomeiREACT_9465. Heme biosynthesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Protoheme IX farnesyltransferase, mitochondrial (EC:2.5.1.-)
Alternative name(s):
Heme O synthase
Gene namesi
Name:COX10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:2260. COX10.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei174 – 19421HelicalSequence AnalysisAdd
BLAST
Transmembranei235 – 25521HelicalSequence AnalysisAdd
BLAST
Transmembranei257 – 27721HelicalSequence AnalysisAdd
BLAST
Transmembranei280 – 30021HelicalSequence AnalysisAdd
BLAST
Transmembranei309 – 32921HelicalSequence AnalysisAdd
BLAST
Transmembranei364 – 38421HelicalSequence AnalysisAdd
BLAST
Transmembranei411 – 43121HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. mitochondrial inner membrane Source: Reactome
  3. mitochondrion Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

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.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti196 – 1961T → K in MT-C4D. 1 Publication
VAR_026562
Natural varianti204 – 2041N → K in MT-C4D. 1 Publication
VAR_026563
Natural varianti225 – 2251P → L in MT-C4D. 1 Publication
Corresponds to variant rs104894556 [ dbSNP | Ensembl ].
VAR_026564
Natural varianti336 – 3361D → G in MT-C4D; associated with Leigh syndrome. 1 Publication
VAR_026565
Natural varianti336 – 3361D → V in MT-C4D; associated with Leigh syndrome. 1 Publication
VAR_026566
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.

Keywords - Diseasei

Disease mutation, Leigh syndrome

Organism-specific databases

MIMi220110. phenotype.
256000. phenotype.
Orphaneti1561. Fatal infantile cytochrome C oxidase deficiency.
70474. Leigh syndrome with cardiomyopathy.
255241. Leigh syndrome with leukodystrophy.
PharmGKBiPA26776.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 443Protoheme IX farnesyltransferase, mitochondrialPRO_0000035923
Transit peptidei1 – ?MitochondrionSequence Analysis

Proteomic databases

MaxQBiQ12887.
PaxDbiQ12887.
PRIDEiQ12887.

PTM databases

PhosphoSiteiQ12887.

Expressioni

Gene expression databases

BgeeiQ12887.
CleanExiHS_COX10.
ExpressionAtlasiQ12887. baseline and differential.
GenevestigatoriQ12887.

Organism-specific databases

HPAiHPA032005.
HPA032006.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000261643.

Structurei

3D structure databases

ProteinModelPortaliQ12887.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the UbiA prenyltransferase family.Curated

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0109.
GeneTreeiENSGT00390000008408.
HOGENOMiHOG000189335.
HOVERGENiHBG051084.
InParanoidiQ12887.
KOiK02257.
OMAiPFDSQMS.
PhylomeDBiQ12887.
TreeFamiTF105071.

Family and domain databases

HAMAPiMF_00154. CyoE_CtaB.
InterProiIPR006369. Protohaem_IX_farnesylTrfase.
IPR016315. Protohaem_IX_farnesylTrfase_mt.
IPR000537. UbiA_prenyltransferase.
[Graphical view]
PfamiPF01040. UbiA. 1 hit.
[Graphical view]
PIRSFiPIRSF001773. COX10. 1 hit.
TIGRFAMsiTIGR01473. cyoE_ctaB. 1 hit.
PROSITEiPS00943. UBIA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q12887-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAASPHTLSS RLLTGCVGGS VWYLERRTIQ DSPHKFLHLL RNVNKQWITF
60 70 80 90 100
QHFSFLKRMY VTQLNRSHNQ QVRPKPEPVA SPFLEKTSSG QAKAEIYEMR
110 120 130 140 150
PLSPPSLSLS RKPNEKELIE LEPDSVIEDS IDVGKETKEE KRWKEMKLQV
160 170 180 190 200
YDLPGILARL SKIKLTALVV STTAAGFALA PGPFDWPCFL LTSVGTGLAS
210 220 230 240 250
CAANSINQFF EVPFDSNMNR TKNRPLVRGQ ISPLLAVSFA TCCAVPGVAI
260 270 280 290 300
LTLGVNPLTG ALGLFNIFLY TCCYTPLKRI SIANTWVGAV VGAIPPVMGW
310 320 330 340 350
TAATGSLDAG AFLLGGILYS WQFPHFNALS WGLREDYSRG GYCMMSVTHP
360 370 380 390 400
GLCRRVALRH CLALLVLSAA APVLDITTWT FPIMALPINA YISYLGFRFY
410 420 430 440
VDADRRSSRR LFFCSLWHLP LLLLLMLTCK RPSGGGDAGP PPS
Length:443
Mass (Da):48,910
Last modified:March 23, 2010 - v3
Checksum:iEC39E8D8966F4094
GO
Isoform 2 (identifier: Q12887-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MAASPHTLSSRLLTG → MICQEFWLDYPKSNS
     16-207: Missing.

Note: No experimental confirmation available

Show »
Length:251
Mass (Da):27,594
Checksum:i432213178F241F5F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti303 – 3031A → T in AAA21148. (PubMed:8078902)Curated
Sequence conflicti394 – 3941Y → H in AAA21148. (PubMed:8078902)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti28 – 281T → I.
Corresponds to variant rs16948978 [ dbSNP | Ensembl ].
VAR_057371
Natural varianti62 – 621T → S.
Corresponds to variant rs2230351 [ dbSNP | Ensembl ].
VAR_057372
Natural varianti97 – 971Y → C.
Corresponds to variant rs16948986 [ dbSNP | Ensembl ].
VAR_057373
Natural varianti159 – 1591R → Q.5 Publications
Corresponds to variant rs8077302 [ dbSNP | Ensembl ].
VAR_060233
Natural varianti196 – 1961T → K in MT-C4D. 1 Publication
VAR_026562
Natural varianti204 – 2041N → K in MT-C4D. 1 Publication
VAR_026563
Natural varianti225 – 2251P → L in MT-C4D. 1 Publication
Corresponds to variant rs104894556 [ dbSNP | Ensembl ].
VAR_026564
Natural varianti258 – 2581L → H.1 Publication
VAR_064768
Natural varianti336 – 3361D → G in MT-C4D; associated with Leigh syndrome. 1 Publication
VAR_026565
Natural varianti336 – 3361D → V in MT-C4D; associated with Leigh syndrome. 1 Publication
VAR_026566
Natural varianti340 – 3401G → D.1 Publication
Corresponds to variant rs1050214 [ dbSNP | Ensembl ].
VAR_060234

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1515MAASP…RLLTG → MICQEFWLDYPKSNS in isoform 2. 1 PublicationVSP_056867Add
BLAST
Alternative sequencei16 – 207192Missing in isoform 2. 1 PublicationVSP_056868Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09466 mRNA. Translation: AAA21148.1.
U82010
, U82004, U82005, U82006, U82007, U82008, U82009 Genomic DNA. Translation: AAC51330.1.
AK295925 mRNA. Translation: BAG58712.1.
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.
CCDSiCCDS11166.1.
PIRiI38603.
RefSeqiNP_001294.2. NM_001303.3.
UniGeneiHs.462278.

Genome annotation databases

EnsembliENST00000261643; ENSP00000261643; ENSG00000006695. [Q12887-1]
GeneIDi1352.
KEGGihsa:1352.
UCSCiuc002gof.4. human. [Q12887-1]

Polymorphism databases

DMDMi292495084.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U09466 mRNA. Translation: AAA21148.1 .
U82010
, U82004 , U82005 , U82006 , U82007 , U82008 , U82009 Genomic DNA. Translation: AAC51330.1 .
AK295925 mRNA. Translation: BAG58712.1 .
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 .
CCDSi CCDS11166.1.
PIRi I38603.
RefSeqi NP_001294.2. NM_001303.3.
UniGenei Hs.462278.

3D structure databases

ProteinModelPortali Q12887.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000261643.

PTM databases

PhosphoSitei Q12887.

Polymorphism databases

DMDMi 292495084.

Proteomic databases

MaxQBi Q12887.
PaxDbi Q12887.
PRIDEi Q12887.

Protocols and materials databases

DNASUi 1352.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261643 ; ENSP00000261643 ; ENSG00000006695 . [Q12887-1 ]
GeneIDi 1352.
KEGGi hsa:1352.
UCSCi uc002gof.4. human. [Q12887-1 ]

Organism-specific databases

CTDi 1352.
GeneCardsi GC17P013972.
H-InvDB HIX0013550.
HGNCi HGNC:2260. COX10.
HPAi HPA032005.
HPA032006.
MIMi 220110. phenotype.
256000. phenotype.
602125. gene.
neXtProti NX_Q12887.
Orphaneti 1561. Fatal infantile cytochrome C oxidase deficiency.
70474. Leigh syndrome with cardiomyopathy.
255241. Leigh syndrome with leukodystrophy.
PharmGKBi PA26776.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0109.
GeneTreei ENSGT00390000008408.
HOGENOMi HOG000189335.
HOVERGENi HBG051084.
InParanoidi Q12887.
KOi K02257.
OMAi PFDSQMS.
PhylomeDBi Q12887.
TreeFami TF105071.

Enzyme and pathway databases

Reactomei REACT_9465. Heme biosynthesis.

Miscellaneous databases

ChiTaRSi COX10. human.
GeneWikii COX10.
GenomeRNAii 1352.
NextBioi 5479.
PROi Q12887.
SOURCEi Search...

Gene expression databases

Bgeei Q12887.
CleanExi HS_COX10.
ExpressionAtlasi Q12887. baseline and differential.
Genevestigatori Q12887.

Family and domain databases

HAMAPi MF_00154. CyoE_CtaB.
InterProi IPR006369. Protohaem_IX_farnesylTrfase.
IPR016315. Protohaem_IX_farnesylTrfase_mt.
IPR000537. UbiA_prenyltransferase.
[Graphical view ]
Pfami PF01040. UbiA. 1 hit.
[Graphical view ]
PIRSFi PIRSF001773. COX10. 1 hit.
TIGRFAMsi TIGR01473. cyoE_ctaB. 1 hit.
PROSITEi PS00943. UBIA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1), 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.
    , 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] (ISOFORMS 1 AND 2), VARIANT GLN-159.
    Tissue: Brain and Substantia nigra.
  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] (ISOFORM 1), 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] [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] (ISOFORM 1), 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. Cited for: VARIANT HIS-258.

Entry informationi

Entry nameiCOX10_HUMAN
AccessioniPrimary (citable) accession number: Q12887
Secondary accession number(s): B2R6U5
, B4DJ50, O15334, Q969F7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: March 23, 2010
Last modified: November 26, 2014
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3