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Q7KZN9 (COX15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome c oxidase assembly protein COX15 homolog
Gene names
Name:COX15
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length410 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May be involved in the biosynthesis of heme A. Ref.2

Pathway

Porphyrin-containing compound metabolism; heme A biosynthesis; heme A from heme O: step 1/1. HAMAP-Rule MF_01665

Subcellular location

Mitochondrion membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

Predominantly found in tissues characterized by high rates of oxidative phosphorylation (OxPhos), including muscle, heart, and brain. Ref.1

Involvement in disease

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (CEMCOX2) [MIM:615119]: An infantile disorder, with a rapidly progressive fatal course, characterized by cytochrome c oxidase deficiency. Clinical features include microcephaly, encephalopathy, hypertrophic cardiomyopathy, persistent lactic acidosis, respiratory distress, hypotonia and seizures. Postmortem cardiac muscle studies show marked complex IV deficiency. Complex IV activity is only slightly decreased in the skeletal muscle.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.12

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. Ref.10 Ref.11

Sequence similarities

Belongs to the COX15/CtaA family.

Ontologies

Keywords
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Leigh syndrome
   DomainTransmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular respiration

Inferred by curator Ref.2. Source: HGNC

heme a biosynthetic process

Inferred from genetic interaction Ref.2. Source: HGNC

heme biosynthetic process

Traceable author statement. Source: Reactome

hydrogen ion transmembrane transport

Inferred from genetic interaction Ref.2. Source: GOC

mitochondrial electron transport, cytochrome c to oxygen

Inferred by curator Ref.2. Source: HGNC

oxidation-reduction process

Traceable author statement Ref.1. Source: UniProtKB

porphyrin-containing compound metabolic process

Traceable author statement. Source: Reactome

respiratory chain complex IV assembly

Inferred from mutant phenotype Ref.2. Source: HGNC

respiratory gaseous exchange

Traceable author statement Ref.1. Source: UniProtKB

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

mitochondrial respiratory chain

Traceable author statement Ref.1. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.1. Source: BHF-UCL

   Molecular_functioncytochrome-c oxidase activity

Traceable author statement Ref.1. Source: UniProtKB

oxidoreductase activity, acting on the CH-CH group of donors

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7KZN9-1)

Also known as: COX15.1;

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.
Isoform 2 (identifier: Q7KZN9-2)

Also known as: COX15.2;

The sequence of this isoform differs from the canonical sequence as follows:
     368-410: VGLGISTLLMYVPTPLAATHQSGSLALLTGALWLMNELRRVPK → GPVLFNFTFKISDLDEGIRNI

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 410410Cytochrome c oxidase assembly protein COX15 homolog HAMAP-Rule MF_01665
PRO_0000183931

Regions

Transmembrane68 – 8821Helical; Potential
Transmembrane154 – 17118Helical; Potential
Transmembrane184 – 20421Helical; Potential
Transmembrane227 – 24721Helical; Potential
Transmembrane269 – 28921Helical; Potential
Transmembrane324 – 34421Helical; Potential
Transmembrane357 – 37721Helical; Potential
Transmembrane382 – 40221Helical; Potential

Natural variations

Alternative sequence368 – 41043VGLGI…RRVPK → GPVLFNFTFKISDLDEGIRN I in isoform 2.
VSP_011281
Natural variant2171R → W in CEMCOX2 and LS. Ref.2 Ref.10 Ref.12
Corresponds to variant rs28939711 [ dbSNP | Ensembl ].
VAR_019596
Natural variant3441S → P in LS. Ref.11
VAR_033117

Experimental info

Sequence conflict281R → K in AAD08639. Ref.1
Sequence conflict281R → K in AAD08646. Ref.1
Sequence conflict931T → A in CAD97781. Ref.3
Isoform 2:
Sequence conflict3741F → L in AAD08646. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (COX15.1) [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 98E9FD9D1D28EFC0

FASTA41046,030
        10         20         30         40         50         60 
MQRLLFPPLR ALKGRQYLPL LAPRAAPRAQ CDCIRRPLRP GQYSTISEVA LQSGRGTVSL 

        70         80         90        100        110        120 
PSKAAERVVG RWLLVCSGTV AGAVILGGVT RLTESGLSMV DWHLIKEMKP PTSQEEWEAE 

       130        140        150        160        170        180 
FQRYQQFPEF KILNHDMTLT EFKFIWYMEY SHRMWGRLVG LVYILPAAYF WRKGWLSRGM 

       190        200        210        220        230        240 
KGRVLALCGL VCFQGLLGWY MVKSGLEEKS DSHDIPRVSQ YRLAAHLGSA LVLYCASLWT 

       250        260        270        280        290        300 
SLSLLLPPHK LPETHQLLQL RRFAHGTAGL VFLTALSGAF VAGLDAGLVY NSFPKMGESW 

       310        320        330        340        350        360 
IPEDLFTFSP ILRNVFENPT MVQFDHRILG ITSVTAITVL YFLSRRIPLP RRTKMAAVTL 

       370        380        390        400        410 
LALAYTQVGL GISTLLMYVP TPLAATHQSG SLALLTGALW LMNELRRVPK 

« Hide

Isoform 2 (COX15.2) [UniParc].

Checksum: 92A2DAEF334460BB
Show »

FASTA38843,835

References

« Hide 'large scale' references
[1]"Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain."
Petruzzella V., Tiranti V., Fernandez P., Ianna P., Carrozzo R., Zeviani M.
Genomics 54:494-504(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy."
Antonicka H., Mattman A., Carlson C.G., Glerum D.M., Hoffbuhr K.C., Leary S.C., Kennaway N.G., Shoubridge E.A.
Am. J. Hum. Genet. 72:101-114(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANT CEMCOX2 TRP-217.
[3]"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).
[4]"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] (ISOFORM 1).
Tissue: Placenta.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Endometrial tumor.
[6]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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).
Tissue: Muscle and Skin.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome."
Oquendo C.E., Antonicka H., Shoubridge E.A., Reardon W., Brown G.K.
J. Med. Genet. 41:540-544(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LS TRP-217.
[11]"Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency."
Bugiani M., Tiranti V., Farina L., Uziel G., Zeviani M.
J. Med. Genet. 42:E28-E28(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LS PRO-344.
[12]"Infantile cardioencephalopathy due to a COX15 gene defect: report and review."
Alfadhel M., Lillquist Y.P., Waters P.J., Sinclair G., Struys E., McFadden D., Hendson G., Hyams L., Shoffner J., Vallance H.D.
Am. J. Med. Genet. A 155:840-844(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CEMCOX2 TRP-217.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF026850 mRNA. Translation: AAD08639.1.
AF044323 mRNA. Translation: AAD08646.1.
BT007129 mRNA. Translation: AAP35793.1.
AK291654 mRNA. Translation: BAF84343.1.
BX537557 mRNA. Translation: CAD97781.1.
AL133353 Genomic DNA. Translation: CAB88197.1.
AL133353 Genomic DNA. Translation: CAB88198.1.
CH471066 Genomic DNA. Translation: EAW49857.1.
BC002382 mRNA. Translation: AAH02382.3.
BC013403 mRNA. Translation: AAH13403.1.
BC078161 mRNA. Translation: AAH78161.1.
CCDSCCDS7481.1. [Q7KZN9-2]
CCDS7482.1. [Q7KZN9-1]
RefSeqNP_004367.2. NM_004376.5. [Q7KZN9-2]
NP_510870.1. NM_078470.4. [Q7KZN9-1]
UniGeneHs.28326.

3D structure databases

ProteinModelPortalQ7KZN9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107747. 14 interactions.
IntActQ7KZN9. 11 interactions.
STRING9606.ENSP00000016171.

PTM databases

PhosphoSiteQ7KZN9.

Polymorphism databases

DMDM51315906.

Proteomic databases

MaxQBQ7KZN9.
PaxDbQ7KZN9.
PRIDEQ7KZN9.

Protocols and materials databases

DNASU1355.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000016171; ENSP00000016171; ENSG00000014919. [Q7KZN9-1]
ENST00000370483; ENSP00000359514; ENSG00000014919. [Q7KZN9-2]
GeneID1355.
KEGGhsa:1355.
UCSCuc001kqb.4. human. [Q7KZN9-1]
uc001kqc.4. human. [Q7KZN9-2]

Organism-specific databases

CTD1355.
GeneCardsGC10M101461.
HGNCHGNC:2263. COX15.
HPAHPA037727.
HPA037728.
MIM256000. phenotype.
603646. gene.
615119. phenotype.
neXtProtNX_Q7KZN9.
Orphanet1561. Fatal infantile cytochrome C oxidase deficiency.
70474. Leigh syndrome with cardiomyopathy.
PharmGKBPA26779.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1612.
HOVERGENHBG051086.
InParanoidQ7KZN9.
KOK02259.
OMALSMVTWK.
OrthoDBEOG7X9G74.
PhylomeDBQ7KZN9.
TreeFamTF105073.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00269; UER00713.

Gene expression databases

ArrayExpressQ7KZN9.
BgeeQ7KZN9.
CleanExHS_COX15.
GenevestigatorQ7KZN9.

Family and domain databases

HAMAPMF_01665. HemeA_synth_type2.
InterProIPR003780. HemeA_syn.
IPR023754. HemeA_Synthase_type2.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF02628. COX15-CtaA. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
ProtoNetSearch...

Other

ChiTaRSCOX15. human.
GeneWikiCOX15.
GenomeRNAi1355.
NextBio5487.
PROQ7KZN9.
SOURCESearch...

Entry information

Entry nameCOX15_HUMAN
AccessionPrimary (citable) accession number: Q7KZN9
Secondary accession number(s): A8K6I9 expand/collapse secondary AC list , O60556, O75878, Q5TD00, Q5TD01, Q7Z3Q3, Q9NTN0
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 106 of the entry and version 1 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 10

Human chromosome 10: entries, gene names and cross-references to MIM