Q7KZN9 (COX15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome c oxidase assembly protein COX15 homolog

Gene names

Name:

COX15

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	410 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the biosynthesis of heme A. Ref.2
Pathway	Porphyrin metabolism; heme A biosynthesis; heme A from heme O: step 1/1.
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	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.2 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 component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Leigh syndrome
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	heme a biosynthetic process Inferred from genetic interaction Ref.2. Source: HGNC mitochondrial electron transport, cytochrome c to oxygen Inferred by curator Ref.2. Source: HGNC respiratory chain complex IV assembly Inferred from mutant phenotype Ref.2. Source: HGNC respiratory gaseous exchange Traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial respiratory chain Traceable author statement Ref.1. Source: UniProtKB
Molecular_function	cytochrome-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 410	410	Cytochrome c oxidase assembly protein COX15 homolog		PRO_0000183931
Regions
	Transmembrane	68 – 88	21	Helical; Potential
	Transmembrane	154 – 171	18	Helical; Potential
	Transmembrane	184 – 204	21	Helical; Potential
	Transmembrane	227 – 247	21	Helical; Potential
	Transmembrane	269 – 289	21	Helical; Potential
	Transmembrane	324 – 344	21	Helical; Potential
	Transmembrane	357 – 377	21	Helical; Potential
	Transmembrane	382 – 402	21	Helical; Potential
Natural variations
	Alternative sequence	368 – 410	43	VGLGI…RRVPK → GPVLFNFTFKISDLDEGIRN I in isoform 2.		VSP_011281
	Natural variant	217	1	R → W in MT-C4D and LS. Ref.2 Ref.10 Corresponds to variant rs28939711 [ dbSNP | Ensembl ].		VAR_019596
	Natural variant	344	1	S → P in LS. Ref.11		VAR_033117
Experimental info
	Sequence conflict	28	1	R → K in AAD08639. Ref.1
	Sequence conflict	28	1	R → K in AAD08646. Ref.1
	Sequence conflict	93	1	T → A in CAD97781. Ref.3
Isoform 2:
	Sequence conflict	374	1	F → L in AAD08646. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (COX15.1) [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 98E9FD9D1D28EFC0	FASTA	410	46,030
	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
	Isoform 2 (COX15.2) [UniParc]. Checksum: 92A2DAEF334460BB	FASTA	388	43,835
	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 LALAYTQGPV LFNFTFKISD LDEGIRNI

References

	« Hide 'large scale' referencesShow '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 MT-C4D 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. , 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. , 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. , 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.
+	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.
IPI	IPI00419869. IPI00455190.
RefSeq	NP_004367.2. NM_004376.5. NP_510870.1. NM_078470.4.
UniGene	Hs.28326.
3D structure databases
ProteinModelPortal	Q7KZN9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q7KZN9. 1 interaction.
STRING	9606.ENSP00000016171.
PTM databases
PhosphoSite	Q7KZN9.
Polymorphism databases
DMDM	51315906.
Proteomic databases
PaxDb	Q7KZN9.
PRIDE	Q7KZN9.
Protocols and materials databases
DNASU	1355.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000016171; ENSP00000016171; ENSG00000014919. ENST00000370483; ENSP00000359514; ENSG00000014919.
GeneID	1355.
KEGG	hsa:1355.
UCSC	uc001kqb.4. human. uc001kqc.4. human.
Organism-specific databases
CTD	1355.
GeneCards	GC10M101461.
HGNC	HGNC:2263. COX15.
HPA	HPA037727. HPA037728.
MIM	220110. phenotype. 256000. phenotype. 603646. gene.
neXtProt	NX_Q7KZN9.
Orphanet	1561. Fatal infantile cytochrome C oxidase deficiency. 70474. Leigh syndrome with cardiomyopathy.
PharmGKB	PA26779.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1612.
HOVERGEN	HBG051086.
InParanoid	Q7KZN9.
KO	K02259.
OMA	KTIFWWE.
PhylomeDB	Q7KZN9.
Enzyme and pathway databases
UniPathway	UPA00269; UER00713.
Gene expression databases
ArrayExpress	Q7KZN9.
Bgee	Q7KZN9.
CleanEx	HS_COX15.
Genevestigator	Q7KZN9.
GermOnline	ENSG00000014919. Homo sapiens.
Family and domain databases
InterPro	IPR003780. HemeA_syn. IPR023754. HemeA_Synthase_type2. IPR009003. Trypsin-like_Pept_dom. [Graphical view]
Pfam	PF02628. COX15-CtaA. 1 hit. [Graphical view]
SUPFAM	SSF50494. Pept_Ser_Cys. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	COX15. human.
GenomeRNAi	1355.
NextBio	5487.
SOURCE	Search...

Entry information

Entry name

COX15_HUMAN

Accession

Primary (citable) accession number: Q7KZN9
Secondary accession number(s): A8K6I9 , O60556, O75878, Q5TD00, Q5TD01, Q7Z3Q3, Q9NTN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2004
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 94 of the entry and version 1 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.