P00414 (COX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome c oxidase subunit 3

Alternative name(s):
Cytochrome c oxidase polypeptide III

Gene names

Name:	MT-CO3
Synonyms:	COIII, COXIII, MTCO3

Encoded on

Mitochondrion

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	261 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	Subunits I, II and III form the functional core of the enzyme complex.
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein By similarity.
Involvement in disease	Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 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.8 Recurrent myoglobinuria mitochondrial (RM-MT) [MIM:550500]: Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion of myoglobin in the urine. Note: The gene represented in this entry may be involved in disease pathogenesis.
Sequence similarities	Belongs to the cytochrome c oxidase subunit 3 family.

Ontologies

Keywords
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leber hereditary optic neuropathy MELAS syndrome
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aerobic electron transport chain Inferred from electronic annotation. Source: InterPro mitochondrial electron transport, cytochrome c to oxygen Non-traceable author statement. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial inner membrane Traceable author statement. Source: Reactome
Molecular_function	cytochrome-c oxidase activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 261	260	Cytochrome c oxidase subunit 3		PRO_0000183793
Regions
	Transmembrane	15 – 35	21	Helical; Potential
	Transmembrane	42 – 59	18	Helical; Potential
	Transmembrane	81 – 101	21	Helical; Potential
	Transmembrane	127 – 147	21	Helical; Potential
	Transmembrane	159 – 179	21	Helical; Potential
	Transmembrane	197 – 217	21	Helical; Potential
	Transmembrane	239 – 259	21	Helical; Potential
Natural variations
	Natural variant	3	1	H → R. Ref.9		VAR_008573
	Natural variant	35	1	F → S. Ref.9		VAR_008574
	Natural variant	78	1	G → S in LHON; secondary mutation; does not seem to directly cause the disease. Ref.6		VAR_002167
	Natural variant	91	1	V → I. Ref.5		VAR_008575
	Natural variant	94 – 98	5	Missing in MT-C4D; with RM-MT.		VAR_033057
	Natural variant	177	1	Q → R. Ref.5		VAR_008576
	Natural variant	200	1	A → T in LHON; possible rare primary mutation. Ref.6		VAR_002168
	Natural variant	251	1	F → L in a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. Ref.7		VAR_002169
	Natural variant	254	1	V → I. Ref.5		VAR_008577
Experimental info
	Sequence conflict	118	1	P → R in CAA24032. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P00414 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: A04385EF748B7C14	FASTA	261	29,951
	10 20 30 40 50 60 MTHQSHAYHM VKPSPWPLTG ALSALLMTSG LAMWFHFHSM TLLMLGLLTN TLTMYQWWRD 70 80 90 100 110 120 VTRESTYQGH HTPPVQKGLR YGMILFITSE VFFFAGFFWA FYHSSLAPTP QLGGHWPPTG 130 140 150 160 170 180 ITPLNPLEVP LLNTSVLLAS GVSITWAHHS LMENNRNQMI QALLITILLG LYFTLLQASE 190 200 210 220 230 240 YFESPFTISD GIYGSTFFVA TGFHGLHVII GSTFLTICFI RQLMFHFTSK HHFGFEAAAW 250 260 YWHFVDVVWL FLYVSIYWWG S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence and organization of the human mitochondrial genome." Anderson S., Bankier A.T., Barrell B.G., de Bruijn M.H.L., Coulson A.R., Drouin J., Eperon I.C., Nierlich D.P., Roe B.A., Sanger F., Schreier P.H., Smith A.J.H., Staden R., Young I.G. Nature 290:457-465(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Kogelnik A., Brown M. Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 118.
[3]	"In situ origin of deep rooting lineages of mitochondrial Macrohaplogroup 'M' in India." Thangaraj K., Chaubey G., Singh V.K., Vanniarajan A., Thanseem I., Reddy A.G., Singh L. BMC Genomics 7:151-151(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31.
[4]	Swanson K.V., Griffiss J. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 167-261. Tissue: Endometrial adenocarcinoma.
[5]	"Normal variants of human mitochondrial DNA and translation products: the building of a reference data base." Marzuki S., Noer A.S., Lertrit P., Thyagarajan D., Kapsa R., Utthanaphol P., Byrne E. Hum. Genet. 88:139-145(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-91; ARG-177 AND ILE-254.
[6]	"Cytochrome c oxidase mutations in Leber hereditary optic neuropathy." Johns D.R., Neufeld M.J. Biochem. Biophys. Res. Commun. 196:810-815(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LHON SER-78 AND THR-200.
[7]	"A new mutation associated with MELAS is located in a mitochondrial DNA polypeptide-coding gene." Manfredi G., Schon E.A., Moraes C.T., Bonilla E., Berry G.T., Sladky J.T., Dimauro S. Neuromuscul. Disord. 5:391-398(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-251.
[8]	"A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria." Keightley J.A., Hoffbuhr K.C., Burton M.D., Salas V.M., Johnston W.S.W., Penn A.M.W., Buist N.R.M., Kennaway N.G. Nat. Genet. 12:410-416(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MT-C4D 94-PHE--PHE-98 DEL.
[9]	"Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome." Rieder M.J., Taylor S.L., Tobe V.O., Nickerson D.A. Nucleic Acids Res. 26:967-973(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-3 AND SER-35.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	J01415 Genomic DNA. Translation: AAB58949.2. V00662 Genomic DNA. Translation: CAA24032.1. DQ654394 Genomic DNA. Translation: ABG27956.1. DQ654395 Genomic DNA. Translation: ABG27958.1. DQ654396 Genomic DNA. Translation: ABG27960.1. DQ654397 Genomic DNA. Translation: ABG27962.1. DQ654398 Genomic DNA. Translation: ABG27964.1. DQ654399 Genomic DNA. Translation: ABG27966.1. DQ654400 Genomic DNA. Translation: ABG27968.1. DQ654401 Genomic DNA. Translation: ABG27970.1. DQ654402 Genomic DNA. Translation: ABG27972.1. DQ654403 Genomic DNA. Translation: ABG27974.1. DQ654404 Genomic DNA. Translation: ABG27976.1. DQ654405 Genomic DNA. Translation: ABG27978.1. DQ654406 Genomic DNA. Translation: ABG27980.1. DQ654407 Genomic DNA. Translation: ABG27982.1. DQ654408 Genomic DNA. Translation: ABG27984.1. DQ654409 Genomic DNA. Translation: ABG27986.1. DQ654410 Genomic DNA. Translation: ABG27988.1. DQ654411 Genomic DNA. Translation: ABG27990.1. DQ654412 Genomic DNA. Translation: ABG27992.1. DQ654413 Genomic DNA. Translation: ABG27994.1. DQ654414 Genomic DNA. Translation: ABG27996.1. DQ654415 Genomic DNA. Translation: ABG27998.1. DQ654416 Genomic DNA. Translation: ABG28000.1. DQ654417 Genomic DNA. Translation: ABG28002.1. DQ654418 Genomic DNA. Translation: ABG28004.1. DQ654419 Genomic DNA. Translation: ABG28006.1. DQ654420 Genomic DNA. Translation: ABG28008.1. DQ654421 Genomic DNA. Translation: ABG28010.1. DQ654422 Genomic DNA. Translation: ABG28012.1. DQ654423 Genomic DNA. Translation: ABG28014.1. DQ654424 Genomic DNA. Translation: ABG28016.1. DQ654425 Genomic DNA. Translation: ABG28018.1. DQ654426 Genomic DNA. Translation: ABG28020.1. DQ654427 Genomic DNA. Translation: ABG28022.1. DQ654428 Genomic DNA. Translation: ABG28024.1. DQ654429 Genomic DNA. Translation: ABG28026.1. DQ654430 Genomic DNA. Translation: ABG28028.1. DQ654431 Genomic DNA. Translation: ABG28030.1. DQ654432 Genomic DNA. Translation: ABG28032.1. DQ654433 Genomic DNA. Translation: ABG28034.1. DQ654434 Genomic DNA. Translation: ABG28036.1. DQ654435 Genomic DNA. Translation: ABG28038.1. DQ654436 Genomic DNA. Translation: ABG28040.1. DQ654437 Genomic DNA. Translation: ABG28042.1. DQ654438 Genomic DNA. Translation: ABG28044.1. DQ654439 Genomic DNA. Translation: ABG28046.1. DQ654440 Genomic DNA. Translation: ABG28048.1. DQ654441 Genomic DNA. Translation: ABG28050.1. DQ654442 Genomic DNA. Translation: ABG28052.1. DQ654443 Genomic DNA. Translation: ABG28054.1. AF004341 Genomic DNA. Translation: AAB63452.1.
IPI	IPI00017533.
PIR	OTHU3. A00482.
RefSeq	YP_003024032.1. NC_012920.1.
3D structure databases
ProteinModelPortal	P00414.
ModBase	Search...
Protein-protein interaction databases
IntAct	P00414. 1 interaction.
Protein family/group databases
TCDB	3.D.4.11.1. proton-translocating cytochrome oxidase (COX) superfamily.
Polymorphism databases
DMDM	6648058.
Proteomic databases
PaxDb	P00414.
PRIDE	P00414.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000362079; ENSP00000354982; ENSG00000198938.
GeneID	4514.
KEGG	hsa:4514.
Organism-specific databases
CTD	4514.
GeneCards	GCMTP009209.
H-InvDB	HIX0060139.
HGNC	HGNC:7422. MT-CO3.
HPA	HPA042788.
MIM	220110. phenotype. 516050. gene. 535000. phenotype. 550500. phenotype.
neXtProt	NX_P00414.
Orphanet	99845. Genetic recurrent myoglobinuria. 254905. Isolated cytochrome C oxidase deficiency. 104. Leber hereditary optic neuropathy. 255210. Maternally-inherited Leigh syndrome. 550. MELAS syndrome.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1845.
HOGENOM	HOG000264954.
HOVERGEN	HBG016686.
InParanoid	P00414.
KO	K02262.
OrthoDB	EOG437RFN.
ProtClustDB	MTH00099.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P00414.
Bgee	P00414.
Genevestigator	P00414.
GermOnline	ENSG00000198938. Homo sapiens.
Family and domain databases
Gene3D	1.20.120.80. 1 hit.
InterPro	IPR024791. Cyt_c/ubiquinol_Oxase_su3. IPR000298. Cyt_c_oxidase_su3. IPR013833. Cyt_c_oxidase_su3_a-hlx. [Graphical view]
PANTHER	PTHR11403. PTHR11403. 1 hit.
Pfam	PF00510. COX3. 1 hit. [Graphical view]
SUPFAM	SSF81452. CytC_oxdse_III. 1 hit.
PROSITE	PS50253. COX3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	17434.
SOURCE	Search...

Entry information

Entry name

COX3_HUMAN

Accession

Primary (citable) accession number: P00414
Secondary accession number(s): Q14Y83

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 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.