ATP synthase subunit a - Homo sapiens (Human)

Names and origin

Protein names

Recommended name:
ATP synthase subunit a
Alternative name(s):
F-ATPase protein 6

Gene names

Name:	MT-ATP6
Synonyms:	ATP6, ATPASE6, MTATP6

Encoded on

Mitochondrion

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	226 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Mitochondrial membrane ATP synthase (F₁F₀ ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F₁ - containing the extramembraneous catalytic core and F₀ - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F₁ is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.
Subunit structure	F-type ATPases have 2 components, CF₁ - the catalytic core - and CF₀ - the membrane proton channel. CF₁ has five subunits: alpha₃, beta₃, gamma₁, delta₁, epsilon₁. CF₀ has three main subunits: a, b and c.
Subcellular location	Mitochondrion inner membrane; Multi-pass membrane protein.
Involvement in disease	Defects in MT-ATP6 are the cause of neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) [MIM:551500]. Ref.17 Defects in MT-ATP6 are a cause of Leber hereditary optic neuropathy (LHON) [MIM:535000]. LHON is 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. Ref.20 Defects in MT-ATP6 are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions. Ref.19 Ref.22 Ref.23 Ref.24 Defects in MT-ATP6 are a cause of infantile bilateral striatal necrosis [MIM:500003]. Bilateral striatal necrosis is a neurological disorder resembling Leigh syndrome. Ref.21
Sequence similarities	Belongs to the ATPase A chain family.

Ontologies

Keywords
Biological process	ATP synthesis Hydrogen ion transport Ion transport Transport
Cellular component	CF(0) Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Leber hereditary optic neuropathy Leigh syndrome
Domain	Transmembrane
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	mitochondrial ATP synthesis coupled proton transport Inferred by curator. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial proton-transporting ATP synthase complex, coupling factor F(o) Non-traceable author statement. Source: UniProtKB
Molecular function	hydrogen ion transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 226

226

ATP synthase subunit a

PRO_0000082128

Regions

Transmembrane

6 – 26

Potential

Transmembrane

68 – 88

Potential

Transmembrane

97 – 117

Potential

Transmembrane

138 – 158

Potential

Transmembrane

164 – 184

Potential

Transmembrane

189 – 209

Potential

Natural variations

Natural variant

VAR_021178

Natural variant

VAR_021179

Natural variant

I → V

VAR_021180

Natural variant

G → S

VAR_021181

Natural variant

T → S

VAR_008556

Natural variant

L → P

VAR_021182

Natural variant

T → I

VAR_021183

Natural variant

VAR_000792

Natural variant

M → T

VAR_021184

Natural variant

H → Y

VAR_008557

Natural variant

VAR_021185

Natural variant

H → Y

VAR_008558

Natural variant

112

VAR_008559

Natural variant

117

F → L

VAR_021186

Natural variant

121

I → V

VAR_021187

Natural variant

133

VAR_021188

Natural variant

155

VAR_008560

Natural variant

156

L → P in LS. Ref.19

VAR_000794

Natural variant

156

L → R in NARP and LS. Ref.17 Ref.23

VAR_000793

Natural variant

177

VAR_008561

Natural variant

178

VAR_021189

Natural variant

182

S → L

VAR_021190

Natural variant

192

I → T in LHON; possible rate primary mutation. Ref.20 Ref.9

VAR_000795

Natural variant

192

I → V

VAR_021191

Natural variant

193

F → L

VAR_021192

Natural variant

204

I → T

VAR_021193

Natural variant

213

V → I

VAR_000796

Natural variant

217

L → P in LS and infantile bilateral striatal necrosis. Ref.22 Ref.24 Ref.21

VAR_000797

Natural variant

219

S → G

VAR_008562

Sequences

Sequence

Length

Mass (Da)

Tools

P00846-1 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 7DB0F0BE86F55207
Show »

FASTA

226

24,817

        10         20         30         40         50         60 
MNENLFASFI APTILGLPAA VLIILFPPLL IPTSKYLINN RLITTQQWLI KLTSKQMMTM 

        70         80         90        100        110        120 
HNTKGRTWSL MLVSLIIFIA TTNLLGLLPH SFTPTTQLSM NLAMAIPLWA GTVIMGFRSK 

       130        140        150        160        170        180 
IKNALAHFLP QGTPTPLIPM LVIIETISLL IQPMALAVRL TANITAGHLL MHLIGSATLA 

       190        200        210        220 
MSTINLPSTL IIFTILILLT ILEIAVALIQ AYVFTLLVSL YLHDNT

« Hide

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: 7219534] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs." Horai S., Hayasaka K., Kondo R., Tsugane K., Takahata N. Proc. Natl. Acad. Sci. U.S.A. 92:532-536(1995) [PubMed: 7530363] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-14. Tissue: Placenta.
[3]	"Mitochondrial genome variation and the origin of modern humans." Ingman M., Kaessmann H., Paeaebo S., Gyllensten U. Nature 408:708-713(2000) [PubMed: 11130070] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-90; ALA-112 AND LEU-193.
[4]	"Major genomic mitochondrial lineages delineate early human expansions." Maca-Meyer N., Gonzalez A.M., Larruga J.M., Flores C., Cabrera V.M. BMC Genet. 2:13-13(2001) [PubMed: 11553319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-90; ALA-112 AND THR-204.
[5]	"Mitochondrial genome diversity of native Americans supports a single early entry of founder populations into America." Silva W.A. Jr., Bonatto S.L., Holanda A.J., Ribeiro-Dos-Santos A.K., Paixao B.M., Goldman G.H., Abe-Sandes K., Rodriguez-Delfin L., Barbosa M., Paco-Larson M.L., Petzl-Erler M.L., Valente V., Santos S.E., Zago M.A. Am. J. Hum. Genet. 71:187-192(2002) [PubMed: 12022039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-80; TYR-90 AND ALA-112.
[6]	"Mitochondrial DNA transit between West Asia and North Africa inferred from U6 phylogeography." Maca-Meyer N., Gonzalez A.M., Pestano J., Flores C., Larruga J.M., Cabrera V.M. BMC Genet. 4:15-15(2003) [PubMed: 14563219] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-14 AND ALA-112.
[7]	"Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines." Ingman M., Gyllensten U. Genome Res. 13:1600-1606(2003) [PubMed: 12840039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-112 AND LEU-193.
[8]	"Lineage-specific selection in human mtDNA: lack of polymorphisms in a segment of MTND5 gene in haplogroup J." Moilanen J.S., Finnila S., Majamaa K. Mol. Biol. Evol. 20:2132-2142(2003) [PubMed: 12949126] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-11; THR-60; ALA-112 AND ALA-133.
[9]	"Natural selection shaped regional mtDNA variation in humans." Mishmar D., Ruiz-Pesini E., Golik P., Macaulay V., Clark A.G., Hosseini S., Brandon M., Easley K., Chen E., Brown M.D., Sukernik R.I., Olckers A., Wallace D.C. Proc. Natl. Acad. Sci. U.S.A. 100:171-176(2003) [PubMed: 12509511] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-60; TYR-90; ALA-112; LEU-117 AND THR-192.
[10]	"Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences." Kong Q.-P., Yao Y.-G., Sun C., Bandelt H.-J., Zhu C.-L., Zhang Y.-P. Am. J. Hum. Genet. 73:671-676(2003) [PubMed: 12870132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-16; PRO-37; TYR-90; ALA-112; ALA-178; LEU-182 AND THR-204.
[11]	"The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool." Achilli A., Rengo C., Magri C., Battaglia V., Olivieri A., Scozzari R., Cruciani F., Zeviani M., Briem E., Carelli V., Moral P., Dugoujon J.M., Roostalu U., Loogvali E.L., Kivisild T., Bandelt H.-J., Richards M., Villems R. Torroni A. Am. J. Hum. Genet. 75:910-918(2004) [PubMed: 15382008] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-11 AND ALA-112.
[12]	"Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia." Palanichamy M.G., Sun C., Agrawal S., Bandelt H.-J., Kong Q.-P., Khan F., Wang C.Y., Chaudhuri T.K., Palla V., Zhang Y.-P. Am. J. Hum. Genet. 75:966-978(2004) [PubMed: 15467980] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-7; THR-11; ILE-53; THR-60; ALA-112; VAL-121 AND ILE-213.
[13]	"Single nucleotide polymorphisms over the entire mtDNA genome that increase the power of forensic testing in Caucasians." Coble M.D., Just R.S., O'Callaghan J.E., Letmanyi I.H., Peterson C.T., Irwin J.A., Parsons T.J. Int. J. Legal Med. 118:137-146(2004) [PubMed: 14760490] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-11; THR-60; ALA-112 AND VAL-192.
[14]	"Mitochondrial DNA diversity in indigenous populations of the southern extent of Siberia, and the origins of native american haplogroups." Starikovskaya E.B., Sukernik R.I., Derbeneva O.A., Volodko N.V., Ruiz-Pesini E., Torroni A., Brown M.D., Lott M.T., Hosseini S.H., Huoponen K., Wallace D.C. Ann. Hum. Genet. 69:67-89(2005) [PubMed: 15638829] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-90 AND ALA-112.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy." Wallace D.C., Singh G., Lott M.T., Hodge J.A., Schurr T.G., Lezza A.M., Elsas L.J. II, Nikoskelainen E.K. Science 242:1427-1430(1988) [PubMed: 3201231] [Abstract] Cited for: VARIANTS ALA-59 AND ILE-213.
[17]	"A new mitochondrial disease associated with mitochondrial DNA heteroplasmy." Holt I.J., Harding A.E., Petty R.K., Morgan-Hughes J.A. Am. J. Hum. Genet. 46:428-433(1990) [PubMed: 2137962] [Abstract] Cited for: VARIANT NARP ARG-156.
[18]	"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: 1757091] [Abstract] Cited for: VARIANTS SER-33; ALA-59; TYR-61; TYR-90; ALA-112; THR-155; ILE-213 AND GLY-219.
[19]	"A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome." de Vries D.D., van Engelen B.G.M., Gabreels F.J.M., Ruitenbeek W., van Oost B.A. Ann. Neurol. 34:410-412(1993) [PubMed: 8395787] [Abstract] Cited for: VARIANT LS PRO-156.
[20]	"A mitochondrial mutation at nt 9101 in the ATP synthase 6 gene associated with deficient oxidative phosphorylation in a family with Leber hereditary optic neuroretinopathy." Lamminen T., Majander A., Juvonen V., Wikstroem M., Aula P., Nikoskelainen E., Savontaus M.-L. Am. J. Hum. Genet. 56:1238-1240(1995) [PubMed: 7726182] [Abstract] Cited for: VARIANT LHON THR-192.
[21]	"A novel mitochondrial ATPase 6 point mutation in familial bilateral striatal necrosis." Thyagarajan D., Shanske S., Vazquez-Memije M., De Vivo D.C., Dimauro S. Ann. Neurol. 38:468-472(1995) [PubMed: 7668837] [Abstract] Cited for: VARIANT INFANTILE BILATERAL STRIATAL NECROSIS PRO-217.
[22]	"Leigh syndrome associated with the T9176C mutation in the ATPase 6 gene of mitochondrial DNA." Campos Y., Martin M.A., Rubio J.C., Solana L.G., Garcia-Benayas C., Terradas J.L., Arenas J. Neurology 49:595-597(1997) [PubMed: 9270604] [Abstract] Cited for: VARIANT LS PRO-217.
[23]	"De novo mtDNA nt 8993 (T-G) mutation resulting in Leigh syndrome." Takahashi S., Makita Y., Oki J., Miyamoto A., Yanagawa J., Naito E., Goto Y., Okuno A. Am. J. Hum. Genet. 62:717-719(1998) [PubMed: 9556461] [Abstract] Cited for: VARIANT LS ARG-156.
[24]	"Fulminant Leigh syndrome and sudden unexpected death in a family with the T9176C mutation of the mitochondrial ATPase 6 gene." Dionisi-Vici C., Seneca S., Zeviani M., Fariello G., Rimoldi M., Bertini E., De Meirleir L. J. Inherit. Metab. Dis. 21:2-8(1998) [PubMed: 9501263] [Abstract] Cited for: VARIANT LS PRO-217.
[25]	"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: 9461455] [Abstract] Cited for: VARIANT THR-155.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	J01415 Genomic DNA. Translation: AAB58948.1. V00662 Genomic DNA. Translation: CAA24031.1. D38112 Genomic DNA. Translation: BAA07295.1. AF346971 Genomic DNA. Translation: AAK17316.1. AF347011 Genomic DNA. Translation: AAK17836.1. AF381997 Genomic DNA. Translation: AAL54597.1. AF382010 Genomic DNA. Translation: AAL54766.1. AF465948 Genomic DNA. Translation: AAN14618.1. AF465949 Genomic DNA. Translation: AAN14629.1. AF465950 Genomic DNA. Translation: AAN14640.1. AF465956 Genomic DNA. Translation: AAN14706.1. AF465957 Genomic DNA. Translation: AAN14717.1. AF465962 Genomic DNA. Translation: AAN14772.1. AF465972 Genomic DNA. Translation: AAN14882.1. AF465974 Genomic DNA. Translation: AAN14904.1. AF465975 Genomic DNA. Translation: AAN14915.1. AF465976 Genomic DNA. Translation: AAN14926.1. AY275529 Genomic DNA. Translation: AAQ19361.1. AY289076 Genomic DNA. Translation: AAP48210.1. AY289100 Genomic DNA. Translation: AAP48521.1. AY339407 Genomic DNA. Translation: AAP89106.1. AY339408 Genomic DNA. Translation: AAP89119.1. AY339510 Genomic DNA. Translation: AAP90445.1. AY339511 Genomic DNA. Translation: AAP90458.1. AY339512 Genomic DNA. Translation: AAP90471.1. AY339513 Genomic DNA. Translation: AAP90484.1. AY339530 Genomic DNA. Translation: AAP90705.1. AY339531 Genomic DNA. Translation: AAP90718.1. AY339532 Genomic DNA. Translation: AAP90731.1. AY339533 Genomic DNA. Translation: AAP90744.1. AY339534 Genomic DNA. Translation: AAP90757.1. AY339535 Genomic DNA. Translation: AAP90770.1. AY339536 Genomic DNA. Translation: AAP90783.1. AY339537 Genomic DNA. Translation: AAP90796.1. AY339538 Genomic DNA. Translation: AAP90809.1. AY339539 Genomic DNA. Translation: AAP90822.1. AY339540 Genomic DNA. Translation: AAP90835.1. AY339541 Genomic DNA. Translation: AAP90848.1. AY339543 Genomic DNA. Translation: AAP90874.1. AY339581 Genomic DNA. Translation: AAP91368.1. AY339582 Genomic DNA. Translation: AAP91381.1. AY339584 Genomic DNA. Translation: AAP91407.1. AY195749 Genomic DNA. Translation: AAO88337.1. AY195764 Genomic DNA. Translation: AAO88532.1. AY195773 Genomic DNA. Translation: AAO88649.1. AY195786 Genomic DNA. Translation: AAO88818.1. AY255144 Genomic DNA. Translation: AAO66766.1. AY255147 Genomic DNA. Translation: AAO66805.1. AY255180 Genomic DNA. Translation: AAO67233.1. AY738945 Genomic DNA. Translation: AAU13022.1. AY738967 Genomic DNA. Translation: AAU13308.1. AY713988 Genomic DNA. Translation: AAU02285.1. AY713999 Genomic DNA. Translation: AAU02428.1. AY714004 Genomic DNA. Translation: AAU02493.1. AY714013 Genomic DNA. Translation: AAU02610.1. AY714014 Genomic DNA. Translation: AAU02623.1. AY714028 Genomic DNA. Translation: AAU02805.1. AY714031 Genomic DNA. Translation: AAU02844.1. AY714035 Genomic DNA. Translation: AAU02896.1. AY714045 Genomic DNA. Translation: AAU03026.1. AY495147 Genomic DNA. Translation: AAR93242.1. AY495199 Genomic DNA. Translation: AAR93918.1. AY495231 Genomic DNA. Translation: AAR94334.1. AY495232 Genomic DNA. Translation: AAR94347.1. AY495233 Genomic DNA. Translation: AAR94360.1. AY495234 Genomic DNA. Translation: AAR94373.1. AY495235 Genomic DNA. Translation: AAR94386.1. AY495236 Genomic DNA. Translation: AAR94399.1. AY495237 Genomic DNA. Translation: AAR94412.1. AY495238 Genomic DNA. Translation: AAR94425.1. AY519488 Genomic DNA. Translation: AAR91263.1.
IPI	IPI00654820.
PIR	PWHU6. A01049.
RefSeq	YP_003024031.1.
3D structure databases
SMR	P00846. Positions 63-222.
ModBase	Search...
Protein-protein interaction databases
IntAct	P00846. 1 interaction.
STRING	P00846.
Proteomic databases
PRIDE	P00846.
Genome annotation databases
Ensembl	ENST00000361899; ENSP00000354632; ENSG00000198899; Homo sapiens. [Genome view]
GeneID	4508.
KEGG	hsa:4508.
Organism-specific databases
CTD	4508.
GeneCards	GCMTP008529.
H-InvDB	HIX0011356.
HGNC	HGNC:7414. MT-ATP6.
MIM	256000. phenotype. 500003. phenotype. 516060. gene. 535000. phenotype. 551500. phenotype.
Orphanet	155. Cardiomyopathy, hypertrophic, primary or idiopathic. 104. Leber hereditary optic neuropathy. 506. Leigh syndrome. 644. NARP/MILS syndrome. 1576. Striatonigral degeneration, infantile.
PharmGKB	PA31221.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P00846.
InParanoid	P00846.
PhylomeDB	P00846.
Enzyme and pathway databases
Reactome	REACT_1505. Integration of energy metabolism. REACT_15380. Diabetes pathways. REACT_1698. Metabolism of nucleotides.
Gene expression databases
Bgee	P00846.
Genevestigator	P00846.
GermOnline	ENSG00000198899. Homo sapiens.
Family and domain databases
InterPro	IPR000568. ATPase_F0-cplx_asu. [Graphical view]
Gene3D	G3DSA:1.20.120.220. ATPase_F0_A. 1 hit.
PANTHER	PTHR11410. ATPase_F0_A. 1 hit.
Pfam	PF00119. ATP-synt_A. 1 hit. [Graphical view]
PRINTS	PR00123. ATPASEA.
TIGRFAMs	TIGR01131. ATP_synt_6_or_A. 1 hit.
PROSITE	PS00449. ATPASE_A. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

ATP6_HUMAN

Accession

Primary (citable) accession number: P00846
Secondary accession number(s): Q34772

Q9B2Z2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	February 9, 2010
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.