ATP6_HUMAN
ID ATP6_HUMAN Reviewed; 226 AA.
AC P00846; Q34772; Q5S8W5; Q5S9E7; Q5S9I6; Q5SA31; Q6RPB7; Q6VHC0; Q6VHE0;
AC Q6WQF4; Q7YCC1; Q7YCF8; Q7YCG1; Q85KU8; Q85KX1; Q85L05; Q8HNQ4; Q8HNQ8;
AC Q8WCX6; Q9B2U5; Q9B2Z2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=ATP synthase subunit a;
DE AltName: Full=F-ATPase protein 6;
GN Name=MT-ATP6; Synonyms=ATP6, ATPASE6, MTATP6;
OS Homo sapiens (Human).
OG Mitochondrion.
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=7219534; DOI=10.1038/290457a0;
RA Anderson S., Bankier A.T., Barrell B.G., de Bruijn M.H.L., Coulson A.R.,
RA Drouin J., Eperon I.C., Nierlich D.P., Roe B.A., Sanger F., Schreier P.H.,
RA Smith A.J.H., Staden R., Young I.G.;
RT "Sequence and organization of the human mitochondrial genome.";
RL Nature 290:457-465(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-14.
RC TISSUE=Placenta;
RX PubMed=7530363; DOI=10.1073/pnas.92.2.532;
RA Horai S., Hayasaka K., Kondo R., Tsugane K., Takahata N.;
RT "Recent African origin of modern humans revealed by complete sequences of
RT hominoid mitochondrial DNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:532-536(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TYR-90; ALA-112 AND
RP LEU-193.
RX PubMed=11130070; DOI=10.1038/35047064;
RA Ingman M., Kaessmann H., Paeaebo S., Gyllensten U.;
RT "Mitochondrial genome variation and the origin of modern humans.";
RL Nature 408:708-713(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TYR-90; ALA-112 AND
RP THR-204.
RX PubMed=11553319; DOI=10.1186/1471-2156-2-13;
RA Maca-Meyer N., Gonzalez A.M., Larruga J.M., Flores C., Cabrera V.M.;
RT "Major genomic mitochondrial lineages delineate early human expansions.";
RL BMC Genet. 2:13-13(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-80; TYR-90 AND ALA-112.
RX PubMed=12022039; DOI=10.1086/341358;
RA Silva W.A. Jr., Bonatto S.L., Holanda A.J., Ribeiro-Dos-Santos A.K.,
RA Paixao B.M., Goldman G.H., Abe-Sandes K., Rodriguez-Delfin L., Barbosa M.,
RA Paco-Larson M.L., Petzl-Erler M.L., Valente V., Santos S.E., Zago M.A.;
RT "Mitochondrial genome diversity of native Americans supports a single early
RT entry of founder populations into America.";
RL Am. J. Hum. Genet. 71:187-192(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-14 AND ALA-112.
RX PubMed=14563219; DOI=10.1186/1471-2156-4-15;
RA Maca-Meyer N., Gonzalez A.M., Pestano J., Flores C., Larruga J.M.,
RA Cabrera V.M.;
RT "Mitochondrial DNA transit between West Asia and North Africa inferred from
RT U6 phylogeography.";
RL BMC Genet. 4:15-15(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-112 AND LEU-193.
RX PubMed=12840039; DOI=10.1101/gr.686603;
RA Ingman M., Gyllensten U.;
RT "Mitochondrial genome variation and evolutionary history of Australian and
RT New Guinean aborigines.";
RL Genome Res. 13:1600-1606(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-11; THR-60; ALA-112 AND
RP ALA-133.
RX PubMed=12949126; DOI=10.1093/molbev/msg230;
RA Moilanen J.S., Finnila S., Majamaa K.;
RT "Lineage-specific selection in human mtDNA: lack of polymorphisms in a
RT segment of MTND5 gene in haplogroup J.";
RL Mol. Biol. Evol. 20:2132-2142(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-60; TYR-90; ALA-112;
RP LEU-117 AND THR-192.
RX PubMed=12509511; DOI=10.1073/pnas.0136972100;
RA Mishmar D., Ruiz-Pesini E., Golik P., Macaulay V., Clark A.G., Hosseini S.,
RA Brandon M., Easley K., Chen E., Brown M.D., Sukernik R.I., Olckers A.,
RA Wallace D.C.;
RT "Natural selection shaped regional mtDNA variation in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:171-176(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-16; PRO-37; TYR-90;
RP ALA-112; ALA-178; LEU-182 AND THR-204.
RX PubMed=12870132; DOI=10.1086/377718;
RA Kong Q.-P., Yao Y.-G., Sun C., Bandelt H.-J., Zhu C.-L., Zhang Y.-P.;
RT "Phylogeny of east Asian mitochondrial DNA lineages inferred from complete
RT sequences.";
RL Am. J. Hum. Genet. 73:671-676(2003).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-11 AND ALA-112.
RX PubMed=15382008; DOI=10.1086/425590;
RA Achilli A., Rengo C., Magri C., Battaglia V., Olivieri A., Scozzari R.,
RA Cruciani F., Zeviani M., Briem E., Carelli V., Moral P., Dugoujon J.M.,
RA Roostalu U., Loogvali E.L., Kivisild T., Bandelt H.-J., Richards M.,
RA Villems R., Santachiara-Benerecetti A.S., Semino O., Torroni A.;
RT "The molecular dissection of mtDNA haplogroup H confirms that the Franco-
RT Cantabrian glacial refuge was a major source for the European gene pool.";
RL Am. J. Hum. Genet. 75:910-918(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-7; THR-11; ILE-53;
RP THR-60; ALA-112; VAL-121 AND ILE-213.
RX PubMed=15467980; DOI=10.1086/425871;
RA Palanichamy M.G., Sun C., Agrawal S., Bandelt H.-J., Kong Q.-P., Khan F.,
RA Wang C.Y., Chaudhuri T.K., Palla V., Zhang Y.-P.;
RT "Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on
RT complete sequencing: implications for the peopling of South Asia.";
RL Am. J. Hum. Genet. 75:966-978(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-11; THR-60; ALA-112 AND
RP VAL-192.
RX PubMed=14760490; DOI=10.1007/s00414-004-0427-6;
RA Coble M.D., Just R.S., O'Callaghan J.E., Letmanyi I.H., Peterson C.T.,
RA Irwin J.A., Parsons T.J.;
RT "Single nucleotide polymorphisms over the entire mtDNA genome that increase
RT the power of forensic testing in Caucasians.";
RL Int. J. Legal Med. 118:137-146(2004).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TYR-90 AND ALA-112.
RX PubMed=15638829; DOI=10.1046/j.1529-8817.2003.00127.x;
RA Starikovskaya E.B., Sukernik R.I., Derbeneva O.A., Volodko N.V.,
RA Ruiz-Pesini E., Torroni A., Brown M.D., Lott M.T., Hosseini S.H.,
RA Huoponen K., Wallace D.C.;
RT "Mitochondrial DNA diversity in indigenous populations of the southern
RT extent of Siberia, and the origins of native american haplogroups.";
RL Ann. Hum. Genet. 69:67-89(2005).
RN [15]
RP INVOLVEMENT IN LS, AND VARIANT LS PRO-220.
RX PubMed=17352390; DOI=10.1002/ajmg.a.31637;
RA Castagna A.E., Addis J., McInnes R.R., Clarke J.T., Ashby P., Blaser S.,
RA Robinson B.H.;
RT "Late onset Leigh syndrome and ataxia due to a T to C mutation at bp 9,185
RT of mitochondrial DNA.";
RL Am. J. Med. Genet. A 143A:808-816(2007).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP INVOLVEMENT IN MLASA3, AND VARIANT MLASA3 ASN-148.
RX PubMed=25037980; DOI=10.1016/j.ymgme.2014.06.004;
RA Burrage L.C., Tang S., Wang J., Donti T.R., Walkiewicz M., Luchak J.M.,
RA Chen L.C., Schmitt E.S., Niu Z., Erana R., Hunter J.V., Graham B.H.,
RA Wong L.J., Scaglia F.;
RT "Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA)
RT plus associated with a novel de novo mutation (m.8969G>A) in the
RT mitochondrial encoded ATP6 gene.";
RL Mol. Genet. Metab. 113:207-212(2014).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [19]
RP INTERACTION WITH DNAJC30.
RX PubMed=30318146; DOI=10.1016/j.cell.2018.09.014;
RA Tebbenkamp A.T.N., Varela L., Choi J., Paredes M.I., Giani A.M., Song J.E.,
RA Sestan-Pesa M., Franjic D., Sousa A.M.M., Liu Z.W., Li M., Bichsel C.,
RA Koch M., Szigeti-Buck K., Liu F., Li Z., Kawasawa Y.I., Paspalas C.D.,
RA Mineur Y.S., Prontera P., Merla G., Picciotto M.R., Arnsten A.F.T.,
RA Horvath T.L., Sestan N.;
RT "The 7q11.23 protein DNAJC30 interacts with ATP synthase and links
RT mitochondria to brain development.";
RL Cell 0:0-0(2018).
RN [20]
RP VARIANTS ALA-59 AND ILE-213.
RX PubMed=3201231; DOI=10.1126/science.3201231;
RA Wallace D.C., Singh G., Lott M.T., Hodge J.A., Schurr T.G., Lezza A.M.,
RA Elsas L.J. II, Nikoskelainen E.K.;
RT "Mitochondrial DNA mutation associated with Leber's hereditary optic
RT neuropathy.";
RL Science 242:1427-1430(1988).
RN [21]
RP VARIANT NARP ARG-156.
RX PubMed=2137962;
RA Holt I.J., Harding A.E., Petty R.K., Morgan-Hughes J.A.;
RT "A new mitochondrial disease associated with mitochondrial DNA
RT heteroplasmy.";
RL Am. J. Hum. Genet. 46:428-433(1990).
RN [22]
RP VARIANTS SER-33; ALA-59; TYR-61; TYR-90; ALA-112; THR-155; ILE-213 AND
RP GLY-219.
RX PubMed=1757091; DOI=10.1007/bf00206061;
RA Marzuki S., Noer A.S., Lertrit P., Thyagarajan D., Kapsa R.,
RA Utthanaphol P., Byrne E.;
RT "Normal variants of human mitochondrial DNA and translation products: the
RT building of a reference data base.";
RL Hum. Genet. 88:139-145(1991).
RN [23]
RP VARIANT LS PRO-156.
RX PubMed=8395787; DOI=10.1002/ana.410340319;
RA de Vries D.D., van Engelen B.G.M., Gabreels F.J.M., Ruitenbeek W.,
RA van Oost B.A.;
RT "A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's
RT syndrome.";
RL Ann. Neurol. 34:410-412(1993).
RN [24]
RP VARIANT LHON THR-192.
RX PubMed=7726182;
RA Lamminen T., Majander A., Juvonen V., Wikstroem M., Aula P.,
RA Nikoskelainen E., Savontaus M.-L.;
RT "A mitochondrial mutation at nt 9101 in the ATP synthase 6 gene associated
RT with deficient oxidative phosphorylation in a family with Leber hereditary
RT optic neuroretinopathy.";
RL Am. J. Hum. Genet. 56:1238-1240(1995).
RN [25]
RP VARIANT MIBSN PRO-217.
RX PubMed=7668837; DOI=10.1002/ana.410380321;
RA Thyagarajan D., Shanske S., Vazquez-Memije M., De Vivo D.C., Dimauro S.;
RT "A novel mitochondrial ATPase 6 point mutation in familial bilateral
RT striatal necrosis.";
RL Ann. Neurol. 38:468-472(1995).
RN [26]
RP VARIANT LS PRO-217.
RX PubMed=9270604; DOI=10.1212/wnl.49.2.595;
RA Campos Y., Martin M.A., Rubio J.C., Solana L.G., Garcia-Benayas C.,
RA Terradas J.L., Arenas J.;
RT "Leigh syndrome associated with the T9176C mutation in the ATPase 6 gene of
RT mitochondrial DNA.";
RL Neurology 49:595-597(1997).
RN [27]
RP VARIANT LS ARG-156.
RX PubMed=9556461; DOI=10.1086/301751;
RA Takahashi S., Makita Y., Oki J., Miyamoto A., Yanagawa J., Naito E.,
RA Goto Y., Okuno A.;
RT "De novo mtDNA nt 8993 (T-G) mutation resulting in Leigh syndrome.";
RL Am. J. Hum. Genet. 62:717-719(1998).
RN [28]
RP VARIANT LS PRO-217.
RX PubMed=9501263; DOI=10.1023/a:1005397227996;
RA Dionisi-Vici C., Seneca S., Zeviani M., Fariello G., Rimoldi M.,
RA Bertini E., De Meirleir L.;
RT "Fulminant Leigh syndrome and sudden unexpected death in a family with the
RT T9176C mutation of the mitochondrial ATPase 6 gene.";
RL J. Inherit. Metab. Dis. 21:2-8(1998).
RN [29]
RP VARIANT THR-155.
RX PubMed=9461455; DOI=10.1093/nar/26.4.967;
RA Rieder M.J., Taylor S.L., Tobe V.O., Nickerson D.A.;
RT "Automating the identification of DNA variations using quality-based
RT fluorescence re-sequencing: analysis of the human mitochondrial genome.";
RL Nucleic Acids Res. 26:967-973(1998).
RN [30]
RP VARIANT MC5DM1 PRO-156, INVOLVEMENT IN APAO, AND VARIANT APAO PRO-156.
RX PubMed=16049925; DOI=10.1002/ana.20555;
RA Rantamaki M.T., Soini H.K., Finnila S.M., Majamaa K., Udd B.;
RT "Adult-onset ataxia and polyneuropathy caused by mitochondrial 8993T-->C
RT mutation.";
RL Ann. Neurol. 58:337-340(2005).
RN [31]
RP VARIANT MC5DM1 PRO-156, AND VARIANT APAO PRO-156.
RX PubMed=18055910; DOI=10.1136/jmg.2007.052902;
RA Craig K., Elliott H.R., Keers S.M., Lambert C., Pyle A., Graves T.D.,
RA Woodward C., Sweeney M.G., Davis M.B., Hanna M.G., Chinnery P.F.;
RT "Episodic ataxia and hemiplegia caused by the 8993T->C mitochondrial DNA
RT mutation.";
RL J. Med. Genet. 44:797-799(2007).
RN [32]
RP INVOLVEMENT IN CMHI.
RX PubMed=19188198; DOI=10.1136/jmg.2008.063149;
RA Ware S.M., El-Hassan N., Kahler S.G., Zhang Q., Ma Y.W., Miller E.,
RA Wong B., Spicer R.L., Craigen W.J., Kozel B.A., Grange D.K., Wong L.J.;
RT "Infantile cardiomyopathy caused by a mutation in the overlapping region of
RT mitochondrial ATPase 6 and 8 genes.";
RL J. Med. Genet. 46:308-314(2009).
CC -!- FUNCTION: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or
CC Complex V) produces ATP from ADP in the presence of a proton gradient
CC across the membrane which is generated by electron transport complexes
CC of the respiratory chain. F-type ATPases consist of two structural
CC domains, F(1) - containing the extramembraneous catalytic core and F(0)
CC - containing the membrane proton channel, linked together by a central
CC stalk and a peripheral stalk. During catalysis, ATP synthesis in the
CC catalytic domain of F(1) is coupled via a rotary mechanism of the
CC central stalk subunits to proton translocation. Key component of the
CC proton channel; it may play a direct role in the translocation of
CC protons across the membrane.
CC -!- SUBUNIT: F-type ATPases have 2 components, CF(1) - the catalytic core
CC - and CF(0) - the membrane proton channel. CF(1) has five subunits:
CC alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main
CC subunits: a, b and c. Component of an ATP synthase complex composed of
CC ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-
CC ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and
CC ATP5MJ (By similarity). Interacts with DNAJC30; interaction is direct
CC (PubMed:30318146). {ECO:0000250|UniProtKB:P00847,
CC ECO:0000269|PubMed:30318146}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane; Multi-pass membrane
CC protein.
CC -!- DISEASE: Neuropathy, ataxia, and retinitis pigmentosa (NARP)
CC [MIM:551500]: A syndrome characterized by variable combination of
CC developmental delay, psychomotor retardation, hearing loss, optic
CC atrophy and retinitis pigmentosa, dementia, seizures, ataxia, proximal
CC neurogenic muscle weakness, and sensory neuropathy.
CC {ECO:0000269|PubMed:2137962}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A
CC maternally inherited form of Leber hereditary optic neuropathy, a
CC mitochondrial disease resulting in bilateral painless loss of central
CC vision due to selective degeneration of the retinal ganglion cells and
CC their axons. The disorder shows incomplete penetrance and male
CC predominance. Cardiac conduction defects and neurological defects have
CC also been described in some LHON patients. LHON results from primary
CC mitochondrial DNA mutations affecting the respiratory chain complexes.
CC {ECO:0000269|PubMed:7726182}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive
CC neurodegenerative disorder characterized by the presence of focal,
CC bilateral lesions in one or more areas of the central nervous system
CC including the brainstem, thalamus, basal ganglia, cerebellum and spinal
CC cord. Clinical features depend on which areas of the central nervous
CC system are involved and include subacute onset of psychomotor
CC retardation, hypotonia, ataxia, weakness, vision loss, eye movement
CC abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:17352390,
CC ECO:0000269|PubMed:8395787, ECO:0000269|PubMed:9270604,
CC ECO:0000269|PubMed:9501263, ECO:0000269|PubMed:9556461}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Mitochondrial infantile bilateral striatal necrosis (MIBSN)
CC [MIM:500003]: Bilateral striatal necrosis is a neurological disorder
CC resembling Leigh syndrome. {ECO:0000269|PubMed:7668837}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Mitochondrial complex V deficiency, mitochondrial 1 (MC5DM1)
CC [MIM:500015]: A mitochondrial disorder with heterogeneous clinical
CC manifestations including neuropathy, ataxia, hypertrophic
CC cardiomyopathy. Hypertrophic cardiomyopathy can present with negligible
CC to extreme hypertrophy, minimal to extensive fibrosis and myocyte
CC disarray, absent to severe left ventricular outflow tract obstruction,
CC and distinct septal contours/morphologies with extremely varying
CC clinical course. {ECO:0000269|PubMed:16049925,
CC ECO:0000269|PubMed:18055910}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Myopathy, lactic acidosis, and sideroblastic anemia 3 (MLASA3)
CC [MIM:500011]: A rare mitochondrial disorder characterized by
CC sideroblastic anemia, muscle weakness, and exercise intolerance
CC associated with persistent lactic acidemia. Additional MLASA3 features
CC are failure to thrive, hearing loss, epilepsy, stroke-like episodes,
CC and severe developmental delay. {ECO:0000269|PubMed:25037980}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Ataxia and polyneuropathy, adult-onset (APAO) [MIM:500010]: A
CC mitochondrial disease characterized by ataxia, axonal sensorimotor
CC polyneuropathy, abnormal eye movements, and dysarthria.
CC {ECO:0000269|PubMed:16049925, ECO:0000269|PubMed:18055910}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, infantile hypertrophic (CMHI) [MIM:500006]: An
CC infantile form of hypertrophic cardiomyopathy, a heart disorder
CC characterized by ventricular hypertrophy, which is usually asymmetric
CC and often involves the interventricular septum. The symptoms include
CC dyspnea, syncope, collapse, palpitations, and chest pain. They can be
CC readily provoked by exercise. The disorder has inter- and intrafamilial
CC variability ranging from benign to malignant forms with high risk of
CC cardiac failure and sudden cardiac death.
CC {ECO:0000269|PubMed:19188198}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ATPase A chain family. {ECO:0000305}.
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DR EMBL; J01415; AAB58948.1; -; Genomic_DNA.
DR EMBL; V00662; CAA24031.1; -; Genomic_DNA.
DR EMBL; D38112; BAA07295.1; -; Genomic_DNA.
DR EMBL; AF346971; AAK17316.1; -; Genomic_DNA.
DR EMBL; AF347011; AAK17836.1; -; Genomic_DNA.
DR EMBL; AF381997; AAL54597.1; -; Genomic_DNA.
DR EMBL; AF382010; AAL54766.1; -; Genomic_DNA.
DR EMBL; AF465948; AAN14618.1; -; Genomic_DNA.
DR EMBL; AF465949; AAN14629.1; -; Genomic_DNA.
DR EMBL; AF465950; AAN14640.1; -; Genomic_DNA.
DR EMBL; AF465956; AAN14706.1; -; Genomic_DNA.
DR EMBL; AF465957; AAN14717.1; -; Genomic_DNA.
DR EMBL; AF465962; AAN14772.1; -; Genomic_DNA.
DR EMBL; AF465972; AAN14882.1; -; Genomic_DNA.
DR EMBL; AF465974; AAN14904.1; -; Genomic_DNA.
DR EMBL; AF465975; AAN14915.1; -; Genomic_DNA.
DR EMBL; AF465976; AAN14926.1; -; Genomic_DNA.
DR EMBL; AY275529; AAQ19361.1; -; Genomic_DNA.
DR EMBL; AY289076; AAP48210.1; -; Genomic_DNA.
DR EMBL; AY289100; AAP48521.1; -; Genomic_DNA.
DR EMBL; AY339407; AAP89106.1; -; Genomic_DNA.
DR EMBL; AY339408; AAP89119.1; -; Genomic_DNA.
DR EMBL; AY339510; AAP90445.1; -; Genomic_DNA.
DR EMBL; AY339511; AAP90458.1; -; Genomic_DNA.
DR EMBL; AY339512; AAP90471.1; -; Genomic_DNA.
DR EMBL; AY339513; AAP90484.1; -; Genomic_DNA.
DR EMBL; AY339530; AAP90705.1; -; Genomic_DNA.
DR EMBL; AY339531; AAP90718.1; -; Genomic_DNA.
DR EMBL; AY339532; AAP90731.1; -; Genomic_DNA.
DR EMBL; AY339533; AAP90744.1; -; Genomic_DNA.
DR EMBL; AY339534; AAP90757.1; -; Genomic_DNA.
DR EMBL; AY339535; AAP90770.1; -; Genomic_DNA.
DR EMBL; AY339536; AAP90783.1; -; Genomic_DNA.
DR EMBL; AY339537; AAP90796.1; -; Genomic_DNA.
DR EMBL; AY339538; AAP90809.1; -; Genomic_DNA.
DR EMBL; AY339539; AAP90822.1; -; Genomic_DNA.
DR EMBL; AY339540; AAP90835.1; -; Genomic_DNA.
DR EMBL; AY339541; AAP90848.1; -; Genomic_DNA.
DR EMBL; AY339543; AAP90874.1; -; Genomic_DNA.
DR EMBL; AY339581; AAP91368.1; -; Genomic_DNA.
DR EMBL; AY339582; AAP91381.1; -; Genomic_DNA.
DR EMBL; AY339584; AAP91407.1; -; Genomic_DNA.
DR EMBL; AY195749; AAO88337.1; -; Genomic_DNA.
DR EMBL; AY195764; AAO88532.1; -; Genomic_DNA.
DR EMBL; AY195773; AAO88649.1; -; Genomic_DNA.
DR EMBL; AY195786; AAO88818.1; -; Genomic_DNA.
DR EMBL; AY255144; AAO66766.1; -; Genomic_DNA.
DR EMBL; AY255147; AAO66805.1; -; Genomic_DNA.
DR EMBL; AY255180; AAO67233.1; -; Genomic_DNA.
DR EMBL; AY738945; AAU13022.1; -; Genomic_DNA.
DR EMBL; AY738967; AAU13308.1; -; Genomic_DNA.
DR EMBL; AY713988; AAU02285.1; -; Genomic_DNA.
DR EMBL; AY713999; AAU02428.1; -; Genomic_DNA.
DR EMBL; AY714004; AAU02493.1; -; Genomic_DNA.
DR EMBL; AY714013; AAU02610.1; -; Genomic_DNA.
DR EMBL; AY714014; AAU02623.1; -; Genomic_DNA.
DR EMBL; AY714028; AAU02805.1; -; Genomic_DNA.
DR EMBL; AY714031; AAU02844.1; -; Genomic_DNA.
DR EMBL; AY714035; AAU02896.1; -; Genomic_DNA.
DR EMBL; AY714045; AAU03026.1; -; Genomic_DNA.
DR EMBL; AY495147; AAR93242.1; -; Genomic_DNA.
DR EMBL; AY495199; AAR93918.1; -; Genomic_DNA.
DR EMBL; AY495231; AAR94334.1; -; Genomic_DNA.
DR EMBL; AY495232; AAR94347.1; -; Genomic_DNA.
DR EMBL; AY495233; AAR94360.1; -; Genomic_DNA.
DR EMBL; AY495234; AAR94373.1; -; Genomic_DNA.
DR EMBL; AY495235; AAR94386.1; -; Genomic_DNA.
DR EMBL; AY495236; AAR94399.1; -; Genomic_DNA.
DR EMBL; AY495237; AAR94412.1; -; Genomic_DNA.
DR EMBL; AY495238; AAR94425.1; -; Genomic_DNA.
DR EMBL; AY519488; AAR91263.1; -; Genomic_DNA.
DR PIR; A01049; PWHU6.
DR RefSeq; YP_003024031.1; NC_012920.1.
DR AlphaFoldDB; P00846; -.
DR SMR; P00846; -.
DR BioGRID; 110612; 24.
DR ComplexPortal; CPX-6151; Mitochondrial proton-transporting ATP synthase complex.
DR CORUM; P00846; -.
DR IntAct; P00846; 21.
DR MINT; P00846; -.
DR STRING; 9606.ENSP00000354632; -.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR TCDB; 3.A.2.1.15; the h(+)- or na(+)-translocating f-type, v-type and a-type atpase (f-atpase) superfamily.
DR GlyGen; P00846; 1 site, 1 O-linked glycan (1 site).
DR SwissPalm; P00846; -.
DR BioMuta; MT-ATP6; -.
DR DMDM; 114443; -.
DR EPD; P00846; -.
DR jPOST; P00846; -.
DR MassIVE; P00846; -.
DR PaxDb; P00846; -.
DR PeptideAtlas; P00846; -.
DR PRIDE; P00846; -.
DR ProteomicsDB; 51290; -.
DR TopDownProteomics; P00846; -.
DR Antibodypedia; 58052; 71 antibodies from 21 providers.
DR DNASU; 4508; -.
DR Ensembl; ENST00000361899.2; ENSP00000354632.2; ENSG00000198899.2.
DR GeneID; 4508; -.
DR KEGG; hsa:4508; -.
DR CTD; 4508; -.
DR DisGeNET; 4508; -.
DR GeneCards; MT-ATP6; -.
DR GeneReviews; MT-ATP6; -.
DR HGNC; HGNC:7414; MT-ATP6.
DR HPA; ENSG00000198899; Tissue enhanced (heart).
DR MalaCards; MT-ATP6; -.
DR MIM; 256000; phenotype.
DR MIM; 500003; phenotype.
DR MIM; 500006; phenotype.
DR MIM; 500010; phenotype.
DR MIM; 500011; phenotype.
DR MIM; 500015; phenotype.
DR MIM; 516060; gene.
DR MIM; 535000; phenotype.
DR MIM; 551500; phenotype.
DR neXtProt; NX_P00846; -.
DR OpenTargets; ENSG00000198899; -.
DR Orphanet; 225154; Familial infantile bilateral striatal necrosis.
DR Orphanet; 254913; Isolated ATP synthase deficiency.
DR Orphanet; 104; Leber hereditary optic neuropathy.
DR Orphanet; 255210; Mitochondrial DNA-associated Leigh syndrome.
DR Orphanet; 320360; MT-ATP6-related mitochondrial spastic paraplegia.
DR Orphanet; 644; NARP syndrome.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR Orphanet; 397750; Periodic paralysis with later-onset distal motor neuropathy.
DR VEuPathDB; HostDB:ENSG00000198899; -.
DR eggNOG; KOG4665; Eukaryota.
DR GeneTree; ENSGT00390000005568; -.
DR HOGENOM; CLU_041018_0_2_1; -.
DR InParanoid; P00846; -.
DR OMA; FFDQFMS; -.
DR OrthoDB; 1095315at2759; -.
DR PhylomeDB; P00846; -.
DR TreeFam; TF343395; -.
DR BioCyc; MetaCyc:HS00024-MON; -.
DR PathwayCommons; P00846; -.
DR Reactome; R-HSA-163210; Formation of ATP by chemiosmotic coupling.
DR Reactome; R-HSA-8949613; Cristae formation.
DR SignaLink; P00846; -.
DR BioGRID-ORCS; 4508; 0 hits in 1 CRISPR screen.
DR ChiTaRS; ATP6; human.
DR GeneWiki; MT-ATP6; -.
DR GenomeRNAi; 4508; -.
DR Pharos; P00846; Tbio.
DR PRO; PR:P00846; -.
DR Proteomes; UP000005640; Mitochondrion.
DR RNAct; P00846; protein.
DR Bgee; ENSG00000198899; Expressed in left uterine tube and 93 other tissues.
DR ExpressionAtlas; P00846; baseline and differential.
DR Genevisible; P00846; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005753; C:mitochondrial proton-transporting ATP synthase complex; IDA:UniProtKB.
DR GO; GO:0045263; C:proton-transporting ATP synthase complex, coupling factor F(o); IEA:UniProtKB-KW.
DR GO; GO:0015078; F:proton transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0015986; P:proton motive force-driven ATP synthesis; IBA:GO_Central.
DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; IDA:UniProtKB.
DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl.
DR Gene3D; 1.20.120.220; -; 1.
DR InterPro; IPR000568; ATP_synth_F0_asu.
DR InterPro; IPR023011; ATP_synth_F0_asu_AS.
DR InterPro; IPR045083; ATP_synth_F0_asu_bact/mt.
DR InterPro; IPR035908; F0_ATP_A_sf.
DR PANTHER; PTHR11410; PTHR11410; 1.
DR Pfam; PF00119; ATP-synt_A; 1.
DR PRINTS; PR00123; ATPASEA.
DR SUPFAM; SSF81336; SSF81336; 1.
DR TIGRFAMs; TIGR01131; ATP_synt_6_or_A; 1.
DR PROSITE; PS00449; ATPASE_A; 1.
PE 1: Evidence at protein level;
KW ATP synthesis; Cardiomyopathy; CF(0); Disease variant;
KW Hydrogen ion transport; Ion transport; Leber hereditary optic neuropathy;
KW Leigh syndrome; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Neuropathy; Primary mitochondrial disease; Reference proteome;
KW Retinitis pigmentosa; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..226
FT /note="ATP synthase subunit a"
FT /id="PRO_0000082128"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 7
FT /note="A -> T (in dbSNP:rs1603221578)"
FT /evidence="ECO:0000269|PubMed:15467980"
FT /id="VAR_021178"
FT VARIANT 11
FT /note="A -> T (in dbSNP:rs386829040)"
FT /evidence="ECO:0000269|PubMed:12949126,
FT ECO:0000269|PubMed:14760490, ECO:0000269|PubMed:15382008,
FT ECO:0000269|PubMed:15467980"
FT /id="VAR_021179"
FT VARIANT 14
FT /note="I -> V (in dbSNP:rs3020563)"
FT /evidence="ECO:0000269|PubMed:14563219,
FT ECO:0000269|PubMed:7530363"
FT /id="VAR_021180"
FT VARIANT 16
FT /note="G -> S (in dbSNP:rs28502681)"
FT /evidence="ECO:0000269|PubMed:12870132"
FT /id="VAR_021181"
FT VARIANT 33
FT /note="T -> S (in dbSNP:rs1603221645)"
FT /evidence="ECO:0000269|PubMed:1757091"
FT /id="VAR_008556"
FT VARIANT 37
FT /note="L -> P"
FT /evidence="ECO:0000269|PubMed:12870132"
FT /id="VAR_021182"
FT VARIANT 53
FT /note="T -> I (in dbSNP:rs201336180)"
FT /evidence="ECO:0000269|PubMed:15467980"
FT /id="VAR_021183"
FT VARIANT 59
FT /note="T -> A (in dbSNP:rs2000975)"
FT /evidence="ECO:0000269|PubMed:1757091,
FT ECO:0000269|PubMed:3201231"
FT /id="VAR_000792"
FT VARIANT 60
FT /note="M -> T (in dbSNP:rs878959404)"
FT /evidence="ECO:0000269|PubMed:12509511,
FT ECO:0000269|PubMed:12949126, ECO:0000269|PubMed:14760490,
FT ECO:0000269|PubMed:15467980"
FT /id="VAR_021184"
FT VARIANT 61
FT /note="H -> Y"
FT /evidence="ECO:0000269|PubMed:1757091"
FT /id="VAR_008557"
FT VARIANT 80
FT /note="A -> T (in dbSNP:rs1556423534)"
FT /evidence="ECO:0000269|PubMed:12022039"
FT /id="VAR_021185"
FT VARIANT 90
FT /note="H -> Y (in dbSNP:rs2298007)"
FT /evidence="ECO:0000269|PubMed:11130070,
FT ECO:0000269|PubMed:11553319, ECO:0000269|PubMed:12022039,
FT ECO:0000269|PubMed:12509511, ECO:0000269|PubMed:12870132,
FT ECO:0000269|PubMed:15638829, ECO:0000269|PubMed:1757091"
FT /id="VAR_008558"
FT VARIANT 112
FT /note="T -> A (in dbSNP:rs2001031)"
FT /evidence="ECO:0000269|PubMed:11130070,
FT ECO:0000269|PubMed:11553319, ECO:0000269|PubMed:12022039,
FT ECO:0000269|PubMed:12509511, ECO:0000269|PubMed:12840039,
FT ECO:0000269|PubMed:12870132, ECO:0000269|PubMed:12949126,
FT ECO:0000269|PubMed:14563219, ECO:0000269|PubMed:14760490,
FT ECO:0000269|PubMed:15382008, ECO:0000269|PubMed:15467980,
FT ECO:0000269|PubMed:15638829, ECO:0000269|PubMed:1757091"
FT /id="VAR_008559"
FT VARIANT 117
FT /note="F -> L (in dbSNP:rs201123510)"
FT /evidence="ECO:0000269|PubMed:12509511"
FT /id="VAR_021186"
FT VARIANT 121
FT /note="I -> V (in dbSNP:rs386829057)"
FT /evidence="ECO:0000269|PubMed:15467980"
FT /id="VAR_021187"
FT VARIANT 133
FT /note="T -> A (in dbSNP:rs200329150)"
FT /evidence="ECO:0000269|PubMed:12949126"
FT /id="VAR_021188"
FT VARIANT 148
FT /note="S -> N (in MLASA3; dbSNP:rs794726857)"
FT /evidence="ECO:0000269|PubMed:25037980"
FT /id="VAR_073699"
FT VARIANT 155
FT /note="A -> T (in dbSNP:rs587776444)"
FT /evidence="ECO:0000269|PubMed:1757091,
FT ECO:0000269|PubMed:9461455"
FT /id="VAR_008560"
FT VARIANT 156
FT /note="L -> P (in LS, MC5DM1 and APAO; dbSNP:rs199476133)"
FT /evidence="ECO:0000269|PubMed:16049925,
FT ECO:0000269|PubMed:18055910, ECO:0000269|PubMed:8395787"
FT /id="VAR_000794"
FT VARIANT 156
FT /note="L -> R (in NARP and LS; dbSNP:rs199476133)"
FT /evidence="ECO:0000269|PubMed:2137962,
FT ECO:0000269|PubMed:9556461"
FT /id="VAR_000793"
FT VARIANT 177
FT /note="A -> T (in dbSNP:rs9645429)"
FT /id="VAR_008561"
FT VARIANT 178
FT /note="T -> A (in dbSNP:rs1556423599)"
FT /evidence="ECO:0000269|PubMed:12870132"
FT /id="VAR_021189"
FT VARIANT 182
FT /note="S -> L (in dbSNP:rs1603222032)"
FT /evidence="ECO:0000269|PubMed:12870132"
FT /id="VAR_021190"
FT VARIANT 192
FT /note="I -> T (in LHON; possible rate primary mutation;
FT dbSNP:rs199476134)"
FT /evidence="ECO:0000269|PubMed:12509511,
FT ECO:0000269|PubMed:7726182"
FT /id="VAR_000795"
FT VARIANT 192
FT /note="I -> V (in dbSNP:rs1603222068)"
FT /evidence="ECO:0000269|PubMed:14760490"
FT /id="VAR_021191"
FT VARIANT 193
FT /note="F -> L (in dbSNP:rs1603222077)"
FT /evidence="ECO:0000269|PubMed:11130070,
FT ECO:0000269|PubMed:12840039"
FT /id="VAR_021192"
FT VARIANT 204
FT /note="I -> T (in dbSNP:rs1603222121)"
FT /evidence="ECO:0000269|PubMed:11553319,
FT ECO:0000269|PubMed:12870132"
FT /id="VAR_021193"
FT VARIANT 213
FT /note="V -> I (in dbSNP:rs2298010)"
FT /evidence="ECO:0000269|PubMed:15467980,
FT ECO:0000269|PubMed:1757091, ECO:0000269|PubMed:3201231"
FT /id="VAR_000796"
FT VARIANT 217
FT /note="L -> P (in LS and MIBSN; dbSNP:rs199476135)"
FT /evidence="ECO:0000269|PubMed:7668837,
FT ECO:0000269|PubMed:9270604, ECO:0000269|PubMed:9501263"
FT /id="VAR_000797"
FT VARIANT 219
FT /note="S -> G (in dbSNP:rs1556423628)"
FT /evidence="ECO:0000269|PubMed:1757091"
FT /id="VAR_008562"
FT VARIANT 220
FT /note="L -> P (in LS; dbSNP:rs199476138)"
FT /evidence="ECO:0000269|PubMed:17352390"
FT /id="VAR_073700"
SQ SEQUENCE 226 AA; 24817 MW; 7DB0F0BE86F55207 CRC64;
MNENLFASFI APTILGLPAA VLIILFPPLL IPTSKYLINN RLITTQQWLI KLTSKQMMTM
HNTKGRTWSL MLVSLIIFIA TTNLLGLLPH SFTPTTQLSM NLAMAIPLWA GTVIMGFRSK
IKNALAHFLP QGTPTPLIPM LVIIETISLL IQPMALAVRL TANITAGHLL MHLIGSATLA
MSTINLPSTL IIFTILILLT ILEIAVALIQ AYVFTLLVSL YLHDNT
