ATPA_HUMAN
ID ATPA_HUMAN Reviewed; 553 AA.
AC P25705; A8K092; B4DY56; K7ENP3; Q53XX6; Q8IXV2; Q96FB4; Q96HW2; Q96IR6;
AC Q9BTV8;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 246.
DE RecName: Full=ATP synthase subunit alpha, mitochondrial {ECO:0000305};
DE AltName: Full=ATP synthase F1 subunit alpha {ECO:0000312|HGNC:HGNC:823};
DE Flags: Precursor;
GN Name=ATP5F1A {ECO:0000312|HGNC:HGNC:823};
GN Synonyms=ATP5A, ATP5A1 {ECO:0000312|HGNC:HGNC:823},
GN ATP5AL2 {ECO:0000312|HGNC:HGNC:823}, ATPM {ECO:0000312|HGNC:HGNC:823};
OS Homo sapiens (Human).
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 [MRNA] (ISOFORM 1).
RC TISSUE=Lung tumor;
RX PubMed=1830491; DOI=10.1016/0167-4781(91)90183-m;
RA Kataoka H., Biswas C.;
RT "Nucleotide sequence of a cDNA for the alpha subunit of human mitochondrial
RT ATP synthase.";
RL Biochim. Biophys. Acta 1089:393-395(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Retinoblastoma;
RX PubMed=8428659; DOI=10.1016/0378-1119(93)90124-l;
RA Godbout R., Bisgrove D.A., Honore L.H., Day R.S. III;
RT "Amplification of the gene encoding the alpha-subunit of the mitochondrial
RT ATP synthase complex in a human retinoblastoma cell line.";
RL Gene 123:195-201(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Colon tumor;
RX PubMed=8086450; DOI=10.1016/0167-4781(94)90255-0;
RA Akiyama S., Endo H., Inohara N., Ohta S., Kagawa Y.;
RT "Gene structure and cell type-specific expression of the human ATP synthase
RT alpha subunit.";
RL Biochim. Biophys. Acta 1219:129-140(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Small intestine, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, Retina, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 44-59.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [9]
RP PROTEIN SEQUENCE OF 46-83; 89-103; 134-161; 176-182; 219-230; 242-252;
RP 306-316; 335-347; 403-416; 435-463 AND 507-527, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 46-73; 104-123; 134-161; 219-230; 232-239; 306-316;
RP 335-347; 403-416; 442-463 AND 507-527, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (MAR-2005) to UniProtKB.
RN [11]
RP PROTEIN SEQUENCE OF 134-141 AND 335-339.
RC TISSUE=Heart;
RX PubMed=7498159; DOI=10.1002/elps.11501601192;
RA Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A.,
RA Ershova E.S., Egorov T.A., Musalyamov A.K.;
RT "The major protein expression profile and two-dimensional protein database
RT of human heart.";
RL Electrophoresis 16:1160-1169(1995).
RN [12]
RP INTERACTION WITH PLG, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10077593; DOI=10.1073/pnas.96.6.2811;
RA Moser T.L., Stack M.S., Asplin I., Enghild J.J., Hojrup P., Everitt L.,
RA Hubchak S., Schnaper H.W., Pizzo S.V.;
RT "Angiostatin binds ATP synthase on the surface of human endothelial
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2811-2816(1999).
RN [13]
RP INTERACTION WITH ATPAF2.
RX PubMed=11410595; DOI=10.1074/jbc.m104133200;
RA Wang Z.-G., White P.S., Ackerman S.H.;
RT "Atp11p and Atp12p are assembly factors for the F(1)-ATPase in human
RT mitochondria.";
RL J. Biol. Chem. 276:30773-30778(2001).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [15]
RP INTERACTION WITH HRG, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19285951; DOI=10.1016/j.bbamem.2009.03.005;
RA Ohta T., Ikemoto Y., Usami A., Koide T., Wakabayashi S.;
RT "High affinity interaction between histidine-rich glycoprotein and the cell
RT surface type ATP synthase on T-cells.";
RL Biochim. Biophys. Acta 1788:1099-1107(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161; LYS-261; LYS-434; LYS-498;
RP LYS-506 AND LYS-539, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP INTERACTION WITH BLOC1S1, AND ACETYLATION.
RX PubMed=22309213; DOI=10.1042/bj20120118;
RA Scott I., Webster B.R., Li J.H., Sack M.N.;
RT "Identification of a molecular component of the mitochondrial acetyl
RT transferase program; a novel role for GCN5L1.";
RL Biochem. J. 443:655-661(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53; SER-65; SER-76; SER-166
RP AND SER-184, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
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 [23]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30146159; DOI=10.1016/j.cell.2018.07.032;
RA Qi B., Han M.;
RT "Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and
RT Development of the Host via Interaction with ATP Synthase.";
RL Cell 175:571-582(2018).
RN [24]
RP VARIANT MC5DN4 CYS-329.
RX PubMed=23599390; DOI=10.1093/brain/awt086;
RA Jonckheere A.I., Renkema G.H., Bras M., van den Heuvel L.P., Hoischen A.,
RA Gilissen C., Nabuurs S.B., Huynen M.A., de Vries M.C., Smeitink J.A.,
RA Rodenburg R.J.;
RT "A complex V ATP5A1 defect causes fatal neonatal mitochondrial
RT encephalopathy.";
RL Brain 136:1544-1554(2013).
RN [25]
RP VARIANT COXPD22 CYS-321, AND INVOLVEMENT IN COXPD22.
RX PubMed=23596069; DOI=10.1212/wnl.0b013e3182918c40;
RA Lieber D.S., Calvo S.E., Shanahan K., Slate N.G., Liu S., Hershman S.G.,
RA Gold N.B., Chapman B.A., Thorburn D.R., Berry G.T., Schmahmann J.D.,
RA Borowsky M.L., Mueller D.M., Sims K.B., Mootha V.K.;
RT "Targeted exome sequencing of suspected mitochondrial disorders.";
RL Neurology 80:1762-1770(2013).
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
CC F(0) - containing the membrane proton channel, linked together by a
CC central stalk and a peripheral stalk. During catalysis, ATP synthesis
CC in the catalytic domain of F(1) is coupled via a rotary mechanism of
CC the central stalk subunits to proton translocation. Subunits alpha and
CC beta form the catalytic core in F(1). Rotation of the central stalk
CC against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of
CC ATP in three separate catalytic sites on the beta subunits. Subunit
CC alpha does not bear the catalytic high-affinity ATP-binding sites (By
CC similarity). Binds the bacterial siderophore enterobactin and can
CC promote mitochondrial accumulation of enterobactin-derived iron ions
CC (PubMed:30146159). {ECO:0000250|UniProtKB:P19483,
CC ECO:0000269|PubMed:30146159}.
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 (By similarity). Interacts with ATPAF2
CC (PubMed:11410595). Interacts with HRG; the interaction occurs on the
CC surface of T-cells and alters the cell morphology when associated with
CC concanavalin (in vitro) (PubMed:19285951). Interacts with PLG
CC (angiostatin peptide); the interaction inhibits most of the angiogenic
CC properties of angiostatin (PubMed:10077593). Component of an ATP
CC synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME,
CC ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C,
CC ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity). Interacts with
CC BLOC1S1 (PubMed:22309213). Interacts with BCL2L1 isoform BCL-X(L); the
CC interaction mediates the association of BCL2L1 isoform BCL-X(L) with
CC the mitochondrial membrane F(1)F(0) ATP synthase and enhances neurons
CC metabolic efficiency (By similarity). Interacts with CLN5 and PPT1 (By
CC similarity). Interacts with S100A1; this interaction increases F1-
CC ATPase activity (By similarity). Interacts with ABCB7; this interaction
CC allows the regulation of cellular iron homeostasis and cellular
CC reactive oxygen species (ROS) levels in cardiomyocytes (By similarity).
CC {ECO:0000250|UniProtKB:P15999, ECO:0000250|UniProtKB:P19483,
CC ECO:0000250|UniProtKB:Q03265, ECO:0000269|PubMed:10077593,
CC ECO:0000269|PubMed:11410595, ECO:0000269|PubMed:19285951,
CC ECO:0000269|PubMed:22309213}.
CC -!- INTERACTION:
CC P25705; P06576: ATP5F1B; NbExp=6; IntAct=EBI-351437, EBI-356231;
CC P25705; P24539: ATP5PB; NbExp=8; IntAct=EBI-351437, EBI-1044810;
CC P25705; P18859: ATP5PF; NbExp=4; IntAct=EBI-351437, EBI-2606700;
CC P25705; P48047: ATP5PO; NbExp=5; IntAct=EBI-351437, EBI-355815;
CC P25705; Q8N5M1: ATPAF2; NbExp=4; IntAct=EBI-351437, EBI-1166928;
CC P25705; P78537: BLOC1S1; NbExp=2; IntAct=EBI-351437, EBI-348630;
CC P25705; P42858: HTT; NbExp=3; IntAct=EBI-351437, EBI-466029;
CC P25705; Q9NTG7: SIRT3; NbExp=2; IntAct=EBI-351437, EBI-724621;
CC P25705; P63104: YWHAZ; NbExp=3; IntAct=EBI-351437, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:30146159}.
CC Mitochondrion inner membrane {ECO:0000250|UniProtKB:P19483}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P19483}; Matrix side
CC {ECO:0000250|UniProtKB:P19483}. Cell membrane
CC {ECO:0000269|PubMed:10077593}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10077593}; Extracellular side
CC {ECO:0000269|PubMed:10077593}. Note=Colocalizes with HRG on the cell
CC surface of T-cells (PubMed:19285951). {ECO:0000269|PubMed:19285951}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P25705-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25705-2; Sequence=VSP_045129;
CC Name=3;
CC IsoId=P25705-3; Sequence=VSP_054688;
CC -!- TISSUE SPECIFICITY: Fetal lung, heart, liver, gut and kidney. Expressed
CC at higher levels in the fetal brain, retina and spinal cord.
CC {ECO:0000269|PubMed:8428659}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Acetylated on lysine residues. BLOC1S1 is required for
CC acetylation. {ECO:0000269|PubMed:22309213}.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 22 (COXPD22)
CC [MIM:616045]: A mitochondrial disorder characterized by intrauterine
CC growth retardation, microcephaly, hypotonia, pulmonary hypertension,
CC failure to thrive, encephalopathy, and heart failure.
CC {ECO:0000269|PubMed:23596069}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Mitochondrial complex V deficiency, nuclear type 4 (MC5DN4)
CC [MIM:615228]: A mitochondrial disorder with heterogeneous clinical
CC manifestations including dysmorphic features, psychomotor retardation,
CC hypotonia, growth retardation, cardiomyopathy, enlarged liver,
CC hypoplastic kidneys and elevated lactate levels in urine, plasma and
CC cerebrospinal fluid. {ECO:0000269|PubMed:23599390}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The siderophore enterobactin (Ent) produced by enteric
CC bacteria binds Fe(3+) and helps bacteria scavenge iron ions from the
CC environment (PubMed:30146159). As a consequence, the mammalian
CC siderocalin LCN2 plays an important role in defense against bacterial
CC infections by sequestering iron bound to microbial siderophores. LCN2
CC can also bind iron bound to endogenous or nutrient-derived iron
CC chelators and plays an important role in cellular iron homeostasis.
CC Enterobactin produced by non-pathogenic E.coli strains can facilitate
CC mitochondrial iron assimilation, suggesting that iron bound to
CC siderophores from non-pathogenic bacteria may contribute to iron
CC absorption by the host (PubMed:30146159). {ECO:0000269|PubMed:30146159,
CC ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ATPase alpha/beta chains family.
CC {ECO:0000305}.
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DR EMBL; X59066; CAA41789.1; -; mRNA.
DR EMBL; X65460; CAA46452.1; -; mRNA.
DR EMBL; D14710; BAA03531.1; -; mRNA.
DR EMBL; D28126; BAA05672.1; -; Genomic_DNA.
DR EMBL; BT007209; AAP35873.1; -; mRNA.
DR EMBL; AK092735; BAG52604.1; -; mRNA.
DR EMBL; AK289457; BAF82146.1; -; mRNA.
DR EMBL; AK302272; BAG63618.1; -; mRNA.
DR EMBL; AC012569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003119; AAH03119.1; -; mRNA.
DR EMBL; BC007299; AAH07299.1; -; mRNA.
DR EMBL; BC008028; AAH08028.2; -; mRNA.
DR EMBL; BC011384; AAH11384.1; -; mRNA.
DR EMBL; BC016046; AAH16046.1; -; mRNA.
DR EMBL; BC019310; AAH19310.1; -; mRNA.
DR EMBL; BC039135; AAH39135.2; -; mRNA.
DR EMBL; BC064562; AAH64562.1; -; mRNA.
DR EMBL; BC067385; AAH67385.1; -; mRNA.
DR CCDS; CCDS11927.1; -. [P25705-1]
DR CCDS; CCDS58620.1; -. [P25705-2]
DR CCDS; CCDS59315.1; -. [P25705-3]
DR PIR; S17193; PWHUA.
DR RefSeq; NP_001001935.1; NM_001001935.2. [P25705-2]
DR RefSeq; NP_001001937.1; NM_001001937.1. [P25705-1]
DR RefSeq; NP_001244263.1; NM_001257334.1. [P25705-3]
DR RefSeq; NP_001244264.1; NM_001257335.1. [P25705-2]
DR RefSeq; NP_004037.1; NM_004046.5. [P25705-1]
DR AlphaFoldDB; P25705; -.
DR SMR; P25705; -.
DR BioGRID; 106987; 425.
DR ComplexPortal; CPX-6151; Mitochondrial proton-transporting ATP synthase complex.
DR CORUM; P25705; -.
DR DIP; DIP-32871N; -.
DR IntAct; P25705; 177.
DR MINT; P25705; -.
DR STRING; 9606.ENSP00000381736; -.
DR ChEMBL; CHEMBL2062351; -.
DR DrugBank; DB07384; 1-ACETYL-2-CARBOXYPIPERIDINE.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB07394; AUROVERTIN B.
DR DrugBank; DB08629; N1-(2-AMINO-4-METHYLPENTYL)OCTAHYDRO-PYRROLO[1,2-A] PYRIMIDINE.
DR DrugBank; DB08399; Piceatannol.
DR DrugBank; DB04216; Quercetin.
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; P25705; 5 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; P25705; -.
DR MetOSite; P25705; -.
DR PhosphoSitePlus; P25705; -.
DR SwissPalm; P25705; -.
DR BioMuta; ATP5A1; -.
DR DMDM; 114517; -.
DR OGP; P25705; -.
DR REPRODUCTION-2DPAGE; P25705; -.
DR UCD-2DPAGE; P25705; -.
DR CPTAC; CPTAC-171; -.
DR CPTAC; CPTAC-172; -.
DR EPD; P25705; -.
DR jPOST; P25705; -.
DR MassIVE; P25705; -.
DR MaxQB; P25705; -.
DR PaxDb; P25705; -.
DR PeptideAtlas; P25705; -.
DR PRIDE; P25705; -.
DR ProteomicsDB; 1832; -.
DR ProteomicsDB; 54283; -. [P25705-1]
DR TopDownProteomics; P25705-1; -. [P25705-1]
DR Antibodypedia; 22447; 348 antibodies from 35 providers.
DR DNASU; 498; -.
DR Ensembl; ENST00000282050.6; ENSP00000282050.2; ENSG00000152234.16. [P25705-1]
DR Ensembl; ENST00000398752.11; ENSP00000381736.5; ENSG00000152234.16. [P25705-1]
DR Ensembl; ENST00000590665.5; ENSP00000467037.1; ENSG00000152234.16. [P25705-3]
DR Ensembl; ENST00000593152.6; ENSP00000465477.2; ENSG00000152234.16. [P25705-2]
DR GeneID; 498; -.
DR KEGG; hsa:498; -.
DR MANE-Select; ENST00000398752.11; ENSP00000381736.5; NM_004046.6; NP_004037.1.
DR UCSC; uc010dnl.2; human. [P25705-1]
DR CTD; 498; -.
DR DisGeNET; 498; -.
DR GeneCards; ATP5F1A; -.
DR HGNC; HGNC:823; ATP5F1A.
DR HPA; ENSG00000152234; Tissue enhanced (tongue).
DR MalaCards; ATP5F1A; -.
DR MIM; 164360; gene.
DR MIM; 615228; phenotype.
DR MIM; 616045; phenotype.
DR neXtProt; NX_P25705; -.
DR OpenTargets; ENSG00000152234; -.
DR Orphanet; 254913; Isolated ATP synthase deficiency.
DR PharmGKB; PA25115; -.
DR VEuPathDB; HostDB:ENSG00000152234; -.
DR eggNOG; KOG1353; Eukaryota.
DR GeneTree; ENSGT00550000074846; -.
DR HOGENOM; CLU_010091_2_1_1; -.
DR InParanoid; P25705; -.
DR OMA; LQAPGVM; -.
DR OrthoDB; 470054at2759; -.
DR PhylomeDB; P25705; -.
DR TreeFam; TF300321; -.
DR BioCyc; MetaCyc:HS07800-MON; -.
DR PathwayCommons; P25705; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-163210; Formation of ATP by chemiosmotic coupling.
DR Reactome; R-HSA-8949613; Cristae formation.
DR SignaLink; P25705; -.
DR SIGNOR; P25705; -.
DR BioGRID-ORCS; 498; 522 hits in 1087 CRISPR screens.
DR ChiTaRS; ATP5A1; human.
DR GenomeRNAi; 498; -.
DR Pharos; P25705; Tbio.
DR PRO; PR:P25705; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P25705; protein.
DR Bgee; ENSG00000152234; Expressed in heart right ventricle and 214 other tissues.
DR ExpressionAtlas; P25705; baseline and differential.
DR Genevisible; P25705; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:CAFA.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005753; C:mitochondrial proton-transporting ATP synthase complex; IDA:UniProtKB.
DR GO; GO:0005754; C:mitochondrial proton-transporting ATP synthase, catalytic core; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045259; C:proton-transporting ATP synthase complex; IDA:CAFA.
DR GO; GO:0045261; C:proton-transporting ATP synthase complex, catalytic core F(1); IBA:GO_Central.
DR GO; GO:0043531; F:ADP binding; IBA:GO_Central.
DR GO; GO:0043532; F:angiostatin binding; IPI:CAFA.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:Ensembl.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0046933; F:proton-transporting ATP synthase activity, rotational mechanism; IMP:CAFA.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0006754; P:ATP biosynthetic process; IMP:CAFA.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IGI:CAFA.
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:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl.
DR CDD; cd18113; ATP-synt_F1_alpha_C; 1.
DR CDD; cd01132; F1_ATPase_alpha; 1.
DR Gene3D; 1.20.150.20; -; 1.
DR Gene3D; 2.40.30.20; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_01346; ATP_synth_alpha_bact; 1.
DR InterPro; IPR023366; ATP_synth_asu-like_sf.
DR InterPro; IPR000793; ATP_synth_asu_C.
DR InterPro; IPR038376; ATP_synth_asu_C_sf.
DR InterPro; IPR033732; ATP_synth_F1_a.
DR InterPro; IPR005294; ATP_synth_F1_asu.
DR InterPro; IPR020003; ATPase_a/bsu_AS.
DR InterPro; IPR004100; ATPase_F1/V1/A1_a/bsu_N.
DR InterPro; IPR036121; ATPase_F1/V1/A1_a/bsu_N_sf.
DR InterPro; IPR000194; ATPase_F1/V1/A1_a/bsu_nucl-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00006; ATP-synt_ab; 1.
DR Pfam; PF00306; ATP-synt_ab_C; 1.
DR Pfam; PF02874; ATP-synt_ab_N; 1.
DR PIRSF; PIRSF039088; F_ATPase_subunit_alpha; 1.
DR SUPFAM; SSF50615; SSF50615; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00962; atpA; 1.
DR PROSITE; PS00152; ATPASE_ALPHA_BETA; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP synthesis; ATP-binding;
KW Cell membrane; CF(1); Direct protein sequencing; Disease variant;
KW Glycoprotein; Hydrogen ion transport; Ion transport; Membrane; Methylation;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Phosphoprotein; Primary mitochondrial disease; Reference proteome;
KW Transit peptide; Transport.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:19892738"
FT CHAIN 44..553
FT /note="ATP synthase subunit alpha, mitochondrial"
FT /id="PRO_0000002424"
FT BINDING 213..220
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P19483"
FT BINDING 473..475
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P19483"
FT SITE 413
FT /note="Required for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 76
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 123
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 132
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 134
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15999"
FT MOD_RES 161
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 161
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 167
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 167
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 204
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 230
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 230
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 239
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 239
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 240
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 261
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 261
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 305
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 305
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 427
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 427
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 434
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 498
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 498
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 506
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 506
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 531
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 531
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 539
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 539
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT MOD_RES 541
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q03265"
FT CARBOHYD 76
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045129"
FT VAR_SEQ 140..161
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054688"
FT VARIANT 32
FT /note="A -> S (in dbSNP:rs2228437)"
FT /id="VAR_048369"
FT VARIANT 321
FT /note="Y -> C (in COXPD22; dbSNP:rs587777788)"
FT /evidence="ECO:0000269|PubMed:23596069"
FT /id="VAR_071982"
FT VARIANT 329
FT /note="R -> C (in MC5DN4; dbSNP:rs587776960)"
FT /evidence="ECO:0000269|PubMed:23599390"
FT /id="VAR_069769"
FT CONFLICT 162
FT /note="G -> V (in Ref. 5; BAG63618)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="I -> T (in Ref. 5; BAG63618)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="R -> L (in Ref. 5; AAH39135)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="N -> D (in Ref. 5; BAG63618)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="A -> D (in Ref. 5; AAH11384)"
FT /evidence="ECO:0000305"
FT CONFLICT 529
FT /note="D -> E (in Ref. 5; AAH11384)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 59751 MW; AA47BBB8EDA77EAC CRC64;
MLSVRVAAAV VRALPRRAGL VSRNALGSSF IAARNFHASN THLQKTGTAE MSSILEERIL
GADTSVDLEE TGRVLSIGDG IARVHGLRNV QAEEMVEFSS GLKGMSLNLE PDNVGVVVFG
NDKLIKEGDI VKRTGAIVDV PVGEELLGRV VDALGNAIDG KGPIGSKTRR RVGLKAPGII
PRISVREPMQ TGIKAVDSLV PIGRGQRELI IGDRQTGKTS IAIDTIINQK RFNDGSDEKK
KLYCIYVAIG QKRSTVAQLV KRLTDADAMK YTIVVSATAS DAAPLQYLAP YSGCSMGEYF
RDNGKHALII YDDLSKQAVA YRQMSLLLRR PPGREAYPGD VFYLHSRLLE RAAKMNDAFG
GGSLTALPVI ETQAGDVSAY IPTNVISITD GQIFLETELF YKGIRPAINV GLSVSRVGSA
AQTRAMKQVA GTMKLELAQY REVAAFAQFG SDLDAATQQL LSRGVRLTEL LKQGQYSPMA
IEEQVAVIYA GVRGYLDKLE PSKITKFENA FLSHVVSQHQ ALLGTIRADG KISEQSDAKL
KEIVTNFLAG FEA
