ID   AT5G3_HUMAN             Reviewed;         142 AA.
AC   P48201; B2R4Z0; D3DPF0; Q4ZFX7;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   02-SEP-2026, entry version 201.
DE   RecName: Full=ATP synthase F(0) complex subunit C3, mitochondrial {ECO:0000305};
DE   AltName: Full=ATP synthase lipid-binding protein;
DE   AltName: Full=ATP synthase membrane subunit c locus 3 {ECO:0000312|HGNC:HGNC:843};
DE   AltName: Full=ATP synthase proteolipid P3;
DE   AltName: Full=ATP synthase proton-transporting mitochondrial F(0) complex subunit C3;
DE   AltName: Full=ATPase protein 9;
DE   AltName: Full=ATPase subunit c;
DE   Flags: Precursor;
GN   Name=ATP5MC3 {ECO:0000312|HGNC:HGNC:843};
GN   Synonyms=ATP5G3 {ECO:0000312|HGNC:HGNC:843};
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].
RC   TISSUE=Liver;
RX   PubMed=7698763; DOI=10.1006/geno.1994.1631;
RA   Yan W.L., Lerner T.J., Haines J.L., Gusella J.F.;
RT   "Sequence analysis and mapping of a novel human mitochondrial ATP synthase
RT   subunit 9 cDNA (ATP5G3).";
RL   Genomics 24:375-377(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Subthalamic nucleus;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [6]
RP   METHYLATION AT LYS-110.
RX   PubMed=30530489; DOI=10.1074/jbc.ra118.005473;
RA   Malecki J.M., Willemen H.L.D.M., Pinto R., Ho A.Y.Y., Moen A.,
RA   Kjoenstad I.F., Burgering B.M.T., Zwartkruis F., Eijkelkamp N.,
RA   Falnes P.O.;
RT   "Lysine methylation by the mitochondrial methyltransferase FAM173B
RT   optimizes the function of mitochondrial ATP synthase.";
RL   J. Biol. Chem. 294:1128-1141(2019).
RN   [7]
RP   INTERACTION WITH TMEM70 AND TMEM242.
RX   PubMed=33753518; DOI=10.1073/pnas.2100558118;
RA   Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.;
RT   "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase
RT   and interact with assembly factors for complex I.";
RL   Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN   [8]
RP   VARIANT DYTSPG LYS-106, AND INVOLVEMENT IN DYTSPG.
RX   PubMed=34636445; DOI=10.1002/mds.28821;
RA   Neilson D.E., Zech M., Hufnagel R.B., Slone J., Wang X., Homan S.,
RA   Gutzwiller L.M., Leslie E.J., Leslie N.D., Xiao J., Hedera P., LeDoux M.S.,
RA   Gebelein B., Wilbert F., Eckenweiler M., Winkelmann J., Gilbert D.L.,
RA   Huang T.;
RT   "A Novel Variant of ATP5MC3 Associated with Both Dystonia and Spastic
RT   Paraplegia.";
RL   Mov. Disord. 37:375-383(2022).
RN   [9]
RP   VARIANTS DYTSPG VAL-79; LYS-106 AND ALA-107.
RX   PubMed=34954817; DOI=10.1002/ana.26293;
RA   Zech M., Kopajtich R., Steinbruecker K., Bris C., Gueguen N.,
RA   Feichtinger R.G., Achleitner M.T., Duzkale N., Perivier M., Koch J.,
RA   Engelhardt H., Freisinger P., Wagner M., Brunet T., Berutti R., Smirnov D.,
RA   Navaratnarajah T., Rodenburg R.J.T., Pais L.S., Austin-Tse C., O'Leary M.,
RA   Boesch S., Jech R., Bakhtiari S., Jin S.C., Wilbert F., Kruer M.C.,
RA   Wortmann S.B., Eckenweiler M., Mayr J.A., Distelmaier F., Steinfeld R.,
RA   Winkelmann J., Prokisch H.;
RT   "Variants in Mitochondrial ATP Synthase Cause Variable Neurologic
RT   Phenotypes.";
RL   Ann. Neurol. 91:225-237(2022).
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. Part of the complex
CC       F(0) domain. A homomeric c-ring of probably 10 subunits is part of the
CC       complex rotary element.
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. Interacts with TMEM70 and TMEM242
CC       (PubMed:33753518). {ECO:0000269|PubMed:33753518}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion membrane; Multi-pass membrane
CC       protein.
CC   -!- PTM: Trimethylated by ATPSCKMT at Lys-110. Methylation is required for
CC       proper incorporation of the C subunit into the ATP synthase complex and
CC       mitochondrial respiration. {ECO:0000269|PubMed:30530489}.
CC   -!- DISEASE: Dystonia, early-onset, and/or spastic paraplegia (DYTSPG)
CC       [MIM:619681]: An autosomal dominant, highly penetrant movement disorder
CC       characterized by spastic paraplegia and/or dystonia to varying degrees
CC       in affected individuals. Cognition is not affected. There is high
CC       intra- and interfamilial variability in phenotype and age of onset.
CC       Some patients have onset of progressive focal or generalized dystonia
CC       in the first decade, whereas others develop progressive spastic
CC       paraplegia as adults. Some affected individuals have manifestations of
CC       both disorders. {ECO:0000269|PubMed:34636445,
CC       ECO:0000269|PubMed:34954817}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: There are three genes which encode the mitochondrial ATP
CC       synthase proteolipid and they specify precursors with different import
CC       sequences but identical mature proteins. Is the major protein stored in
CC       the storage bodies of animals or humans affected with ceroid
CC       lipofuscinosis (Batten disease).
CC   -!- SIMILARITY: Belongs to the ATPase C chain family. {ECO:0000305}.
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DR   EMBL; U09813; AAA78807.1; -; mRNA.
DR   EMBL; AK311999; BAG34937.1; -; mRNA.
DR   EMBL; AC096649; AAX88970.1; -; Genomic_DNA.
DR   EMBL; CH471058; EAX11106.1; -; Genomic_DNA.
DR   EMBL; CH471058; EAX11107.1; -; Genomic_DNA.
DR   EMBL; BC106881; AAI06882.1; -; mRNA.
DR   CCDS; CCDS2263.1; -.
DR   PIR; I38612; I38612.
DR   RefSeq; NP_001002258.1; NM_001002258.5.
DR   RefSeq; NP_001680.1; NM_001689.5.
DR   AlphaFoldDB; P48201; -.
DR   SMR; P48201; -.
DR   BioGRID; 107003; 31.
DR   ComplexPortal; CPX-6151; Mitochondrial proton-transporting ATP synthase complex.
DR   FunCoup; P48201; 551.
DR   IntAct; P48201; 18.
DR   NDEx; IQUERY-CP-ATP5MC3; 1 NDEx IQuery Curated Pathway.
DR   STRING; 9606.ENSP00000284727; -.
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; P48201; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P48201; -.
DR   PhosphoSitePlus; P48201; -.
DR   BioMuta; ATP5G3; -.
DR   DMDM; 1352048; -.
DR   jPOST; P48201; -.
DR   MassIVE; P48201; -.
DR   PaxDb; 9606-ENSP00000284727; -.
DR   PeptideAtlas; P48201; -.
DR   ProteomicsDB; 55872; -.
DR   Pumba; P48201; -.
DR   TopDownProteomics; P48201; -.
DR   Antibodypedia; 53295; 51 antibodies from 19 providers.
DR   DNASU; 518; -.
DR   Ensembl; ENST00000284727.9; ENSP00000284727.4; ENSG00000154518.11.
DR   Ensembl; ENST00000392541.3; ENSP00000376324.3; ENSG00000154518.11.
DR   Ensembl; ENST00000409194.5; ENSP00000387317.1; ENSG00000154518.11.
DR   Ensembl; ENST00000877858.1; ENSP00000547917.1; ENSG00000154518.11.
DR   Ensembl; ENST00000877860.1; ENSP00000547919.1; ENSG00000154518.11.
DR   Ensembl; ENST00000877861.1; ENSP00000547920.1; ENSG00000154518.11.
DR   Ensembl; ENST00000937346.1; ENSP00000607405.1; ENSG00000154518.11.
DR   Ensembl; ENST00000937347.1; ENSP00000607406.1; ENSG00000154518.11.
DR   Ensembl; ENST00000937348.1; ENSP00000607407.1; ENSG00000154518.11.
DR   Ensembl; ENST00000937349.1; ENSP00000607408.1; ENSG00000154518.11.
DR   GeneID; 518; -.
DR   KEGG; hsa:518; -.
DR   MANE-Select; ENST00000284727.9; ENSP00000284727.4; NM_001689.5; NP_001680.1.
DR   UCSC; uc002ujz.5; human.
DR   AGR; HGNC:843; -.
DR   ClinPGx; PA25133; -.
DR   CTD; 518; -.
DR   DisGeNET; 518; -.
DR   GeneCards; ATP5MC3; -.
DR   HGNC; HGNC:843; ATP5MC3.
DR   HPA; ENSG00000154518; Tissue enhanced (heart muscle, tongue).
DR   MalaCards; ATP5MC3; -.
DR   MIM; 602736; gene.
DR   MIM; 619681; phenotype.
DR   OpenTargets; ENSG00000154518; -.
DR   VEuPathDB; HostDB:ENSG00000154518; -.
DR   eggNOG; KOG3025; Eukaryota.
DR   GeneTree; ENSGT00940000154298; -.
DR   HOGENOM; CLU_116822_1_0_1; -.
DR   InParanoid; P48201; -.
DR   OMA; CTSALIR; -.
DR   OrthoDB; 438052at2759; -.
DR   PAN-GO; P48201; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; P48201; -.
DR   BioCyc; MetaCyc:ENSG00000154518-MONOMER; -.
DR   PathwayCommons; P48201; -.
DR   Reactome; R-HSA-163210; Formation of ATP by chemiosmotic coupling.
DR   Reactome; R-HSA-8949613; Cristae formation.
DR   SignaLink; P48201; -.
DR   Agora; ENSG00000154518; -.
DR   BioGRID-ORCS; 518; 13 hits in 1154 CRISPR screens.
DR   ChiTaRS; ATP5G3; human.
DR   GeneWiki; ATP5G3; -.
DR   GenomeRNAi; 518; -.
DR   Pharos; P48201; Tdark.
DR   PRO; PR:P48201; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; P48201; protein.
DR   Bgee; ENSG00000154518; Expressed in heart right ventricle and 215 other cell types or tissues.
DR   GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; HTP:FlyBase.
DR   GO; GO:0045259; C:proton-transporting ATP synthase complex; IBA:GO_Central.
DR   GO; GO:0033177; C:proton-transporting two-sector ATPase complex, proton-transporting domain; IEA:InterPro.
DR   GO; GO:0015078; F:proton transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0015986; P:proton motive force-driven ATP synthesis; IBA:GO_Central.
DR   CDD; cd18182; ATP-synt_Fo_c_ATP5G3; 1.
DR   FunFam; 1.20.20.10:FF:000003; Atp synthase f complex subunit mitochondrial; 1.
DR   Gene3D; 1.20.20.10; F1F0 ATP synthase subunit C; 1.
DR   HAMAP; MF_01396; ATP_synth_c_bact; 1.
DR   InterPro; IPR000454; ATP_synth_F0_csu.
DR   InterPro; IPR020537; ATP_synth_F0_csu_DDCD_BS.
DR   InterPro; IPR038662; ATP_synth_F0_csu_sf.
DR   InterPro; IPR002379; ATPase_proteolipid_c-like_dom.
DR   InterPro; IPR035921; F/V-ATP_Csub_sf.
DR   PANTHER; PTHR10031; ATP SYNTHASE LIPID-BINDING PROTEIN, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR10031:SF0; ATPASE PROTEIN 9; 1.
DR   Pfam; PF00137; ATP-synt_C; 1.
DR   PRINTS; PR00124; ATPASEC.
DR   SUPFAM; SSF81333; F1F0 ATP synthase subunit C; 1.
DR   PROSITE; PS00605; ATPASE_C; 1.
PE   1: Evidence at protein level;
KW   CF(0); Disease variant; Dystonia; Hereditary spastic paraplegia;
KW   Hydrogen ion transport; Ion transport; Lipid-binding; Membrane;
KW   Methylation; Mitochondrion; Neurodegeneration; Proteomics identification;
KW   Reference proteome; Transit peptide; Transmembrane; Transmembrane helix;
KW   Transport.
FT   TRANSIT         1..67
FT                   /note="Mitochondrion"
FT   CHAIN           68..142
FT                   /note="ATP synthase F(0) complex subunit C3, mitochondrial"
FT                   /id="PRO_0000002567"
FT   TRANSMEM        83..103
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   SITE            125
FT                   /note="Reversibly protonated during proton transport"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         110
FT                   /note="N6,N6,N6-trimethyllysine"
FT                   /evidence="ECO:0000269|PubMed:30530489"
FT   VARIANT         79
FT                   /note="G -> V (in DYTSPG; likely pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:34954817"
FT                   /id="VAR_088544"
FT   VARIANT         93
FT                   /note="G -> E (in dbSNP:rs1802622)"
FT                   /id="VAR_011922"
FT   VARIANT         106
FT                   /note="N -> K (in DYTSPG; likely pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:34636445,
FT                   ECO:0000269|PubMed:34954817"
FT                   /id="VAR_086710"
FT   VARIANT         107
FT                   /note="P -> A (in DYTSPG; likely pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:34954817"
FT                   /id="VAR_088545"
SQ   SEQUENCE   142 AA;  14693 MW;  19EC0D1710A0AA3F CRC64;
     MFACAKLACT PSLIRAGSRV AYRPISASVL SRPEASRTGE GSTVFNGAQN GVSQLIQREF
     QTSAISRDID TAAKFIGAGA ATVGVAGSGA GIGTVFGSLI IGYARNPSLK QQLFSYAILG
     FALSEAMGLF CLMVAFLILF AM
//