Full text data of ATP5A1
ATP5A1
(ATP5A, ATP5AL2, ATPM)
[Confidence: high (present in two of the MS resources)]
ATP synthase subunit alpha, mitochondrial; Flags: Precursor
ATP synthase subunit alpha, mitochondrial; Flags: Precursor
UniProt
P25705
ID ATPA_HUMAN Reviewed; 553 AA.
AC P25705; A8K092; Q53XX6; Q8IXV2; Q96FB4; Q96HW2; Q96IR6; Q9BTV8;
read moreDT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 22-JAN-2014, entry version 168.
DE RecName: Full=ATP synthase subunit alpha, mitochondrial;
DE Flags: Precursor;
GN Name=ATP5A1; Synonyms=ATP5A, ATP5AL2, ATPM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT mitochondrial 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
RT mitochondrial ATP synthase complex in a human retinoblastoma cell
RT 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
RT synthase 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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA 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
RT project: 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
RT labeling of 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 MASS 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;
RP 306-316; 335-347; 403-416; 442-463 AND 507-527, AND MASS 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
RT database of human heart.";
RL Electrophoresis 16:1160-1169(1995).
RN [12]
RP INTERACTION WITH PLG, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=10077593; DOI=10.1073/pnas.96.6.2811;
RA Moser T.L., Stack M.S., Asplin I., Enghild J.J., Hojrup P.,
RA Everitt L., 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 INTERACTION WITH HRG, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
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
RT cell surface type ATP synthase on T-cells.";
RL Biochim. Biophys. Acta 1788:1099-1107(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161; LYS-261; LYS-434;
RP LYS-498; LYS-506 AND LYS-539, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [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.,
RA Buerckstuemmer T., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
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 [19]
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.,
RA Hoischen A., Gilissen C., Nabuurs S.B., Huynen M.A., de Vries M.C.,
RA Smeitink J.A., Rodenburg R.J.;
RT "A complex V ATP5A1 defect causes fatal neonatal mitochondrial
RT encephalopathy.";
RL Brain 136:1544-1554(2013).
CC -!- FUNCTION: Mitochondrial membrane ATP synthase (F(1)F(0) ATP
CC synthase or Complex V) produces ATP from ADP in the presence of a
CC proton gradient across the membrane which is generated by electron
CC transport complexes of the respiratory chain. F-type ATPases
CC consist of two structural domains, F(1) - containing the
CC extramembraneous catalytic core, and F(0) - containing the
CC membrane proton channel, linked together by a central stalk and a
CC peripheral stalk. During catalysis, ATP synthesis in the catalytic
CC domain of F(1) is coupled via a rotary mechanism of the central
CC stalk subunits to proton translocation. Subunits alpha and beta
CC form the catalytic core in F(1). Rotation of the central stalk
CC against the surrounding alpha(3)beta(3) subunits leads to
CC hydrolysis of ATP in three separate catalytic sites on the beta
CC subunits. Subunit alpha does not bear the catalytic high-affinity
CC ATP-binding sites (By similarity).
CC -!- SUBUNIT: F-type ATPases have 2 components, CF(1) - the catalytic
CC core - and CF(0) - the membrane proton channel. CF(1) has five
CC subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0)
CC has three main subunits: a, b and c. Interacts with ATPAF2.
CC Interacts with HRG; the interaction occurs on the surface of T-
CC cells and alters the cell morphology when associated with
CC concanavalin (in vitro). Interacts with PLG (angiostatin peptide);
CC the interaction inhibits most of the angiogenic properties of
CC angiostatin. Component of an ATP synthase complex composed of
CC ATP5F1, ATP5G1, ATP5E, ATP5H, ATP5I, ATP5J, ATP5J2, MT-ATP6, MT-
CC ATP8, ATP5A1, ATP5B, ATP5D, ATP5C1, ATP5O, ATP5L, USMG5 and MP68.
CC Interacts with BLOC1S1. Interacts with BCL2L1 isoform BCL-X(L);
CC the interaction mediates the association of BCL2L1 isoform BCL-
CC X(L) with the mitochondrial membrane F(1)F(0) ATP synthase and
CC enhances neurons metabolic efficency.
CC -!- INTERACTION:
CC P78537:BLOC1S1; NbExp=2; IntAct=EBI-351437, EBI-348630;
CC Q9NTG7:SIRT3; NbExp=2; IntAct=EBI-351437, EBI-724621;
CC P63104:YWHAZ; NbExp=3; IntAct=EBI-351437, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane. Cell membrane;
CC Peripheral membrane protein; Extracellular side. Note=Colocalizes
CC with HRG on the cell surface of T-cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25705-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25705-2; Sequence=VSP_045129;
CC -!- TISSUE SPECIFICITY: Fetal lung, heart, liver, gut and kidney.
CC Expressed at higher levels in the fetal brain, retina and spinal
CC cord.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Acetylated on lysine residues. BLOC1S1 is required for
CC acetylation.
CC -!- DISEASE: Mitochondrial complex V deficiency, nuclear 4 (MC5DN4)
CC [MIM:615228]: A mitochondrial disorder with heterogeneous clinical
CC manifestations including dysmorphic features, psychomotor
CC retardation, hypotonia, growth retardation, cardiomyopathy,
CC enlarged liver, hypoplastic kidneys and elevated lactate levels in
CC urine, plasma and cerebrospinal fluid. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ATPase alpha/beta chains family.
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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; 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 PIR; S17193; PWHUA.
DR RefSeq; NP_001001935.1; NM_001001935.2.
DR RefSeq; NP_001001937.1; NM_001001937.1.
DR RefSeq; NP_001244263.1; NM_001257334.1.
DR RefSeq; NP_001244264.1; NM_001257335.1.
DR RefSeq; NP_004037.1; NM_004046.5.
DR UniGene; Hs.298280; -.
DR ProteinModelPortal; P25705; -.
DR SMR; P25705; 56-553.
DR DIP; DIP-32871N; -.
DR IntAct; P25705; 31.
DR MINT; MINT-1163289; -.
DR STRING; 9606.ENSP00000282050; -.
DR ChEMBL; CHEMBL2062351; -.
DR PhosphoSite; P25705; -.
DR DMDM; 114517; -.
DR OGP; P25705; -.
DR REPRODUCTION-2DPAGE; P25705; -.
DR UCD-2DPAGE; P25705; -.
DR PaxDb; P25705; -.
DR PRIDE; P25705; -.
DR DNASU; 498; -.
DR Ensembl; ENST00000282050; ENSP00000282050; ENSG00000152234.
DR Ensembl; ENST00000398752; ENSP00000381736; ENSG00000152234.
DR Ensembl; ENST00000593152; ENSP00000465477; ENSG00000152234.
DR GeneID; 498; -.
DR KEGG; hsa:498; -.
DR UCSC; uc002lbr.2; human.
DR CTD; 498; -.
DR GeneCards; GC18M043664; -.
DR HGNC; HGNC:823; ATP5A1.
DR HPA; CAB013067; -.
DR MIM; 164360; gene.
DR MIM; 615228; phenotype.
DR neXtProt; NX_P25705; -.
DR Orphanet; 254913; Isolated ATP synthase deficiency.
DR PharmGKB; PA25115; -.
DR eggNOG; COG0056; -.
DR HOVERGEN; HBG001536; -.
DR InParanoid; P25705; -.
DR KO; K02132; -.
DR OMA; FRVGIKA; -.
DR OrthoDB; EOG773XFP; -.
DR PhylomeDB; P25705; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; ATP5A1; human.
DR GenomeRNAi; 498; -.
DR NextBio; 2089; -.
DR PMAP-CutDB; P25705; -.
DR PRO; PR:P25705; -.
DR ArrayExpress; P25705; -.
DR Bgee; P25705; -.
DR CleanEx; HS_ATP5A1; -.
DR Genevestigator; P25705; -.
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:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045261; C:proton-transporting ATP synthase complex, catalytic core F(1); IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB.
DR GO; GO:0046933; F:proton-transporting ATP synthase activity, rotational mechanism; ISS:UniProtKB.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:InterPro.
DR GO; GO:0015991; P:ATP hydrolysis coupled proton transport; IEA:InterPro.
DR GO; GO:0009790; P:embryo development; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0042776; P:mitochondrial ATP synthesis coupled proton transport; IC:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0022904; P:respiratory electron transport chain; TAS:Reactome.
DR Gene3D; 2.40.30.20; -; 1.
DR InterPro; IPR020003; ATPase_a/bsu_AS.
DR InterPro; IPR023366; ATPase_asu-like.
DR InterPro; IPR005294; ATPase_F1-cplx_asu.
DR InterPro; IPR000793; ATPase_F1/V1/A1-cplx_a/bsu_C.
DR InterPro; IPR000194; ATPase_F1/V1/A1_a/bsu_nucl-bd.
DR InterPro; IPR004100; ATPase_F1_a/bsu_N.
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 SUPFAM; SSF47917; SSF47917; 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); Complete proteome; Direct protein sequencing;
KW Disease mutation; Hydrogen ion transport; Ion transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Pyrrolidone carboxylic acid;
KW Reference proteome; Transit peptide; Transport.
FT TRANSIT 1 43 Mitochondrion.
FT CHAIN 44 553 ATP synthase subunit alpha,
FT mitochondrial.
FT /FTId=PRO_0000002424.
FT NP_BIND 212 219 ATP (By similarity).
FT SITE 413 413 Required for activity (By similarity).
FT MOD_RES 44 44 Pyrrolidone carboxylic acid (By
FT similarity).
FT MOD_RES 76 76 Phosphoserine (By similarity).
FT MOD_RES 123 123 N6-acetyllysine (By similarity).
FT MOD_RES 126 126 N6-acetyllysine (By similarity).
FT MOD_RES 132 132 N6-acetyllysine (By similarity).
FT MOD_RES 161 161 N6-acetyllysine.
FT MOD_RES 166 166 Phosphoserine.
FT MOD_RES 167 167 N6-acetyllysine (By similarity).
FT MOD_RES 230 230 N6-acetyllysine (By similarity).
FT MOD_RES 239 239 N6-acetyllysine (By similarity).
FT MOD_RES 240 240 N6-acetyllysine (By similarity).
FT MOD_RES 261 261 N6-acetyllysine.
FT MOD_RES 305 305 N6-acetyllysine.
FT MOD_RES 427 427 N6-acetyllysine (By similarity).
FT MOD_RES 434 434 N6-acetyllysine.
FT MOD_RES 498 498 N6-acetyllysine.
FT MOD_RES 506 506 N6-acetyllysine.
FT MOD_RES 531 531 N6-acetyllysine (By similarity).
FT MOD_RES 539 539 N6-acetyllysine.
FT MOD_RES 541 541 N6-acetyllysine (By similarity).
FT VAR_SEQ 1 50 Missing (in isoform 2).
FT /FTId=VSP_045129.
FT VARIANT 32 32 A -> S (in dbSNP:rs2228437).
FT /FTId=VAR_048369.
FT VARIANT 223 223 I -> V (in dbSNP:rs2228436).
FT /FTId=VAR_048370.
FT VARIANT 329 329 R -> C (in MC5DN4).
FT /FTId=VAR_069769.
FT CONFLICT 329 329 R -> L (in Ref. 5; AAH39135).
FT CONFLICT 510 510 A -> D (in Ref. 5; AAH11384).
FT CONFLICT 529 529 D -> E (in Ref. 5; AAH11384).
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
//
ID ATPA_HUMAN Reviewed; 553 AA.
AC P25705; A8K092; Q53XX6; Q8IXV2; Q96FB4; Q96HW2; Q96IR6; Q9BTV8;
read moreDT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 22-JAN-2014, entry version 168.
DE RecName: Full=ATP synthase subunit alpha, mitochondrial;
DE Flags: Precursor;
GN Name=ATP5A1; Synonyms=ATP5A, ATP5AL2, ATPM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT mitochondrial 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
RT mitochondrial ATP synthase complex in a human retinoblastoma cell
RT 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
RT synthase 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
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Small intestine;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA 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
RT project: 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
RT labeling of 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 MASS 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;
RP 306-316; 335-347; 403-416; 442-463 AND 507-527, AND MASS 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
RT database of human heart.";
RL Electrophoresis 16:1160-1169(1995).
RN [12]
RP INTERACTION WITH PLG, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=10077593; DOI=10.1073/pnas.96.6.2811;
RA Moser T.L., Stack M.S., Asplin I., Enghild J.J., Hojrup P.,
RA Everitt L., 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 INTERACTION WITH HRG, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR
RP LOCATION, AND FUNCTION.
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
RT cell surface type ATP synthase on T-cells.";
RL Biochim. Biophys. Acta 1788:1099-1107(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-161; LYS-261; LYS-434;
RP LYS-498; LYS-506 AND LYS-539, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [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.,
RA Buerckstuemmer T., 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
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 [19]
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.,
RA Hoischen A., Gilissen C., Nabuurs S.B., Huynen M.A., de Vries M.C.,
RA Smeitink J.A., Rodenburg R.J.;
RT "A complex V ATP5A1 defect causes fatal neonatal mitochondrial
RT encephalopathy.";
RL Brain 136:1544-1554(2013).
CC -!- FUNCTION: Mitochondrial membrane ATP synthase (F(1)F(0) ATP
CC synthase or Complex V) produces ATP from ADP in the presence of a
CC proton gradient across the membrane which is generated by electron
CC transport complexes of the respiratory chain. F-type ATPases
CC consist of two structural domains, F(1) - containing the
CC extramembraneous catalytic core, and F(0) - containing the
CC membrane proton channel, linked together by a central stalk and a
CC peripheral stalk. During catalysis, ATP synthesis in the catalytic
CC domain of F(1) is coupled via a rotary mechanism of the central
CC stalk subunits to proton translocation. Subunits alpha and beta
CC form the catalytic core in F(1). Rotation of the central stalk
CC against the surrounding alpha(3)beta(3) subunits leads to
CC hydrolysis of ATP in three separate catalytic sites on the beta
CC subunits. Subunit alpha does not bear the catalytic high-affinity
CC ATP-binding sites (By similarity).
CC -!- SUBUNIT: F-type ATPases have 2 components, CF(1) - the catalytic
CC core - and CF(0) - the membrane proton channel. CF(1) has five
CC subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0)
CC has three main subunits: a, b and c. Interacts with ATPAF2.
CC Interacts with HRG; the interaction occurs on the surface of T-
CC cells and alters the cell morphology when associated with
CC concanavalin (in vitro). Interacts with PLG (angiostatin peptide);
CC the interaction inhibits most of the angiogenic properties of
CC angiostatin. Component of an ATP synthase complex composed of
CC ATP5F1, ATP5G1, ATP5E, ATP5H, ATP5I, ATP5J, ATP5J2, MT-ATP6, MT-
CC ATP8, ATP5A1, ATP5B, ATP5D, ATP5C1, ATP5O, ATP5L, USMG5 and MP68.
CC Interacts with BLOC1S1. Interacts with BCL2L1 isoform BCL-X(L);
CC the interaction mediates the association of BCL2L1 isoform BCL-
CC X(L) with the mitochondrial membrane F(1)F(0) ATP synthase and
CC enhances neurons metabolic efficency.
CC -!- INTERACTION:
CC P78537:BLOC1S1; NbExp=2; IntAct=EBI-351437, EBI-348630;
CC Q9NTG7:SIRT3; NbExp=2; IntAct=EBI-351437, EBI-724621;
CC P63104:YWHAZ; NbExp=3; IntAct=EBI-351437, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane. Cell membrane;
CC Peripheral membrane protein; Extracellular side. Note=Colocalizes
CC with HRG on the cell surface of T-cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25705-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25705-2; Sequence=VSP_045129;
CC -!- TISSUE SPECIFICITY: Fetal lung, heart, liver, gut and kidney.
CC Expressed at higher levels in the fetal brain, retina and spinal
CC cord.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Acetylated on lysine residues. BLOC1S1 is required for
CC acetylation.
CC -!- DISEASE: Mitochondrial complex V deficiency, nuclear 4 (MC5DN4)
CC [MIM:615228]: A mitochondrial disorder with heterogeneous clinical
CC manifestations including dysmorphic features, psychomotor
CC retardation, hypotonia, growth retardation, cardiomyopathy,
CC enlarged liver, hypoplastic kidneys and elevated lactate levels in
CC urine, plasma and cerebrospinal fluid. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ATPase alpha/beta chains family.
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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; 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 PIR; S17193; PWHUA.
DR RefSeq; NP_001001935.1; NM_001001935.2.
DR RefSeq; NP_001001937.1; NM_001001937.1.
DR RefSeq; NP_001244263.1; NM_001257334.1.
DR RefSeq; NP_001244264.1; NM_001257335.1.
DR RefSeq; NP_004037.1; NM_004046.5.
DR UniGene; Hs.298280; -.
DR ProteinModelPortal; P25705; -.
DR SMR; P25705; 56-553.
DR DIP; DIP-32871N; -.
DR IntAct; P25705; 31.
DR MINT; MINT-1163289; -.
DR STRING; 9606.ENSP00000282050; -.
DR ChEMBL; CHEMBL2062351; -.
DR PhosphoSite; P25705; -.
DR DMDM; 114517; -.
DR OGP; P25705; -.
DR REPRODUCTION-2DPAGE; P25705; -.
DR UCD-2DPAGE; P25705; -.
DR PaxDb; P25705; -.
DR PRIDE; P25705; -.
DR DNASU; 498; -.
DR Ensembl; ENST00000282050; ENSP00000282050; ENSG00000152234.
DR Ensembl; ENST00000398752; ENSP00000381736; ENSG00000152234.
DR Ensembl; ENST00000593152; ENSP00000465477; ENSG00000152234.
DR GeneID; 498; -.
DR KEGG; hsa:498; -.
DR UCSC; uc002lbr.2; human.
DR CTD; 498; -.
DR GeneCards; GC18M043664; -.
DR HGNC; HGNC:823; ATP5A1.
DR HPA; CAB013067; -.
DR MIM; 164360; gene.
DR MIM; 615228; phenotype.
DR neXtProt; NX_P25705; -.
DR Orphanet; 254913; Isolated ATP synthase deficiency.
DR PharmGKB; PA25115; -.
DR eggNOG; COG0056; -.
DR HOVERGEN; HBG001536; -.
DR InParanoid; P25705; -.
DR KO; K02132; -.
DR OMA; FRVGIKA; -.
DR OrthoDB; EOG773XFP; -.
DR PhylomeDB; P25705; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; ATP5A1; human.
DR GenomeRNAi; 498; -.
DR NextBio; 2089; -.
DR PMAP-CutDB; P25705; -.
DR PRO; PR:P25705; -.
DR ArrayExpress; P25705; -.
DR Bgee; P25705; -.
DR CleanEx; HS_ATP5A1; -.
DR Genevestigator; P25705; -.
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:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045261; C:proton-transporting ATP synthase complex, catalytic core F(1); IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB.
DR GO; GO:0046933; F:proton-transporting ATP synthase activity, rotational mechanism; ISS:UniProtKB.
DR GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:InterPro.
DR GO; GO:0015991; P:ATP hydrolysis coupled proton transport; IEA:InterPro.
DR GO; GO:0009790; P:embryo development; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0042776; P:mitochondrial ATP synthesis coupled proton transport; IC:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0022904; P:respiratory electron transport chain; TAS:Reactome.
DR Gene3D; 2.40.30.20; -; 1.
DR InterPro; IPR020003; ATPase_a/bsu_AS.
DR InterPro; IPR023366; ATPase_asu-like.
DR InterPro; IPR005294; ATPase_F1-cplx_asu.
DR InterPro; IPR000793; ATPase_F1/V1/A1-cplx_a/bsu_C.
DR InterPro; IPR000194; ATPase_F1/V1/A1_a/bsu_nucl-bd.
DR InterPro; IPR004100; ATPase_F1_a/bsu_N.
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 SUPFAM; SSF47917; SSF47917; 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); Complete proteome; Direct protein sequencing;
KW Disease mutation; Hydrogen ion transport; Ion transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Pyrrolidone carboxylic acid;
KW Reference proteome; Transit peptide; Transport.
FT TRANSIT 1 43 Mitochondrion.
FT CHAIN 44 553 ATP synthase subunit alpha,
FT mitochondrial.
FT /FTId=PRO_0000002424.
FT NP_BIND 212 219 ATP (By similarity).
FT SITE 413 413 Required for activity (By similarity).
FT MOD_RES 44 44 Pyrrolidone carboxylic acid (By
FT similarity).
FT MOD_RES 76 76 Phosphoserine (By similarity).
FT MOD_RES 123 123 N6-acetyllysine (By similarity).
FT MOD_RES 126 126 N6-acetyllysine (By similarity).
FT MOD_RES 132 132 N6-acetyllysine (By similarity).
FT MOD_RES 161 161 N6-acetyllysine.
FT MOD_RES 166 166 Phosphoserine.
FT MOD_RES 167 167 N6-acetyllysine (By similarity).
FT MOD_RES 230 230 N6-acetyllysine (By similarity).
FT MOD_RES 239 239 N6-acetyllysine (By similarity).
FT MOD_RES 240 240 N6-acetyllysine (By similarity).
FT MOD_RES 261 261 N6-acetyllysine.
FT MOD_RES 305 305 N6-acetyllysine.
FT MOD_RES 427 427 N6-acetyllysine (By similarity).
FT MOD_RES 434 434 N6-acetyllysine.
FT MOD_RES 498 498 N6-acetyllysine.
FT MOD_RES 506 506 N6-acetyllysine.
FT MOD_RES 531 531 N6-acetyllysine (By similarity).
FT MOD_RES 539 539 N6-acetyllysine.
FT MOD_RES 541 541 N6-acetyllysine (By similarity).
FT VAR_SEQ 1 50 Missing (in isoform 2).
FT /FTId=VSP_045129.
FT VARIANT 32 32 A -> S (in dbSNP:rs2228437).
FT /FTId=VAR_048369.
FT VARIANT 223 223 I -> V (in dbSNP:rs2228436).
FT /FTId=VAR_048370.
FT VARIANT 329 329 R -> C (in MC5DN4).
FT /FTId=VAR_069769.
FT CONFLICT 329 329 R -> L (in Ref. 5; AAH39135).
FT CONFLICT 510 510 A -> D (in Ref. 5; AAH11384).
FT CONFLICT 529 529 D -> E (in Ref. 5; AAH11384).
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
//
MIM
164360
*RECORD*
*FIELD* NO
164360
*FIELD* TI
*164360 ATP SYNTHASE, H+ TRANSPORTING, MITOCHONDRIAL F1 COMPLEX, ALPHA SUBUNIT
1; ATP5A1
read more;;ATP5A;;
MITOCHONDRIAL ATP SYNTHETASE; ATPM;;
MITOCHONDRIAL ATP SYNTHETASE, OLIGOMYCIN-RESISTANT; OMR;;
MODIFIER OF MIN 2, MOUSE, HOMOLOG OF; MOM2
*FIELD* TX
DESCRIPTION
The ATP5A1 gene encodes the alpha subunit of the mitochondrial ATP
synthase F1 complex (Kataoka and Biswas, 1991).
CLONING
ATP synthase is a multimeric complex consisting of at least 16 different
polypeptides; 2 of these subunits are mitochondrially encoded and the
remainder are produced by nuclear genes. Kataoka and Biswas (1991)
reported the cloning of an ATP5A cDNA from a human LX-1 tumor cell
library. They found that the gene encoded a 553-amino acid polypeptide
that was 97% and 68% similar to the rat and yeast F1-ATP5A genes,
respectively.
Akiyama et al. (1994) isolated the human genomic clone of the ATP5A
gene. Comparison of the promoter region of the ATP5A gene with the
promoter region of the genes for the human ATP synthase beta subunit
(ATP5B; 102910), and the human ATP synthase gamma subunit (ATP5C;
108729) indicated 3 common promoter sequences, suggesting that these 3
ATP synthase genes are coordinately regulated. Akiyama et al. (1994)
presented evidence of cell type-specific regulation of ATP5A.
GENE STRUCTURE
Akiyama et al. (1994) determined that the ATP5A gene contains 12 exons
spanning 14 kb of the genome. Southern blot analysis revealed the
presence of a single copy of the ATP5A gene and 2 pseudogenes in the
human genome.
MAPPING
Using a rat liver cDNA as a probe in the analysis of somatic cell hybrid
DNAs, Jabs et al. (1994) found hybridization of ATP5A to both
chromosomes 9 and 18. One of these may represent a pseudogene.
Godbout et al. (1997) stated that ATP5A is the only functional gene
among the 4 ATP5A-related genes in the human genome. By fluorescence in
situ hybridization, they mapped this functional gene to chromosome
18q12-q21. Using somatic cell hybrids and fluorescence in situ
hybridization, Godbout et al. (1997) mapped ATP5AP1, an ATP5A
pseudogene, to chromosome 9p12. The other 2 pseudogenes are located on
chromosomes 2 and 16.
Baran et al. (2007) determined that the mouse Atp5a1 gene maps to distal
chromosome 18.
MOLECULAR GENETICS
In 2 sibs with fatal infantile mitochondrial encephalopathy and
biochemical evidence of mitochondrial complex V deficiency (MC5DN4;
615228), Jonckheere et al. (2013) identified a heterozygous missense
mutation in the ATP5A1 gene (R329C; 164360.0001) inherited from the
unaffected father. The mutation, which was found by exome sequencing and
confirmed by Sanger sequencing, was not present in 1,200 control exomes.
The sibs expressed only the mutant allele, the father expressed both the
mutant and wildtype allele, and the mother expressed only the wildtype
allele. Although no mutations were identified in the mother's ATP5A1
gene, there was no evidence for a splicing defect, and MLPA excluded
gene rearrangements; the mother had only about 60% ATP5A1 mRNA,
consistent with a gene expression defect. SNP analysis indicated that
both patients inherited the same maternal allele. Complementation of
patient fibroblasts with wildtype ATP5A1 completely normalized complex V
amount and activity. The findings indicated that the ATP5A1 defect found
in these patients was disease-causing, even though the exact nature of
the mutation inherited from the mother remained unknown.
ANIMAL MODEL
Baran et al. (2007) found that homozygosity for a spontaneous 4-bp
duplication in exon 3 of the mouse Atp5a1 gene resulted in embryonic
lethality before 12.5 days postcoitus. However, mice heterozygous for
the Atp5a1 mutation who also carried a tumor-associated mutation in the
Apc gene (611731) showed resistance to intestinal polyposis. Polyp
formation was inhibited when the Atp5a1 mutation resided on the same
chromosome 18 as the Apc mutation, but not when the mutations resided on
different chromosomes.
*FIELD* AV
.0001
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4
(1 family)
ATP5A1, ARG329CYS
In 2 sibs, born of unrelated Dutch parents, with mitochondrial complex V
deficiency, nuclear type 4 (MC5DN4; 615228) resulting in death early in
infancy from progressive encephalopathy, Jonckheere et al. (2013)
identified a heterozygous c.985C-T transition in exon 9 of the ATP5A1
gene, resulting in an arg329-to-cys (R329C) substitution at a highly
conserved residue. The mutation, which was found by exome sequencing and
confirmed by Sanger sequencing, was present in the heterozygous state in
the unaffected father and was not found in 1,200 control exomes. No
mutation in the ATP5A1 gene was found in the mother. The sibs expressed
only the mutant allele and had about 50% decreased mRNA levels of ATP5A1
compared to controls, whereas the father expressed both the mutant and
wildtype allele and the mother expressed only the wildtype allele.
Although no mutations were identified in the mother's ATP5A1 gene, there
was no evidence for a splicing defect, and MLPA excluded gene
rearrangements; the mother had only about 60% ATP5A1 mRNA, consistent
with a gene expression defect. SNP analysis indicated that both patients
inherited the same maternal allele. Protein modeling suggested that the
R329C substitution would disrupt stabilizing interactions with other
complex V subunits. Patient fibroblasts showed an isolated defect of
complex V activity, and immunoblotting techniques showed disturbed
complex V assembly at an early stage. Complementation of patient
fibroblasts with wildtype ATP5A1 completely normalized complex V amount
and activity.
*FIELD* RF
1. Akiyama, S.; Endo, H.; Inohara, N.; Ohta, S.; Kagawa, Y.: Gene
structure and cell type-specific expression of the human ATP synthase
alpha subunit. Biochim. Biophys. Acta 1219: 129-140, 1994.
2. Baran, A. A.; Silverman, K. A.; Zeskand, J.; Koratkar, R.; Palmer,
A.; McCullen, K.; Curran, W. J., Jr.; Edmonston, T. B.; Siracusa,
L. D.; Buchberg, A. M.: The modifier of Min 2 (Mom2) locus: embryonic
lethality of a mutation in the Atp5a1 gene suggests a novel mechanism
of polyp suppression. Genome Res. 17: 566-576, 2007.
3. Godbout, R.; Pandita, A.; Beatty, B.; Bie, W.; Squire, J. A.:
Comparative genomic hybridization analysis of Y79 and FISH mapping
indicate the amplified human mitochondrial ATP synthase alpha-subunit
gene (ATP5A) maps to chromosome 18q12-q21. Cytogenet. Cell Genet. 77:
253-256, 1997.
4. Jabs, E. W.; Thomas, P. J.; Bernstein, M.; Coss, C.; Ferreira,
G. C.; Pedersen, P. L.: Chromosomal localization of genes required
for the terminal steps of oxidative metabolism: alpha and gamma subunits
of ATP synthase and the phosphate carrier. Hum. Genet. 93: 600-602,
1994.
5. Jonckheere, A. I.; Renkema, G. H.; Bras, M.; van den Heuvel, L.
P.; Hoischen, A.; Gilissen, C.; Nabuurs, S. B.; Huynen, M. A.; de
Vries, M. C.; Smeitink, J. A. M.; Rodenburg, R. J. T.: A complex
V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy. Brain 136:
1544-1554, 2013.
6. Kataoka, H; Biswas, C.: Nucleotide sequence of a cDNA for the
alpha subunit of human mitochondrial ATP synthase. Biochim. Biophys.
Acta 1089: 393-395, 1991.
*FIELD* CN
Cassandra L. Kniffin - updated: 5/13/2013
Patricia A. Hartz - updated: 7/3/2007
Rebekah S. Rasooly - updated: 5/19/1999
Jennifer P. Macke - updated: 5/19/1999
Jennifer P. Macke - updated: 5/22/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 05/15/2013
alopez: 5/14/2013
ckniffin: 5/13/2013
alopez: 5/7/2010
ckniffin: 2/5/2008
mgross: 7/10/2007
terry: 7/3/2007
alopez: 3/24/2004
terry: 3/23/2004
alopez: 5/19/1999
carol: 6/24/1998
alopez: 8/1/1997
alopez: 7/24/1997
alopez: 7/17/1997
carol: 2/6/1995
carol: 3/24/1993
supermim: 3/16/1992
carol: 7/2/1991
supermim: 3/20/1990
ddp: 10/27/1989
*RECORD*
*FIELD* NO
164360
*FIELD* TI
*164360 ATP SYNTHASE, H+ TRANSPORTING, MITOCHONDRIAL F1 COMPLEX, ALPHA SUBUNIT
1; ATP5A1
read more;;ATP5A;;
MITOCHONDRIAL ATP SYNTHETASE; ATPM;;
MITOCHONDRIAL ATP SYNTHETASE, OLIGOMYCIN-RESISTANT; OMR;;
MODIFIER OF MIN 2, MOUSE, HOMOLOG OF; MOM2
*FIELD* TX
DESCRIPTION
The ATP5A1 gene encodes the alpha subunit of the mitochondrial ATP
synthase F1 complex (Kataoka and Biswas, 1991).
CLONING
ATP synthase is a multimeric complex consisting of at least 16 different
polypeptides; 2 of these subunits are mitochondrially encoded and the
remainder are produced by nuclear genes. Kataoka and Biswas (1991)
reported the cloning of an ATP5A cDNA from a human LX-1 tumor cell
library. They found that the gene encoded a 553-amino acid polypeptide
that was 97% and 68% similar to the rat and yeast F1-ATP5A genes,
respectively.
Akiyama et al. (1994) isolated the human genomic clone of the ATP5A
gene. Comparison of the promoter region of the ATP5A gene with the
promoter region of the genes for the human ATP synthase beta subunit
(ATP5B; 102910), and the human ATP synthase gamma subunit (ATP5C;
108729) indicated 3 common promoter sequences, suggesting that these 3
ATP synthase genes are coordinately regulated. Akiyama et al. (1994)
presented evidence of cell type-specific regulation of ATP5A.
GENE STRUCTURE
Akiyama et al. (1994) determined that the ATP5A gene contains 12 exons
spanning 14 kb of the genome. Southern blot analysis revealed the
presence of a single copy of the ATP5A gene and 2 pseudogenes in the
human genome.
MAPPING
Using a rat liver cDNA as a probe in the analysis of somatic cell hybrid
DNAs, Jabs et al. (1994) found hybridization of ATP5A to both
chromosomes 9 and 18. One of these may represent a pseudogene.
Godbout et al. (1997) stated that ATP5A is the only functional gene
among the 4 ATP5A-related genes in the human genome. By fluorescence in
situ hybridization, they mapped this functional gene to chromosome
18q12-q21. Using somatic cell hybrids and fluorescence in situ
hybridization, Godbout et al. (1997) mapped ATP5AP1, an ATP5A
pseudogene, to chromosome 9p12. The other 2 pseudogenes are located on
chromosomes 2 and 16.
Baran et al. (2007) determined that the mouse Atp5a1 gene maps to distal
chromosome 18.
MOLECULAR GENETICS
In 2 sibs with fatal infantile mitochondrial encephalopathy and
biochemical evidence of mitochondrial complex V deficiency (MC5DN4;
615228), Jonckheere et al. (2013) identified a heterozygous missense
mutation in the ATP5A1 gene (R329C; 164360.0001) inherited from the
unaffected father. The mutation, which was found by exome sequencing and
confirmed by Sanger sequencing, was not present in 1,200 control exomes.
The sibs expressed only the mutant allele, the father expressed both the
mutant and wildtype allele, and the mother expressed only the wildtype
allele. Although no mutations were identified in the mother's ATP5A1
gene, there was no evidence for a splicing defect, and MLPA excluded
gene rearrangements; the mother had only about 60% ATP5A1 mRNA,
consistent with a gene expression defect. SNP analysis indicated that
both patients inherited the same maternal allele. Complementation of
patient fibroblasts with wildtype ATP5A1 completely normalized complex V
amount and activity. The findings indicated that the ATP5A1 defect found
in these patients was disease-causing, even though the exact nature of
the mutation inherited from the mother remained unknown.
ANIMAL MODEL
Baran et al. (2007) found that homozygosity for a spontaneous 4-bp
duplication in exon 3 of the mouse Atp5a1 gene resulted in embryonic
lethality before 12.5 days postcoitus. However, mice heterozygous for
the Atp5a1 mutation who also carried a tumor-associated mutation in the
Apc gene (611731) showed resistance to intestinal polyposis. Polyp
formation was inhibited when the Atp5a1 mutation resided on the same
chromosome 18 as the Apc mutation, but not when the mutations resided on
different chromosomes.
*FIELD* AV
.0001
MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4
(1 family)
ATP5A1, ARG329CYS
In 2 sibs, born of unrelated Dutch parents, with mitochondrial complex V
deficiency, nuclear type 4 (MC5DN4; 615228) resulting in death early in
infancy from progressive encephalopathy, Jonckheere et al. (2013)
identified a heterozygous c.985C-T transition in exon 9 of the ATP5A1
gene, resulting in an arg329-to-cys (R329C) substitution at a highly
conserved residue. The mutation, which was found by exome sequencing and
confirmed by Sanger sequencing, was present in the heterozygous state in
the unaffected father and was not found in 1,200 control exomes. No
mutation in the ATP5A1 gene was found in the mother. The sibs expressed
only the mutant allele and had about 50% decreased mRNA levels of ATP5A1
compared to controls, whereas the father expressed both the mutant and
wildtype allele and the mother expressed only the wildtype allele.
Although no mutations were identified in the mother's ATP5A1 gene, there
was no evidence for a splicing defect, and MLPA excluded gene
rearrangements; the mother had only about 60% ATP5A1 mRNA, consistent
with a gene expression defect. SNP analysis indicated that both patients
inherited the same maternal allele. Protein modeling suggested that the
R329C substitution would disrupt stabilizing interactions with other
complex V subunits. Patient fibroblasts showed an isolated defect of
complex V activity, and immunoblotting techniques showed disturbed
complex V assembly at an early stage. Complementation of patient
fibroblasts with wildtype ATP5A1 completely normalized complex V amount
and activity.
*FIELD* RF
1. Akiyama, S.; Endo, H.; Inohara, N.; Ohta, S.; Kagawa, Y.: Gene
structure and cell type-specific expression of the human ATP synthase
alpha subunit. Biochim. Biophys. Acta 1219: 129-140, 1994.
2. Baran, A. A.; Silverman, K. A.; Zeskand, J.; Koratkar, R.; Palmer,
A.; McCullen, K.; Curran, W. J., Jr.; Edmonston, T. B.; Siracusa,
L. D.; Buchberg, A. M.: The modifier of Min 2 (Mom2) locus: embryonic
lethality of a mutation in the Atp5a1 gene suggests a novel mechanism
of polyp suppression. Genome Res. 17: 566-576, 2007.
3. Godbout, R.; Pandita, A.; Beatty, B.; Bie, W.; Squire, J. A.:
Comparative genomic hybridization analysis of Y79 and FISH mapping
indicate the amplified human mitochondrial ATP synthase alpha-subunit
gene (ATP5A) maps to chromosome 18q12-q21. Cytogenet. Cell Genet. 77:
253-256, 1997.
4. Jabs, E. W.; Thomas, P. J.; Bernstein, M.; Coss, C.; Ferreira,
G. C.; Pedersen, P. L.: Chromosomal localization of genes required
for the terminal steps of oxidative metabolism: alpha and gamma subunits
of ATP synthase and the phosphate carrier. Hum. Genet. 93: 600-602,
1994.
5. Jonckheere, A. I.; Renkema, G. H.; Bras, M.; van den Heuvel, L.
P.; Hoischen, A.; Gilissen, C.; Nabuurs, S. B.; Huynen, M. A.; de
Vries, M. C.; Smeitink, J. A. M.; Rodenburg, R. J. T.: A complex
V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy. Brain 136:
1544-1554, 2013.
6. Kataoka, H; Biswas, C.: Nucleotide sequence of a cDNA for the
alpha subunit of human mitochondrial ATP synthase. Biochim. Biophys.
Acta 1089: 393-395, 1991.
*FIELD* CN
Cassandra L. Kniffin - updated: 5/13/2013
Patricia A. Hartz - updated: 7/3/2007
Rebekah S. Rasooly - updated: 5/19/1999
Jennifer P. Macke - updated: 5/19/1999
Jennifer P. Macke - updated: 5/22/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 05/15/2013
alopez: 5/14/2013
ckniffin: 5/13/2013
alopez: 5/7/2010
ckniffin: 2/5/2008
mgross: 7/10/2007
terry: 7/3/2007
alopez: 3/24/2004
terry: 3/23/2004
alopez: 5/19/1999
carol: 6/24/1998
alopez: 8/1/1997
alopez: 7/24/1997
alopez: 7/17/1997
carol: 2/6/1995
carol: 3/24/1993
supermim: 3/16/1992
carol: 7/2/1991
supermim: 3/20/1990
ddp: 10/27/1989
MIM
615228
*RECORD*
*FIELD* NO
615228
*FIELD* TI
#615228 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4;
MC5DN4
;;MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, ATP5A1 TYPE
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
mitochondrial complex V deficiency nuclear type 4 (MC5DN4) is caused by
mutation in the ATP5A1 gene (164360) on chromosome 18q. One such family
has been reported.
For a general phenotypic description of the nuclear type of
mitochondrial complex V deficiency and a discussion of genetic
heterogeneity of mitochondrial complex V deficiency, see MC5DN1
(604273).
CLINICAL FEATURES
Jonckheere et al. (2013) reported 2 sibs, born of unrelated Dutch
parents, with fatal infantile encephalopathy. After birth, the infants
were irritable with a high-pitched cry and showed horizontal and
vertical nystagmus, abnormal primitive reflexes, and tonus
dysregulation. Both died in the first weeks of life due to a severe
encephalopathy characterized by intractable seizures manifest as apneic
spells. Brain MRI of one of the sibs showed a progressive and severe
encephalopathy characterized by hyperdense thalami and subcortical
densities. Postmortem examination showed extensive cerebral damage,
small cerebellum, damaged pons and brainstem, and cystic degeneration of
the white matter. Other findings included hypoplastic lungs, small renal
cysts, and small lipid droplets in skeletal muscle, all suggestive of a
mitochondrial disease. Brain MRI of the younger sib showed progressive
damage to the frontal and parietooccipital regions, the pyramidal tract,
basal ganglia, cerebellum, and pons. Metabolic screening showed no
abnormalities in either case. Patient fibroblasts showed decreased
oxygen consumption rate, isolated complex V deficiency, and decreased
complex V assembly.
INHERITANCE
The transmission pattern in the family with MC5DN4 reported by
Jonckheere et al. (2013) was consistent with autosomal recessive
inheritance.
MOLECULAR GENETICS
In 2 sibs with fatal infantile mitochondrial encephalopathy, Jonckheere
et al. (2013) identified a heterozygous missense mutation in the ATP5A1
gene (R329C; 164360.0001) inherited from the unaffected father. The
mutation, which was found by exome sequencing and confirmed by Sanger
sequencing, was not present in 1,200 control exomes. The sibs expressed
only the mutant allele, the father expressed both the mutant and
wildtype allele, and the mother expressed only the wildtype allele.
Although no mutations were identified in the mother's ATP5A1 gene, there
was no evidence for a splicing defect, and MLPA excluded gene
rearrangements; the mother had only about 60% ATP5A1 mRNA, consistent
with a gene expression defect. SNP analysis indicated that both patients
inherited the same maternal allele. Complementation of patient
fibroblasts with wildtype ATP5A1 completely normalized complex V amount
and activity. The findings indicated that the ATP5A1 defect found in
these patients was disease-causing, even though the exact nature of the
mutation inherited from the mother remained unknown.
*FIELD* RF
1. Jonckheere, A. I.; Renkema, G. H.; Bras, M.; van den Heuvel, L.
P.; Hoischen, A.; Gilissen, C.; Nabuurs, S. B.; Huynen, M. A.; de
Vries, M. C.; Smeitink, J. A. M.; Rodenburg, R. J. T.: A complex
V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy. Brain 136:
1544-1554, 2013.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Nystagmus
RESPIRATORY:
Apneic episodes;
[Lungs];
Hypoplastic lungs
GENITOURINARY:
[Kidneys];
Small renal cysts
MUSCLE, SOFT TISSUE:
Lipid droplets seen on muscle biopsy
NEUROLOGIC:
[Central nervous system];
Encephalopathy, progressive;
Irritability;
Seizures, intractable;
Abnormal primitive reflexes;
Tonus dysregulation;
Cerebral damage;
Thalamic lesions;
Subcortical lesions;
Small cerebellum;
Cystic degeneration of the white matter;
Pons damage;
Brainstem damage
VOICE:
High-pitched cry
LABORATORY ABNORMALITIES:
Fibroblasts show decreased mitochondrial complex V activity;
Decreased mitochondrial complex V assembly
MISCELLANEOUS:
Onset at birth;
Death in first weeks of life;
Two sibs have been reported (last curated May 2013)
MOLECULAR BASIS:
Caused by mutation in the ATP synthase, H+ transporting, mitochondrial
F1 complex, alpha subunit 1 (ATP5A1, 164360.0001)
*FIELD* CD
Cassandra L. Kniffin: 5/13/2013
*FIELD* ED
joanna: 06/04/2013
ckniffin: 5/13/2013
*FIELD* CN
]: 05/15/2013
*FIELD* CD
Cassandra L. Kniffin: 5/13/2013
*FIELD* ED
alopez: 05/15/2013
alopez: 5/14/2013
ckniffin: 5/13/2013
*RECORD*
*FIELD* NO
615228
*FIELD* TI
#615228 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 4;
MC5DN4
;;MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, ATP5A1 TYPE
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
mitochondrial complex V deficiency nuclear type 4 (MC5DN4) is caused by
mutation in the ATP5A1 gene (164360) on chromosome 18q. One such family
has been reported.
For a general phenotypic description of the nuclear type of
mitochondrial complex V deficiency and a discussion of genetic
heterogeneity of mitochondrial complex V deficiency, see MC5DN1
(604273).
CLINICAL FEATURES
Jonckheere et al. (2013) reported 2 sibs, born of unrelated Dutch
parents, with fatal infantile encephalopathy. After birth, the infants
were irritable with a high-pitched cry and showed horizontal and
vertical nystagmus, abnormal primitive reflexes, and tonus
dysregulation. Both died in the first weeks of life due to a severe
encephalopathy characterized by intractable seizures manifest as apneic
spells. Brain MRI of one of the sibs showed a progressive and severe
encephalopathy characterized by hyperdense thalami and subcortical
densities. Postmortem examination showed extensive cerebral damage,
small cerebellum, damaged pons and brainstem, and cystic degeneration of
the white matter. Other findings included hypoplastic lungs, small renal
cysts, and small lipid droplets in skeletal muscle, all suggestive of a
mitochondrial disease. Brain MRI of the younger sib showed progressive
damage to the frontal and parietooccipital regions, the pyramidal tract,
basal ganglia, cerebellum, and pons. Metabolic screening showed no
abnormalities in either case. Patient fibroblasts showed decreased
oxygen consumption rate, isolated complex V deficiency, and decreased
complex V assembly.
INHERITANCE
The transmission pattern in the family with MC5DN4 reported by
Jonckheere et al. (2013) was consistent with autosomal recessive
inheritance.
MOLECULAR GENETICS
In 2 sibs with fatal infantile mitochondrial encephalopathy, Jonckheere
et al. (2013) identified a heterozygous missense mutation in the ATP5A1
gene (R329C; 164360.0001) inherited from the unaffected father. The
mutation, which was found by exome sequencing and confirmed by Sanger
sequencing, was not present in 1,200 control exomes. The sibs expressed
only the mutant allele, the father expressed both the mutant and
wildtype allele, and the mother expressed only the wildtype allele.
Although no mutations were identified in the mother's ATP5A1 gene, there
was no evidence for a splicing defect, and MLPA excluded gene
rearrangements; the mother had only about 60% ATP5A1 mRNA, consistent
with a gene expression defect. SNP analysis indicated that both patients
inherited the same maternal allele. Complementation of patient
fibroblasts with wildtype ATP5A1 completely normalized complex V amount
and activity. The findings indicated that the ATP5A1 defect found in
these patients was disease-causing, even though the exact nature of the
mutation inherited from the mother remained unknown.
*FIELD* RF
1. Jonckheere, A. I.; Renkema, G. H.; Bras, M.; van den Heuvel, L.
P.; Hoischen, A.; Gilissen, C.; Nabuurs, S. B.; Huynen, M. A.; de
Vries, M. C.; Smeitink, J. A. M.; Rodenburg, R. J. T.: A complex
V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy. Brain 136:
1544-1554, 2013.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Nystagmus
RESPIRATORY:
Apneic episodes;
[Lungs];
Hypoplastic lungs
GENITOURINARY:
[Kidneys];
Small renal cysts
MUSCLE, SOFT TISSUE:
Lipid droplets seen on muscle biopsy
NEUROLOGIC:
[Central nervous system];
Encephalopathy, progressive;
Irritability;
Seizures, intractable;
Abnormal primitive reflexes;
Tonus dysregulation;
Cerebral damage;
Thalamic lesions;
Subcortical lesions;
Small cerebellum;
Cystic degeneration of the white matter;
Pons damage;
Brainstem damage
VOICE:
High-pitched cry
LABORATORY ABNORMALITIES:
Fibroblasts show decreased mitochondrial complex V activity;
Decreased mitochondrial complex V assembly
MISCELLANEOUS:
Onset at birth;
Death in first weeks of life;
Two sibs have been reported (last curated May 2013)
MOLECULAR BASIS:
Caused by mutation in the ATP synthase, H+ transporting, mitochondrial
F1 complex, alpha subunit 1 (ATP5A1, 164360.0001)
*FIELD* CD
Cassandra L. Kniffin: 5/13/2013
*FIELD* ED
joanna: 06/04/2013
ckniffin: 5/13/2013
*FIELD* CN
]: 05/15/2013
*FIELD* CD
Cassandra L. Kniffin: 5/13/2013
*FIELD* ED
alopez: 05/15/2013
alopez: 5/14/2013
ckniffin: 5/13/2013