ATPD_HUMAN
ID ATPD_HUMAN Reviewed; 168 AA.
AC P30049; D6W5Y3; Q6FG90;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=ATP synthase subunit delta, mitochondrial {ECO:0000305};
DE AltName: Full=ATP synthase F1 subunit delta {ECO:0000312|HGNC:HGNC:837};
DE AltName: Full=F-ATPase delta subunit;
DE Flags: Precursor;
GN Name=ATP5F1D {ECO:0000312|HGNC:HGNC:837};
GN Synonyms=ATP5D {ECO:0000312|HGNC:HGNC:837};
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], AND FUNCTION.
RX PubMed=1531933; DOI=10.1016/0167-4781(92)90477-h;
RA Jordan E.M., Breen G.A.M.;
RT "Molecular cloning of an import precursor of the delta-subunit of the human
RT mitochondrial ATP synthase complex.";
RL Biochim. Biophys. Acta 1130:123-126(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
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].
RC TISSUE=Brain, and Lung;
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 PROTEIN SEQUENCE OF 23-38.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [7]
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 [8]
RP IDENTIFICATION BY 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 [9]
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 [10]
RP FUNCTION, INVOLVEMENT IN MC5DN5, VARIANTS MC5DN5 LEU-82 AND GLY-106, AND
RP CHARACTERIZATION OF VARIANTS MC5DN5 LEU-82 AND GLY-106.
RX PubMed=29478781; DOI=10.1016/j.ajhg.2018.01.020;
RG Undiagnosed Diseases Network;
RA Olahova M., Yoon W.H., Thompson K., Jangam S., Fernandez L., Davidson J.M.,
RA Kyle J.E., Grove M.E., Fisk D.G., Kohler J.N., Holmes M., Dries A.M.,
RA Huang Y., Zhao C., Contrepois K., Zappala Z., Fresard L., Waggott D.,
RA Zink E.M., Kim Y.M., Heyman H.M., Stratton K.G., Webb-Robertson B.M.,
RA Snyder M., Merker J.D., Montgomery S.B., Fisher P.G., Feichtinger R.G.,
RA Mayr J.A., Hall J., Barbosa I.A., Simpson M.A., Deshpande C., Waters K.M.,
RA Koeller D.M., Metz T.O., Morris A.A., Schelley S., Cowan T.,
RA Friederich M.W., McFarland R., Van Hove J.L.K., Enns G.M., Yamamoto S.,
RA Ashley E.A., Wangler M.F., Taylor R.W., Bellen H.J., Bernstein J.A.,
RA Wheeler M.T.;
RT "Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase,
RT Cause a Metabolic Disorder.";
RL Am. J. Hum. Genet. 102:494-504(2018).
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 (PubMed:29478781). F-type ATPases consist of
CC two structural domains, F(1) - containing the extramembraneous
CC catalytic core, and F(0) - containing the membrane proton channel,
CC linked together by a central stalk and a peripheral stalk. During
CC catalysis, ATP turnover in the catalytic domain of F(1) is coupled via
CC a rotary mechanism of the central stalk subunits to proton
CC translocation. Part of the complex F(1) domain and of the central stalk
CC which is part of the complex rotary element. Rotation of the central
CC stalk against the surrounding alpha(3)beta(3) subunits leads to
CC hydrolysis of ATP in three separate catalytic sites on the beta
CC subunits (PubMed:1531933). {ECO:0000269|PubMed:29478781,
CC ECO:0000303|PubMed:1531933}.
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) seems to have
CC nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an
CC ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD,
CC ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D,
CC ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P30049; P56381: ATP5F1E; NbExp=4; IntAct=EBI-1049505, EBI-3904845;
CC P30049; P54253: ATXN1; NbExp=3; IntAct=EBI-1049505, EBI-930964;
CC P30049; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-1049505, EBI-10171774;
CC P30049; Q99750: MDFI; NbExp=3; IntAct=EBI-1049505, EBI-724076;
CC P30049; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-1049505, EBI-22310682;
CC P30049; Q05519-2: SRSF11; NbExp=3; IntAct=EBI-1049505, EBI-11975029;
CC P30049; Q63HR2: TNS2; NbExp=3; IntAct=EBI-1049505, EBI-949753;
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane.
CC -!- DISEASE: Mitochondrial complex V deficiency, nuclear type 5 (MC5DN5)
CC [MIM:618120]: A mitochondrial disorder characterized by childhood onset
CC of episodic metabolic decompensation featuring lactic acidosis and
CC hyperammonemia accompanied by ketoacidosis or hypoglycemia. Chronic
CC manifestations include developmental delay, easy fatiguability, and 3-
CC methylglutaconic aciduria. The transmission pattern of MC5DN5 is
CC consistent with autosomal recessive inheritance.
CC {ECO:0000269|PubMed:29478781}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ATPase epsilon chain family. {ECO:0000305}.
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DR EMBL; S87916; AAA08055.1; -; mRNA.
DR EMBL; S87918; ABB76284.1; -; mRNA.
DR EMBL; X63422; CAA45016.1; -; mRNA.
DR EMBL; X63423; CAA45017.1; -; mRNA.
DR EMBL; CR542218; CAG47014.1; -; mRNA.
DR EMBL; AC004221; AAC04304.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69532.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69533.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69534.1; -; Genomic_DNA.
DR EMBL; BC002389; AAH02389.1; -; mRNA.
DR EMBL; BC004426; AAH04426.1; -; mRNA.
DR EMBL; BC018079; AAH18079.1; -; mRNA.
DR CCDS; CCDS12058.1; -.
DR PIR; S22348; S22348.
DR RefSeq; NP_001001975.1; NM_001001975.1.
DR RefSeq; NP_001678.1; NM_001687.4.
DR AlphaFoldDB; P30049; -.
DR SMR; P30049; -.
DR BioGRID; 106998; 138.
DR ComplexPortal; CPX-6151; Mitochondrial proton-transporting ATP synthase complex.
DR CORUM; P30049; -.
DR IntAct; P30049; 64.
DR MINT; P30049; -.
DR STRING; 9606.ENSP00000215375; -.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB13749; Magnesium gluconate.
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; P30049; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30049; -.
DR PhosphoSitePlus; P30049; -.
DR BioMuta; ATP5D; -.
DR DMDM; 584812; -.
DR OGP; P30049; -.
DR SWISS-2DPAGE; P30049; -.
DR UCD-2DPAGE; P30049; -.
DR EPD; P30049; -.
DR jPOST; P30049; -.
DR MassIVE; P30049; -.
DR MaxQB; P30049; -.
DR PaxDb; P30049; -.
DR PeptideAtlas; P30049; -.
DR PRIDE; P30049; -.
DR ProteomicsDB; 54629; -.
DR TopDownProteomics; P30049; -.
DR Antibodypedia; 1258; 318 antibodies from 29 providers.
DR DNASU; 513; -.
DR Ensembl; ENST00000215375.7; ENSP00000215375.1; ENSG00000099624.8.
DR Ensembl; ENST00000395633.5; ENSP00000378995.1; ENSG00000099624.8.
DR Ensembl; ENST00000591660.5; ENSP00000464863.1; ENSG00000099624.8.
DR GeneID; 513; -.
DR KEGG; hsa:513; -.
DR MANE-Select; ENST00000215375.7; ENSP00000215375.1; NM_001687.5; NP_001678.1.
DR UCSC; uc002lrn.4; human.
DR CTD; 513; -.
DR DisGeNET; 513; -.
DR GeneCards; ATP5F1D; -.
DR HGNC; HGNC:837; ATP5F1D.
DR HPA; ENSG00000099624; Tissue enhanced (skeletal).
DR MalaCards; ATP5F1D; -.
DR MIM; 603150; gene.
DR MIM; 618120; phenotype.
DR neXtProt; NX_P30049; -.
DR OpenTargets; ENSG00000099624; -.
DR Orphanet; 254913; Isolated ATP synthase deficiency.
DR PharmGKB; PA25127; -.
DR VEuPathDB; HostDB:ENSG00000099624; -.
DR eggNOG; KOG1758; Eukaryota.
DR GeneTree; ENSGT00390000017576; -.
DR HOGENOM; CLU_084338_0_1_1; -.
DR InParanoid; P30049; -.
DR OMA; TLPHQTI; -.
DR OrthoDB; 1286602at2759; -.
DR PhylomeDB; P30049; -.
DR TreeFam; TF313029; -.
DR BioCyc; MetaCyc:HS01900-MON; -.
DR PathwayCommons; P30049; -.
DR Reactome; R-HSA-163210; Formation of ATP by chemiosmotic coupling.
DR Reactome; R-HSA-8949613; Cristae formation.
DR SignaLink; P30049; -.
DR SIGNOR; P30049; -.
DR BioGRID-ORCS; 513; 630 hits in 1075 CRISPR screens.
DR ChiTaRS; ATP5D; human.
DR GeneWiki; ATP5D; -.
DR GenomeRNAi; 513; -.
DR Pharos; P30049; Tbio.
DR PRO; PR:P30049; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P30049; protein.
DR Bgee; ENSG00000099624; Expressed in apex of heart and 202 other tissues.
DR ExpressionAtlas; P30049; baseline and differential.
DR Genevisible; P30049; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS: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:0000275; C:mitochondrial proton-transporting ATP synthase complex, catalytic sector F(1); IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; NAS:UniProtKB.
DR GO; GO:0046933; F:proton-transporting ATP synthase activity, rotational mechanism; IEA:InterPro.
DR GO; GO:0009060; P:aerobic respiration; IMP:UniProtKB.
DR GO; GO:0033615; P:mitochondrial proton-transporting ATP synthase complex assembly; IMP:UniProtKB.
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:0046688; P:response to copper ion; NAS:UniProtKB.
DR CDD; cd12152; F1-ATPase_delta; 1.
DR Gene3D; 2.60.15.10; -; 1.
DR HAMAP; MF_00530; ATP_synth_epsil_bac; 1.
DR InterPro; IPR036794; ATP_F1_dsu/esu_C_sf.
DR InterPro; IPR001469; ATP_synth_F1_dsu/esu.
DR InterPro; IPR020546; ATP_synth_F1_dsu/esu_N.
DR InterPro; IPR036771; ATPsynth_dsu/esu_N.
DR PANTHER; PTHR13822; PTHR13822; 1.
DR Pfam; PF02823; ATP-synt_DE_N; 1.
DR SUPFAM; SSF46604; SSF46604; 1.
DR SUPFAM; SSF51344; SSF51344; 1.
DR TIGRFAMs; TIGR01216; ATP_synt_epsi; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP synthesis; CF(1); Direct protein sequencing;
KW Disease variant; Hydrogen ion transport; Ion transport; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease;
KW Reference proteome; Transit peptide; Transport.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1286669"
FT CHAIN 23..168
FT /note="ATP synthase subunit delta, mitochondrial"
FT /id="PRO_0000002661"
FT MOD_RES 136
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D3D9"
FT MOD_RES 136
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D3D9"
FT MOD_RES 165
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D3D9"
FT MOD_RES 165
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9D3D9"
FT VARIANT 82
FT /note="P -> L (in MC5DN5; no effect on protein abundance;
FT decreased mitochondrial proton-transporting ATP synthase
FT complex assembly; decreased aerobic respiration in patient
FT cells homozygous for the mutation; partial loss of function
FT confirmed by complementation assays; dbSNP:rs867410737)"
FT /evidence="ECO:0000269|PubMed:29478781"
FT /id="VAR_081452"
FT VARIANT 106
FT /note="V -> G (in MC5DN5; no effect on protein abundance;
FT decreased mitochondrial proton-transporting ATP synthase
FT complex assembly; decreased aerobic respiration in patient
FT cells homozygous for the mutation; partial loss of function
FT confirmed by complementation assays; dbSNP:rs1555745989)"
FT /evidence="ECO:0000269|PubMed:29478781"
FT /id="VAR_081453"
SQ SEQUENCE 168 AA; 17490 MW; B7F0D1D01ADFDFE7 CRC64;
MLPAALLRRP GLGRLVRHAR AYAEAAAAPA AASGPNQMSF TFASPTQVFF NGANVRQVDV
PTLTGAFGIL AAHVPTLQVL RPGLVVVHAE DGTTSKYFVS SGSIAVNADS SVQLLAEEAV
TLDMLDLGAA KANLEKAQAE LVGTADEATR AEIQIRIEAN EALVKALE
