ATP5D

ATP5F1D
Identifiers
Aliases	ATP5F1D,ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit, ATP synthase F1 subunit delta, ATP5D, MC5DN5
External IDs	OMIM:603150;MGI:1913293;HomoloGene:37514;GeneCards:ATP5F1D;OMA:ATP5F1D - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19p13.3 Start 1,241,746bp End 1,244,825bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10|10 C1 Start 80,138,632bp End 80,145,818bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in apex of heart muscle of thigh mucosa of transverse colon right auricle gastrocnemius muscle left ventricle right frontal lobe right lobe of liver body of pancreas body of stomach Top expressed in right ventricle extraocular muscle ankle right kidney vestibular membrane of cochlear duct condyle digastric muscle fossa facial motor nucleus sternocleidomastoid muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function proton-transporting ATP synthase activity, rotational mechanism transmembrane transporter activity transporter activity ADP binding ATP binding ATPase activity Cellular component mitochondrial proton-transporting ATP synthase complex membrane mitochondrial matrix mitochondrion mitochondrial proton-transporting ATP synthase complex, catalytic sector F(1) mitochondrial inner membrane proton-transporting ATP synthase complex, catalytic core F(1) Biological process response to copper ion mitochondrial ATP synthesis coupled proton transport ion transport oxidative phosphorylation ATP synthesis coupled proton transport ATP biosynthetic process cristae formation aerobic respiration mitochondrial proton-transporting ATP synthase complex assembly Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 513 66043 Ensembl ENSG00000099624 ENSMUSG00000003072 UniProt P30049 Q9D3D9 RefSeq (mRNA) NM_001687 NM_001001975 NM_025313 NM_001347092 RefSeq (protein) NP_001001975 NP_001678 NP_001334021 NP_079589 Location (UCSC) Chr 19: 1.24 – 1.24 Mb Chr 10: 80.14 – 80.15 Mb PubMedsearch
Wikidata
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ATP synthase subunit delta, mitochondrial,also known asATP synthase F1 subunit deltaorF-ATPase delta subunitis anenzymethat in humans is encoded by theATP5F1D(formerlyATP5D)gene.This gene encodes a subunit of mitochondrialATP synthase.MitochondrialATP synthasecatalyzesATP synthesis,utilizing anelectrochemical gradientofprotonsacross theinner membraneduringoxidative phosphorylation.

Structure

TheATP5F1Dgene is located on thep armofchromosome 19at position 13.3 and it spans 3,075 base pairs.TheATP5F1Dgene produces a 17.5 kDa protein composed of 168amino acids.The codedproteinis a subunit of themitochondrial ATP synthase(Complex V), which is composed of two linked multi-subunit complexes: the solublecatalytic core,F₁,and themembrane-spanning component, F_o,comprising theproton channel.The catalytic portion ofmitochondrial ATP synthaseconsists of 5 differentsubunits(alpha, beta, gamma, delta, and epsilon) assembled with astoichiometryof 3 alpha, 3 beta, and a single representative of the other 3. Theproton channelconsists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core.Alternatively splicedtranscript variants encoding the sameisoformhave been identified.The structure of the protein has been known to resemble a 'lollipop' structure due to the attachment of the F1 catalytic unit to themitochondrial inner membraneby the F0 unit.

Function

This gene encodes a subunit of the mitochondrialATP synthase(Complex V) of themitochondrial respiratory chain,which is necessary for thecatalysisofATP synthesis.Utilizing an electrochemicalgradient of protonsproduced byelectron transportcomplexes of the respiratory chain, thesynthaseconvertsADPintoATPacross theinner membraneduringoxidative phosphorylation.F-type ATPases consist of twostructural domains,F1 and F0, that contribute tocatalysis.The F1 domain contains an extramembranous catalytic core and the F0 domain contains the membraneproton channellinked by a central and a peripheral stalk. During catalysis,ATPturnover in the catalyticdomainof F1 is coupled by a rotary mechanism of the central stalk subunits toproton transport.The encoded protein is a part of the complex F1 domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surroundingalpha3beta3 subunitsleads to thehydrolysisofATPin three separatecatalytic siteson thebeta subunits.

Clinical significance

Mutations ofATP5F1Dhave been associated with childhoodmitochondrial disorderswithphenotypessuch as episodic decompensations,lactic acidosis,andhyperammonemiaaccompanied byketoacidosisorhypoglycemia.Biallelicmutationsof c.245C>T and c.317T>G inATP5F1Dwere shown to cause ametabolic disorderwith such phenotypes due to mitochondrial dysfunction in two unrelated individuals.Mutations ofATP5F1Dwith decreased expression of the protein have also been found to result insynapticdysfunction of the mitochondria that could play an essential role inamyotrophic lateral sclerosis(ALS) pathogenesis.

Interactions

Among the two components, CF1 - the catalytic core - and CF0 - the membrane proton channel of the F-type ATPase, ATP5F1D is associated with the catalytic core. The catalytic core is composed of five different subunits including alpha, beta, gamma, delta, and epsilon subunits. The protein has additional interactions withATP5I,ATP5O,PUS1,NDUFB5,GTPBP6,ATP5L,ATP5Jand others.

Further reading

• Yoshida M, Muneyuki E, Hisabori T (September 2001). "ATP synthase--a marvellous rotary engine of the cell".Nature Reviews. Molecular Cell Biology.2(9): 669–77.doi:10.1038/35089509.PMID11533724.S2CID3926411.
• Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R (December 1992). "Human liver protein map: a reference database established by microsequencing and gel comparison".Electrophoresis.13(12): 992–1001.doi:10.1002/elps.11501301201.PMID1286669.S2CID23518983.
• Yasuda R, Noji H, Kinosita K, Yoshida M (June 1998)."F1-ATPase is a highly efficient molecular motor that rotates with discrete 120 degree steps".Cell.93(7): 1117–24.doi:10.1016/S0092-8674(00)81456-7.PMID9657145.S2CID14106130.
• Wang H, Oster G (November 1998). "Energy transduction in the F1 motor of ATP synthase".Nature.396(6708): 279–82.Bibcode:1998Natur.396..279W.doi:10.1038/24409.PMID9834036.S2CID4424498.
• Cross RL (January 2004)."Molecular motors: turning the ATP motor".Nature.427(6973): 407–8.Bibcode:2004Natur.427..407C.doi:10.1038/427407b.PMID14749816.S2CID52819856.
• Itoh H, Takahashi A, Adachi K, Noji H, Yasuda R, Yoshida M, Kinosita K (January 2004). "Mechanically driven ATP synthesis by F1-ATPase".Nature.427(6973): 465–8.Bibcode:2004Natur.427..465I.doi:10.1038/nature02212.PMID14749837.S2CID4428646.

External links

• HumanATP5Dgenome location andATP5Dgene details page in theUCSC Genome Browser.

This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.