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Protein

ATP synthase subunit alpha, mitochondrial

Gene

ATP5F1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Mitochondrial membrane ATP synthase (F1F0 ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F1 - containing the extramembraneous catalytic core, and F0 - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F1. Rotation of the central stalk against the surrounding alpha3beta3 subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei413Required for activityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi213 – 220ATPBy similarity8
Nucleotide bindingi473 – 475ATPBy similarity3

GO - Molecular functioni

  • angiostatin binding Source: CAFA
  • ATP binding Source: UniProtKB
  • MHC class I protein binding Source: UniProtKB
  • proton-transporting ATP synthase activity, rotational mechanism Source: CAFA
  • RNA binding Source: UniProtKB
  • transmembrane transporter activity Source: UniProtKB

GO - Biological processi

  • ATP biosynthetic process Source: CAFA
  • cristae formation Source: Reactome
  • lipid metabolic process Source: UniProtKB
  • mitochondrial ATP synthesis coupled proton transport Source: UniProtKB
  • negative regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of blood vessel endothelial cell migration Source: CAFA

Keywordsi

Biological processATP synthesis, Hydrogen ion transport, Ion transport, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1268020 Mitochondrial protein import
R-HSA-163210 Formation of ATP by chemiosmotic coupling
R-HSA-8949613 Cristae formation

Names & Taxonomyi

Protein namesi
Recommended name:
ATP synthase subunit alpha, mitochondrialCurated
Alternative name(s):
ATP synthase F1 subunit alphaImported
Gene namesi
Name:ATP5F1AImported
Synonyms:ATP5A, ATP5A1Imported, ATP5AL2Imported, ATPMImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000152234.15
HGNCiHGNC:823 ATP5F1A
MIMi164360 gene
neXtProtiNX_P25705

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, CF(1), Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Combined oxidative phosphorylation deficiency 22 (COXPD22)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA mitochondrial disorder characterized by intrauterine growth retardation, microcephaly, hypotonia, pulmonary hypertension, failure to thrive, encephalopathy, and heart failure.
See also OMIM:616045
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071982321Y → C in COXPD22. 1 PublicationCorresponds to variant dbSNP:rs587777788EnsemblClinVar.1
Mitochondrial complex V deficiency, nuclear 4 (MC5DN4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid.
See also OMIM:615228
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069769329R → C in MC5DN4. 1 PublicationCorresponds to variant dbSNP:rs587776960EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Primary mitochondrial disease

Organism-specific databases

DisGeNETi498
MalaCardsiATP5F1A
MIMi615228 phenotype
616045 phenotype
OpenTargetsiENSG00000152234
Orphaneti254913 Isolated ATP synthase deficiency
PharmGKBiPA25115

Chemistry databases

ChEMBLiCHEMBL2062351
DrugBankiDB07384 1-ACETYL-2-CARBOXYPIPERIDINE
DB07394 AUROVERTIN B
DB08399 PICEATANNOL
DB04216 Quercetin

Polymorphism and mutation databases

BioMutaiATP5A1
DMDMi114517

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 43Mitochondrion1 PublicationAdd BLAST43
ChainiPRO_000000242444 – 553ATP synthase subunit alpha, mitochondrialAdd BLAST510

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53PhosphoserineCombined sources1
Modified residuei65PhosphoserineCombined sources1
Modified residuei76Phosphoserine; alternateCombined sources1
Glycosylationi76O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei106PhosphoserineBy similarity1
Modified residuei123N6-acetyllysineBy similarity1
Modified residuei126N6-acetyllysineBy similarity1
Modified residuei132N6-acetyllysineBy similarity1
Modified residuei134PhosphothreonineBy similarity1
Modified residuei161N6-acetyllysine; alternateCombined sources1
Modified residuei161N6-succinyllysine; alternateBy similarity1
Modified residuei166PhosphoserineCombined sources1
Modified residuei167N6-acetyllysine; alternateBy similarity1
Modified residuei167N6-succinyllysine; alternateBy similarity1
Modified residuei184PhosphoserineCombined sources1
Modified residuei204Omega-N-methylarginineBy similarity1
Modified residuei230N6-acetyllysine; alternateBy similarity1
Modified residuei230N6-succinyllysine; alternateBy similarity1
Modified residuei239N6-acetyllysine; alternateBy similarity1
Modified residuei239N6-succinyllysine; alternateBy similarity1
Modified residuei240N6-acetyllysineBy similarity1
Modified residuei261N6-acetyllysine; alternateCombined sources1
Modified residuei261N6-succinyllysine; alternateBy similarity1
Modified residuei305N6-acetyllysine; alternateBy similarity1
Modified residuei305N6-succinyllysine; alternateBy similarity1
Modified residuei427N6-acetyllysine; alternateBy similarity1
Modified residuei427N6-succinyllysine; alternateBy similarity1
Modified residuei434N6-acetyllysineCombined sources1
Modified residuei498N6-acetyllysine; alternateCombined sources1
Modified residuei498N6-succinyllysine; alternateBy similarity1
Modified residuei506N6-acetyllysine; alternateCombined sources1
Modified residuei506N6-succinyllysine; alternateBy similarity1
Modified residuei531N6-acetyllysine; alternateBy similarity1
Modified residuei531N6-succinyllysine; alternateBy similarity1
Modified residuei539N6-acetyllysine; alternateCombined sources1
Modified residuei539N6-succinyllysine; alternateBy similarity1
Modified residuei541N6-acetyllysineBy similarity1

Post-translational modificationi

The N-terminus is blocked.
Acetylated on lysine residues. BLOC1S1 is required for acetylation.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

EPDiP25705
PaxDbiP25705
PeptideAtlasiP25705
PRIDEiP25705
ProteomicsDBi54283
TopDownProteomicsiP25705-1 [P25705-1]

2D gel databases

OGPiP25705
REPRODUCTION-2DPAGEiP25705
UCD-2DPAGEiP25705

PTM databases

iPTMnetiP25705
PhosphoSitePlusiP25705
SwissPalmiP25705

Miscellaneous databases

PMAP-CutDBiP25705

Expressioni

Tissue specificityi

Fetal lung, heart, liver, gut and kidney. Expressed at higher levels in the fetal brain, retina and spinal cord.1 Publication

Gene expression databases

BgeeiENSG00000152234
CleanExiHS_ATP5A1
ExpressionAtlasiP25705 baseline and differential
GenevisibleiP25705 HS

Organism-specific databases

HPAiCAB013067
HPA040622
HPA044202

Interactioni

Subunit structurei

F-type ATPases have 2 components, CF1 - the catalytic core - and CF0 - the membrane proton channel. CF1 has five subunits: alpha3, beta3, gamma1, delta1, epsilon1. CF0 has three main subunits: a, b and c. Interacts with ATPAF2 (PubMed:11410595). Interacts with HRG; the interaction occurs on the surface of T-cells and alters the cell morphology when associated with concanavalin (in vitro) (PubMed:19285951). Interacts with PLG (angiostatin peptide); the interaction inhibits most of the angiogenic properties of angiostatin (PubMed:10077593). Component of an ATP synthase complex composed of ATP5F1, ATP5MC1, ATP5F1E, ATP5H, ATP5ME, ATP5J, ATP5J2, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5O, ATP5L, USMG5 and MP68. Interacts with BLOC1S1 (PubMed:22309213). Interacts with BCL2L1 isoform BCL-X(L); the interaction mediates the association of BCL2L1 isoform BCL-X(L) with the mitochondrial membrane F1F0 ATP synthase and enhances neurons metabolic efficency. Interacts with CLN5 and PPT1 (By similarity).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • angiostatin binding Source: CAFA
  • MHC class I protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106987, 186 interactors
CORUMiP25705
DIPiDIP-32871N
IntActiP25705, 73 interactors
MINTiP25705
STRINGi9606.ENSP00000282050

Structurei

3D structure databases

ProteinModelPortaliP25705
SMRiP25705
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ATPase alpha/beta chains family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1353 Eukaryota
COG0056 LUCA
GeneTreeiENSGT00550000074846
HOVERGENiHBG001536
InParanoidiP25705
KOiK02132
OMAiGNAQIKS
OrthoDBiEOG091G0D1M
PhylomeDBiP25705
TreeFamiTF300321

Family and domain databases

CDDicd01132 F1_ATPase_alpha, 1 hit
Gene3Di1.20.150.20, 1 hit
2.40.30.20, 1 hit
HAMAPiMF_01346 ATP_synth_alpha_bact, 1 hit
InterProiView protein in InterPro
IPR023366 ATP_synth_asu-like_sf
IPR000793 ATP_synth_asu_C
IPR038376 ATP_synth_asu_C_sf
IPR033732 ATP_synth_F1_a
IPR005294 ATP_synth_F1_asu
IPR020003 ATPase_a/bsu_AS
IPR004100 ATPase_F1/V1/A1_a/bsu_N
IPR036121 ATPase_F1/V1/A1_a/bsu_N_sf
IPR000194 ATPase_F1/V1/A1_a/bsu_nucl-bd
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF00006 ATP-synt_ab, 1 hit
PF00306 ATP-synt_ab_C, 1 hit
PF02874 ATP-synt_ab_N, 1 hit
PIRSFiPIRSF039088 F_ATPase_subunit_alpha, 1 hit
SUPFAMiSSF50615 SSF50615, 1 hit
SSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR00962 atpA, 1 hit
PROSITEiView protein in PROSITE
PS00152 ATPASE_ALPHA_BETA, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P25705-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLSVRVAAAV VRALPRRAGL VSRNALGSSF IAARNFHASN THLQKTGTAE
60 70 80 90 100
MSSILEERIL GADTSVDLEE TGRVLSIGDG IARVHGLRNV QAEEMVEFSS
110 120 130 140 150
GLKGMSLNLE PDNVGVVVFG NDKLIKEGDI VKRTGAIVDV PVGEELLGRV
160 170 180 190 200
VDALGNAIDG KGPIGSKTRR RVGLKAPGII PRISVREPMQ TGIKAVDSLV
210 220 230 240 250
PIGRGQRELI IGDRQTGKTS IAIDTIINQK RFNDGSDEKK KLYCIYVAIG
260 270 280 290 300
QKRSTVAQLV KRLTDADAMK YTIVVSATAS DAAPLQYLAP YSGCSMGEYF
310 320 330 340 350
RDNGKHALII YDDLSKQAVA YRQMSLLLRR PPGREAYPGD VFYLHSRLLE
360 370 380 390 400
RAAKMNDAFG GGSLTALPVI ETQAGDVSAY IPTNVISITD GQIFLETELF
410 420 430 440 450
YKGIRPAINV GLSVSRVGSA AQTRAMKQVA GTMKLELAQY REVAAFAQFG
460 470 480 490 500
SDLDAATQQL LSRGVRLTEL LKQGQYSPMA IEEQVAVIYA GVRGYLDKLE
510 520 530 540 550
PSKITKFENA FLSHVVSQHQ ALLGTIRADG KISEQSDAKL KEIVTNFLAG

FEA
Length:553
Mass (Da):59,751
Last modified:May 1, 1992 - v1
Checksum:iAA47BBB8EDA77EAC
GO
Isoform 2 (identifier: P25705-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Show »
Length:503
Mass (Da):54,494
Checksum:i03AE2040A4C147EA
GO
Isoform 3 (identifier: P25705-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     140-161: Missing.

Note: No experimental confirmation available.
Show »
Length:531
Mass (Da):57,547
Checksum:i616061583D30DF52
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162G → V in BAG63618 (PubMed:14702039).Curated1
Sequence conflicti183I → T in BAG63618 (PubMed:14702039).Curated1
Sequence conflicti329R → L in AAH39135 (PubMed:14702039).Curated1
Sequence conflicti356N → D in BAG63618 (PubMed:14702039).Curated1
Sequence conflicti510A → D in AAH11384 (PubMed:14702039).Curated1
Sequence conflicti529D → E in AAH11384 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04836932A → S. Corresponds to variant dbSNP:rs2228437Ensembl.1
Natural variantiVAR_071982321Y → C in COXPD22. 1 PublicationCorresponds to variant dbSNP:rs587777788EnsemblClinVar.1
Natural variantiVAR_069769329R → C in MC5DN4. 1 PublicationCorresponds to variant dbSNP:rs587776960EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0451291 – 50Missing in isoform 2. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_054688140 – 161Missing in isoform 3. 1 PublicationAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59066 mRNA Translation: CAA41789.1
X65460 mRNA Translation: CAA46452.1
D14710 mRNA Translation: BAA03531.1
D28126 Genomic DNA Translation: BAA05672.1
BT007209 mRNA Translation: AAP35873.1
AK092735 mRNA Translation: BAG52604.1
AK289457 mRNA Translation: BAF82146.1
AK302272 mRNA Translation: BAG63618.1
AC012569 Genomic DNA No translation available.
BC003119 mRNA Translation: AAH03119.1
BC007299 mRNA Translation: AAH07299.1
BC008028 mRNA Translation: AAH08028.2
BC011384 mRNA Translation: AAH11384.1
BC016046 mRNA Translation: AAH16046.1
BC019310 mRNA Translation: AAH19310.1
BC039135 mRNA Translation: AAH39135.2
BC064562 mRNA Translation: AAH64562.1
BC067385 mRNA Translation: AAH67385.1
CCDSiCCDS11927.1 [P25705-1]
CCDS58620.1 [P25705-2]
CCDS59315.1 [P25705-3]
PIRiS17193 PWHUA
RefSeqiNP_001001935.1, NM_001001935.2 [P25705-2]
NP_001001937.1, NM_001001937.1 [P25705-1]
NP_001244263.1, NM_001257334.1 [P25705-3]
NP_001244264.1, NM_001257335.1 [P25705-2]
NP_004037.1, NM_004046.5 [P25705-1]
UniGeneiHs.298280

Genome annotation databases

EnsembliENST00000282050; ENSP00000282050; ENSG00000152234 [P25705-1]
ENST00000398752; ENSP00000381736; ENSG00000152234 [P25705-1]
ENST00000590665; ENSP00000467037; ENSG00000152234 [P25705-3]
ENST00000593152; ENSP00000465477; ENSG00000152234 [P25705-2]
GeneIDi498
KEGGihsa:498
UCSCiuc010dnl.2 human [P25705-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiATPA_HUMAN
AccessioniPrimary (citable) accession number: P25705
Secondary accession number(s): A8K092
, B4DY56, K7ENP3, Q53XX6, Q8IXV2, Q96FB4, Q96HW2, Q96IR6, Q9BTV8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: July 18, 2018
This is version 218 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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