ATP5F1A

Protein identityUniProt · HPA

UniProt accession

P25705

Gene

ATP5F1A

Ensembl

ENSG00000152234

Chromosome

18

Canonical length

553 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Transporters

Subcellular location

Mitochondria,End piece

Quaternary structure

Homooctamer

OverviewNCBI Gene

This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the different isoforms have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16. [provided by RefSeq, Mar 2012]

Canonical amino-acid sequenceUniProt

553 residues, UniProt reviewed canonical sequence.

>P25705|ATP5F1A
     1  MLSVRVAAAV VRALPRRAGL VSRNALGSSF IAARNFHASN THLQKTGTAE MSSILEERIL
    61  GADTSVDLEE TGRVLSIGDG IARVHGLRNV QAEEMVEFSS GLKGMSLNLE PDNVGVVVFG
   121  NDKLIKEGDI VKRTGAIVDV PVGEELLGRV VDALGNAIDG KGPIGSKTRR RVGLKAPGII
   181  PRISVREPMQ TGIKAVDSLV PIGRGQRELI IGDRQTGKTS IAIDTIINQK RFNDGSDEKK
   241  KLYCIYVAIG QKRSTVAQLV KRLTDADAMK YTIVVSATAS DAAPLQYLAP YSGCSMGEYF
   301  RDNGKHALII YDDLSKQAVA YRQMSLLLRR PPGREAYPGD VFYLHSRLLE RAAKMNDAFG
   361  GGSLTALPVI ETQAGDVSAY IPTNVISITD GQIFLETELF YKGIRPAINV GLSVSRVGSA
   421  AQTRAMKQVA GTMKLELAQY REVAAFAQFG SDLDAATQQL LSRGVRLTEL LKQGQYSPMA
   481  IEEQVAVIYA GVRGYLDKLE PSKITKFENA FLSHVVSQHQ ALLGTIRADG KISEQSDAKL
   541  KEIVTNFLAG FEA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP5F1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

1,644 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP5F1A.

Disease | AllUniProt

Conditions ATP5F1A is implicated in, by any mechanism.

• Combined oxidative phosphorylation deficiency 22 (COXPD22) MIM:616045
• Mitochondrial complex V deficiency, nuclear type 4A (MC5DN4A) MIM:620358
• Mitochondrial complex V deficiency, nuclear type 4B (MC5DN4B) MIM:615228

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 314 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Combined oxidative phosphorylation deficiency 22
• Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A
• Lactic acidosis
• ATP5F1A-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.18

gnomAD pLI

1

DepMap mean gene effect

-0.67

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATP biosynthetic process
• cellular response to dexamethasone stimulus
• cellular response to nitric oxide
• lipid metabolic process
• negative regulation of endothelial cell proliferation
• positive regulation of blood vessel endothelial cell migration
• proton motive force-driven ATP synthesis
• proton motive force-driven mitochondrial ATP synthesis
• response to ethanol
• response to muscle activity

Molecular functions

• ADP binding
• angiostatin binding
• ATP binding
• ATP hydrolysis activity
• MHC class I protein binding
• protease binding
• proton-transporting ATP synthase activity, rotational mechanism
• RNA binding

Cellular components

• cell surface
• extracellular exosome
• membrane
• membrane raft
• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion
• plasma membrane
• proton-transporting ATP synthase complex
• sperm end piece

Protein domainsUniProt · Pfam · InterPro

• ATPase, F1/V1/A1 complex, alpha/beta subunit, nucleotide-binding domain
• ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain
• ATPase, alpha/beta subunit, nucleotide-binding domain, active site
• ATP synthase subunit alpha, N-terminal domain-like superfamily
• P-loop containing nucleoside triphosphate hydrolase
• ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain superfamily
• ATP synthase alpha/beta family, nucleotide-binding domain
• ATP synthase alpha/beta family, beta-barrel domain
• ATP synthase, alpha subunit, C-terminal
• ATP synthase, F1 complex, alpha subunit
• ATP synthase, F1 complex, alpha subunit nucleotide-binding domain
• ATP synthase, alpha subunit, C-terminal domain superfamily
• ATP synthase alpha/beta chain, C terminal domain

KeywordsUniProt

• Acetylation
• ATP synthesis
• ATP-binding
• Cell membrane
• CF(1)
• Glycoprotein
• Hydrogen ion transport
• Ion transport
• Membrane
• Methylation
• Mitochondrion
• Mitochondrion inner membrane
• Nucleotide-binding
• Phosphoprotein
• Primary mitochondrial disease
• Transit peptide
• Translocase
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP5F1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ABCB7
• ATPAF2
• BLOC1S1
• CLN5
• HRG
• PLG
• PPT1
• S100A1
• BCL2L1
• ATP5F1B
• ATP5IF1
• ATP5PB
• ATP5PF
• ATP5PO
• PHGDH
• SIRT3
• YWHAZ