ATP5E

ATP5F1E
Identifiers
Aliases	ATP5F1E, ATPE, MC5DN3, ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit, ATP synthase F1 subunit epsilon, ATP5E
External IDs	OMIM: 606153; MGI: 1855697; HomoloGene: 128187; GeneCards: ATP5F1E; OMA:ATP5F1E - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.32 Start 59,025,475 bp[1] End 59,032,345 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 H4 Start 174,302,865 bp[2] End 174,305,898 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla optic nerve pars reticulata trabecular bone superior surface of tongue pars compacta pylorus lateral nuclear group of thalamus external globus pallidus skin of hip Top expressed in muscle of thigh right kidney sternocleidomastoid muscle digastric muscle temporal muscle intercostal muscle medial head of gastrocnemius muscle triceps brachii muscle atrioventricular valve lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function hydrolase activity transmembrane transporter activity proton-transporting ATP synthase activity, rotational mechanism ATPase activity Cellular component membrane mitochondrial proton-transporting ATP synthase complex, catalytic sector F(1) proton-transporting ATP synthase complex, catalytic core F(1) mitochondrial matrix mitochondrion mitochondrial inner membrane mitochondrial proton-transporting ATP synthase complex Biological process ion transport ATP synthesis coupled proton transport mitochondrial ATP synthesis coupled proton transport ATP biosynthetic process cristae formation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 514 67126 Ensembl ENSG00000124172 ENSMUSG00000016252 UniProt P56381 P56382 RefSeq (mRNA) NM_006886 NM_025983 RefSeq (protein) NP_008817 NP_080259 Location (UCSC) Chr 20: 59.03 – 59.03 Mb Chr 2: 174.3 – 174.31 Mb PubMed search [3] [4]
Wikidata
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Mitochondrial ATP synthase epsilon chain
ground state structure of f1-atpase from bovine heart mitochondria (bovine f1-atpase crystallised in the absence of azide)
Identifiers
Symbol	ATP-synt_Eps
Pfam	PF04627
InterPro	IPR006721
SCOP2	1e79 / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

ATP synthase F1 subunit epsilon, mitochondrial is an enzyme that in humans is encoded by the ATP5F1E gene.^[5][6] The protein encoded by ATP5F1E is a subunit of ATP synthase, also known as Complex V. Variations of this gene have been associated with a condition called mitochondrial complex V deficiency, nuclear 3 (MC5DN3) and papillary thyroid cancer.^[7][8]

The ATP5F1E gene, located on the q arm of chromosome 20 in position 13.32, is made up of 3 exons and is 3,690 base pairs in length.^[6] The ATP5F1E protein weighs 5.7 kDa and is composed of 51 amino acids.^[9][10] Two pseudogenes of this gene are located on chromosomes 4 and 13.^[6]

ATP5F1E is located on the rotating central stalk of ATP synthase, and can be contracted or extended. When it is contracted, it inhibits the ATP synthase active site, preventing ATP from being produced or degraded. It changes shape based on the rotation of the gamma subunit of the stalk, and is also thought to become extended in the presence of ADP, acting as a "safety lock" preventing the wasteful degradation of ATP.

This gene is named for the subunit it encodes of the version of ATP synthase found in mitochondria. Mitochondrial ATP synthase catalyzes ATP synthesis through the difference in protein concentrations across a cellular membrane. ATP synthase is composed of two linked multi-subunit complexes, each composed of multiple proteins: the water-soluble catalytic core, F₁, and the membrane-spanning component, F_o, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different kinds of subunits (alpha, beta, gamma, delta, and epsilon), each catalytic core containing 3 alpha, 3 beta, one gamma, one delta, and one epsilon. This gene encodes the epsilon subunit of the catalytic core.^[6]

Mitochondrial membrane ATP synthase (F₁F_o ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient (difference in proton concentration) across the membrane generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains or parts: F₁, which contains the catalytic core outside of the membrane; and F_o, which contains the proton channel reaching across the membrane; both linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the active site of F₁ is coupled, through a mechanism involving the rotation of the central stalk, to the motion of protons across the membrane. ATP5F1E is part of the F₁ domain, and more specifically part of the rotating central stalk. Rotation of the central stalk against the surrounding alpha₃beta₃ subunits, leads to the hydrolysis of ATP in three separate catalytic sites on the beta subunits (By similarity).^{[11][clarification needed]}

Being located in the stalk region of the F₁ complex, the epsilon unit acts as an inhibitor of the active site of the ATPase. The epsilon subunit can assume two conformations, or shapes: contracted and extended. The latter inhibits ATP hydrolysis, while the former does not. The conformation of the epsilon subunit is determined by the direction of rotation of the gamma subunit of the ATPase, and possibly by the presence of ADP. The epsilon subunit is thought to become extended in the presence of ADP, thereby acting as a safety lock to prevent the wasteful degradation of ATP to ADP through hydrolysis.^[12]

Mutations in the ATP5F1E gene cause mitochondrial complex V deficiency, nuclear 3 (MC5DN3), a 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.^[7] Pathogenic variations have included a homozygous Tyr12Cys mutation in the ATP5E gene, which has been linked with neonatal onset complex V deficiency with lactic acidosis, 3-methylglutaconic aciduria, mild mental retardation and developed peripheral neuropathy.^[13]

Reduced expression of ATP5F1E is significantly associated with the diagnosis of papillary thyroid cancer and may serve as an early tumor marker of the disease.^[8] Papillary thyroid cancer is the most common type of thyroid cancer,^[14] representing 75 percent to 85 percent of all thyroid cancer cases.^[15] It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck.^[16]

ATP5F1E has been shown to have 34 binary protein-protein interactions including 28 co-complex interactions. ATP5F1E appears to interact with ATP5F1D, AGTRAP, CYP17A1, UBE2N.^[17]

• Human ATP5F1E genome location and ATP5F1E gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine ([1]), which is in the public domain.