ATP5E

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Mitochondrial ATP synthase epsilon chain
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
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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)
End	59,032,345 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	174,305,898 bp
RNA expression pattern
	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
	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
	514
	67126
	ENSG00000124172
	ENSMUSG00000016252
	P56381
	P56382
	NM_006886
	NM_025983
	NP_008817
	NP_080259
	Wikidata
View/Edit Human	View/Edit Mouse

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]

Naming

This gene encodes a subunit of the version of ATP synthase found in mitochondria. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing 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, 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]

Function

Mitochondrial membrane ATP synthase (F₁F_o 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 F_o - 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. 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 surrounding alpha₃beta₃ subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits (By similarity).^[11]

The epsilon subunit is located in the stalk region of the F₁ complex, and acts as an inhibitor of the ATPase catalytic core. The epsilon subunit can assume two conformations, contracted and extended, where the latter inhibits ATP hydrolysis. The conformation of the epsilon subunit is determined by the direction of rotation of the gamma subunit, 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 wasteful ATP hydrolysis.^[12]

Clinical significance

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]

Interactions

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]