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 HomoloGene: 128187 GeneCards: ATP5F1E
Gene location (Human) Chr. Chromosome 20 (human) Band 20q13.32 Start 59,025,475 bp End 59,032,345 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla optic nerve trabecular bone superior surface of tongue pylorus external globus pallidus cardia vena cava pons superior vestibular nucleus n/a 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 n/a Ensembl ENSG00000124172 n/a UniProt P56381 n/a RefSeq (mRNA) NM_006886 n/a RefSeq (protein) NP_008817 n/a Location (UCSC) Chr 20: 59.03 – 59.03 Mb n/a PubMed search n/a
Wikidata
View/Edit Human

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. 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.

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. The ATP5F1E protein weighs 5.7 kDa and is composed of 51 amino acids. Two pseudogenes of this gene are located on chromosomes 4 and 13.

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.

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).

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.

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. 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.

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. Papillary Thyroid Cancer is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. 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.

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.

Further reading

• Viñas O, Powell SJ, Runswick MJ, Iacobazzi V, Walker JE (January 1990). "The epsilon-subunit of ATP synthase from bovine heart mitochondria. Complementary DNA sequence, expression in bovine tissues and evidence of homologous sequences in man and rat". The Biochemical Journal. 265 (2): 321–6. doi:10.1042/bj2650321. PMC 1136890. PMID 2137333.
• Elston T, Wang H, Oster G (January 1998). "Energy transduction in ATP synthase". Nature. 391 (6666): 510–3. Bibcode:1998Natur.391..510E. doi:10.1038/35185. PMID 9461222. S2CID 4406161.
• 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. PMID 9834036. S2CID 4424498.
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (August 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9543–8. Bibcode:2000PNAS...97.9543H. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Gross C, Kussmann S, Hehr A, Hansmann I, Schlote D (2001). "Epsilon subunit gene of F(1)F(0)-ATP synthase (ATP5E) on human chromosome 20q13.2-->q13.3 localizes between D20S171 and GNAS1". Cytogenetics and Cell Genetics. 91 (1–4): 105–6. doi:10.1159/000056828. PMID 11173840. S2CID 19946536.
• Cross RL (January 2004). "Molecular motors: turning the ATP motor". Nature. 427 (6973): 407–8. Bibcode:2004Natur.427..407C. doi:10.1038/427407b. PMID 14749816. S2CID 52819856.

External links

• 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, which is in the public domain.

This article incorporates text from the public domain Pfam and InterPro: IPR006721