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 HomoloGene: 128187 GeneCards: ATP5F1E
Gene location (Human)
Chr.	Chromosome 20 (human)
End	59,032,345 bp
RNA expression pattern
	Top expressed in
	renal medulla; ; optic nerve; ; spongy bone; ; superior surface of tongue; ; pylorus; ; external globus pallidus; ; cardia; ; vena cava; ; pons; ; superior vestibular nucleus;
	n/a
	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
	n/a
	ENSG00000124172
	n/a
	P56381
	n/a
	NM_006886
	n/a
	NP_008817
	n/a
	Wikidata
View/Edit Human

ATP synthase F1 subunit epsilon, mitochondrial is an enzyme that in humans is encoded by the ATP5F1E gene.^[3]^[4] 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.^[5]^[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.^[4]

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).^[9]

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.^[10]

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.^[5] 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.^[11]

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.^[6] Papillary Thyroid Cancer is the most common type of thyroid cancer,^[12] representing 75 percent to 85 percent of all thyroid cancer cases.^[13] 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.^[14]

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.^[15]

Related Research Articles

ATPases (EC 3.6.1.3, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca²⁺ + Mg²⁺)-ATPase, HCO₃⁻-ATPase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or the inverse reaction. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.

ATP synthase is an enzyme that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (P_i). ATP synthase is a molecular machine. The overall reaction catalyzed by ATP synthase is:

MT-ATP8 is a mitochondrial gene with the full name 'mitochondrially encoded ATP synthase membrane subunit 8' that encodes a subunit of mitochondrial ATP synthase, ATP synthase F_o subunit 8. This subunit belongs to the F_o complex of the large, transmembrane F-type ATP synthase. This enzyme, which is also known as complex V, is responsible for the final step of oxidative phosphorylation in the electron transport chain. Specifically, one segment of ATP synthase allows positively charged ions, called protons, to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to ATP. Subunit 8 differs in sequence between Metazoa, plants and Fungi.

MT-ATP6 is a mitochondrial gene with the full name 'mitochondrially encoded ATP synthase membrane subunit 6' that encodes the ATP synthase F_o subunit 6. This subunit belongs to the F_o complex of the large, transmembrane F-type ATP synthase. This enzyme, which is also known as complex V, is responsible for the final step of oxidative phosphorylation in the electron transport chain. Specifically, one segment of ATP synthase allows positively charged ions, called protons, to flow across a specialized membrane inside mitochondria. Another segment of the enzyme uses the energy created by this proton flow to convert a molecule called adenosine diphosphate (ADP) to ATP. Mutations in the MT-ATP6 gene have been found in approximately 10 to 20 percent of people with Leigh syndrome.

<span class="mw-page-title-main">ATP synthase subunit C</span>

ATPase, subunit C of Fo/Vo complex is the main transmembrane subunit of V-type, A-type and F-type ATP synthases. Subunit C was found in the Fo or Vo complex of F- and V-ATPases, respectively. The subunits form an oligomeric c ring that make up the Fo/Vo/Ao rotor, where the actual number of subunits vary greatly among specific enzymes.

ATP synthase F1 subunit beta, mitochondrial is an enzyme that in humans is encoded by the ATP5F1B gene.

ATP synthase F1 subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5F1A gene.

ATP synthase-coupling factor 6, mitochondrial is an enzyme subunit that in humans is encoded by the ATP5PF gene.

The ATP5MC1 gene is one of three human paralogs that encode membrane subunit c of the mitochondrial ATP synthase.

The ATP5MF gene encodes the ATP synthase subunit f, mitochondrial enzyme in humans.

<span class="mw-page-title-main">ATP synthase alpha/beta subunits</span>

The alpha and beta subunits are found in the F1, V1, and A1 complexes of F-, V- and A-ATPases, respectively, as well as flagellar (T3SS) ATPase and the termination factor Rho. The subunits make up a ring that contains the ATP-hydrolyzing catalytic core. The F-ATPases, V-ATPases and A-ATPases are composed of two linked complexes: the F1, V1 or A1 complex containsthat synthesizes/hydrolyses ATP, and the Fo, Vo or Ao complex that forms the membrane-spanning pore. The F-, V- and A-ATPases all contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis.

ATP synthase delta subunit is a subunit of bacterial and chloroplast F-ATPase/synthase. It is known as OSCP in mitochondrial ATPase.

ATP synthase subunit g, mitochondrial is an enzyme that in humans is encoded by the ATP5MG gene.

The human ATP5F1C gene encodes the gamma subunit of an enzyme called mitochondrial ATP synthase.

ATP synthase subunit b, mitochondrial is an enzyme that in humans is encoded by the ATP5PB gene.

The ATP5MC2 gene is one of three human paralogs that encode membrane subunit c of the mitochondrial ATP synthase.

ATP synthase subunit e, mitochondrial is an enzyme that in humans is encoded by the ATP5ME gene.

The human gene ATP5PD encodes subunit d of the peripheral stalk part of the enzyme mitochondrial ATP synthase.

ATP synthase subunit delta, mitochondrial, also known as ATP synthase F1 subunit delta or F-ATPase delta subunit is an enzyme that in humans is encoded by the ATP5F1D gene. This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation.

The ATP5MC3 gene is one of three human paralogs that encode membrane subunit c of the mitochondrial ATP synthase.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000124172 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Tu Q, Yu L, Zhang P, Zhang M, Zhang H, Jiang J, Chen C, Zhao S (April 2000). "Cloning, characterization and mapping of the human ATP5E gene, identification of pseudogene ATP5EP1, and definition of the ATP5E motif". The Biochemical Journal. 347 (1): 17–21. doi:10.1042/0264-6021:3470017. PMC 1220925 . PMID 10727396.
1 2 3 4 "Entrez Gene: ATP5F1E ATP synthase F1 subunit epsilon".
1 2 "ATP5F1E". Genetics Home Resource. NCBI.
1 2 Hurtado-López LM, Fernández-Ramírez F, Martínez-Peñafiel E, Carrillo Ruiz JD, Herrera González NE (June 2015). "Molecular Analysis by Gene Expression of Mitochondrial ATPase Subunits in Papillary Thyroid Cancer: Is ATP5E Transcript a Possible Early Tumor Marker?". Medical Science Monitor. 21: 1745–51. doi:10.12659/MSM.893597. PMC 4482184 . PMID 26079849.
↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475 . PMID 23965338.
↑ "ATP synthase subunit epsilon, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).^{[ permanent dead link ]}
↑ "ATP synthase subunit epsilon, mitochondrial". UniProt. The UniProt Consortium.
↑ Feniouk BA, Junge W (September 2005). "Regulation of the F0F1-ATP synthase: the conformation of subunit epsilon might be determined by directionality of subunit gamma rotation". FEBS Letters. 579 (23): 5114–8. doi: 10.1016/j.febslet.2005.08.030 . PMID 16154570. S2CID 84231010.
↑ Mayr JA, Havlícková V, Zimmermann F, Magler I, Kaplanová V, Jesina P, Pecinová A, Nusková H, Koch J, Sperl W, Houstek J (September 2010). "Mitochondrial ATP synthase deficiency due to a mutation in the ATP5E gene for the F1 epsilon subunit". Human Molecular Genetics. 19 (17): 3430–9. doi: 10.1093/hmg/ddq254 . PMID 20566710.
↑ Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP "Thyroid and Parathyroid Cancers" Archived 2010-02-28 at the Wayback Machine in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach Archived 2013-10-04 at the Wayback Machine . 11 ed. 2008.
↑ Chapter 20 in: Mitchell, Richard Sheppard, Kumar, Vinay, Abbas, Abul K, Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.
↑ Dinets A, Hulchiy M, Sofiadis A, Ghaderi M, Höög A, Larsson C, Zedenius J (June 2012). "Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma". European Journal of Endocrinology. 166 (6): 1049–60. doi:10.1530/EJE-12-0144. PMC 3361791 . PMID 22457234.
↑ "34 binary interactions found for search term ATP5F1E". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-11-21.

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

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000124172 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10727396-3] Tu Q, Yu L, Zhang P, Zhang M, Zhang H, Jiang J, Chen C, Zhao S (April 2000). "Cloning, characterization and mapping of the human ATP5E gene, identification of pseudogene ATP5EP1, and definition of the ATP5E motif". The Biochemical Journal. 347 (1): 17–21. doi:10.1042/0264-6021:3470017. PMC 1220925 . PMID 10727396.

[entrez-4] 1 2 3 4 "Entrez Gene: ATP5F1E ATP synthase F1 subunit epsilon".

[GHR-5] 1 2 "ATP5F1E". Genetics Home Resource. NCBI.

[:0-6] 1 2 Hurtado-López LM, Fernández-Ramírez F, Martínez-Peñafiel E, Carrillo Ruiz JD, Herrera González NE (June 2015). "Molecular Analysis by Gene Expression of Mitochondrial ATPase Subunits in Papillary Thyroid Cancer: Is ATP5E Transcript a Possible Early Tumor Marker?". Medical Science Monitor. 21: 1745–51. doi:10.12659/MSM.893597. PMC 4482184 . PMID 26079849.

[COPaKB-7] Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475 . PMID 23965338.

[url_COPaKB-8] "ATP synthase subunit epsilon, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).^{[ permanent dead link ]}

[uniprot-9] "ATP synthase subunit epsilon, mitochondrial". UniProt. The UniProt Consortium.

[pmid16154570-10] Feniouk BA, Junge W (September 2005). "Regulation of the F0F1-ATP synthase: the conformation of subunit epsilon might be determined by directionality of subunit gamma rotation". FEBS Letters. 579 (23): 5114–8. doi: 10.1016/j.febslet.2005.08.030 . PMID 16154570. S2CID 84231010.

[11] Mayr JA, Havlícková V, Zimmermann F, Magler I, Kaplanová V, Jesina P, Pecinová A, Nusková H, Koch J, Sperl W, Houstek J (September 2010). "Mitochondrial ATP synthase deficiency due to a mutation in the ATP5E gene for the F1 epsilon subunit". Human Molecular Genetics. 19 (17): 3430–9. doi: 10.1093/hmg/ddq254 . PMID 20566710.

[12] Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP "Thyroid and Parathyroid Cancers" Archived 2010-02-28 at the Wayback Machine in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach Archived 2013-10-04 at the Wayback Machine . 11 ed. 2008.

[Kumar20-13] Chapter 20 in: Mitchell, Richard Sheppard, Kumar, Vinay, Abbas, Abul K, Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. ISBN 978-1-4160-2973-1. 8th edition.

[Dinets-14] Dinets A, Hulchiy M, Sofiadis A, Ghaderi M, Höög A, Larsson C, Zedenius J (June 2012). "Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma". European Journal of Endocrinology. 166 (6): 1049–60. doi:10.1530/EJE-12-0144. PMC 3361791 . PMID 22457234.

[15] "34 binary interactions found for search term ATP5F1E". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-11-21.

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