ATP5E

Last updated
ATP5F1E
Protein ATP5E PDB 1e79.png
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
Orthologs
SpeciesHumanMouse
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
View/Edit Human View/Edit Mouse
Mitochondrial ATP synthase epsilon chain
PDB 2jdi EBI.jpg
ground state structure of f1-atpase from bovine heart mitochondria (bovine f1-atpase crystallised in the absence of azide)
Identifiers
SymbolATP-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]

Contents

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 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, Fo, 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 (F1Fo 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 Fo, 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]

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]

Related Research Articles

<span class="mw-page-title-main">ATPase</span> Dephosphorylation enzyme

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.

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

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

<span class="mw-page-title-main">MT-ATP8</span> Mitochondrial protein-coding gene whose product is involved in ATP synthesis

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 Fo subunit 8. This subunit belongs to the Fo 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.

<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.

<span class="mw-page-title-main">ATP5B</span> Protein-coding gene in humans

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

<span class="mw-page-title-main">ATP5F1A</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5PF</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5G1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5J2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">ATP synthase delta/OSCP subunit</span> Subunit of bacterial and chloroplast F-ATPase/synthase

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

<span class="mw-page-title-main">ATP5L</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5C1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5F1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5S</span> Protein-coding gene in the species Homo sapiens

ATP synthase subunit s, mitochondrial is an enzyme that in humans is encoded by the ATP5S gene.

<span class="mw-page-title-main">ATP5G2</span> Protein-coding gene in humans

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

<span class="mw-page-title-main">ATP5I</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5H</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">ATP5D</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">ATP5G3</span> Protein-coding gene in the species Homo sapiens

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000124172 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000016252 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ 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.
  6. 1 2 3 4 "Entrez Gene: ATP5F1E ATP synthase F1 subunit epsilon".
  7. 1 2 "ATP5F1E". Genetics Home Resource. NCBI.
  8. 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.
  9. ↑ 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.
  10. ↑ "ATP synthase subunit epsilon, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).[ permanent dead link ]
  11. ↑ "ATP synthase subunit epsilon, mitochondrial". UniProt. The UniProt Consortium. Creative Commons by small.svg  This article incorporates textfrom this source, which is available under the CC BY 4.0 license.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ "34 binary interactions found for search term ATP5F1E". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-11-21.

Further reading

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
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