ATP5D

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ATP5F1D
Protein ATP5D PDB 1e79.png
Identifiers
Aliases ATP5F1D , ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit, ATP synthase F1 subunit delta, ATP5D, MC5DN5
External IDs OMIM: 603150 MGI: 1913293 HomoloGene: 37514 GeneCards: ATP5F1D
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001687
NM_001001975

NM_025313
NM_001347092

RefSeq (protein)

NP_001001975
NP_001678

NP_001334021
NP_079589

Location (UCSC) Chr 19: 1.24 – 1.24 Mb Chr 10: 80.14 – 80.15 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 (formerly ATP5D) gene. [5] [6] [7] 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. [8]

Contents

Structure

The ATP5F1D gene is located on the p arm of chromosome 19 at position 13.3 and it spans 3,075 base pairs. [8] The ATP5F1D gene produces a 17.5 kDa protein composed of 168 amino acids. [9] [10] The coded protein is a subunit of the mitochondrial ATP synthase (Complex V), which is composed of two linked multi-subunit complexes: the 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 subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the delta subunit of the catalytic core. Alternatively spliced transcript variants encoding the same isoform have been identified. [8] The structure of the protein has been known to resemble a 'lollipop' structure due to the attachment of the F1 catalytic unit to the mitochondrial inner membrane by the F0 unit. [11]

Function

This gene encodes a subunit of the mitochondrial ATP synthase (Complex V) of the mitochondrial respiratory chain, which is necessary for the catalysis of ATP synthesis. Utilizing an electrochemical gradient of protons produced by electron transport complexes of the respiratory chain, the synthase converts ADP into ATP across the inner membrane during oxidative phosphorylation. [8] F-type ATPases consist of two structural domains, F1 and F0, that contribute to catalysis. The F1 domain contains an extramembranous catalytic core and the F0 domain contains the membrane proton channel linked by a central and a peripheral stalk. During catalysis, ATP turnover in the catalytic domain of F1 is coupled by a rotary mechanism of the central stalk subunits to proton transport. The encoded protein is a 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 the hydrolysis of ATP in three separate catalytic sites on the beta subunits. [5] [6]

Clinical significance

Mutations of ATP5F1D have been associated with childhood mitochondrial disorders with phenotypes such as episodic decompensations, lactic acidosis, and hyperammonemia accompanied by ketoacidosis or hypoglycemia. Biallelic mutations of c.245C>T and c.317T>G in ATP5F1D were shown to cause a metabolic disorder with such phenotypes due to mitochondrial dysfunction in two unrelated individuals. [12] Mutations of ATP5F1D with decreased expression of the protein have also been found to result in synaptic dysfunction of the mitochondria that could play an essential role in amyotrophic lateral sclerosis (ALS) pathogenesis. [13]

Interactions

Among the two components, CF1 - the catalytic core - and CF0 - the membrane proton channel of the F-type ATPase, ATP5F1D is associated with the catalytic core. The catalytic core is composed of five different subunits including alpha, beta, gamma, delta, and epsilon subunits. The protein has additional interactions with ATP5I, ATP5O, PUS1, NDUFB5, GTPBP6, ATP5L, ATP5J and others. [14] [5] [6]

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">F-ATPase</span> Membrane protein

F-ATPase, also known as F-Type ATPase, is an ATPase/synthase found in bacterial plasma membranes, in mitochondrial inner membranes, and in chloroplast thylakoid membranes. It uses a proton gradient to drive ATP synthesis by allowing the passive flux of protons across the membrane down their electrochemical gradient and using the energy released by the transport reaction to release newly formed ATP from the active site of F-ATPase. Together with V-ATPases and A-ATPases, F-ATPases belong to superfamily of related rotary ATPases.

<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">MT-ATP6</span> Mitochondrial protein-coding gene whose product is involved in ATP synthesis

MT-ATP6 is a mitochondrial gene with the full name 'mitochondrially encoded ATP synthase membrane subunit 6' that encodes the ATP synthase Fo subunit 6. 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. 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">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">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">ATP5E</span> Protein-coding gene in the species Homo sapiens

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 mitochondrial complex V deficiency, nuclear 3 (MC5DN3) and Papillary Thyroid Cancer.

<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.

In molecular biology, ATP10 protein (mitochondrial ATPase complex subunit ATP10) is an ATP synthase assembly factor. It is essential for the assembly of the mitochondrial F1-F0 complex. A yeast nuclear gene (ATP10) encodes a product that is essential for the assembly of a functional mitochondrial ATPase complex. Mutations in ATP10 induce a loss of rutamycin sensitivity in the mitochondrial ATPase, but do not affect the respiratory enzymes. ATP10 has a molecular weight of 30,293 Da and its primary structure is not related to any known subunit of the yeast or mammalian mitochondrial ATPase complexes. ATP10 is associated with the mitochondrial membrane. It is suggested that the ATP10 product is not a subunit of the ATPase complex but rather a protein required for the assembly of the F0 sector of the complex.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000099624 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000003072 - 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. 1 2 3 "ATP5F1D - ATP synthase subunit delta, mitochondrial precursor - Homo sapiens (Human) - ATP5F1D gene & protein" . Retrieved 2018-08-07. Creative Commons by small.svg  This article incorporates text available under the CC BY 4.0 license.
  6. 1 2 3 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC   5210571 . PMID   27899622.
  7. Jordan EM, Breen GA (February 1992). "Molecular cloning of an import precursor of the delta-subunit of the human mitochondrial ATP synthase complex". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1130 (1): 123–6. doi:10.1016/0167-4781(92)90477-h. PMID   1531933.
  8. 1 2 3 4 "Entrez Gene: ATP5D ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit".PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (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 delta, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).[ permanent dead link ]
  11. Walker JE (May 1995). "Determination of the structures of respiratory enzyme complexes from mammalian mitochondria". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1271 (1): 221–7. doi: 10.1016/0925-4439(95)00031-x . PMID   7599212.
  12. Oláhová M, Yoon WH, Thompson K, Jangam S, Fernandez L, Davidson JM, et al. (March 2018). "Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder". American Journal of Human Genetics. 102 (3): 494–504. doi:10.1016/j.ajhg.2018.01.020. PMC   6117612 . PMID   29478781.
  13. Engelen-Lee J, Blokhuis AM, Spliet WG, Pasterkamp RJ, Aronica E, Demmers JA, et al. (May 2017). "Proteomic profiling of the spinal cord in ALS: decreased ATP5D levels suggest synaptic dysfunction in ALS pathogenesis" (PDF). Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 18 (3–4): 210–220. doi: 10.1080/21678421.2016.1245757 . PMID   27899032.
  14. Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I, Sasarman F, Weraarpachai W, Shoubridge EA, Warscheid B, Rehling P (2012). "MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation". Cell. 151 (7): 1528–41. doi: 10.1016/j.cell.2012.11.053 . hdl: 11858/00-001M-0000-000E-DDDF-4 . PMID   23260140.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.