ATP5D

ATP5F1D
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
Gene location (Human) Chr. Chromosome 19 (human) [1] Band 19p13.3 Start 1,241,746 bp [1] End 1,244,825 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 C1 Start 80,138,632 bp [2] End 80,145,818 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle left ventricle right lobe of liver body of pancreas body of stomach cingulate gyrus right adrenal gland prefrontal cortex anterior pituitary amygdala Top expressed in right ventricle extraocular muscle ankle condyle digastric muscle fossa facial motor nucleus sternocleidomastoid muscle motor neuron temporal muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function proton-transporting ATP synthase activity, rotational mechanism transmembrane transporter activity transporter activity ADP binding ATP binding ATPase activity Cellular component mitochondrial proton-transporting ATP synthase complex membrane mitochondrial matrix mitochondrion mitochondrial proton-transporting ATP synthase complex, catalytic sector F(1) mitochondrial inner membrane proton-transporting ATP synthase complex, catalytic core F(1) Biological process response to copper ion mitochondrial ATP synthesis coupled proton transport ion transport oxidative phosphorylation ATP synthesis coupled proton transport ATP biosynthetic process cristae formation aerobic respiration mitochondrial proton-transporting ATP synthase complex assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 513 66043 Ensembl ENSG00000099624 ENSMUSG00000003072 UniProt P30049 Q9D3D9 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]

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, F_o, 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]}

References

1. GRCh38: Ensembl release 89: ENSG00000099624 - Ensembl, May 2017
2. 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. "ATP5F1D - ATP synthase subunit delta, mitochondrial precursor - Homo sapiens (Human) - ATP5F1D gene & protein" . Retrieved 2018-08-07.  This article incorporates text available under the CC BY 4.0 license.
6. "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. "Entrez Gene: ATP5D ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit". 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

• Yoshida M, Muneyuki E, Hisabori T (September 2001). "ATP synthase--a marvellous rotary engine of the cell". Nature Reviews. Molecular Cell Biology. 2 (9): 669–77. doi:10.1038/35089509. PMID   11533724. S2CID   3926411.
• Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R (December 1992). "Human liver protein map: a reference database established by microsequencing and gel comparison". Electrophoresis. 13 (12): 992–1001. doi:10.1002/elps.11501301201. PMID   1286669. S2CID   23518983.
• Yasuda R, Noji H, Kinosita K, Yoshida M (June 1998). "F1-ATPase is a highly efficient molecular motor that rotates with discrete 120 degree steps". Cell. 93 (7): 1117–24. doi: 10.1016/S0092-8674(00)81456-7 . PMID   9657145. S2CID   14106130.
• 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.
• 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.
• Itoh H, Takahashi A, Adachi K, Noji H, Yasuda R, Yoshida M, Kinosita K (January 2004). "Mechanically driven ATP synthesis by F1-ATPase". Nature. 427 (6973): 465–8. Bibcode:2004Natur.427..465I. doi:10.1038/nature02212. PMID   14749837. S2CID   4428646.

External links

• Human ATP5D genome location and ATP5D 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.