View source for NDUFA3

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3''' is a [[protein]] that in humans is encoded by the ''NDUFA3'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NDUFA1 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 3, 9kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4694| accessdate = }}</ref> The NDUFA3 protein is a subunit of [[NADH dehydrogenase (ubiquinone)]], which is located in the [[mitochondrial inner membrane]] and is the largest of the five complexes of the [[electron transport chain]].<ref name = Biochem>{{cite book | last1 = Voet | first1 = Donald | last2 = Voet | first2= Judith G. | last3 = Pratt | first3 = Charlotte W. | title = Fundamentals of biochemistry: life at the molecular level | date = 2013 | publisher = Wiley | location = Hoboken, NJ | isbn = 9780470547847 | chapter = 18 | pages = 581–620 | edition = 4th | name-list-style = vanc }}</ref>
== Structure ==
The NDUFA3 gene is located on the q arm of [[chromosome 19]] at position 13.42, and it has a total span of 4,123 base pairs.<ref name = entrez /> The NDUFA3 gene produces a 9.3 kDa protein composed of 84 [[amino acids]].<ref name=COPaKB>{{cite journal | vauthors = 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 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = https://amino.heartproteome.org/web/protein/O95167 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 }}</ref> NDUFA3 is a subunit of the enzyme [[NADH dehydrogenase (ubiquinone)]], the largest of the respiratory complexes. The structure is L-shaped with a long, [[hydrophobic]] [[transmembrane]] domain and a [[hydrophilic]] domain for the peripheral arm that includes all the known redox centers and the NADH binding site.<ref name = Biochem /> NDUFA3 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. It has been noted that the [[N-terminus|N-terminal]] hydrophobic domain has the potential to be folded into an [[alpha helix]] spanning the inner [[mitochondrion|mitochondrial membrane]] with a [[C-terminus|C-terminal]] hydrophilic domain interacting with globular subunits of Complex I. The highly [[conserved sequence|conserved]] two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH:ubiquinone [[oxidoreductase]] complex at the inner mitochondrial membrane.<ref name = "entrez" />
== Function ==
The human NDUFA3 gene codes for a subunit of [[NADH dehydrogenase|Complex I]] of the [[electron transport chain|respiratory chain]], which transfers electrons from [[nicotinamide adenine dinucleotide|NADH]] to [[ubiquinone]].<ref name="entrez"/> However, NDUFA3 is an accessory subunit of the complex that is believed not to be involved in catalysis.<ref>{{cite web|title=NDUFA3 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3|url=https://www.uniprot.org/uniprot/O95167|website=UniProt: a hub for protein information|publisher=The UniProt Consortium|accessdate=24 March 2015}}</ref> Initially, [[NADH]] binds to Complex I and transfers two electrons to the [[isoalloxazine ring]] of the [[flavin mononucleotide]] (FMN) prosthetic arm to form FMNH<sub>2</sub>. The electrons are transferred through a series of [[iron-sulfur protein|iron-sulfur (Fe-S) clusters]] in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to [[ubiquinol]] (CoQH<sub>2</sub>). The flow of electrons changes the redox state of the protein, resulting in a conformational change and p''K'' shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.<ref name=Biochem />
== Interactions ==
NDUFA3 has been shown to interact with [[ubiquitin C]], a polyubiquitin precursor.<ref name= "entrez"/><ref>{{cite journal | vauthors = Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C | title = A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles | journal = Molecular & Cellular Proteomics | volume = 10 | issue = 10 | date = Oct 2011 | pmid = 21890473 | doi = 10.1074/mcp.M111.013284 | pmc=3205876 | pages=M111.013284| doi-access = free }}</ref>
== References ==
{{reflist|33em}}
{{Mitochondrial enzymes}}
{{NLM content}}
[[Category:Human proteins|Mitochondria]]