NDUFA9

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NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9, 39kDa
Identifiers
Symbols NDUFA9 ; CC6; CI-39k; CI39k; NDUFS2L; SDR22E1
External IDs OMIM603834 MGI1913358 HomoloGene3666 GeneCards: NDUFA9 Gene
RNA expression pattern
PBB GE NDUFA9 208969 at tn.png
PBB GE NDUFA9 gnf1h08868 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4704 66108
Ensembl ENSG00000139180 ENSMUSG00000000399
UniProt Q16795 Q9DC69
RefSeq (mRNA) NM_005002 NM_025358
RefSeq (protein) NP_004993 NP_079634
Location (UCSC) Chr 12:
4.76 – 4.8 Mb
Chr 6:
126.82 – 126.85 Mb
PubMed search [1] [2]

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 is an enzyme that in humans is encoded by the NDUFA9 gene.[1][2][3] The NDUFA9 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.[4][5]

Structure[edit]

The NDUFA9 gene is located on the p arm of chromosome 12 in position 13.3 and spans 38,457 base pairs.[1] The gene produces a 42.5 kDa protein composed of 377 amino acids.[6] NDUFA9 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.[4] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly 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 dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA9 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[7] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal. [1][5][8]

Function[edit]

The human NDUFA9 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[1] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[4]

References[edit]

  1. ^ a b c d "Entrez Gene: NDUFA9 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9". 
  2. ^ Baens M, Chaffanet M, Cassiman JJ, van den Berghe H, Marynen P (Jun 1993). "Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid". Genomics 16 (1): 214–8. doi:10.1006/geno.1993.1161. PMID 8486360. 
  3. ^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jornvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem Biol Interact 178 (1-3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726. 
  4. ^ a b c Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed. ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847. 
  5. ^ a b Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenet Cell Genet 82 (1-2): 115–9. doi:10.1159/000015082. PMID 9763677. 
  6. ^ "NDUFA9 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). 
  7. ^ "NDUFA9 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial". UniProt.org. The UniProt Consortium. 
  8. ^ Ton C, Hwang DM, Dempsey AA, Liew CC (Jan 1998). "Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits". Biochem Biophys Res Commun 241 (2): 589–94. doi:10.1006/bbrc.1997.7707. PMID 9425316. 

Further reading[edit]

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