From Wikipedia, the free encyclopedia
Jump to: navigation, search
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13
Symbols NDUFA13 ; B16.6; CDA016; GRIM-19; GRIM19
External IDs OMIM609435 MGI1914434 HomoloGene41083 GeneCards: NDUFA13 Gene
RNA expression pattern
PBB GE NDUFA13 220864 s at tn.png
More reference expression data
Species Human Mouse
Entrez 51079 67184
Ensembl ENSG00000186010 ENSMUSG00000036199
UniProt Q9P0J0 F6W8I0
RefSeq (mRNA) NM_015965 NM_023312
RefSeq (protein) NP_057049 NP_075801
Location (UCSC) Chr 19:
19.63 – 19.64 Mb
Chr 8:
69.89 – 69.9 Mb
PubMed search [1] [2]

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 is an enzyme that in humans is encoded by the NDUFA13 gene.[1][2][3][4] The NDUFA13 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.[5][6]


The NDUFA13 gene is located on the p arm of chromosome 19 in position 13.2 and spans 11,995 base pairs.[4] The gene produces a 17 kDa protein composed of 144 amino acids.[7] NDUFA13 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.[5] 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. NDUFA13 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.[8] 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. [4][6][9]


The human NDUFA13 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[4] 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.[5]

NDUFA13 has a homologous protein known as GRIM-19, a cell-death regulatory protein. It is involved in interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This form of apoptotic activity is inhibited by interaction with viral IRF1. GRIM-19 prevents the transactivation of signal-transducer and activator of transcription 3 (STAT3) target genes.[8]

Clinical significance[edit]

The homologous protein to NDUFA13, GRIM-19, may play a role in Chron's disease (CD), an inflammatory bowel disease (IBD) characterized by chronic inflammation of the intestinal epithelium. Its expression is decreased in the inflamed mucosa of patients with these diseases. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), functions as a mammalian cytosolic pathogen recognition molecule and plays an anti-bacterial role by limiting survival of intracellular invasive bacteria. GRIM-19 acts as a downstream anti-bacterial effector in CARD15-mediated innate mucosal responses by regulating intestinal epithelial cell responses to microbes. Following NOD2-mediated recognition of bacterial muramyl dipeptide, GRIM-19 is required for NF-κB activation, a key component in regulating the immune response to infection.[10][8]


NDUFA13 has been shown to interact with STAT3.[11]


  1. ^ Hirst J, Carroll J, Fearnley IM, Shannon RJ, Walker JE (Jul 2003). "The nuclear encoded subunits of complex I from bovine heart mitochondria". Biochim Biophys Acta 1604 (3): 135–50. doi:10.1016/S0005-2728(03)00059-8. PMID 12837546. 
  2. ^ Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV (Nov 2000). "Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach". J Biol Chem 275 (43): 33416–26. doi:10.1074/jbc.M003929200. PMID 10924506. 
  3. ^ Huang G, Lu H, Hao A, Ng DC, Ponniah S, Guo K et al. (Sep 2004). "GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I". Mol Cell Biol 24 (19): 8447–56. doi:10.1128/MCB.24.19.8447-8456.2004. PMC 516758. PMID 15367666. 
  4. ^ a b c d "Entrez Gene: NDUFA13 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13". 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ "NDUFA13 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). 
  8. ^ a b c "NDUFA13". UniProt.org. The UniProt Consortium. 
  9. ^ 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. 
  10. ^ Barnich, N; Hisamatsu, T; Aguirre, JE; Xavier, R; Reinecker, HC; Podolsky, DK (13 May 2005). "GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells.". The Journal of biological chemistry 280 (19): 19021–6. doi:10.1074/jbc.m413776200. PMID 15753091. 
  11. ^ Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF et al. (Aug 2003). "The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3". Proc. Natl. Acad. Sci. U.S.A. 100 (16): 9342–7. doi:10.1073/pnas.1633516100. PMC 170920. PMID 12867595. 

Further reading[edit]

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