NDUFA13 is a protein-coding gene, which encodes a subunit of the mitochondrial respiratory chain NADH dehydrogenase (Complex I).

The NDUFA13 gene, with 18995 bases in length (NG_013380), consists 5 exons and 4 introns. It was first identified and isolated by antisense knock-out techniques, in a study aiming the identification of gene products that participate in synergistic growth-suppressive actions (Angell et al., 2000). Expression of NDUFA13 is induced by IFNB1/IFN-beta combined with all-trans-retinoic acid.

The NDUFA gene is characterized by 7 transcripts. Three are protein coding transcripts. The transcribed mRNA of NDUFA13 gene has 557 bp (NM_015965). RNA is expressed in all tissues. Two other transcripts are protein coding, one with 120 aa and another with 150 aa. Two transcripts are nonsense mediated decay and two other retain an intron, none of these 4 coding for proteins. Transcripts originating from an upstream promoter and capable of expressing a protein with a longer N-terminus have been found, but their biological validity has not been determined. (Provided by RefSeq, Oct 2009).

Protein class: disease related genes, mitochondrial proteins, predicted membrane proteins.

The human NDUFA13 gene encodes for a 16KDa protein and 144 aminoacids, purified from mitochondria. It was first identified as a novel cell death-regulatory gene whose inactivation confers growth advantage to cells in the presence of IFN/RA (Angell et al., 2000). This protein has a modified residue at position 2, an alanine that can be acetylated. The transmembrane portion of NDUFA13 protein encompasses aminoacids at positions 30 to 51, being 22 residues long, and has a helical shape. The 43 aa region consisting of residues 102 to 144, is important for inducing cell death.
Translation (144 aa)
Amino acids: 144. Molecular weight: 16KD. The NDUFA13 gene encodes for a protein that belongs to the family of NADH dehydrogenase ubiquitone 1 alpha subcomplex 13.

Widely expressed with highest expression in heart, skeletal muscle, liver, kidney and placenta. (Angell et al., 2000) Ubiquitous cytoplasmatic expression with a granular pattern. Membrane.

Mitochondria inner membrane, Single-pass membrane protein, Matrix side, Nucleus. (UniProt Q9P0J0).

Molecular function: catalytic - oxiredutase activity - and it is involved in metabolic processes and biological regulation.
NDUFA13 was described in 2004 as a gene product with a specific role in IFN-RA-induced cell death, as a functional component of mitochondrial complex I and as being essential for early embryonic development (Huang et al., 2004).
Cell death regulatory protein that promotes apoptosis, is a negative regulator of cell growth, and it is involved in mitochondrial metabolism (Angell et al., 2000; Lufei et al., 2003).
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I). Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death, which is inhibited by interaction with viral IRF1. Prevents the transactivation of STAT3 target genes (Lufei et al., 2003; Zhang et al., 2003).
Diseases associated with NDUFA13 include thyroid Hürthle cell carcinoma, and kidney cancer. GO annotations related to this gene include NADH dehydrogenase activity and NADH dehydrogenase (ubiquinone) activity.

NDUFA13 score . There are still 120 uncharacterized proteins in different species including Homo sapiens, with homologies varying from 28% to 100% (Homo sapiens). Nine predicted proteins with homologies between 40% and 52% have also been identified in different species (B2014110593WH1M8NCV)

Loss of expression and occurrence of mutations in the NDUFA13 gene in a variety of primary human cancers-lung, kidney, prostate, thyroid, ovary, colon, esophagus and brain (Alchanati et al., 2006; Máximo et al., 2008; Zhou et al., 2009; Fan et al., 2012) - have been described, indicating its potential role as tumor suppressor. Depletion or overexpression of NDUFA13 promotes and suppresses, respectively, tumor growth (Angell et al., 2000; Máximo et al., 2008; Huang et al., 2010). Levels of expression of NDUFA13 are a good prognostic marker for colorectal cancer (Hao et al., 2015) and loss of expression correlate with malignancy in Hürthle cell tumours (Donatini et al., 2015).

One germline missense mutation of NDUFA13 has been identified in one patient with apparently sporadic Hürthle cell carcinoma: G264C substitution in exon 1 (Máximo et al., 2005).

Three missense mutations have been identified in three out of 20 cases of sporadic Hürthle cell carcinomas: a C77T and a A247G in exon 1, and a G593C in exon 5 (Máximo et al., 2005). Three somatic mutations of NDUFA13 gene have been identified in a set of primary head and neck tumors (Nallar et al., 2013). Wild-type NDUFA13 suppresses cellular transformation by a constitutively active form of STAT3, whereas tumor-derived mutants (L71P, L91P and A95T) significantly lost their ability to associate with STAT3, block gene expression and suppress cell transformation and tumor growth in vivo. These three mutants have also lost their capacity to prevent metastasis.