Abstract
Review on AARD, with data on DNA, on the protein encoded, and where the gene is implicated.
DNA/RNA
Description
A potential androgen response element (ARE) sequence (u001e1637 tou001e1632, TGTTCT) was found in the mouse Aard promoter (see below).
Transcription
Transcript (hg38), including UTRs: chr8:116,938,199-116,944,487, size: 6,289bp on strand +; coding region: chr8:116,938,244-116,942,701, size: 4,458bp, according to UCSC.
AARD has 2 splice variants, one of these 2 transcripts codes for a protein. Transcript length: 2299 bp, coding sequence: 468 nt. 2 exons; exon 1 codes for aa 1-109, exon 2 codes for aa 110-155 (Vega).
AARD has 2 splice variants, one of these 2 transcripts codes for a protein. Transcript length: 2299 bp, coding sequence: 468 nt. 2 exons; exon 1 codes for aa 1-109, exon 2 codes for aa 110-155 (Vega).
Proteins
Figure 1: AARD gene and protein
Description
155 amino acids (aa), 17575Da. Of note are an Ala/Arg-rich domain of 46 aa in aa 60-105, with a long stretch of alanine in aa 82-88, four leucine zippers at aa 56-63 (LEDLRRRL), 101-108 (LARLRAEL), 118-125 (LARTLLDL), 125-132 (LNMKVQQL), and 3 phosphorylation sites (serine/threonine kinases) in aa 95-98 (TGVE), 121-124 (TLLD) and 146-149 (SPKD).
The rat Aard (named rA5D3) 165 aa long is sequenced and described in Blomberg et al., 2002.
The rat Aard (named rA5D3) 165 aa long is sequenced and described in Blomberg et al., 2002.
Figure 2: ModBase predicted comparative 3D structure (Pieper et al., 2014)
Expression
AARD is expressed prenatally in male gonads, and in most organs postnatally (see below).
Localisation
AARD is detected in lipid droplets (The Human Protein Database).
Function
The presence of leucine-zipper domains and phosphorylation sites suggest that AARD is a transcription factor, and may be involved in signal transduction pathways (Blomberg et al., 2002).
Aard is upregulated early during postnatal rat lung development, but also in the heart, kidney, liver, and testis, but the developmental expression pattern, although comparable in levels of expression, was different -in term of timing- in each of the tissues studied (Blomberg et al., 2002). Aard is one of the 266 or 1083 genes, according to the different studies, upregulated in gonads of male but -not in female- mice embryos. This strong expression was restricted to the sex cords (Menke and Page, 2002; Bouma et al., 2004; Nef et al., 2005; Beverdam and Koopman, 2006). Strong testis-specific expression was also detected in the adult mouse (Svingen et al., 2007). It is also expressed in adult liver, kidney, brain, lung, muscle, heart and bladder of mice (Geng et al., 2017).
AR (androgen receptor) mediates the effects of androgens by binding to the androgen response elements (ARE) of target genes. An ARE (TGTTCT) was identified at position -1637 to -1632 in the promoter region near the mouse Aard transcription initiation site. AR binds this ARE and activates Aard transcription. Aard is directly regulated by AR in Sertoli cells of mouse testis (Geng et al., 2017).
Aard is upregulated early during postnatal rat lung development, but also in the heart, kidney, liver, and testis, but the developmental expression pattern, although comparable in levels of expression, was different -in term of timing- in each of the tissues studied (Blomberg et al., 2002). Aard is one of the 266 or 1083 genes, according to the different studies, upregulated in gonads of male but -not in female- mice embryos. This strong expression was restricted to the sex cords (Menke and Page, 2002; Bouma et al., 2004; Nef et al., 2005; Beverdam and Koopman, 2006). Strong testis-specific expression was also detected in the adult mouse (Svingen et al., 2007). It is also expressed in adult liver, kidney, brain, lung, muscle, heart and bladder of mice (Geng et al., 2017).
AR (androgen receptor) mediates the effects of androgens by binding to the androgen response elements (ARE) of target genes. An ARE (TGTTCT) was identified at position -1637 to -1632 in the promoter region near the mouse Aard transcription initiation site. AR binds this ARE and activates Aard transcription. Aard is directly regulated by AR in Sertoli cells of mouse testis (Geng et al., 2017).
Implicated in
Top note
AARD RNA is enriched in breast cancer, but the gene product is not prognostic (The Human Protein Database).
Entity name
Lung adenocarcinoma
Note
A t(8;9)(q24;p24) RIC1 /AARD has been found in lung adenocarcinoma (Yoshihara et al. 2015; Hu et al., 2018).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16399799 | 2006 | Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes. | Beverdam A et al |
| 11997109 | 2002 | Molecular cloning and characterization of a novel gene upregulated early during postnatal rat lung development. | Blomberg LA et al |
| 15533830 | 2004 | Using real time RT-PCR analysis to determine multiple gene expression patterns during XX and XY mouse fetal gonad development. | Bouma GJ et al |
| 27959439 | 2017 | Alanine and arginine rich domain containing protein, Aard, is directly regulated by androgen receptor in mouse Sertoli cells. | Geng Q et al |
| 29099951 | 2018 | TumorFusions: an integrative resource for cancer-associated transcript fusions. | Hu X et al |
| 12617826 | 2002 | Sexually dimorphic gene expression in the developing mouse gonad. | Menke DB et al |
| 16214126 | 2005 | Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development. | Nef S et al |
| 24271400 | 2014 | ModBase, a database of annotated comparative protein structure models and associated resources. | Pieper U et al |
| 17486547 | 2007 | Aard is specifically up-regulated in Sertoli cells during mouse testis differentiation. | Svingen T et al |
| 25500544 | 2015 | The landscape and therapeutic relevance of cancer-associated transcript fusions. | Yoshihara K et al |
Other Information
Locus ID:
NCBI: 441376
HGNC: 33842
Ensembl: ENSG00000205002
Variants:
dbSNP: 441376
ClinVar: 441376
TCGA: ENSG00000205002
COSMIC: AARD
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000205002 | ENST00000378279 | Q4LEZ3 |
Expression (GTEx)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 20549515 | 2010 | Genome-wide searching of rare genetic variants in WTCCC data. | 31 |
| 20549515 | 2010 | Genome-wide searching of rare genetic variants in WTCCC data. | 31 |
Citation
Jean Loup Huret
AARD (alanine and arginine rich domain containing protein)
Atlas Genet Cytogenet Oncol Haematol. 2019-01-01
Online version: http://atlasgeneticsoncology.org/gene/60018/aard-(alanine-and-arginine-rich-domain-containing-protein)
