AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene. [5] [6] [7]
AT rich interactive domain 4A (RBP1-like), also known as ARID4A, is a protein which in humans is encoded by the ARID4A gene. [5] [6] [7]
The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described. [5]
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Abnormal [8] |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Abnormal [9] |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Abnormal [10] |
| Radiography | Abnormal [11] |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Abnormal [12] |
| Haematology | Abnormal [13] |
| Peripheral blood lymphocytes | Abnormal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Skin Histopathology | Normal |
| Eye Histopathology | Normal |
| Salmonella infection | Normal [14] |
| Citrobacter infection | Normal [15] |
| All tests and analysis from [16] [17] |
Model organisms have been used in the study of ARID4A function. A conditional knockout mouse line, called Arid4atm1a(EUCOMM)Wtsi [18] [19] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. [20] [21] [22] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [16] [23]
Twenty five tests were carried out and nine phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than expected, and in a separate study less than the predicted Mendelian ratio survived until weaning. Homozygous mutant male adults has a reduced body weight curve and a decreased grip strength. Homozygous mutant adults of both sexes had a decreased body weight as determined by DEXA, displayed vertebral fusion and had clinical chemistry abnormalities including hypoalbuminemia and decreased circulating fructosamine levels. They also had haematological defects and an increased NK cell number. [16]
ARID4A has been shown to interact with Retinoblastoma protein. [24]
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.
Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.
Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene.
Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene.
Retinoblastoma-like 1 (p107), also known as RBL1, is a protein that in humans is encoded by the RBL1 gene.
Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.
AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.
Histone-lysine N-methyltransferase SETMAR is an enzyme that in humans is encoded by the SETMAR gene.
AT-rich interactive domain-containing protein 4B is a protein that in humans is encoded by the ARID4B gene.
Histone deacetylase complex subunit SAP130 is an enzyme that in humans is encoded by the SAP130 gene.
Lysine-specific demethylase 4C is an enzyme that in humans is encoded by the KDM4C gene.
Protein Jumonji is a protein that in humans is encoded by the JARID2 gene. JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.
Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene.
Bromodomain testis-specific protein is a protein that in humans is encoded by the BRDT gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family.
Putative sodium-coupled neutral amino acid transporter 10, also known as solute carrier family 38 member 10, is a protein that in humans is encoded by the SLC38A10 gene.
CSRP2 binding protein is a protein that in humans is encoded by the CSRP2BP gene.
Rtf1, Paf1/RNA polymerase II complex component, homolog is a protein that in humans is encoded by the RTF1 gene.
Malignant Brain Tumor domain containing 1 is a protein that in humans is encoded by the MBTD1 gene. The gene is also known as SA49P01.
Chromobox homolog 7 is a protein that in humans is encoded by the CBX7 gene. The loss of CBX7 gene expression has been shown to correlate with a malignant form of thyroid cancer.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.