Bromodomain testis-specific protein

UniProt Q58F21 Organism Homo sapiens Gene BRDT

Also known as: BRDT

Function

Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis. Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA. Also recognizes and binds a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (By similarity). Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids (By similarity). Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin.

Classification

Family (Pfam): PF17035 BET, PF17105 BRD4_CDT, PF00439 Bromodomain
InterPro: BRD4_CDT, Bromo_Brdt_I, Bromo_Brdt_II, Bromo_chromatin_reader, Bromodomain, Bromodomain-like_sf, Bromodomain_CS, NET_dom, NET_sf
Functional cluster: RRM RNA-Binding & Protein Kinases

Experimental structures · PDB · 21

2RFJ X-ray 2.05A
4FLP X-ray 2.23A
4KCX X-ray 2.00A
5VBQ X-ray 1.65A
5VBR X-ray 1.90A
7BJY X-ray 2.22A
7L73 X-ray 1.46A
7L99 X-ray 1.90A
7L9A X-ray 2.27A
7LEJ X-ray 1.73A
7LEK X-ray 2.75A
7LEL X-ray 2.15A
… and 9 more

A predicted model is available from AlphaFold.

Gene Ontology · 18

Disease associations

spermatogenic failure 21 MONDO:0054725

Drugs targeting this protein · 6

MOLIBRESIB inhibitor
APABETALONE inhibitor
BIRABRESIB inhibitor
RO-6870810 inhibitor
EZOBRESIB inhibitor
PELABRESIB inhibitor

Related proteins · sequence + function similarity

Bromodomain testis-specific protein 0.99
Bromodomain testis-specific protein 0.94
Bromodomain testis-specific protein 0.91
Bromodomain testis-specific protein 0.88
Bromodomain testis-specific protein 0.82
Bromodomain-containing protein 3 0.77
Bromodomain-containing protein 3 0.75
Bromodomain-containing protein 2 0.74
Bromodomain-containing protein 2 0.74
Bromodomain-containing protein 2 0.72
Bromodomain-containing protein 2 0.72
Bromodomain-containing protein 4 0.71

Co-cited proteins · studied together in the literature

Bromodomain testis-specific protein 1 shared papers
ATPase family AAA domain-containing protein 2B 1 shared papers
Transcription initiation factor TFIID subunit 1-like 1 shared papers
Bromodomain adjacent to zinc finger domain protein 2B 1 shared papers
Bromodomain and WD repeat-containing protein 1 1 shared papers
Histone-lysine N-methyltransferase ASH1L 1 shared papers
ATPase family AAA domain-containing protein 2 1 shared papers
Bromodomain-containing protein 9 1 shared papers
Chromatin remodeling regulator CECR2 1 shared papers
Protein polybromo-1 1 shared papers
PH-interacting protein 1 shared papers
Bromodomain-containing protein 1 1 shared papers

Literature · 13 cited papers

Whole-exome sequencing identified a homozygous BRDT mutation in a patient with acephalic spermatozoa. Oncotarget · 2017
Screen identifies bromodomain protein ZMYND8 in chromatin recognition of transcription-associated DNA damage that promotes homologous recombination. Genes Dev. · 2015
The conserved 12-amino acid stretch in the inter-bromodomain region of BET family proteins functions as a nuclear localization signal. Biol. Pharm. Bull. · 2012
Small-molecule inhibition of BRDT for male contraception. Cell · 2012
Histone recognition and large-scale structural analysis of the human bromodomain family. Cell · 2012
The interaction of modified histones with the bromodomain testis-specific (BRDT) gene and its mRNA level in sperm of fertile donors and subfertile men. Reproduction · 2010
Patterns of somatic mutation in human cancer genomes. Nature · 2007
The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
Molecular cloning and expression of a novel alternative splice variant of BRDT gene. Int. J. Mol. Med. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Expression of cancer-testis antigens in lung cancer: definition of bromodomain testis-specific gene (BRDT) as a new CT gene, CT9. Cancer Lett. · 2000
… and 1 more in the literature graph

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