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FLASH GENE
Symbol BRDT contributors: mct/npt/pgu - updated : 13-04-2021
HGNC name bromodomain, testis-specific
HGNC id 1105
Corresponding disease
SPGF21 spermatogenic failure 21
Location 1p22.1      Physical location : 92.414.927 - 92.479.983
Synonym name
  • cancer/testis antigen 9
  • RING3-like protein
  • testis-specific bromodomain protein
  • Synonym symbol(s) BRD6, CT9, SPGF21
    DNA
    TYPE functioning gene
    STRUCTURE 65.06 kb     19 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3361 107.9 947 - 2005 15647849
    19 - 3156 - 947 - 2005 15647849
    20 - 3430 - 947 only expressed in testis 2005 15647849
  • also called BRDT-NY
  • has two bromodomains in N-terminal . may have an important role in the process of spermatogenesis and may be correlated with male infertility
  • 19 - 3717 - 874 - 2005 15647849
    19 - 3373 - 951 - 2005 15647849
    18 - 3223 - 901 - 2005 15647849
    19 - 3029 - 901 - 2005 15647849
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegerm cell Homo sapiens
    Reproductivespermatid Homo sapiens
    Reproductivespermatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus of BRDT is involved in the recognition of SMARCE1 as well as in the reorganization of hyperacetylated round spermatid chromatin
  • two bromodomain motifs, a single bromodomain (BD1 is responsible for selectively recognizing histone H4 tails bearing two or more acetylation marks , and inhibitor JQ1 binds to the Kac binding site of BET bromodomain
  • a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation
  • HOMOLOGY
    interspecies homolog to Drosophila fsh
    intraspecies homolog to RING3 domain (D6S113E)
    Homologene
    FAMILY
  • BET (bromodomain and extra terminal motif) family of proteins
  • CATEGORY enzyme , regulatory , transcription factor , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in protein-protein interaction
  • regulating signal-dependent transcription
  • having a structural role in the remodelling of acetylated chromatin
  • required maternally for proper expression of other homeotic genes involved in pattern formation, such as UBX
  • could also have a new biological role, specific to germ cells, which could be performed by its nonconserved domains
  • implicated in the marked chromatin remodelling that follows histone hyperacetylation during spermiogenesis, the stage of spermatogenesis in which post-meiotic germ cells mature into fully differentiated sperm
  • BET family members have been recognized as essential genes for the replication of viruses and in mediating inflammatory responses
  • BET family proteins recognize acetylated chromatin through their two bromodomains, acting as transcriptional activators or tethering viral genomes to the mitotic chromosomes of their host
  • along with modulating transcription, BRDT modulates likely gene expression as part of the splicing machinery, and these modulations alter 3'-UTR processing in round spermatid
  • BRD2, BRD3, BRD4, and BRDT are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression
  • is essential for the normal progression of spermatogenesis as mutations in the BRDT gene result in complete male sterility
  • is an essential regulator of chromatin organization and reprograming during prophase I of meiosis
  • also controls the global chromatin organization and histone modifications of the chromatin attached to the synaptonemal complex
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specifically binds hyperacetylated histone H4 tail depending on the integrity of both bromodomains
  • bind to hyperacetylated chromatin in elongating spermatids and recruit machinery to remove the acetylated histones, replaced by protamines
  • interaction between SMARCE1 and BRDT increases dramatically upon histone hyperacetylation, and likely this interaction to be a vital step in the chromatin remodeling process during mammalian spermiogenesis
  • BRDT has novel interactions with the histone deacetylase HDAC1, the arginine-specific histone methyltransferase 5 PRMT5, and the Tripartite motif-containing 28 protein TRIM28, and functions in transcriptional repression during spermatogenesis
  • BRDT interacts with nucleosomes through its first (BD1), but not second (BD2) bromodomain, and acetylated histone recognition by BD1 is complemented by a bromodomain-DNA interaction
  • E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT
  • cell & other
    REGULATION
    inhibited by JQ1, a selective and potent inhibitor of BET family bromodomains
    ASSOCIATED DISORDERS
    corresponding disease(s) SPGF21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductioncontraception 
    potent inhibition of the testis-specific member BRDT cause a complete and reversible contraceptive effect
    cancer  
    inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer
    cancerreproductiveprostate
    potential value of selectively targeting the BD2 domain of BET family proteins for cancer therapy
    ANIMAL & CELL MODELS
  • mutant mice that expressed truncated Brdt had impaired testicular histology with severely reduced sperm concentration and abnormal sperm morphology, while a model of knockout Brdt mice with no Brdt protein had complete meiotic arrest