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Q91Y44 (BRDT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bromodomain testis-specific protein
Alternative name(s):
Bromodomain-containing female sterile homeotic-like protein
RING3-like protein
Gene names
Name:Brdt
Synonyms:Fsrg3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length956 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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. Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin. Ref.5 Ref.9 Ref.10 Ref.11 Ref.12

Subunit structure

Interacts with SMARCE1 By similarity. Interacts with mRNA splicing machinery proteins SRSF2, DDX5, HNRNPK and TARDBP. Interacts with the acetylated N-terminus of histone H1, H2, H3 and H4. Interacts with P-TEFb components CDK9 and CCNT1/cyclin-T1. Ref.5 Ref.10 Ref.11 Ref.12

Subcellular location

Nucleus. Note: Detected on chromatin. Excluded from the chromocenter. Ref.6 Ref.8 Ref.12

Tissue specificity

Testis-specific. Expressed in germinal cells from the early meiotic (pachytene) spermatocytes and during spermiogenesis in the round and elongating spermatids until the condensed late spermatids. No expression seen in spermatogonia. Ref.1 Ref.6 Ref.7

Developmental stage

First detected when type B spermatogonia give rise to early meiotic cells (preleptotene, leptotene and zygotene) at 10-12 days post partum (dpp), producing a clearly detectable protein at 12 dpp (at protein level). Ref.10

Domain

Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions. Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) (Ref.12).

Disruption phenotype

Mice are viable but males are sterile, producing fewer and morphologically abnormal sperm. Aberrant morphogenesis are first detected in step 9 elongating spermatids, and those elongated spermatids that are formed lack the distinctive foci of heterochromatin at the peri-nuclear envelope. Spermatid nuclei show a fragmented chromocenter. Ref.6 Ref.8 Ref.10

Miscellaneous

Brdt is a promising target for male contraception. Inhibition by thienodiazepine inhibitor (+)-JQ1 that binds Asn-108, prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduces seminiferous tubule area, testis size and spermatozoa number and motility without affecting hormone levels. JQ1 causes a complete and reversible contraceptive effect in male mice (Ref.9).

Sequence similarities

Contains 2 bromo domains.

Contains 1 NET domain.

Ontologies

Keywords
   Biological processDifferentiation
Meiosis
mRNA processing
mRNA splicing
Spermatogenesis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainBromodomain
Coiled coil
Repeat
   Molecular functionActivator
Chromatin regulator
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA splicing

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

chromatin remodeling

Inferred from direct assay Ref.12. Source: UniProtKB

histone displacement

Inferred from mutant phenotype Ref.10. Source: UniProtKB

mRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

male meiosis

Inferred from mutant phenotype Ref.10. Source: UniProtKB

male meiosis I

Inferred from mutant phenotype Ref.10. Source: UniProtKB

positive regulation of transcription during meiosis

Inferred from mutant phenotype Ref.10. Source: UniProtKB

regulation of RNA splicing

Inferred from mutant phenotype Ref.11. Source: UniProtKB

spermatogenesis

Inferred from mutant phenotype Ref.6Ref.10. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentnucleus

Inferred from direct assay Ref.6Ref.12. Source: UniProtKB

   Molecular_functionhistone binding

Inferred from direct assay Ref.12. Source: UniProtKB

lysine-acetylated histone binding

Inferred from mutant phenotype Ref.10. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.11Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q91Y44-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q91Y44-2)

The sequence of this isoform differs from the canonical sequence as follows:
     323-326: GKMD → VNTA
     327-956: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 956956Bromodomain testis-specific protein
PRO_0000239227

Regions

Domain43 – 11573Bromo 1
Domain286 – 35873Bromo 2
Domain496 – 57883NET
Coiled coil417 – 44226 Potential
Coiled coil844 – 94097 Potential
Motif208 – 21912Nuclear localization signal By similarity
Compositional bias446 – 49651Lys-rich
Compositional bias625 – 63915Pro-rich
Compositional bias643 – 68947Ser-rich

Sites

Binding site1081Histone H4K5ac
Binding site1081JQ1 inhibitor By similarity
Binding site1131Histone H4K5ac

Natural variations

Alternative sequence323 – 3264GKMD → VNTA in isoform 2.
VSP_019119
Alternative sequence327 – 956630Missing in isoform 2.
VSP_019120

Experimental info

Mutagenesis50 – 512PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-55.
Mutagenesis551V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 50-AA-51. Ref.5
Mutagenesis293 – 2942PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-298.
Mutagenesis2981V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 293-AA-294. Ref.5
Sequence conflict2081K → R in BAD91553. Ref.2
Sequence conflict6911S → F in AAK50736. Ref.1

Secondary structure

................................... 956
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 28, 2012. Version 3.
Checksum: E727044706A67260

FASTA956107,255
        10         20         30         40         50         60 
MSLPSRQTAI VNPPPPEYIN TKKSGRLTNQ LQFLQRVVLK ALWKHGFSWP FQQPVDAVKL 

        70         80         90        100        110        120 
KLPDYYTIIK TPMDLNTIKK RLENKYYEKA SECIEDFNTM FSNCYLYNKT GDDIVVMAQA 

       130        140        150        160        170        180 
LEKLFMQKLS QMPQEEQVVG GKERIKKDIQ QKIAVSSAKE QIPSKAAENV FKRQEIPSGL 

       190        200        210        220        230        240 
PDISLSPLNM AQEAPPICDS QSLVQITKGV KRRADTTTPT TSIAKASSES PPTLRETKPV 

       250        260        270        280        290        300 
NMPVKENTVK NVLPDSQQQH KVLKTVKVTE QLKHCSEILK EMLAKKHLPY AWPFYNPVDA 

       310        320        330        340        350        360 
DALGLHNYYD VVKNPMDLGT IKGKMDNQEY KDAYEFAADV RLMFMNCYKY NPPDHEVVAM 

       370        380        390        400        410        420 
ARTLQDVFEL HFAKIPDEPI ESMHACHLTT NSAQALSRES SSEASSGDAS SEDSEDERVQ 

       430        440        450        460        470        480 
HLAKLQEQLN AVHQQLQVLS QVPLRKLKKK NEKSKRAPKR KKVNNRDENP RKKPKQMKQK 

       490        500        510        520        530        540 
EKAKINQPKK KKPLLKSEEE DNAKPMNYDE KRQLSLDINK LPGDKLGRIV HIIQSREPSL 

       550        560        570        580        590        600 
RNSNPDEIEI DFETLKASTL RELEKYVLAC LRKRSLKPQA KKVVRSKEEL HSEKKLELER 

       610        620        630        640        650        660 
RLLDVNNQLN CRKRQTKRPA KVEKPPPPPP PPPPPPPPPE LASGSRLTDS SSSSGSGSGS 

       670        680        690        700        710        720 
SSSSSGSSSS SSSSGSASSS SDSSSSDSSD SEPEIFPKFT GVKQNDLPPK ENIKQIQSSV 

       730        740        750        760        770        780 
QDITSAEAPL AQQSTAPCGA PGKHSQQMLG CQVTQHLQAT ENTASVQTQP LSGDCKRVLL 

       790        800        810        820        830        840 
GPPVVHTSAE SLTVLEPECH APAQKDIKIK NADSWKSLGK PVKASSVLKS SDELFNQFRK 

       850        860        870        880        890        900 
AAIEKEVKAR TQEQMRKHLE HNAKDPKVSQ ENQREPGSGL TLESLSSKVQ DKSLEEDQSE 

       910        920        930        940        950 
QQPPSEAQDV SKLWLLKDRN LAREKEQERR RREAMAGTID MTLQSDIMTM FENNFD 

« Hide

Isoform 2 [UniParc].

Checksum: 26432C1A10E68E1C
Show »

FASTA32636,914

References

« Hide 'large scale' references
[1]"Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis."
Shang E., Salazar G., Crowley T.E., Wang X., Lopez R.A., Wang X., Wolgemuth D.J.
Gene Expr. Patterns 4:513-519(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Testis.
[2]"The Brd paralogous genes: testis-specific expression of the splicing variants."
Taniguchi Y.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Testis.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Acetylation-dependent chromatin reorganization by BRDT, a testis-specific bromodomain-containing protein."
Pivot-Pajot C., Caron C., Govin J., Vion A., Rousseaux S., Khochbin S.
Mol. Cell. Biol. 23:5354-5365(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HISTONE H4, MUTAGENESIS OF 50-PRO-PHE-51; VAL-55; 293-PRO-PHE-294 AND VAL-298.
[6]"The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation."
Shang E., Nickerson H.D., Wen D., Wang X., Wolgemuth D.J.
Development 134:3507-3515(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[7]"Bromodomain testis-specific protein is expressed in mouse oocyte and evolves faster than its ubiquitously expressed paralogs BRD2, -3, and -4."
Paillisson A., Levasseur A., Gouret P., Callebaut I., Bontoux M., Pontarotti P., Monget P.
Genomics 89:215-223(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"The first bromodomain of the testis-specific double bromodomain protein Brdt is required for chromocenter organization that is modulated by genetic background."
Berkovits B.D., Wolgemuth D.J.
Dev. Biol. 360:358-368(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
[9]"Small-molecule inhibition of BRDT for male contraception."
Matzuk M.M., McKeown M.R., Filippakopoulos P., Li Q., Ma L., Agno J.E., Lemieux M.E., Picaud S., Yu R.N., Qi J., Knapp S., Bradner J.E.
Cell 150:673-684(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Bromodomain-dependent stage-specific male genome programming by Brdt."
Gaucher J., Boussouar F., Montellier E., Curtet S., Buchou T., Bertrand S., Hery P., Jounier S., Depaux A., Vitte A.L., Guardiola P., Pernet K., Debernardi A., Lopez F., Holota H., Imbert J., Wolgemuth D.J., Gerard M., Rousseaux S., Khochbin S.
EMBO J. 31:3809-3820(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, INTERACTION WITH CDK9 AND CCNT1.
[11]"The testis-specific double bromodomain-containing protein BRDT forms a complex with multiple spliceosome components and is required for mRNA splicing and 3'-UTR truncation in round spermatids."
Berkovits B.D., Wang L., Guarnieri P., Wolgemuth D.J.
Nucleic Acids Res. 40:7162-7175(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SRSF2; DDX5; HNRNPK AND TARDBP.
[12]"Cooperative binding of two acetylation marks on a histone tail by a single bromodomain."
Moriniere J., Rousseaux S., Steuerwald U., Soler-Lopez M., Curtet S., Vitte A.L., Govin J., Gaucher J., Sadoul K., Hart D.J., Krijgsveld J., Khochbin S., Muller C.W., Petosa C.
Nature 461:664-668(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 17-136 AND 257-382 IN COMPLEX WITH HISTONE H4 PEPTIDE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Asking life to be patient - Issue 144 of November 2012

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF358660 mRNA. Translation: AAK50736.1.
AB208640 mRNA. Translation: BAD91553.1.
AC126598 Genomic DNA. No translation available.
CH466529 Genomic DNA. Translation: EDL20168.1.
CCDSCCDS19500.1. [Q91Y44-1]
CCDS39197.1. [Q91Y44-2]
RefSeqNP_001073342.1. NM_001079873.1. [Q91Y44-2]
NP_473395.2. NM_054054.2. [Q91Y44-1]
UniGeneMm.182836.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WP1X-ray2.10A/B257-382[»]
2WP2X-ray2.37A/B17-136[»]
ProteinModelPortalQ91Y44.
SMRQ91Y44. Positions 27-136, 259-381, 501-579.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid227777. 1 interaction.
DIPDIP-48975N.
IntActQ91Y44. 5 interactions.
MINTMINT-8409453.
STRING10090.ENSMUSP00000108297.

PTM databases

PhosphoSiteQ91Y44.

Proteomic databases

PaxDbQ91Y44.
PRIDEQ91Y44.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031215; ENSMUSP00000031215; ENSMUSG00000029279. [Q91Y44-1]
ENSMUST00000112677; ENSMUSP00000108297; ENSMUSG00000029279. [Q91Y44-2]
GeneID114642.
KEGGmmu:114642.
UCSCuc008ymb.1. mouse. [Q91Y44-2]
uc008ymc.1. mouse.

Organism-specific databases

CTD676.
MGIMGI:1891374. Brdt.

Phylogenomic databases

eggNOGCOG5076.
GeneTreeENSGT00730000110626.
HOGENOMHOG000231200.
HOVERGENHBG004896.
InParanoidQ91Y44.
KOK11724.
OMAENQRDLG.
OrthoDBEOG7TTQ86.
TreeFamTF317345.

Gene expression databases

ArrayExpressQ91Y44.
BgeeQ91Y44.
CleanExMM_BRDT.
GenevestigatorQ91Y44.

Family and domain databases

Gene3D1.20.920.10. 2 hits.
InterProIPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamPF00439. Bromodomain. 2 hits.
[Graphical view]
PRINTSPR00503. BROMODOMAIN.
SMARTSM00297. BROMO. 2 hits.
[Graphical view]
SUPFAMSSF47370. SSF47370. 2 hits.
PROSITEPS00633. BROMODOMAIN_1. 2 hits.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBRDT. mouse.
EvolutionaryTraceQ91Y44.
NextBio368594.
PROQ91Y44.
SOURCESearch...

Entry information

Entry nameBRDT_MOUSE
AccessionPrimary (citable) accession number: Q91Y44
Secondary accession number(s): G3X8Z8, Q59HJ4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: November 28, 2012
Last modified: July 9, 2014
This is version 95 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot