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Q91Y44

- BRDT_MOUSE

UniProt

Q91Y44 - BRDT_MOUSE

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Protein

Bromodomain testis-specific protein

Gene

Brdt

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei108 – 1081Histone H4K5ac
Binding sitei108 – 1081JQ1 inhibitorBy similarity
Binding sitei113 – 1131Histone H4K5ac

GO - Molecular functioni

  1. histone binding Source: UniProtKB
  2. lysine-acetylated histone binding Source: UniProtKB

GO - Biological processi

  1. cell differentiation Source: UniProtKB-KW
  2. chromatin remodeling Source: UniProtKB
  3. histone displacement Source: UniProtKB
  4. male meiosis Source: UniProtKB
  5. male meiosis I Source: UniProtKB
  6. mRNA processing Source: UniProtKB-KW
  7. positive regulation of transcription during meiosis Source: UniProtKB
  8. regulation of RNA splicing Source: UniProtKB
  9. RNA splicing Source: UniProtKB-KW
  10. spermatogenesis Source: UniProtKB
  11. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator

Keywords - Biological processi

Differentiation, Meiosis, mRNA processing, mRNA splicing, Spermatogenesis, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Bromodomain testis-specific protein
Alternative name(s):
Bromodomain-containing female sterile homeotic-like protein
RING3-like protein
Gene namesi
Name:Brdt
Synonyms:Fsrg3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:1891374. Brdt.

Subcellular locationi

Nucleus 3 Publications
Note: Detected on chromatin. Excluded from the chromocenter.

GO - Cellular componenti

  1. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi50 – 512PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-55. 1 Publication
Mutagenesisi55 – 551V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 50-AA-51. 1 Publication
Mutagenesisi293 – 2942PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-298. 1 Publication
Mutagenesisi298 – 2981V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 293-AA-294. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 956956Bromodomain testis-specific proteinPRO_0000239227Add
BLAST

Proteomic databases

PaxDbiQ91Y44.
PRIDEiQ91Y44.

PTM databases

PhosphoSiteiQ91Y44.

Expressioni

Tissue specificityi

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.3 Publications

Developmental stagei

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).1 Publication

Gene expression databases

BgeeiQ91Y44.
CleanExiMM_BRDT.
ExpressionAtlasiQ91Y44. baseline and differential.
GenevestigatoriQ91Y44.

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ccnt1Q9QWV92EBI-6260929,EBI-2655009
Cdk9Q99J953EBI-6260929,EBI-2654963

Protein-protein interaction databases

BioGridi227777. 1 interaction.
DIPiDIP-48975N.
IntActiQ91Y44. 5 interactions.
MINTiMINT-8409453.
STRINGi10090.ENSMUSP00000108297.

Structurei

Secondary structure

1
956
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi29 – 368
Helixi38 – 436
Helixi46 – 516
Turni57 – 615
Helixi65 – 684
Helixi75 – 839
Helixi90 – 10718
Helixi113 – 12917
Helixi264 – 28219
Helixi285 – 2873
Helixi288 – 2914
Helixi292 – 2943
Helixi300 – 3034
Helixi308 – 3114
Helixi318 – 3269
Helixi333 – 35018
Helixi356 – 37217
Beta strandi375 – 3773

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2WP1X-ray2.10A/B257-382[»]
2WP2X-ray2.37A/B17-136[»]
ProteinModelPortaliQ91Y44.
SMRiQ91Y44. Positions 27-136, 259-381, 501-579.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ91Y44.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini43 – 11573Bromo 1PROSITE-ProRule annotationAdd
BLAST
Domaini286 – 35873Bromo 2PROSITE-ProRule annotationAdd
BLAST
Domaini496 – 57883NETPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili417 – 44226Sequence AnalysisAdd
BLAST
Coiled coili844 – 94097Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi208 – 21912Nuclear localization signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi446 – 49651Lys-richAdd
BLAST
Compositional biasi625 – 63915Pro-richAdd
BLAST
Compositional biasi643 – 68947Ser-richAdd
BLAST

Domaini

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) (PubMed:19794495).1 Publication

Sequence similaritiesi

Contains 2 bromo domains.PROSITE-ProRule annotation
Contains 1 NET domain.PROSITE-ProRule annotation

Keywords - Domaini

Bromodomain, Coiled coil, Repeat

Phylogenomic databases

eggNOGiCOG5076.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiQ91Y44.
KOiK11724.
OMAiENQRDLG.
OrthoDBiEOG7TTQ86.
TreeFamiTF317345.

Family and domain databases

Gene3Di1.20.920.10. 2 hits.
InterProiIPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamiPF00439. Bromodomain. 2 hits.
[Graphical view]
PRINTSiPR00503. BROMODOMAIN.
SMARTiSM00297. BROMO. 2 hits.
[Graphical view]
SUPFAMiSSF47370. SSF47370. 2 hits.
PROSITEiPS00633. BROMODOMAIN_1. 2 hits.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q91Y44-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MSLPSRQTAI VNPPPPEYIN TKKSGRLTNQ LQFLQRVVLK ALWKHGFSWP
60 70 80 90 100
FQQPVDAVKL KLPDYYTIIK TPMDLNTIKK RLENKYYEKA SECIEDFNTM
110 120 130 140 150
FSNCYLYNKT GDDIVVMAQA LEKLFMQKLS QMPQEEQVVG GKERIKKDIQ
160 170 180 190 200
QKIAVSSAKE QIPSKAAENV FKRQEIPSGL PDISLSPLNM AQEAPPICDS
210 220 230 240 250
QSLVQITKGV KRRADTTTPT TSIAKASSES PPTLRETKPV NMPVKENTVK
260 270 280 290 300
NVLPDSQQQH KVLKTVKVTE QLKHCSEILK EMLAKKHLPY AWPFYNPVDA
310 320 330 340 350
DALGLHNYYD VVKNPMDLGT IKGKMDNQEY KDAYEFAADV RLMFMNCYKY
360 370 380 390 400
NPPDHEVVAM ARTLQDVFEL HFAKIPDEPI ESMHACHLTT NSAQALSRES
410 420 430 440 450
SSEASSGDAS SEDSEDERVQ HLAKLQEQLN AVHQQLQVLS QVPLRKLKKK
460 470 480 490 500
NEKSKRAPKR KKVNNRDENP RKKPKQMKQK EKAKINQPKK KKPLLKSEEE
510 520 530 540 550
DNAKPMNYDE KRQLSLDINK LPGDKLGRIV HIIQSREPSL RNSNPDEIEI
560 570 580 590 600
DFETLKASTL RELEKYVLAC LRKRSLKPQA KKVVRSKEEL HSEKKLELER
610 620 630 640 650
RLLDVNNQLN CRKRQTKRPA KVEKPPPPPP PPPPPPPPPE LASGSRLTDS
660 670 680 690 700
SSSSGSGSGS SSSSSGSSSS SSSSGSASSS SDSSSSDSSD SEPEIFPKFT
710 720 730 740 750
GVKQNDLPPK ENIKQIQSSV QDITSAEAPL AQQSTAPCGA PGKHSQQMLG
760 770 780 790 800
CQVTQHLQAT ENTASVQTQP LSGDCKRVLL GPPVVHTSAE SLTVLEPECH
810 820 830 840 850
APAQKDIKIK NADSWKSLGK PVKASSVLKS SDELFNQFRK AAIEKEVKAR
860 870 880 890 900
TQEQMRKHLE HNAKDPKVSQ ENQREPGSGL TLESLSSKVQ DKSLEEDQSE
910 920 930 940 950
QQPPSEAQDV SKLWLLKDRN LAREKEQERR RREAMAGTID MTLQSDIMTM

FENNFD
Length:956
Mass (Da):107,255
Last modified:November 28, 2012 - v3
Checksum:iE727044706A67260
GO
Isoform 2 (identifier: Q91Y44-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:326
Mass (Da):36,914
Checksum:i26432C1A10E68E1C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti208 – 2081K → R in BAD91553. 1 PublicationCurated
Sequence conflicti691 – 6911S → F in AAK50736. (PubMed:15261828)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei323 – 3264GKMD → VNTA in isoform 2. 1 PublicationVSP_019119
Alternative sequencei327 – 956630Missing in isoform 2. 1 PublicationVSP_019120Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF358660 mRNA. Translation: AAK50736.1.
AB208640 mRNA. Translation: BAD91553.1.
AC126598 Genomic DNA. No translation available.
CH466529 Genomic DNA. Translation: EDL20168.1.
CCDSiCCDS19500.1. [Q91Y44-1]
CCDS39197.1. [Q91Y44-2]
RefSeqiNP_001073342.1. NM_001079873.1. [Q91Y44-2]
NP_473395.2. NM_054054.2. [Q91Y44-1]
UniGeneiMm.182836.

Genome annotation databases

EnsembliENSMUST00000031215; ENSMUSP00000031215; ENSMUSG00000029279. [Q91Y44-1]
ENSMUST00000112677; ENSMUSP00000108297; ENSMUSG00000029279. [Q91Y44-2]
GeneIDi114642.
KEGGimmu:114642.
UCSCiuc008ymb.1. mouse. [Q91Y44-2]
uc008ymc.1. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Protein Spotlight

Asking life to be patient - Issue 144 of November 2012

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF358660 mRNA. Translation: AAK50736.1 .
AB208640 mRNA. Translation: BAD91553.1 .
AC126598 Genomic DNA. No translation available.
CH466529 Genomic DNA. Translation: EDL20168.1 .
CCDSi CCDS19500.1. [Q91Y44-1 ]
CCDS39197.1. [Q91Y44-2 ]
RefSeqi NP_001073342.1. NM_001079873.1. [Q91Y44-2 ]
NP_473395.2. NM_054054.2. [Q91Y44-1 ]
UniGenei Mm.182836.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2WP1 X-ray 2.10 A/B 257-382 [» ]
2WP2 X-ray 2.37 A/B 17-136 [» ]
ProteinModelPortali Q91Y44.
SMRi Q91Y44. Positions 27-136, 259-381, 501-579.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 227777. 1 interaction.
DIPi DIP-48975N.
IntActi Q91Y44. 5 interactions.
MINTi MINT-8409453.
STRINGi 10090.ENSMUSP00000108297.

PTM databases

PhosphoSitei Q91Y44.

Proteomic databases

PaxDbi Q91Y44.
PRIDEi Q91Y44.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000031215 ; ENSMUSP00000031215 ; ENSMUSG00000029279 . [Q91Y44-1 ]
ENSMUST00000112677 ; ENSMUSP00000108297 ; ENSMUSG00000029279 . [Q91Y44-2 ]
GeneIDi 114642.
KEGGi mmu:114642.
UCSCi uc008ymb.1. mouse. [Q91Y44-2 ]
uc008ymc.1. mouse.

Organism-specific databases

CTDi 676.
MGIi MGI:1891374. Brdt.

Phylogenomic databases

eggNOGi COG5076.
GeneTreei ENSGT00760000119206.
HOGENOMi HOG000231200.
HOVERGENi HBG004896.
InParanoidi Q91Y44.
KOi K11724.
OMAi ENQRDLG.
OrthoDBi EOG7TTQ86.
TreeFami TF317345.

Miscellaneous databases

ChiTaRSi BRDT. mouse.
EvolutionaryTracei Q91Y44.
NextBioi 368594.
PROi Q91Y44.
SOURCEi Search...

Gene expression databases

Bgeei Q91Y44.
CleanExi MM_BRDT.
ExpressionAtlasi Q91Y44. baseline and differential.
Genevestigatori Q91Y44.

Family and domain databases

Gene3Di 1.20.920.10. 2 hits.
InterProi IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view ]
Pfami PF00439. Bromodomain. 2 hits.
[Graphical view ]
PRINTSi PR00503. BROMODOMAIN.
SMARTi SM00297. BROMO. 2 hits.
[Graphical view ]
SUPFAMi SSF47370. SSF47370. 2 hits.
PROSITEi PS00633. BROMODOMAIN_1. 2 hits.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: FUNCTION.
  10. 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. Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 17-136 AND 257-382 IN COMPLEX WITH HISTONE H4 PEPTIDE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiBRDT_MOUSE
AccessioniPrimary (citable) accession number: Q91Y44
Secondary accession number(s): G3X8Z8, Q59HJ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: November 28, 2012
Last modified: October 29, 2014
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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 (PubMed:22901802).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3