Q91Y44 (BRDT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bromodomain testis-specific protein

Alternative name(s):
Bromodomain-containing female sterile homeotic-like protein
RING3-like protein

Gene names

Name:	Brdt
Synonyms:	Fsrg3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	956 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Differentiation Meiosis Spermatogenesis Transcription Transcription regulation mRNA processing mRNA splicing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Bromodomain Coiled coil Repeat
Molecular function	Activator Chromatin regulator
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA 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 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.6Ref.12. Source: UniProtKB
Molecular_function	histone acetyl-lysine binding Inferred from mutant phenotype Ref.10. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 956

956

Bromodomain testis-specific protein

PRO_0000239227

Regions

Domain

43 – 115

73

Bromo 1

Domain

286 – 358

73

Bromo 2

Domain

496 – 578

83

NET

Coiled coil

417 – 442

26

Potential

Coiled coil

844 – 940

97

Potential

Motif

208 – 219

12

Nuclear localization signal By similarity

Compositional bias

446 – 496

51

Lys-rich

Compositional bias

625 – 639

15

Pro-rich

Compositional bias

643 – 689

47

Ser-rich

Sites

Binding site

108

1

Histone H4K5ac

Binding site

108

1

JQ1 inhibitor By similarity

Binding site

113

1

Histone H4K5ac

Natural variations

Alternative sequence

323 – 326

4

GKMD → VNTA in isoform 2.

VSP_019119

Alternative sequence

327 – 956

630

Missing in isoform 2.

VSP_019120

Experimental info

Mutagenesis

50 – 51

2

PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-55.

Mutagenesis

55

1

V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 50-AA-51. Ref.5

Mutagenesis

293 – 294

2

PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-298.

Mutagenesis

298

1

V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 293-AA-294. Ref.5

Sequence conflict

208

1

K → R in BAD91553. Ref.2

Sequence conflict

691

1

S → F in AAK50736. Ref.1

Secondary structure

1

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956

Helix Strand Turn

Details...

Helix

29 – 36

8

Helix

38 – 43

6

Helix

46 – 51

6

Turn

57 – 61

5

Helix

65 – 68

4

Helix

75 – 83

9

Helix

90 – 107

18

Helix

113 – 129

17

Helix

264 – 282

19

Helix

285 – 287

3

Helix

288 – 291

4

Helix

292 – 294

3

Helix

300 – 303

4

Helix

308 – 311

4

Helix

318 – 326

9

Helix

333 – 350

18

Helix

356 – 372

17

Beta strand

375 – 377

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2012. Version 3. Checksum: E727044706A67260	FASTA	956	107,255
	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
	Isoform 2 [UniParc]. Checksum: 26432C1A10E68E1C	FASTA	326	36,914
	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 DALGLHNYYD VVKNPMDLGT IKVNTA

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00129480.
IPI00760098.

RefSeq

NP_001073342.1. NM_001079873.1.
NP_473395.2. NM_054054.2.

UniGene

Mm.182836.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q91Y44.

SMR

Q91Y44. Positions 27-136, 259-381, 501-579.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48975N.

IntAct

Q91Y44. 1 interaction.

MINT

MINT-8409453.

STRING

10090.ENSMUSP00000108297.

PTM databases

PhosphoSite

Q91Y44.

Proteomic databases

PaxDb

Q91Y44.

PRIDE

Q91Y44.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000031215; ENSMUSP00000031215; ENSMUSG00000029279.
ENSMUST00000112677; ENSMUSP00000108297; ENSMUSG00000029279.

GeneID

114642.

KEGG

mmu:114642.

UCSC

uc008ymb.1. mouse.
uc008ymc.1. mouse.

Organism-specific databases

CTD

676.

MGI

MGI:1891374. Brdt.

Phylogenomic databases

eggNOG

COG5076.

GeneTree

ENSGT00700000104261.

HOGENOM

HOG000231200.

HOVERGEN

HBG004896.

InParanoid

Q91Y44.

KO

K11724.

OMA

GVMKSSD.

OrthoDB

EOG4NVZJT.

Gene expression databases

ArrayExpress

Q91Y44.

Bgee

Q91Y44.

CleanEx

MM_BRDT.

Genevestigator

Q91Y44.

GermOnline

ENSMUSG00000029279. Mus musculus.

Family and domain databases

Gene3D

1.20.920.10. 2 hits.

InterPro

IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]

Pfam

PF00439. Bromodomain. 2 hits.
[Graphical view]

PRINTS

PR00503. BROMODOMAIN.

SMART

SM00297. BROMO. 2 hits.
[Graphical view]

SUPFAM

SSF47370. Bromodomain. 2 hits.

PROSITE

PS00633. BROMODOMAIN_1. 2 hits.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BRDT. mouse.

EvolutionaryTrace

Q91Y44.

NextBio

368594.

SOURCE

Search...

Entry information

Entry name

BRDT_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program