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Protein

Bromodomain testis-specific protein

Gene

Brdt

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei108Histone H4K5ac1
Binding sitei108JQ1 inhibitorBy similarity1
Binding sitei113Histone H4K5ac1

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • lysine-acetylated histone binding Source: UniProtKB

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • chromatin modification Source: UniProtKB-KW
  • chromatin remodeling Source: UniProtKB
  • histone displacement Source: UniProtKB
  • male meiosis Source: UniProtKB
  • male meiosis I Source: UniProtKB
  • mRNA processing Source: UniProtKB-KW
  • positive regulation of transcription involved in meiotic cell cycle Source: UniProtKB
  • regulation of RNA splicing Source: UniProtKB
  • RNA splicing Source: UniProtKB-KW
  • spermatogenesis Source: UniProtKB
  • 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
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1891374. Brdt.

Subcellular locationi

GO - Cellular componenti

  • 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)DescriptionActionsGraphical viewLength
Mutagenesisi50 – 51PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-55. 1 Publication2
Mutagenesisi55V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 50-AA-51. 1 Publication1
Mutagenesisi293 – 294PF → AA: Abolishes interaction with histone H4 acetylated N-terminus; when associated with A-298. 1 Publication2
Mutagenesisi298V → A: Abolishes interaction with histone H4 acetylated N-terminus; when associated with 293-AA-294. 1 Publication1

Chemistry databases

GuidetoPHARMACOLOGYi2729.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002392271 – 956Bromodomain testis-specific proteinAdd BLAST956

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei186PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ91Y44.
PeptideAtlasiQ91Y44.
PRIDEiQ91Y44.

PTM databases

iPTMnetiQ91Y44.
PhosphoSitePlusiQ91Y44.

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

BgeeiENSMUSG00000029279.
CleanExiMM_BRDT.
GenevisibleiQ91Y44. MM.

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

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • lysine-acetylated histone binding Source: UniProtKB

Protein-protein interaction databases

BioGridi227777. 1 interactor.
DIPiDIP-48975N.
IntActiQ91Y44. 6 interactors.
MINTiMINT-8409453.
STRINGi10090.ENSMUSP00000031215.

Structurei

Secondary structure

1956
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 36Combined sources8
Helixi38 – 43Combined sources6
Helixi46 – 51Combined sources6
Turni57 – 61Combined sources5
Helixi65 – 68Combined sources4
Helixi75 – 83Combined sources9
Helixi90 – 107Combined sources18
Helixi113 – 129Combined sources17
Helixi264 – 282Combined sources19
Helixi285 – 287Combined sources3
Helixi288 – 291Combined sources4
Helixi292 – 294Combined sources3
Helixi300 – 303Combined sources4
Helixi308 – 311Combined sources4
Helixi318 – 326Combined sources9
Helixi333 – 350Combined sources18
Helixi356 – 372Combined sources17
Beta strandi375 – 377Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WP1X-ray2.10A/B257-382[»]
2WP2X-ray2.37A/B17-136[»]
ProteinModelPortaliQ91Y44.
SMRiQ91Y44.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ91Y44.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 115Bromo 1PROSITE-ProRule annotationAdd BLAST73
Domaini286 – 358Bromo 2PROSITE-ProRule annotationAdd BLAST73
Domaini496 – 578NETPROSITE-ProRule annotationAdd BLAST83

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili417 – 442Sequence analysisAdd BLAST26
Coiled coili844 – 940Sequence analysisAdd BLAST97

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi208 – 219Nuclear localization signalBy similarityAdd BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi446 – 496Lys-richAdd BLAST51
Compositional biasi625 – 639Pro-richAdd BLAST15
Compositional biasi643 – 689Ser-richAdd BLAST47

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

eggNOGiKOG1474. Eukaryota.
COG5076. LUCA.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiQ91Y44.
KOiK11724.
OMAiENQRDLG.
OrthoDBiEOG091G01QC.
TreeFamiTF317345.

Family and domain databases

Gene3Di1.20.920.10. 2 hits.
InterProiIPR031354. BRD4_CDT.
IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamiPF17035. BET. 1 hit.
PF17105. BRD4_CDT. 1 hit.
PF00439. 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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Sequence conflicti208K → R in BAD91553 (Ref. 2) Curated1
Sequence conflicti691S → F in AAK50736 (PubMed:15261828).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_019119323 – 326GKMD → VNTA in isoform 2. 1 Publication4
Alternative sequenceiVSP_019120327 – 956Missing in isoform 2. 1 PublicationAdd BLAST630

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [Q91Y44-1]

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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WP1X-ray2.10A/B257-382[»]
2WP2X-ray2.37A/B17-136[»]
ProteinModelPortaliQ91Y44.
SMRiQ91Y44.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi227777. 1 interactor.
DIPiDIP-48975N.
IntActiQ91Y44. 6 interactors.
MINTiMINT-8409453.
STRINGi10090.ENSMUSP00000031215.

Chemistry databases

GuidetoPHARMACOLOGYi2729.

PTM databases

iPTMnetiQ91Y44.
PhosphoSitePlusiQ91Y44.

Proteomic databases

PaxDbiQ91Y44.
PeptideAtlasiQ91Y44.
PRIDEiQ91Y44.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi676.
MGIiMGI:1891374. Brdt.

Phylogenomic databases

eggNOGiKOG1474. Eukaryota.
COG5076. LUCA.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiQ91Y44.
KOiK11724.
OMAiENQRDLG.
OrthoDBiEOG091G01QC.
TreeFamiTF317345.

Miscellaneous databases

ChiTaRSiBrdt. mouse.
EvolutionaryTraceiQ91Y44.
PROiQ91Y44.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029279.
CleanExiMM_BRDT.
GenevisibleiQ91Y44. MM.

Family and domain databases

Gene3Di1.20.920.10. 2 hits.
InterProiIPR031354. BRD4_CDT.
IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamiPF17035. BET. 1 hit.
PF17105. BRD4_CDT. 1 hit.
PF00439. 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]
ProtoNetiSearch...

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: November 2, 2016
This is version 111 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.