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Protein

Bromodomain testis-specific protein

Gene

Brdt

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (PubMed:12861021, PubMed:19794495, PubMed:22901802, PubMed:22922464). 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 (PubMed:22901802). Also recognizes and binds a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (PubMed:27105113). 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 (PubMed:22570411). Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin (PubMed:22020252).7 Publications

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei108Histone H4K5ac1 Publication1
Binding sitei108JQ1 inhibitorBy similarity1
Binding sitei113Histone H4K5ac1 Publication1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator
Biological processDifferentiation, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1891374 Brdt

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 214 organ(s), highest expression level in oocyte
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi227777, 1 interactor
DIPiDIP-48975N
IntActiQ91Y44, 6 interactors
MINTiQ91Y44
STRINGi10090.ENSMUSP00000031215

Structurei

Secondary structure

1956
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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). The bromo domains also recognize and bind a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (PubMed:27105113).2 Publications

Keywords - Domaini

Bromodomain, Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1474 Eukaryota
COG5076 LUCA
GeneTreeiENSGT00930000150866
HOGENOMiHOG000231200
HOVERGENiHBG004896
InParanoidiQ91Y44
KOiK11724
OMAiKEPKVSQ
OrthoDBiEOG091G01QC
TreeFamiTF317345

Family and domain databases

Gene3Di1.20.1270.220, 1 hit
1.20.920.10, 2 hits
InterProiView protein in InterPro
IPR031354 BRD4_CDT
IPR001487 Bromodomain
IPR036427 Bromodomain-like_sf
IPR018359 Bromodomain_CS
IPR027353 NET_dom
IPR038336 NET_sf
PfamiView protein in Pfam
PF17035 BET, 1 hit
PF17105 BRD4_CDT, 1 hit
PF00439 Bromodomain, 2 hits
PRINTSiPR00503 BROMODOMAIN
SMARTiView protein in SMART
SM00297 BROMO, 2 hits
SUPFAMiSSF47370 SSF47370, 2 hits
PROSITEiView protein in PROSITE
PS00633 BROMODOMAIN_1, 2 hits
PS50014 BROMODOMAIN_2, 2 hits
PS51525 NET, 1 hit

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

Similar proteinsi

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
MINTiQ91Y44
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
GeneTreeiENSGT00930000150866
HOGENOMiHOG000231200
HOVERGENiHBG004896
InParanoidiQ91Y44
KOiK11724
OMAiKEPKVSQ
OrthoDBiEOG091G01QC
TreeFamiTF317345

Miscellaneous databases

ChiTaRSiBrdt mouse
EvolutionaryTraceiQ91Y44
PROiPR:Q91Y44
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029279 Expressed in 214 organ(s), highest expression level in oocyte
CleanExiMM_BRDT
GenevisibleiQ91Y44 MM

Family and domain databases

Gene3Di1.20.1270.220, 1 hit
1.20.920.10, 2 hits
InterProiView protein in InterPro
IPR031354 BRD4_CDT
IPR001487 Bromodomain
IPR036427 Bromodomain-like_sf
IPR018359 Bromodomain_CS
IPR027353 NET_dom
IPR038336 NET_sf
PfamiView protein in Pfam
PF17035 BET, 1 hit
PF17105 BRD4_CDT, 1 hit
PF00439 Bromodomain, 2 hits
PRINTSiPR00503 BROMODOMAIN
SMARTiView protein in SMART
SM00297 BROMO, 2 hits
SUPFAMiSSF47370 SSF47370, 2 hits
PROSITEiView protein in PROSITE
PS00633 BROMODOMAIN_1, 2 hits
PS50014 BROMODOMAIN_2, 2 hits
PS51525 NET, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBRDT_MOUSE
AccessioniPrimary (citable) accession number: Q91Y44
Secondary accession number(s): G3X8Z8, Q59HJ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: November 28, 2012
Last modified: November 7, 2018
This is version 124 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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
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