UniProt functional annotation for Q91Y44



	UniProt functional annotation for Q91Y44

UniProt code: Q91Y44.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 (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). {ECO:0000269|PubMed:12861021, ECO:0000269|PubMed:19794495, ECO:0000269|PubMed:22020252, ECO:0000269|PubMed:22570411, ECO:0000269|PubMed:22901802, ECO:0000269|PubMed:22922464, ECO:0000269|PubMed:27105113}.

Subunit: 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. {ECO:0000250|UniProtKB:Q58F21, ECO:0000269|PubMed:12861021, ECO:0000269|PubMed:19794495, ECO:0000269|PubMed:22570411, ECO:0000269|PubMed:22922464}.

Subcellular location: Nucleus {ECO:0000269|PubMed:17728347, ECO:0000269|PubMed:19794495, ECO:0000269|PubMed:22020252}. Note=Detected on chromatin (PubMed:19794495). Excluded from the chromocenter. {ECO:0000269|PubMed:19794495, ECO:0000269|PubMed:22020252}.

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. {ECO:0000269|PubMed:15261828, ECO:0000269|PubMed:17049203, ECO:0000269|PubMed:17728347}.

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). {ECO:0000269|PubMed:22922464}.

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) (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). {ECO:0000269|PubMed:19794495, ECO:0000269|PubMed:27105113}.

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. {ECO:0000269|PubMed:17728347, ECO:0000269|PubMed:22020252, ECO:0000269|PubMed:22922464}.

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). {ECO:0000305|PubMed:22901802}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 (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). {ECO:0000269\|PubMed:12861021, ECO:0000269\|PubMed:19794495, ECO:0000269\|PubMed:22020252, ECO:0000269\|PubMed:22570411, ECO:0000269\|PubMed:22901802, ECO:0000269\|PubMed:22922464, ECO:0000269\|PubMed:27105113}.


Subunit:		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. {ECO:0000250\|UniProtKB:Q58F21, ECO:0000269\|PubMed:12861021, ECO:0000269\|PubMed:19794495, ECO:0000269\|PubMed:22570411, ECO:0000269\|PubMed:22922464}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:17728347, ECO:0000269\|PubMed:19794495, ECO:0000269\|PubMed:22020252}. Note=Detected on chromatin (PubMed:19794495). Excluded from the chromocenter. {ECO:0000269\|PubMed:19794495, ECO:0000269\|PubMed:22020252}.
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. {ECO:0000269\|PubMed:15261828, ECO:0000269\|PubMed:17049203, ECO:0000269\|PubMed:17728347}.
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). {ECO:0000269\|PubMed:22922464}.
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) (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). {ECO:0000269\|PubMed:19794495, ECO:0000269\|PubMed:27105113}.
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. {ECO:0000269\|PubMed:17728347, ECO:0000269\|PubMed:22020252, ECO:0000269\|PubMed:22922464}.
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). {ECO:0000305\|PubMed:22901802}.