UniProt functional annotation for Q58F21



	UniProt functional annotation for Q58F21

UniProt code: Q58F21.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:22464331, PubMed:22901802). 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 (PubMed:22901802). 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) (By similarity). 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 (By similarity). Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin. {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:15647849, ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:22901802, ECO:0000269|PubMed:9367677}.

Subunit: 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. Interacts with SMARCE1 (By similarity). Interacts with the acetylated N-terminus of histone H1.4, H2A, H2B, H3 and H4. {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:22901802}.

Subcellular location: Nucleus {ECO:0000269|PubMed:20538714, ECO:0000269|PubMed:22901802, ECO:0000269|PubMed:22971749}. Note=Detected on chromatin. {ECO:0000250|UniProtKB:Q91Y44}.

Tissue specificity: Testis-specific. A 3-fold higher expression is seen in adult testis than in embryo testis. Expression seems to be correlated with histone H4 hyperacetylation during the haploid phase of spermatogenesis (spermiogenesis). No expression, or very low expression is seen in patients' testes with abnormal spermatogenesis. Expressed in cancers such as non-small cell lung cancer and squamous cell carcinomas of the head and neck as well as of esophagus, but not in melanoma or in cancers of the colon, breast, kidney and bladder. {ECO:0000269|PubMed:10704737, ECO:0000269|PubMed:15647849, ECO:0000269|PubMed:9367677}.

Developmental stage: Expressed in embryo testis.

Domain: Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions (PubMed:22464331). Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) (PubMed:22901802). 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) (By similarity). {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:22901802}.

Disease: Spermatogenic failure 21 (SPGF21) [MIM:617644]: An infertility disorder caused by spermatogenesis defects and characterized by acephalic spermatozoa in the semen of affected individuals. SPGF21 inheritance is autosomal recessive. {ECO:0000269|PubMed:28199965}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: BRDT is a promising target for male contraception. Inhibition by thienodiazepine inhibitor (+)-JQ1 that binds Asn-109, prevents recognition of acetylated histone H4, causing a complete and reversible contraceptive effect in male mice (PubMed:22901802). {ECO:0000305|PubMed:22901802}.

Sequence caution: Sequence=AAH05281.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH47900.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH62700.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:22464331, PubMed:22901802). 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 (PubMed:22901802). 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) (By similarity). 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 (By similarity). Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin. {ECO:0000250\|UniProtKB:Q91Y44, ECO:0000269\|PubMed:15647849, ECO:0000269\|PubMed:22464331, ECO:0000269\|PubMed:22901802, ECO:0000269\|PubMed:9367677}.


Subunit:		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. Interacts with SMARCE1 (By similarity). Interacts with the acetylated N-terminus of histone H1.4, H2A, H2B, H3 and H4. {ECO:0000250\|UniProtKB:Q91Y44, ECO:0000269\|PubMed:22464331, ECO:0000269\|PubMed:22901802}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:20538714, ECO:0000269\|PubMed:22901802, ECO:0000269\|PubMed:22971749}. Note=Detected on chromatin. {ECO:0000250\|UniProtKB:Q91Y44}.
Tissue specificity:		Testis-specific. A 3-fold higher expression is seen in adult testis than in embryo testis. Expression seems to be correlated with histone H4 hyperacetylation during the haploid phase of spermatogenesis (spermiogenesis). No expression, or very low expression is seen in patients' testes with abnormal spermatogenesis. Expressed in cancers such as non-small cell lung cancer and squamous cell carcinomas of the head and neck as well as of esophagus, but not in melanoma or in cancers of the colon, breast, kidney and bladder. {ECO:0000269\|PubMed:10704737, ECO:0000269\|PubMed:15647849, ECO:0000269\|PubMed:9367677}.
Developmental stage:		Expressed in embryo testis.
Domain:		Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions (PubMed:22464331). Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) (PubMed:22901802). 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) (By similarity). {ECO:0000250\|UniProtKB:Q91Y44, ECO:0000269\|PubMed:22464331, ECO:0000269\|PubMed:22901802}.
Disease:		Spermatogenic failure 21 (SPGF21) [MIM:617644]: An infertility disorder caused by spermatogenesis defects and characterized by acephalic spermatozoa in the semen of affected individuals. SPGF21 inheritance is autosomal recessive. {ECO:0000269\|PubMed:28199965}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		BRDT is a promising target for male contraception. Inhibition by thienodiazepine inhibitor (+)-JQ1 that binds Asn-109, prevents recognition of acetylated histone H4, causing a complete and reversible contraceptive effect in male mice (PubMed:22901802). {ECO:0000305\|PubMed:22901802}.
Sequence caution:		Sequence=AAH05281.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH47900.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH62700.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};