BRDT_HUMAN
ID BRDT_HUMAN Reviewed; 947 AA.
AC Q58F21; A6NF68; B7Z811; B7Z890; B7ZAX7; D3DT32; O14789; Q05DQ4; Q6P5T1;
AC Q7Z4A6; Q8IWI6;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 4.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Bromodomain testis-specific protein;
DE AltName: Full=Cancer/testis antigen 9;
DE Short=CT9;
DE AltName: Full=RING3-like protein;
GN Name=BRDT;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP VARIANTS LYS-62 AND LEU-696.
RX PubMed=9367677; DOI=10.1006/geno.1997.5000;
RA Jones M.H., Numata M., Shimane M.;
RT "Identification and characterization of BRDT: a testis-specific gene
RT related to the bromodomain genes RING3 and Drosophila fsh.";
RL Genomics 45:529-534(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ALTERNATIVE SPLICING,
RP TISSUE SPECIFICITY, AND VARIANTS LYS-62 AND LEU-696.
RC TISSUE=Testis;
RX PubMed=15647849;
RA Zheng Y., Yuan W., Zhou Z., Xu M., Sha J.-H.;
RT "Molecular cloning and expression of a novel alternative splice variant of
RT BRDT gene.";
RL Int. J. Mol. Med. 15:315-321(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANTS
RP LYS-62 AND LEU-696.
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-62 AND
RP LEU-696.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-462 (ISOFORM 1), AND VARIANTS
RP LYS-62; ASN-238 AND LYS-410.
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY, AND IDENTIFICATION AS A CANCER/TESTIS ANTIGEN.
RX PubMed=10704737; DOI=10.1016/s0304-3835(99)00385-7;
RA Scanlan M.J., Altorki N.K., Gure A.O., Williamson B., Jungbluth A.,
RA Chen Y.-T., Old L.J.;
RT "Expression of cancer-testis antigens in lung cancer: definition of
RT bromodomain testis-specific gene (BRDT) as a new CT gene, CT9.";
RL Cancer Lett. 150:155-164(2000).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-2; GLN-6; VAL-89; ASN-238; TYR-288;
RP LYS-357; LYS-410 AND ALA-542.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=20538714; DOI=10.1530/rep-10-0139;
RA Steilmann C., Cavalcanti M.C., Bartkuhn M., Pons-Kuhnemann J.,
RA Schuppe H.C., Weidner W., Steger K., Paradowska A.;
RT "The interaction of modified histones with the bromodomain testis-specific
RT (BRDT) gene and its mRNA level in sperm of fertile donors and subfertile
RT men.";
RL Reproduction 140:435-443(2010).
RN [10]
RP SUBCELLULAR LOCATION, AND MOTIF NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=22971749; DOI=10.1248/bpb.b12-00527;
RA Fukazawa H., Masumi A.;
RT "The conserved 12-amino acid stretch in the inter-bromodomain region of BET
RT family proteins functions as a nuclear localization signal.";
RL Biol. Pharm. Bull. 35:2064-2068(2012).
RN [11] {ECO:0007744|PDB:2RFJ}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 21-137, FUNCTION, SUBUNIT, AND
RP DOMAIN.
RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA Gingras A.C., Arrowsmith C.H., Knapp S.;
RT "Histone recognition and large-scale structural analysis of the human
RT bromodomain family.";
RL Cell 149:214-231(2012).
RN [12] {ECO:0007744|PDB:4FLP}
RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 21-137 IN COMPLEX WITH JQ1,
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=22901802; DOI=10.1016/j.cell.2012.06.045;
RA Matzuk M.M., McKeown M.R., Filippakopoulos P., Li Q., Ma L., Agno J.E.,
RA Lemieux M.E., Picaud S., Yu R.N., Qi J., Knapp S., Bradner J.E.;
RT "Small-molecule inhibition of BRDT for male contraception.";
RL Cell 150:673-684(2012).
RN [13]
RP VARIANT SPGF21 ASP-928, AND CHARACTERIZATION OF VARIANT SPGF21 ASP-928.
RX PubMed=28199965; DOI=10.18632/oncotarget.15251;
RA Li L., Sha Y., Wang X., Li P., Wang J., Kee K., Wang B.;
RT "Whole-exome sequencing identified a homozygous BRDT mutation in a patient
RT with acephalic spermatozoa.";
RL Oncotarget 8:19914-19922(2017).
CC -!- FUNCTION: Testis-specific chromatin protein that specifically binds
CC histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac,
CC respectively) and plays a key role in spermatogenesis (PubMed:22464331,
CC PubMed:22901802). Required in late pachytene spermatocytes: plays a
CC role in meiotic and post-meiotic cells by binding to acetylated
CC histones at the promoter of specific meiotic and post-meiotic genes,
CC facilitating their activation at the appropriate time
CC (PubMed:22901802). In the post-meiotic phase of spermatogenesis, binds
CC to hyperacetylated histones and participates in their general removal
CC from DNA (PubMed:22901802). Also recognizes and binds a subset of
CC butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8'
CC (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5'
CC (H4K5ac) (By similarity). Also acts as a component of the splicing
CC machinery in pachytene spermatocytes and round spermatids and
CC participates in 3'-UTR truncation of specific mRNAs in post-meiotic
CC spermatids (By similarity). Required for chromocenter organization, a
CC structure comprised of peri-centromeric heterochromatin.
CC {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:15647849,
CC ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:22901802,
CC ECO:0000269|PubMed:9367677}.
CC -!- SUBUNIT: Interacts with mRNA splicing machinery proteins SRSF2, DDX5,
CC HNRNPK and TARDBP. Interacts with the acetylated N-terminus of histone
CC H1, H2, H3 and H4. Interacts with P-TEFb components CDK9 and
CC CCNT1/cyclin-T1. Interacts with SMARCE1 (By similarity). Interacts with
CC the acetylated N-terminus of histone H1.4, H2A, H2B, H3 and H4.
CC {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:22464331,
CC ECO:0000269|PubMed:22901802}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20538714,
CC ECO:0000269|PubMed:22901802, ECO:0000269|PubMed:22971749}.
CC Note=Detected on chromatin. {ECO:0000250|UniProtKB:Q91Y44}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q58F21-1; Sequence=Displayed;
CC Name=2; Synonyms=BRDT-NY;
CC IsoId=Q58F21-2; Sequence=VSP_019118;
CC Name=3;
CC IsoId=Q58F21-3; Sequence=VSP_044511;
CC Name=4;
CC IsoId=Q58F21-4; Sequence=VSP_044510;
CC Name=5;
CC IsoId=Q58F21-5; Sequence=VSP_044509;
CC -!- TISSUE SPECIFICITY: Testis-specific. A 3-fold higher expression is seen
CC in adult testis than in embryo testis. Expression seems to be
CC correlated with histone H4 hyperacetylation during the haploid phase of
CC spermatogenesis (spermiogenesis). No expression, or very low expression
CC is seen in patients' testes with abnormal spermatogenesis. Expressed in
CC cancers such as non-small cell lung cancer and squamous cell carcinomas
CC of the head and neck as well as of esophagus, but not in melanoma or in
CC cancers of the colon, breast, kidney and bladder.
CC {ECO:0000269|PubMed:10704737, ECO:0000269|PubMed:15647849,
CC ECO:0000269|PubMed:9367677}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryo testis.
CC -!- DOMAIN: Bromo domains mediate interaction with histones that have
CC acetylated lysine residues at specific positions (PubMed:22464331).
CC Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5'
CC and 'Lys-8' (H4K5ac and H4K8ac, respectively) (PubMed:22901802). The
CC bromo domains also recognize and bind a subset of butyrylated histones:
CC able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is
CC not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (By similarity).
CC {ECO:0000250|UniProtKB:Q91Y44, ECO:0000269|PubMed:22464331,
CC ECO:0000269|PubMed:22901802}.
CC -!- DISEASE: Spermatogenic failure 21 (SPGF21) [MIM:617644]: An infertility
CC disorder caused by spermatogenesis defects and characterized by
CC acephalic spermatozoa in the semen of affected individuals. SPGF21
CC inheritance is autosomal recessive. {ECO:0000269|PubMed:28199965}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: BRDT is a promising target for male contraception.
CC Inhibition by thienodiazepine inhibitor (+)-JQ1 that binds Asn-109,
CC prevents recognition of acetylated histone H4, causing a complete and
CC reversible contraceptive effect in male mice (PubMed:22901802).
CC {ECO:0000305|PubMed:22901802}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH05281.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH47900.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH62700.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Asking life to be patient
CC - Issue 144 of November 2012;
CC URL="https://web.expasy.org/spotlight/back_issues/144";
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DR EMBL; AF019085; AAB87862.1; -; mRNA.
DR EMBL; AY338951; AAQ16198.1; -; mRNA.
DR EMBL; AK303008; BAH13876.1; -; mRNA.
DR EMBL; AK302758; BAH13797.1; -; mRNA.
DR EMBL; AK316442; BAH14813.1; -; mRNA.
DR EMBL; AC114486; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73106.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73107.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73108.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73110.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73111.1; -; Genomic_DNA.
DR EMBL; BC005281; AAH05281.1; ALT_SEQ; mRNA.
DR EMBL; BC017582; AAH17582.1; -; mRNA.
DR EMBL; BC047900; AAH47900.1; ALT_SEQ; mRNA.
DR EMBL; BC062700; AAH62700.1; ALT_SEQ; mRNA.
DR CCDS; CCDS55615.1; -. [Q58F21-4]
DR CCDS; CCDS55616.1; -. [Q58F21-5]
DR CCDS; CCDS72820.1; -. [Q58F21-3]
DR CCDS; CCDS735.1; -. [Q58F21-1]
DR RefSeq; NP_001229734.2; NM_001242805.2. [Q58F21-1]
DR RefSeq; NP_001229735.2; NM_001242806.2. [Q58F21-3]
DR RefSeq; NP_001229736.2; NM_001242807.2. [Q58F21-4]
DR RefSeq; NP_001229737.2; NM_001242808.2. [Q58F21-4]
DR RefSeq; NP_001229739.2; NM_001242810.2. [Q58F21-5]
DR RefSeq; NP_001717.3; NM_001726.4. [Q58F21-1]
DR RefSeq; NP_997072.2; NM_207189.3. [Q58F21-1]
DR RefSeq; XP_006710916.1; XM_006710853.3. [Q58F21-1]
DR RefSeq; XP_006710917.1; XM_006710854.3. [Q58F21-1]
DR RefSeq; XP_006710918.1; XM_006710855.3. [Q58F21-1]
DR RefSeq; XP_006710919.1; XM_006710856.3. [Q58F21-1]
DR RefSeq; XP_006710920.1; XM_006710857.3. [Q58F21-1]
DR RefSeq; XP_011540334.1; XM_011542032.2. [Q58F21-1]
DR RefSeq; XP_011540335.1; XM_011542033.2. [Q58F21-1]
DR RefSeq; XP_011540336.1; XM_011542034.2. [Q58F21-1]
DR RefSeq; XP_011540337.1; XM_011542035.2. [Q58F21-1]
DR RefSeq; XP_011540338.1; XM_011542036.2. [Q58F21-1]
DR PDB; 2RFJ; X-ray; 2.05 A; A/B/C=21-137.
DR PDB; 4FLP; X-ray; 2.23 A; A/B=21-137.
DR PDB; 4KCX; X-ray; 2.00 A; A/B=21-137.
DR PDB; 5VBQ; X-ray; 1.65 A; A/B=29-137.
DR PDB; 5VBR; X-ray; 1.90 A; A/B=29-137.
DR PDB; 7BJY; X-ray; 2.22 A; A/B=29-137.
DR PDB; 7L73; X-ray; 1.46 A; A=29-137.
DR PDB; 7L99; X-ray; 1.90 A; A/B/C/D=269-380.
DR PDB; 7L9A; X-ray; 2.27 A; A/B=269-380.
DR PDB; 7LEJ; X-ray; 1.73 A; A=266-378.
DR PDB; 7LEK; X-ray; 2.75 A; A/B/C/D=266-378.
DR PDB; 7LEL; X-ray; 2.15 A; A/B/C/D=266-378.
DR PDB; 7LEM; X-ray; 1.89 A; A/B=29-137.
DR PDBsum; 2RFJ; -.
DR PDBsum; 4FLP; -.
DR PDBsum; 4KCX; -.
DR PDBsum; 5VBQ; -.
DR PDBsum; 5VBR; -.
DR PDBsum; 7BJY; -.
DR PDBsum; 7L73; -.
DR PDBsum; 7L99; -.
DR PDBsum; 7L9A; -.
DR PDBsum; 7LEJ; -.
DR PDBsum; 7LEK; -.
DR PDBsum; 7LEL; -.
DR PDBsum; 7LEM; -.
DR AlphaFoldDB; Q58F21; -.
DR SASBDB; Q58F21; -.
DR SMR; Q58F21; -.
DR BioGRID; 107143; 76.
DR IntAct; Q58F21; 2.
DR STRING; 9606.ENSP00000387822; -.
DR BindingDB; Q58F21; -.
DR ChEMBL; CHEMBL1795185; -.
DR GuidetoPHARMACOLOGY; 2729; -.
DR iPTMnet; Q58F21; -.
DR PhosphoSitePlus; Q58F21; -.
DR BioMuta; BRDT; -.
DR DMDM; 226694198; -.
DR EPD; Q58F21; -.
DR jPOST; Q58F21; -.
DR MassIVE; Q58F21; -.
DR MaxQB; Q58F21; -.
DR PaxDb; Q58F21; -.
DR PeptideAtlas; Q58F21; -.
DR PRIDE; Q58F21; -.
DR ProteomicsDB; 1029; -.
DR ProteomicsDB; 62618; -. [Q58F21-1]
DR ProteomicsDB; 62619; -. [Q58F21-2]
DR Antibodypedia; 3212; 135 antibodies from 23 providers.
DR DNASU; 676; -.
DR Ensembl; ENST00000362005.7; ENSP00000354568.3; ENSG00000137948.19. [Q58F21-1]
DR Ensembl; ENST00000370389.6; ENSP00000359416.2; ENSG00000137948.19. [Q58F21-5]
DR Ensembl; ENST00000394530.7; ENSP00000378038.3; ENSG00000137948.19. [Q58F21-4]
DR Ensembl; ENST00000399546.7; ENSP00000387822.3; ENSG00000137948.19. [Q58F21-1]
DR Ensembl; ENST00000402388.1; ENSP00000384051.1; ENSG00000137948.19. [Q58F21-1]
DR GeneID; 676; -.
DR KEGG; hsa:676; -.
DR MANE-Select; ENST00000399546.7; ENSP00000387822.3; NM_207189.4; NP_997072.2.
DR UCSC; uc001dol.5; human. [Q58F21-1]
DR CTD; 676; -.
DR DisGeNET; 676; -.
DR GeneCards; BRDT; -.
DR HGNC; HGNC:1105; BRDT.
DR HPA; ENSG00000137948; Tissue enriched (testis).
DR MalaCards; BRDT; -.
DR MIM; 602144; gene.
DR MIM; 617644; phenotype.
DR neXtProt; NX_Q58F21; -.
DR OpenTargets; ENSG00000137948; -.
DR PharmGKB; PA25418; -.
DR VEuPathDB; HostDB:ENSG00000137948; -.
DR eggNOG; KOG1474; Eukaryota.
DR GeneTree; ENSGT00940000154549; -.
DR HOGENOM; CLU_001499_0_0_1; -.
DR InParanoid; Q58F21; -.
DR OMA; FMQKIAQ; -.
DR OrthoDB; 619848at2759; -.
DR PhylomeDB; Q58F21; -.
DR TreeFam; TF317345; -.
DR PathwayCommons; Q58F21; -.
DR SignaLink; Q58F21; -.
DR SIGNOR; Q58F21; -.
DR BioGRID-ORCS; 676; 14 hits in 1086 CRISPR screens.
DR ChiTaRS; BRDT; human.
DR EvolutionaryTrace; Q58F21; -.
DR GeneWiki; BRDT; -.
DR GenomeRNAi; 676; -.
DR Pharos; Q58F21; Tchem.
DR PRO; PR:Q58F21; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q58F21; protein.
DR Bgee; ENSG00000137948; Expressed in left testis and 95 other tissues.
DR ExpressionAtlas; Q58F21; baseline and differential.
DR Genevisible; Q58F21; HS.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0140566; F:histone reader activity; ISS:UniProtKB.
DR GO; GO:0070577; F:lysine-acetylated histone binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR GO; GO:0007141; P:male meiosis I; ISS:UniProtKB.
DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0051039; P:positive regulation of transcription involved in meiotic cell cycle; ISS:UniProtKB.
DR GO; GO:0043484; P:regulation of RNA splicing; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0035093; P:spermatogenesis, exchange of chromosomal proteins; ISS:UniProtKB.
DR CDD; cd05497; Bromo_Brdt_I_like; 1.
DR CDD; cd05498; Bromo_Brdt_II_like; 1.
DR Gene3D; 1.20.1270.220; -; 1.
DR Gene3D; 1.20.920.10; -; 2.
DR InterPro; IPR031354; BRD4_CDT.
DR InterPro; IPR043508; Bromo_Brdt_I.
DR InterPro; IPR043509; Bromo_Brdt_II.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR027353; NET_dom.
DR InterPro; IPR038336; NET_sf.
DR Pfam; PF17035; BET; 1.
DR Pfam; PF17105; BRD4_CDT; 1.
DR Pfam; PF00439; Bromodomain; 2.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 2.
DR SUPFAM; SSF47370; SSF47370; 2.
DR PROSITE; PS00633; BROMODOMAIN_1; 2.
DR PROSITE; PS50014; BROMODOMAIN_2; 2.
DR PROSITE; PS51525; NET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Bromodomain;
KW Chromatin regulator; Coiled coil; Differentiation; Disease variant;
KW Meiosis; mRNA processing; mRNA splicing; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Spermatogenesis; Transcription;
KW Transcription regulation.
FT CHAIN 1..947
FT /note="Bromodomain testis-specific protein"
FT /id="PRO_0000239225"
FT DOMAIN 44..116
FT /note="Bromo 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 287..359
FT /note="Bromo 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 500..582
FT /note="NET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00857"
FT REGION 202..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 610..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 882..924
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 417..470
FT /evidence="ECO:0000255"
FT COILED 591..621
FT /evidence="ECO:0000255"
FT MOTIF 209..220
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:22971749"
FT COMPBIAS 395..409
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..483
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 495..511
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..667
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..695
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 884..924
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 109
FT /ligand="JQ1"
FT /ligand_id="ChEBI:CHEBI:137113"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:22901802,
FT ECO:0007744|PDB:4FLP"
FT SITE 109
FT /note="Histone H4K5ac binding"
FT /evidence="ECO:0000250|UniProtKB:Q91Y44"
FT SITE 114
FT /note="Histone H4K5ac binding"
FT /evidence="ECO:0000250|UniProtKB:Q91Y44"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Y44"
FT VAR_SEQ 1..73
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_044509"
FT VAR_SEQ 1
FT /note="M -> MTCTCRQDSKQLRM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15647849"
FT /id="VSP_019118"
FT VAR_SEQ 65..110
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044510"
FT VAR_SEQ 148
FT /note="K -> KGKAG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044511"
FT VARIANT 2
FT /note="S -> F (in dbSNP:rs55806733)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041924"
FT VARIANT 6
FT /note="R -> Q (in dbSNP:rs56273490)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041925"
FT VARIANT 62
FT /note="Q -> K (in dbSNP:rs10783071)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15647849,
FT ECO:0000269|PubMed:9367677, ECO:0000269|Ref.5"
FT /id="VAR_026584"
FT VARIANT 89
FT /note="A -> V (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs781375003)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041926"
FT VARIANT 238
FT /note="K -> N (in dbSNP:rs1156281)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_026585"
FT VARIANT 288
FT /note="H -> Y (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041927"
FT VARIANT 336
FT /note="K -> T (in dbSNP:rs1064567)"
FT /id="VAR_047327"
FT VARIANT 357
FT /note="E -> K (in dbSNP:rs34674879)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041928"
FT VARIANT 410
FT /note="N -> K (in dbSNP:rs3088232)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_026586"
FT VARIANT 542
FT /note="P -> A (in dbSNP:rs55912588)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041929"
FT VARIANT 605
FT /note="R -> Q (in dbSNP:rs35327986)"
FT /id="VAR_047328"
FT VARIANT 696
FT /note="P -> L (in dbSNP:rs10747493)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15647849, ECO:0000269|PubMed:9367677,
FT ECO:0000269|Ref.5"
FT /id="VAR_047329"
FT VARIANT 928
FT /note="G -> D (in SPGF21; no effect on protein expression;
FT unknown pathological significance; dbSNP:rs754258809)"
FT /evidence="ECO:0000269|PubMed:28199965"
FT /id="VAR_079306"
FT CONFLICT 42
FT /note="D -> N (in Ref. 3; BAH13876)"
FT /evidence="ECO:0000305"
FT CONFLICT 73
FT /note="P -> S (in Ref. 6; AAH05281)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="K -> I (in Ref. 6; AAH62700)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="K -> E (in Ref. 1; AAB87862)"
FT /evidence="ECO:0000305"
FT CONFLICT 336
FT /note="K -> S (in Ref. 1; AAB87862)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="E -> K (in Ref. 6; AAH17582)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="Q -> R (in Ref. 3; BAH13876)"
FT /evidence="ECO:0000305"
FT CONFLICT 552
FT /note="I -> M (in Ref. 2; AAQ16198)"
FT /evidence="ECO:0000305"
FT CONFLICT 686
FT /note="N -> H (in Ref. 1; AAB87862)"
FT /evidence="ECO:0000305"
FT CONFLICT 893
FT /note="Q -> P (in Ref. 1; AAB87862)"
FT /evidence="ECO:0000305"
FT CONFLICT 915
FT /note="Q -> P (in Ref. 1; AAB87862)"
FT /evidence="ECO:0000305"
FT HELIX 29..37
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 39..45
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:7L73"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:2RFJ"
FT TURN 58..62
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 66..69
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 76..84
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 91..108
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 114..131
FT /evidence="ECO:0007829|PDB:7L73"
FT HELIX 266..284
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 289..292
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:7LEJ"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:7L99"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 319..327
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 334..351
FT /evidence="ECO:0007829|PDB:7LEJ"
FT HELIX 357..373
FT /evidence="ECO:0007829|PDB:7LEJ"
SQ SEQUENCE 947 AA; 107954 MW; 09C0FD8690E217BB CRC64;
MSLPSRQTAI IVNPPPPEYI NTKKNGRLTN QLQYLQKVVL KDLWKHSFSW PFQRPVDAVK
LQLPDYYTII KNPMDLNTIK KRLENKYYAK ASECIEDFNT MFSNCYLYNK PGDDIVLMAQ
ALEKLFMQKL SQMPQEEQVV GVKERIKKGT QQNIAVSSAK EKSSPSATEK VFKQQEIPSV
FPKTSISPLN VVQGASVNSS SQTAAQVTKG VKRKADTTTP ATSAVKASSE FSPTFTEKSV
ALPPIKENMP KNVLPDSQQQ YNVVKTVKVT EQLRHCSEIL KEMLAKKHFS YAWPFYNPVD
VNALGLHNYY DVVKNPMDLG TIKEKMDNQE YKDAYKFAAD VRLMFMNCYK YNPPDHEVVT
MARMLQDVFE THFSKIPIEP VESMPLCYIK TDITETTGRE NTNEASSEGN SSDDSEDERV
KRLAKLQEQL KAVHQQLQVL SQVPFRKLNK KKEKSKKEKK KEKVNNSNEN PRKMCEQMRL
KEKSKRNQPK KRKQQFIGLK SEDEDNAKPM NYDEKRQLSL NINKLPGDKL GRVVHIIQSR
EPSLSNSNPD EIEIDFETLK ASTLRELEKY VSACLRKRPL KPPAKKIMMS KEELHSQKKQ
ELEKRLLDVN NQLNSRKRQT KSDKTQPSKA VENVSRLSES SSSSSSSSES ESSSSDLSSS
DSSDSESEMF PKFTEVKPND SPSKENVKKM KNECIPPEGR TGVTQIGYCV QDTTSANTTL
VHQTTPSHVM PPNHHQLAFN YQELEHLQTV KNISPLQILP PSGDSEQLSN GITVMHPSGD
SDTTMLESEC QAPVQKDIKI KNADSWKSLG KPVKPSGVMK SSDELFNQFR KAAIEKEVKA
RTQELIRKHL EQNTKELKAS QENQRDLGNG LTVESFSNKI QNKCSGEEQK EHQQSSEAQD
KSKLWLLKDR DLARQKEQER RRREAMVGTI DMTLQSDIMT MFENNFD
