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    BRD2 bromodomain containing 2 [ Homo sapiens (human) ]

    Gene ID: 6046, updated on 10-Dec-2024

    Summary

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    Official Symbol
    BRD2provided by HGNC
    Official Full Name
    bromodomain containing 2provided by HGNC
    Primary source
    HGNC:HGNC:1103
    See related
    Ensembl:ENSG00000204256 MIM:601540; AllianceGenome:HGNC:1103
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FSH; NAT; RNF3; FSRG1; RING3; FSHRG1; D6S113E; O27.1.1; BRD2-IT1
    Summary
    This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene. [provided by RefSeq, Dec 2010]
    Expression
    Ubiquitous expression in bone marrow (RPKM 74.5), thyroid (RPKM 55.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See BRD2 in Genome Data Viewer
    Location:
    6p21.32
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (32968594..32981505)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (32789953..32802871)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (32936371..32949282)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene major histocompatibility complex, class II, DM alpha Neighboring gene uncharacterized LOC124901302 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:32935448-32935987 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:32937286-32938485 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:32939954-32940562 Neighboring gene meiotic recombination hotspot DNA3 Neighboring gene meiotic recombination hotspot DNA2 Neighboring gene meiotic recombination hotspot DNA1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:32977249-32977764 Neighboring gene major histocompatibility complex, class II, DO alpha Neighboring gene meiotic recombination hotspot DPA1 Neighboring gene major histocompatibility complex, class II, DP alpha 1 Neighboring gene major histocompatibility complex, class II, DP beta 1 Neighboring gene ribosomal protein L32 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Activation-induced nuclear translocation of RING3. Guo N, et al. J Cell Sci, 2000 Sep. PMID 10934046, Free PMC Article
    2. Bromodomain-containing protein 2 gene in photosensitive epilepsy. Yavuz EN, et al. Seizure, 2012 Oct. PMID 22766109
    3. Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A. Sinha A, et al. Biochem J, 2005 Apr 1. PMID 15548137, Free PMC Article
    4. Identification of transcription complexes that contain the double bromodomain protein Brd2 and chromatin remodeling machines. Denis GV, et al. J Proteome Res, 2006 Mar. PMID 16512664, Free PMC Article
    5. BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma. Tian XP, et al. Cancer Commun (Lond), 2020 Jun. PMID 32459053, Free PMC Article

    See all (167) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Epigenetic Reader, Bromodomain Containing 2, Mediates Cholangiocyte Senescence via Interaction With ETS Proto-Oncogene 1.
      Title: The Epigenetic Reader, Bromodomain Containing 2, Mediates Cholangiocyte Senescence via Interaction With ETS Proto-Oncogene 1.
    2. PD-L1 is upregulated via BRD2 in head and neck squamous cell carcinoma models of acquired cetuximab resistance.
      Title: PD-L1 is upregulated via BRD2 in head and neck squamous cell carcinoma models of acquired cetuximab resistance.
    3. Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.
      Title: Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.
    4. BRD2 regulation of sigma-2 receptor upon cholesterol deprivation.
      Title: BRD2 regulation of sigma-2 receptor upon cholesterol deprivation.
    5. BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma.
      Title: BRD2 induces drug resistance through activation of the RasGRP1/Ras/ERK signaling pathway in adult T-cell lymphoblastic lymphoma.
    6. Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation.
      Title: Bromodomain and extra-terminal domain (BET) proteins regulate melanocyte differentiation.
    7. Comparative structure-function analysis of bromodomain and extraterminal motif (BET) proteins in a gene-complementation system.
      Title: Comparative structure-function analysis of bromodomain and extraterminal motif (BET) proteins in a gene-complementation system.
    8. There is a uniform low average percentage of BRD2 promoter CpG methylation (<4.5%) for 13 CpG76-CpGs in whole blood cells from 782 unrelated European Caucasian. (SNP) rs3918149 alleles were not associated with JME or CpG76 methylation. Our results do not support the previous observation that a high DNA methylation level of the BRD2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians.
      Title: No evidence for a BRD2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy.
    9. a number of genes important for keratinocyte homeostasis and cornification were dysregulated in BRD2-deficient keratinocytes. In IL17A/TNF/IL22 stimulated three-dimensional organotypic raft cultures, pan-BRD inhibition reduced inflammatory factor production but elicited aberrant cornification, consistent with RNA-Seq analysis
      Title: Small Molecule and Pooled CRISPR Screens Investigating IL17 Signaling Identify BRD2 as a Novel Contributor to Keratinocyte Inflammatory Responses.
    10. These data suggest that LYAR promotes the association of the BRD2-KAT7 and BRD4-KAT7 complexes with transcription-competent rDNA loci but not to transcriptionally silent rDNA loci, thereby increasing rRNA synthesis by altering the local acetylation status of histone H3 and H4.
      Title: LYAR potentiates rRNA synthesis by recruiting BRD2/4 and the MYST-type acetyltransferase KAT7 to rDNA.
    Submit: New GeneRIF Correction See all GeneRIFs (58)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ31942, KIAA9001, DKFZp686N0336

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables acetylation-dependent protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables chromatin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables chromatin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histone binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables lysine-acetylated histone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in chromatin looping IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in chromatin remodeling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in neural tube closure IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nucleosome assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of T-helper 17 cell lineage commitment IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein localization to chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in spermatogenesis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    bromodomain-containing protein 2
    Names
    BRD2 intronic transcript 1
    female sterile homeotic-related gene 1
    really interesting new gene 3 protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_042801.1 RefSeqGene

      Range
      4935..17842
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001113182.3 → NP_001106653.1  bromodomain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001106653.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AK056504, AL645941, AL832722, BX648109, D42040, DC379337
      Consensus CDS
      CCDS4762.1
      UniProtKB/Swiss-Prot
      A2AAU0, B0S7P0, B1AZT1, O00699, O00700, P25440, Q15310, Q5STC9, Q63HQ9, Q658Y7, Q6P3U2, Q969U4
      UniProtKB/TrEMBL
      H0Y6K2
      Related
      ENSP00000363964.4, ENST00000374831.8
      Conserved Domains (4) summary
      cd05497
      Location:74 → 180
      Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      cd05498
      Location:349 → 450
      Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      PHA03247
      Location:216 → 333
      PHA03247; large tegument protein UL36; Provisional
      pfam17035
      Location:641 → 703
      BET; Bromodomain extra-terminal - transcription regulation

    2. NM_001199455.1 → NP_001186384.1  bromodomain-containing protein 2 isoform 2

      See identical proteins and their annotated locations for NP_001186384.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an additional in-frame exon in the CDS compared to variant 1. The resulting isoform (2) is longer than isoform 1.
      Source sequence(s)
      AL645941, AL832722, BC063840, CN398334, DC379337
      Consensus CDS
      CCDS56420.1
      UniProtKB/TrEMBL
      A0A0G2JK44
      Related
      ENSP00000378702.1, ENST00000395287.5
      Conserved Domains (4) summary
      cd05497
      Location:74 → 180
      Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      cd05498
      Location:349 → 450
      Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      pfam13900
      Location:616 → 651
      GVQW; Putative domain of unknown function
      pfam17035
      Location:676 → 740
      BET; Bromodomain extra-terminal - transcription regulation

    3. NM_001199456.2 → NP_001186385.1  bromodomain-containing protein 2 isoform 3

      See identical proteins and their annotated locations for NP_001186385.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has an alternate 5' exon, resulting in a downstream AUG start codon compared to variant 1. The resulting isoform (3) is shorter at the N-terminus, as compared to isoform 1.
      Source sequence(s)
      AL645941, BX647233, D42040
      UniProtKB/TrEMBL
      H0Y6K2, X5CF57
      Related
      ENSP00000409613.1, ENST00000449025.5
      Conserved Domains (3) summary
      cd05497
      Location:27 → 133
      Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      cd05498
      Location:302 → 403
      Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      pfam17035
      Location:594 → 658
      BET; Bromodomain extra-terminal - transcription regulation

    4. NM_001291986.2 → NP_001278915.1  bromodomain-containing protein 2 isoform 4

      See identical proteins and their annotated locations for NP_001278915.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) has an alternate 5' exon and an additional internal exon compared to variant 1. The resulting isoform (4) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AL645941, AL832722, D42040, HY065625
      UniProtKB/TrEMBL
      A0A1U9X7A8, A0A1U9X7B3, A0A1U9X7B4, A0A1U9X7B8
      Conserved Domains (4) summary
      cd05498
      Location:229 → 330
      Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      PHA03247
      Location:96 → 213
      PHA03247; large tegument protein UL36; Provisional
      pfam17035
      Location:521 → 583
      BET; Bromodomain extra-terminal - transcription regulation
      cl02556
      Location:1 → 60
      Bromodomain; Bromodomains are found in many chromatin-associated proteins and in nuclear histone acetyltransferases. They interact specifically with acetylated lysine.

    5. NM_005104.4 → NP_005095.1  bromodomain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_005095.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) and variant 2 encode the same predominant isoform (1).
      Source sequence(s)
      AI983495, AL645941, AL832722, BP271262, D42040, DA127395, DC379337, H11588
      Consensus CDS
      CCDS4762.1
      UniProtKB/Swiss-Prot
      A2AAU0, B0S7P0, B1AZT1, O00699, O00700, P25440, Q15310, Q5STC9, Q63HQ9, Q658Y7, Q6P3U2, Q969U4
      UniProtKB/TrEMBL
      H0Y6K2
      Related
      ENSP00000363958.4, ENST00000374825.9
      Conserved Domains (4) summary
      cd05497
      Location:74 → 180
      Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      cd05498
      Location:349 → 450
      Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
      PHA03247
      Location:216 → 333
      PHA03247; large tegument protein UL36; Provisional
      pfam17035
      Location:641 → 703
      BET; Bromodomain extra-terminal - transcription regulation

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      32968594..32981505
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419222.1 → XP_047275178.1  bromodomain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      U3KQA6
      Related
      ENSP00000475691.1, ENST00000607833.5

    2. XM_047419223.1 → XP_047275179.1  bromodomain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      E9PIQ3
      Related
      ENSP00000436322.1, ENST00000495733.5

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      4380803..4393720
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329844.1 → XP_054185819.1  bromodomain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      U3KQA6

    2. XM_054329845.1 → XP_054185820.1  bromodomain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      E9PIQ3

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

      Range
      4190197..4225039
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

      Range
      4387978..4400883
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330618.1 → XP_054186593.1  bromodomain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      U3KQA6

    2. XM_054330619.1 → XP_054186594.1  bromodomain-containing protein 2 isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      4267651..4278257
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

      Range
      4162919..4175823
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331105.1 → XP_054187080.1  bromodomain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      U3KQA6

    2. XM_054331106.1 → XP_054187081.1  bromodomain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      E9PIQ3

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      4367841..4430762
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331369.1 → XP_054187344.1  bromodomain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      U3KQA6

    2. XM_054331370.1 → XP_054187345.1  bromodomain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      E9PIQ3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      32789953..32802871
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356162.1 → XP_054212137.1  bromodomain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      U3KQA6

    2. XM_054356163.1 → XP_054212138.1  bromodomain-containing protein 2 isoform X2

      UniProtKB/TrEMBL
      E9PIQ3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_037625.1: Suppressed sequence

      Description
      NR_037625.1: This RefSeq was permanently suppressed because it is now thought that this transcript does encode a protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P25440.2 GenPept UniProtKB/Swiss-Prot:P25440

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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