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    BRCA1 BRCA1, DNA repair associated [ Homo sapiens (human) ]

    Gene ID: 672, updated on 25-Aug-2016
    Official Symbol
    BRCA1provided by HGNC
    Official Full Name
    BRCA1, DNA repair associatedprovided by HGNC
    Primary source
    HGNC:HGNC:1100
    See related
    Ensembl:ENSG00000012048 HPRD:00218; MIM:113705; Vega:OTTHUMG00000157426
    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
    IRIS; PSCP; BRCAI; BRCC1; FANCS; PNCA4; RNF53; BROVCA1; PPP1R53
    Summary
    This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009]
    Orthologs
    Location:
    17q21
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 17 NC_000017.11 (43044295..43125483, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (41196312..41277500, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene vesicle amine transport 1 Neighboring gene Rho family GTPase 2 Neighboring gene ribosomal protein L21 pseudogene 4 Neighboring gene neighbor of BRCA1 gene 2 (non-protein coding) Neighboring gene uncharacterized LOC101929767 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 29 Neighboring gene uncharacterized LOC107985003 Neighboring gene BRCA1 pseudogene 1

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in BRCA1 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2015-11-16)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2015-11-16)

    ClinGen Genome Curation Page

    Replication interactions

    Interaction Pubs
    Knockdown of breast cancer 1, early onset (BRCA1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat associates with BRCA1 in cells and the amino-acid 504-802 region of BRCA1 physically interacts with HIV-1 Tat PubMed
    tat BRCA1 enhances HIV-1 Tat-dependent transcription in cells, and BRCA1 phosphorylation at positions S1387, S1423, S1457, and S1524 is important for the enhancement of Tat-dependent transcription PubMed
    Vpr vpr HIV-1 Vpr stimulates the focus formation of Rad51 and BRCA1, which are involved in repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) PubMed
    vpr HIV-1 Vpr induces phosphorylation of BRCA1 at serine 1423 in an ATR-dependent manner PubMed
    vpr HIV-1 Vpr expression in HeLa cells induces formation of nuclear foci containing H2AFX and BRCA1 PubMed

    Go to the HIV-1, Human Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding TAS
    Traceable Author Statement
    more info
    PubMed 
    RNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    androgen receptor binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    damaged DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    ligase activity IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    transcription coactivator activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    transcription regulatory region DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    tubulin binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator TAS
    Traceable Author Statement
    more info
    PubMed 
    DNA double-strand break processing TAS
    Traceable Author Statement
    more info
     
    DNA replication TAS
    Traceable Author Statement
    more info
     
    DNA synthesis involved in DNA repair TAS
    Traceable Author Statement
    more info
     
    G2 DNA damage checkpoint IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    androgen receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    brain development IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to DNA damage stimulus TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to indole-3-methanol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to tumor necrosis factor IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    centrosome cycle IEA
    Inferred from Electronic Annotation
    more info
     
    chordate embryonic development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    chromosome breakage IEA
    Inferred from Electronic Annotation
    more info
     
    chromosome segregation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    dosage compensation by inactivation of X chromosome IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    double-strand break repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    double-strand break repair IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    double-strand break repair via homologous recombination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    double-strand break repair via nonhomologous end joining TAS
    Traceable Author Statement
    more info
     
    fatty acid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    intrinsic apoptotic signaling pathway in response to DNA damage IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of centriole replication NAS
    Non-traceable Author Statement
    more info
    PubMed 
    negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of fatty acid biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of histone H3-K4 methylation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of histone H3-K9 methylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of histone acetylation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative regulation of intracellular estrogen receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of reactive oxygen species metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of histone H3-K4 methylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of histone H3-K9 acetylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of histone H3-K9 methylation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of histone H4-K16 acetylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of histone H4-K20 methylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of histone acetylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of protein import into nucleus, translocation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription, DNA-templated NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of transcription, DNA-templated TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of vascular endothelial growth factor production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    postreplication repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein K6-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein autoubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein sumoylation TAS
    Traceable Author Statement
    more info
     
    protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of DNA methylation IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of gene expression by genetic imprinting IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of signal transduction by p53 class mediator TAS
    Traceable Author Statement
    more info
     
    regulation of transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of transcription from RNA polymerase III promoter TAS
    Traceable Author Statement
    more info
    PubMed 
    response to estradiol IEA
    Inferred from Electronic Annotation
    more info
     
    response to estrogen IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to ionizing radiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to nutrient IEA
    Inferred from Electronic Annotation
    more info
     
    strand displacement TAS
    Traceable Author Statement
    more info
     
    transcription, DNA-templated IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    BRCA1-A complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    BRCA1-BARD1 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chromosome ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    condensed nuclear chromosome IEA
    Inferred from Electronic Annotation
    more info
     
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    gamma-tubulin ring complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    intracellular ribonucleoprotein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    ubiquitin ligase complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Preferred Names
    breast cancer type 1 susceptibility protein
    Names
    BRCA1/BRCA2-containing complex, subunit 1
    Fanconi anemia, complementation group S
    RING finger protein 53
    breast and ovarian cancer susceptibility protein 1
    breast and ovarian cancer sususceptibility protein 1
    breast cancer 1, early onset
    early onset breast cancer 1
    protein phosphatase 1, regulatory subunit 53

    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_005905.2 RefSeqGene

      Range
      92501..173689
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_292

    mRNA and Protein(s)

    1. NM_007294.3NP_009225.1  breast cancer type 1 susceptibility protein isoform 1

      See identical proteins and their annotated locations for NP_009225.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as BRCA1a) represents the more frequently occurring transcript. It encodes the full-length BRCA1 protein (isoform 1), which is also known as p220.
      Source sequence(s)
      AL701927, BC072418, BU617173, BU679389, U14680
      Consensus CDS
      CCDS11453.1
      UniProtKB/Swiss-Prot
      P38398
      Related
      ENSP00000350283, OTTHUMP00000212143, ENST00000357654, OTTHUMT00000348798
      Conserved Domains (4) summary
      smart00292
      Location:17581842
      BRCT; breast cancer carboxy-terminal domain
      cd00027
      Location:16501724
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      cd00162
      Location:2368
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam12820
      Location:345507
      BRCT_assoc; Serine-rich domain associated with BRCT
    2. NM_007297.3NP_009228.2  breast cancer type 1 susceptibility protein isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and uses a downstream translational start codon, compared to variant 1. The encoded isoform (3) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      BC072418, BU617173, BU679389, U14680
      Consensus CDS
      CCDS11459.2
      UniProtKB/Swiss-Prot
      P38398
      Related
      ENSP00000418775, OTTHUMP00000212148, ENST00000493795, OTTHUMT00000348803
      Conserved Domains (3) summary
      smart00292
      Location:17111795
      BRCT; breast cancer carboxy-terminal domain
      cd00027
      Location:16031677
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      pfam12820
      Location:298460
      BRCT_assoc; Serine-rich domain associated with BRCT
    3. NM_007298.3NP_009229.2  breast cancer type 1 susceptibility protein isoform 4

      See identical proteins and their annotated locations for NP_009229.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as BRCA1-delta11b) differs in the 5' UTR and uses two alternate in-frame splice sites in the central coding region, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.
      Source sequence(s)
      AL701927, BC072418, BU617173, BU679389, U64805
      Consensus CDS
      CCDS11454.2
      UniProtKB/Swiss-Prot
      P38398
      UniProtKB/TrEMBL
      A0A024R1V0
      Related
      ENSP00000420705, OTTHUMP00000212155, ENST00000491747, OTTHUMT00000348811
      Conserved Domains (2) summary
      cd00027
      Location:546620
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      cd00162
      Location:2368
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    4. NM_007299.3NP_009230.2  breast cancer type 1 susceptibility protein isoform 5

      See identical proteins and their annotated locations for NP_009230.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, uses two alternate in-frame splice sites in the central coding region, and lacks an alternate exon in the 3' coding region that results in a frameshift, compared to variant 1. The encoded isoform (5) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      BC072418, BU617173, BU679389
      Consensus CDS
      CCDS11455.2
      UniProtKB/Swiss-Prot
      P38398
      Related
      ENSP00000417148, OTTHUMP00000212149, ENST00000468300, OTTHUMT00000348804
      Conserved Domains (2) summary
      cd00027
      Location:546620
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      cd00162
      Location:2368
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
    5. NM_007300.3NP_009231.2  breast cancer type 1 susceptibility protein isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate in-frame exon and an alternate in-frame splice site in the central coding region, compared to variant 1. The encoded isoform (2) is longer than isoform 1.
      Source sequence(s)
      AC135721, AL701927, BC072418, BC115037, BU617173, BU679389, U14680
      Consensus CDS
      CCDS11456.2
      UniProtKB/Swiss-Prot
      P38398
      Related
      ENSP00000418960, OTTHUMP00000212147, ENST00000471181, OTTHUMT00000348802
      Conserved Domains (4) summary
      smart00292
      Location:17791863
      BRCT; breast cancer carboxy-terminal domain
      cd00027
      Location:16711745
      BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
      cd00162
      Location:2368
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam12820
      Location:345507
      BRCT_assoc; Serine-rich domain associated with BRCT

    RNA

    1. NR_027676.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) includes an alternate 5' exon and alternate splice sites in two internal exons, compared to variant 1. This variant is represented as non-coding because the use of the supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AF005068, AK308084, BC072418, BU617173, BU679389, U14680
      Related
      ENST00000461221, OTTHUMT00000348807

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p7 Primary Assembly

      Range
      43044295..43125483 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018928.2 Alternate CHM1_1.1

      Range
      41431851..41513018 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_007295.2: Suppressed sequence

      Description
      NM_007295.2: This RefSeq was permanently suppressed because only partial transcript evidence exists for this transcript variant, and its full-length exon combination is unclear.
    2. NM_007296.2: Suppressed sequence

      Description
      NM_007296.2: This RefSeq was permanently suppressed because there is no full-length transcript support for the exon combination of this variant.
    3. NM_007301.2: Suppressed sequence

      Description
      NM_007301.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    4. NM_007302.2: Suppressed sequence

      Description
      NM_007302.2: This RefSeq was permanently suppressed because only partial transcript evidence exists for this transcript variant, and its full-length exon combination is unclear.
    5. NM_007303.2: Suppressed sequence

      Description
      NM_007303.2: This RefSeq was permanently suppressed because the full-length sequence of this transcript variant is unavailable, and its full-length exon combination is unclear.
    6. NM_007305.2: Suppressed sequence

      Description
      NM_007305.2: This RefSeq was permanently suppressed because the full-length sequence of this transcript variant is unavailable, and its full-length exon combination is unclear.
    7. NM_007306.2: Suppressed sequence

      Description
      NM_007306.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.