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

Gene ID: 672, updated on 17-May-2020

Summary

Official Symbol
BRCA1provided by HGNC
Official Full Name
BRCA1 DNA repair associatedprovided by HGNC
Primary source
HGNC:HGNC:1100
See related
Ensembl:ENSG00000012048 MIM:113705
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 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. 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 2020]
Expression
Broad expression in testis (RPKM 5.2), lymph node (RPKM 3.3) and 23 other tissues See more
Orthologs

Genomic context

See BRCA1 in Genome Data Viewer
Location:
17q21.31
Exon count:
24
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 17 NC_000017.11 (43044295..43125364, 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 BRCA1 intronic recombination region Neighboring gene BRCA1 intron 2 regulatory region Neighboring gene BRCA1 promoter region Neighboring gene neighbor of BRCA1 lncRNA 2 Neighboring gene uncharacterized LOC101929767 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 29 Neighboring gene BRCA1P1 intergenic recombination region

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 
RNA polymerase binding IDA
Inferred from Direct Assay
more info
PubMed 
androgen receptor binding NAS
Non-traceable Author Statement
more info
PubMed 
damaged DNA binding IEA
Inferred from Electronic Annotation
more info
 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription coactivator activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription coactivator activity NAS
Non-traceable Author Statement
more info
PubMed 
transcription regulatory region sequence-specific 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 IBA
Inferred from Biological aspect of Ancestor
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
 
androgen receptor signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
apoptotic process TAS
Traceable Author Statement
more info
PubMed 
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
PubMed 
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
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
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 
mitotic G2/M transition checkpoint IEA
Inferred from Electronic Annotation
more info
 
negative regulation of G0 to G1 transition TAS
Traceable Author Statement
more info
 
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 IBA
Inferred from Biological aspect of Ancestor
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
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of histone acetylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II 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 deubiquitination 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 by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of transcription by RNA polymerase III TAS
Traceable Author Statement
more info
PubMed 
response to estrogen IDA
Inferred from Direct Assay
more info
PubMed 
response to ionizing radiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
signal transduction involved in G2 DNA damage checkpoint IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
BRCA1-A complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
BRCA1-A complex IDA
Inferred from Direct Assay
more info
PubMed 
BRCA1-BARD1 complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
BRCA1-BARD1 complex IDA
Inferred from Direct Assay
more info
PubMed 
chromosome ISS
Inferred from Sequence or Structural Similarity
more info
 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
gamma-tubulin ring complex NAS
Non-traceable Author Statement
more info
PubMed 
lateral element IDA
Inferred from Direct Assay
more info
PubMed 
nuclear body IDA
Inferred from Direct Assay
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 
ribonucleoprotein complex IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin ligase complex NAS
Non-traceable Author Statement
more info
PubMed 

General protein information

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 cancer 1, early onset
early onset breast cancer 1
protein phosphatase 1, regulatory subunit 53
NP_009225.1
NP_009228.2
NP_009229.2
NP_009230.2
NP_009231.2

NCBI Reference Sequences (RefSeq)

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_007294.4NP_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
    ENSP00000350283.3, ENST00000357654.9
    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_007297.4NP_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
    ENSP00000418775.1, ENST00000493795.5
    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
    ENSP00000420705.2, ENST00000491747.6
    Conserved Domains (3) summary
    smart00292
    Location:654738
    BRCT; breast cancer carboxy-terminal domain
    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_007299.4NP_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
    ENSP00000417148.1, ENST00000468300.5
    Conserved Domains (2) summary
    pfam00533
    Location:546619
    BRCT; BRCA1 C Terminus (BRCT) domain
    cd16498
    Location:1865
    RING-HC_BRCA1; RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins
  5. NM_007300.4NP_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, BC072418, BC115037, BU617173, BU679389, U14680
    Consensus CDS
    CCDS11456.2
    UniProtKB/Swiss-Prot
    P38398
    Related
    ENSP00000418960.2, ENST00000471181.7
    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_027676.2 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)
    AC135721, AF005068, AK308084, BC072418, BU617173, BU679389, U14680

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p13 Primary Assembly

    Range
    43044295..43125364 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.
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