Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003954
UniProt IDP38398
Primary gene name(s)BRCA1
Synonym gene name(s)RNF53
Protein nameBreast cancer type 1 susceptibility protein
Protein functionE3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair, HRR via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator, PubMed:20160719. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:14990569, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:20364141}.
Subcellular locationNucleus {ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:26778126, ECO:0000269|PubMed:9528852}. Chromosome {ECO:0000250|UniProtKB:P48754}. Cytoplasm {ECO:0000269|PubMed:20160719}. Note=Localizes at sites of DNA damage at double-strand breaks, DSBs;
recruitment to DNA damage sites is mediated by FAM175A and the BRCA1-A complex, PubMed:26778126. Translocated to the cytoplasm during UV-induced apoptosis, PubMed:20160719. {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:26778126}.;
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.;
SUBCELLULAR LOCATION: Isoform 5: Cytoplasm {ECO:0000269|PubMed:8972225}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P38398
Gene Ontology
(Biological Process)
Complete annatation
androgen receptor signaling pathway [GO:0030521];
apoptotic process [GO:0006915];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to indole-3-methanol [GO:0071681];
cellular response to tumor necrosis factor [GO:0071356];
centrosome cycle [GO:0007098];
chordate embryonic development [GO:0043009];
chromosome breakage [GO:0031052];
chromosome segregation [GO:0007059];
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator [GO:0006978];
DNA double-strand break processing [GO:0000729];
DNA replication [GO:0006260];
DNA synthesis involved in DNA repair [GO:0000731];
dosage compensation by inactivation of X chromosome [GO:0009048];
double-strand break repair [GO:0006302];
double-strand break repair via homologous recombination [GO:0000724];
double-strand break repair via nonhomologous end joining [GO:0006303];
fatty acid biosynthetic process [GO:0006633];
G2 DNA damage checkpoint [GO:0031572];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
negative regulation of centriole replication [GO:0046600];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of fatty acid biosynthetic process [GO:0045717];
negative regulation of histone acetylation [GO:0035067];
negative regulation of histone H3-K4 methylation [GO:0051572];
negative regulation of histone H3-K9 methylation [GO:0051573];
negative regulation of intracellular estrogen receptor signaling pathway [GO:0033147];
negative regulation of reactive oxygen species metabolic process [GO:2000378];
negative regulation of transcription, DNA-templated [GO:0045892];
positive regulation of angiogenesis [GO:0045766];
positive regulation of cell cycle arrest [GO:0071158];
positive regulation of DNA repair [GO:0045739];
positive regulation of gene expression [GO:0010628];
positive regulation of histone acetylation [GO:0035066];
positive regulation of histone H3-K4 methylation [GO:0051571];
positive regulation of histone H3-K9 acetylation [GO:2000617];
positive regulation of histone H3-K9 methylation [GO:0051574];
positive regulation of histone H4-K16 acetylation [GO:2000620];
positive regulation of histone H4-K20 methylation [GO:0070512];
positive regulation of protein ubiquitination [GO:0031398];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of vascular endothelial growth factor production [GO:0010575];
postreplication repair [GO:0006301];
protein autoubiquitination [GO:0051865];
protein K6-linked ubiquitination [GO:0085020];
protein sumoylation [GO:0016925];
protein ubiquitination [GO:0016567];
regulation of apoptotic process [GO:0042981];
regulation of cell proliferation [GO:0042127];
regulation of DNA methylation [GO:0044030];
regulation of gene expression by genetic imprinting [GO:0006349];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription from RNA polymerase III promoter [GO:0006359];
regulation of transcription from RNA polymerase II promoter [GO:0006357];
response to estrogen [GO:0043627];
response to ionizing radiation [GO:0010212];
strand displacement [GO:0000732];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
androgen receptor binding [GO:0050681];
chromatin binding [GO:0003682];
damaged DNA binding [GO:0003684];
DNA binding [GO:0003677];
enzyme binding [GO:0019899];
ligase activity [GO:0016874];
RNA binding [GO:0003723];
transcription coactivator activity [GO:0003713];
transcription regulatory region DNA binding [GO:0044212];
tubulin binding [GO:0015631];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
BRCA1-A complex [GO:0070531];
BRCA1-BARD1 complex [GO:0031436];
chromosome [GO:0005694];
condensed nuclear chromosome [GO:0000794];
cytoplasm [GO:0005737];
gamma-tubulin ring complex [GO:0008274];
intracellular ribonucleoprotein complex [GO:0030529];
mitochondrial matrix [GO:0005759];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
protein complex [GO:0043234];
ubiquitin ligase complex [GO:0000151]
Protein-protein interaction107140
Phylogenetic treeP38398
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is not observed
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD32.011145333384010.1198043557901760.203363695830553
AZA vs. DISU0.2708718305643830.448578569136140.918669250520452
AZA vs. IL71.056057153449210.05881726335058710.700253052677785
AZA vs. SAHA-0.4839405001566960.07437029031598730.33838145373474
DISU vs. CD3-1.754083377440410.1633172536756030.273000339657086
DISU vs. IL70.7769645763154310.190554439442120.56449587499868
DISU vs. SAHA-0.7538122753056420.03810657196768260.2389667212949
DMSO vs. AZA-0.02310005668727230.9304214731204161
DMSO vs. CD3-2.048430889376410.1076497445412540.181504577673642
DMSO vs. DISU-0.2969169601672990.3979544443927380.862858673780775
DMSO vs. IL71.087035775018870.04970581790031570.440025453657364
DMSO vs. SAHA-0.4685826570243130.07619666571054370.322442658112345
HIV vs. Mock in Activation-0.1691573324231210.9389102213077360.999983755607037
HIV vs. Mock in Latency0.05247847470951470.8374290666619570.999834320637052
IL7 vs. CD3-0.9455225543707080.445670752509730.579952970092304
SAHA vs. CD3-2.520645797461440.05747004693608750.111106299849498
SAHA vs. IL7-1.542972024712730.007019647518542340.0489200955591804
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
2 0.001008344 1.4 0.041966461 1.6 0.1949238
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.394875 0.00551063
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.092 1.12 1.126 0.983 1.097
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
204531_s_at 4.46 No upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1JM7 NMR - A=1-110.
1JNX X-ray 2.5Å X=1646-1859.
1N5O X-ray 2.8Å X=1646-1859.
1OQA NMR - A=1755-1863.
1T15 X-ray 1.8Å A=1646-1859.
1T29 X-ray 2.3Å A=1646-1859.
1T2U X-ray 2.8Å A=1646-1859.
1T2V X-ray 3.3Å A/B/C/D/E=1646-1859.
1Y98 X-ray 2.5Å A=1646-1859.
2ING X-ray 3.6Å X=1649-1859.
3COJ X-ray 3.2Å A/B/C/D/E/F/G/X=1646-1859.
3K0H X-ray 2.7Å A=1646-1859.
3K0K X-ray 2.7Å A=1646-1859.
3K15 X-ray 2.8Å A=1646-1859.
3K16 X-ray 3.0Å A=1646-1859.
3PXA X-ray 2.5Å A=1646-1859.
3PXB X-ray 2.5Å A=1646-1859.
3PXC X-ray 2.8Å X=1646-1859.
3PXD X-ray 2.8Å A=1646-1859.
3PXE X-ray 2.8Å A/B/C/D=1646-1859.
4IFI X-ray 2.2Å A=1646-1859.
4IGK X-ray 1.7Å A/B=1646-1859.
4JLU X-ray 3.5Å A=1649-1859.
4OFB X-ray 3.0Å A=1646-1859.
4U4A X-ray 3.5Å A/B/C=1646-1859.
4Y18 X-ray 3.5Å A/B/C/D/E/F/G/H=1646-1859.
4Y2G X-ray 2.5Å A=1646-1859.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat associates with 25879655
Vpr induces phosphorylation of 15650754
19275580
Tat enhanced by 25879655
Vpr stimulates 16983346
19275579
19275580
19275588
HIV-1 virus replication enhanced by expression of human gene 18976975
Vpr relocalizes 15485898
16983346
19275579
19275588
24158819

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa03440 Homologous recombination - Homo sapiens (human)
hsa03460 Fanconi anemia pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
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