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Protein

Breast cancer type 1 susceptibility protein

Gene

BRCA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

E3 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).16 Publications

Enzyme regulationi

The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment.1 Publication

Pathway:iprotein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri24 – 6542RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • damaged DNA binding Source: Ensembl
  • DNA binding Source: ProtInc
  • enzyme binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • RNA binding Source: MGI
  • transcription coactivator activity Source: UniProtKB
  • transcription regulatory region DNA binding Source: BHF-UCL
  • tubulin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: ProtInc

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • apoptotic process Source: UniProtKB
  • cellular protein metabolic process Source: Reactome
  • cellular response to DNA damage stimulus Source: ProtInc
  • cellular response to indole-3-methanol Source: UniProtKB
  • cellular response to tumor necrosis factor Source: BHF-UCL
  • centrosome cycle Source: Ensembl
  • chordate embryonic development Source: GO_Central
  • chromosome segregation Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: UniProtKB
  • DNA repair Source: Reactome
  • DNA replication Source: Ensembl
  • dosage compensation by inactivation of X chromosome Source: GO_Central
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via homologous recombination Source: HGNC
  • fatty acid biosynthetic process Source: UniProtKB-KW
  • G2 DNA damage checkpoint Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  • negative regulation of centriole replication Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  • negative regulation of fatty acid biosynthetic process Source: UniProtKB
  • negative regulation of histone acetylation Source: GO_Central
  • negative regulation of histone H3-K4 methylation Source: Ensembl
  • negative regulation of histone H3-K9 methylation Source: BHF-UCL
  • negative regulation of intracellular estrogen receptor signaling pathway Source: CACAO
  • negative regulation of reactive oxygen species metabolic process Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of cell cycle arrest Source: BHF-UCL
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of histone acetylation Source: BHF-UCL
  • positive regulation of histone H3-K4 methylation Source: BHF-UCL
  • positive regulation of histone H3-K9 acetylation Source: BHF-UCL
  • positive regulation of histone H3-K9 methylation Source: Ensembl
  • positive regulation of histone H4-K16 acetylation Source: BHF-UCL
  • positive regulation of histone H4-K20 methylation Source: BHF-UCL
  • positive regulation of protein ubiquitination Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • postreplication repair Source: HGNC
  • post-translational protein modification Source: Reactome
  • protein autoubiquitination Source: UniProtKB
  • protein K6-linked ubiquitination Source: UniProtKB
  • protein sumoylation Source: Reactome
  • protein ubiquitination Source: HGNC
  • regulation of apoptotic process Source: UniProtKB
  • regulation of cell proliferation Source: UniProtKB
  • regulation of DNA methylation Source: Ensembl
  • regulation of gene expression by genetic imprinting Source: Ensembl
  • regulation of transcription from RNA polymerase III promoter Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • response to estrogen Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Ligase

Keywords - Biological processi

Cell cycle, DNA damage, DNA recombination, DNA repair, Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19. 2681.
ReactomeiREACT_18410. Fanconi Anemia pathway.
REACT_1924. ATM mediated phosphorylation of repair proteins.
REACT_27271. Meiotic recombination.
REACT_355174. SUMOylation of DNA damage response and repair proteins.
REACT_75792. Meiotic synapsis.
REACT_97. Recruitment of repair and signaling proteins to double-strand breaks.
SignaLinkiP38398.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Breast cancer type 1 susceptibility protein (EC:6.3.2.-)
Alternative name(s):
RING finger protein 53
Gene namesi
Name:BRCA1
Synonyms:RNF53
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:1100. BRCA1.

Subcellular locationi

Isoform 5 :

GO - Cellular componenti

  • BRCA1-A complex Source: UniProtKB
  • BRCA1-BARD1 complex Source: UniProtKB
  • chromosome Source: UniProtKB
  • condensed nuclear chromosome Source: Ensembl
  • cytoplasm Source: UniProtKB
  • gamma-tubulin ring complex Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: BHF-UCL
  • protein complex Source: UniProtKB
  • ribonucleoprotein complex Source: MGI
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Breast cancer (BC)15 Publications

Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.

Disease descriptionA common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.

See also OMIM:114480
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti4 – 41S → F in BC; unknown pathological significance. 1 Publication
VAR_070458
Natural varianti10 – 101E → K in BC and BROVCA1. 1 Publication
VAR_020679
Natural varianti18 – 181M → T in BC; unknown pathological significance. 2 Publications
VAR_063899
Natural varianti22 – 221L → S in BC. 1 Publication
VAR_007756
Natural varianti23 – 231E → K in BC and BROVCA1. 1 Publication
VAR_020680
Natural varianti45 – 451K → Q in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070459
Natural varianti61 – 611C → G in BC and ovarian cancer; no interaction with BAP1. 7 Publications
Corresponds to variant rs28897672 [ dbSNP | Ensembl ].
VAR_007757
Natural varianti64 – 641C → G in BC; no interaction with BAP1. 4 Publications
VAR_007758
Natural varianti67 – 671D → Y in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070460
Natural varianti71 – 711R → K in BC; unknown pathological significance. 1 Publication
VAR_020681
Natural varianti132 – 1321N → K in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070462
Natural varianti142 – 1421P → H in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070463
Natural varianti147 – 1471L → F in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070464
Natural varianti165 – 1651L → P in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070465
Natural varianti170 – 1701R → W in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070466
Natural varianti186 – 1861S → Y in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070467
Natural varianti191 – 1911V → I in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070468
Natural varianti231 – 2311T → M in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070469
Natural varianti245 – 2451D → V in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070470
Natural varianti246 – 2461L → V in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070471
Natural varianti271 – 2711V → L in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070472
Natural varianti271 – 2711V → M in BC. 1 Publication
Corresponds to variant rs80357244 [ dbSNP | Ensembl ].
VAR_007761
Natural varianti346 – 3461P → S in BC; unknown pathological significance. 1 Publication
VAR_008760
Natural varianti369 – 3691Missing in BC.
VAR_007763
Natural varianti461 – 4611F → L in BC. 1 Publication
Corresponds to variant rs56046357 [ dbSNP | Ensembl ].
VAR_007765
Natural varianti465 – 4651Y → D in BC. 1 Publication
VAR_007766
Natural varianti552 – 5521G → V in BC. 1 Publication
VAR_007768
Natural varianti668 – 6681L → F in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070473
Natural varianti695 – 6951D → N in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070474
Natural varianti749 – 7491D → Y in BC. 1 Publication
VAR_020683
Natural varianti798 – 7981P → L in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070475
Natural varianti810 – 8101N → Y in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070476
Natural varianti826 – 8261T → K in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
Corresponds to variant rs28897683 [ dbSNP | Ensembl ].
VAR_007772
Natural varianti841 – 8411R → Q in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070477
Natural varianti866 – 8661R → Q in BC; unknown pathological significance. 1 Publication
VAR_020686
Natural varianti888 – 8881H → Y in BC; unknown pathological significance. 1 Publication
VAR_020687
Natural varianti892 – 8921L → S in BC. 1 Publication
VAR_007775
Natural varianti960 – 9601G → D in BC. 1 Publication
VAR_007776
Natural varianti1025 – 10251T → I in BC. 1 Publication
VAR_007778
Natural varianti1047 – 10471V → A in BC. 1 Publication
VAR_007781
Natural varianti1101 – 11011S → N in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070479
Natural varianti1139 – 11391S → I in BC; unknown pathological significance. 1 Publication
VAR_020689
Natural varianti1140 – 11401S → G in BC; unknown pathological significance; functionally neutral in vitro. 2 Publications
Corresponds to variant rs2227945 [ dbSNP | Ensembl ].
VAR_019945
Natural varianti1140 – 11401S → N in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070480
Natural varianti1150 – 11501P → S in BC. 1 Publication
Corresponds to variant rs80357272 [ dbSNP | Ensembl ].
VAR_007782
Natural varianti1187 – 11871S → I in BC and BROVCA1. 1 Publication
VAR_020690
Natural varianti1200 – 12001Q → H in BC and BROVCA1. 1 Publication
Corresponds to variant rs56214134 [ dbSNP | Ensembl ].
VAR_020691
Natural varianti1204 – 12041R → I in BC. 1 Publication
VAR_020692
Natural varianti1207 – 12071K → N in BC. 1 Publication
VAR_020693
Natural varianti1210 – 12101E → G in BC; unknown pathological significance. 1 Publication
VAR_020694
Natural varianti1214 – 12141E → K in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070481
Natural varianti1217 – 12171S → Y in BC and BROVCA1. 1 Publication
VAR_020695
Natural varianti1236 – 12361N → K in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
Corresponds to variant rs28897687 [ dbSNP | Ensembl ].
VAR_052078
Natural varianti1267 – 12671L → S in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070482
Natural varianti1282 – 12821E → V in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070483
Natural varianti1297 – 12971S → P in BC; unknown pathological significance. 1 Publication
VAR_020698
Natural varianti1297 – 12971Missing in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070484
Natural varianti1301 – 13011S → R in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070485
Natural varianti1346 – 13461E → K in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070486
Natural varianti1378 – 13781V → I in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070487
Natural varianti1400 – 14001M → V in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070488
Natural varianti1407 – 14071L → P in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070489
Natural varianti1411 – 14111M → T in BC and ovarian cancer; unknown pathological significance; decreased interaction with PALB2. 2 Publications
VAR_020699
Natural varianti1443 – 14431R → G in BC; unknown pathological significance; functionally neutral in vitro. 3 Publications
VAR_007787
Natural varianti1448 – 14481S → G in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070490
Natural varianti1486 – 14861S → C in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070491
Natural varianti1495 – 14951R → M in BC; unknown pathological significance. 1 Publication
VAR_063900
Natural varianti1534 – 15341V → M in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070492
Natural varianti1589 – 15891R → P in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070493
Natural varianti1651 – 16511S → F in BC; unknown pathological significance. 1 Publication
VAR_070494
Natural varianti1651 – 16511S → P in BC; unknown pathological significance. 1 Publication
VAR_070495
Natural varianti1655 – 16551S → F in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070496
Natural varianti1685 – 16851T → A in BC; unknown pathological significance. 1 Publication
VAR_063902
Natural varianti1686 – 16861H → Q in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070497
Natural varianti1686 – 16861H → R in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070498
Natural varianti1688 – 16881Missing in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070499
Natural varianti1689 – 16891M → R in BC; unknown pathological significance. 1 Publication
VAR_063904
Natural varianti1691 – 16911T → I in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070500
Natural varianti1699 – 16991R → Q in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070501
Natural varianti1699 – 16991R → W in BC and ovarian cancer; functionally impaired in vitro. 3 Publications
VAR_020703
Natural varianti1706 – 17061G → A in BC; unknown pathological significance. 1 Publication
VAR_070502
Natural varianti1706 – 17061G → E in BC; unknown pathological significance. 2 Publications
Corresponds to variant rs80356860 [ dbSNP | Ensembl ].
VAR_063905
Natural varianti1708 – 17081A → E in BC; abolishes ACACA binding. 3 Publications
Corresponds to variant rs28897696 [ dbSNP | Ensembl ].
VAR_007796
Natural varianti1715 – 17151S → R in BC; unknown pathological significance. 1 Publication
VAR_063906
Natural varianti1718 – 17181W → C in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070503
Natural varianti1720 – 17201T → A in BC; unknown pathological significance; functionally neutral in vitro; no effect on in vitro phosphorylation by ATR. 2 Publications
VAR_070504
Natural varianti1735 – 17351E → K in BC; unknown pathological significance. 1 Publication
VAR_070505
Natural varianti1736 – 17361V → A in BC; unknown pathological significance. 1 Publication
VAR_070506
Natural varianti1738 – 17381G → R in BC; unknown pathological significance. 1 Publication
VAR_063907
Natural varianti1739 – 17391D → G in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070507
Natural varianti1739 – 17391D → V in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070508
Natural varianti1746 – 17461H → Q in BC; unknown pathological significance. 1 Publication
VAR_070509
Natural varianti1753 – 17531R → T in BC; unknown pathological significance. 1 Publication
VAR_070510
Natural varianti1764 – 17641L → P in BC; unknown pathological significance; functionally impaired in vitro. 2 Publications
VAR_063908
Natural varianti1766 – 17661I → S in BC; unknown pathological significance. 1 Publication
VAR_063909
Natural varianti1767 – 17671C → S in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070511
Natural varianti1770 – 17701G → V in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070512
Natural varianti1775 – 17751M → K in BC; strongly reduced transcription transactivation; abolishes interaction with BRIP1 and RBBP8. 1 Publication
VAR_063212
Natural varianti1775 – 17751M → R in BC; alters protein stability and abolishes ACACA and BRIP1 binding. 5 Publications
VAR_007799
Natural varianti1782 – 17821W → C in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070513
Natural varianti1788 – 17881G → V in BC; unknown pathological significance. 1 Publication
VAR_063910
Natural varianti1789 – 17891A → T in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070514
Natural varianti1794 – 17941E → D in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070515
Natural varianti1804 – 18041V → D in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070516
Natural varianti1812 – 18121P → R in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070517
Natural varianti1837 – 18371W → R in BC; unknown pathological significance; functionally impaired in vitro. 1 Publication
VAR_070518
Natural varianti1862 – 18621H → L in BC; unknown pathological significance; functionally neutral in vitro. 1 Publication
VAR_070519
Breast-ovarian cancer, familial, 1 (BROVCA1)3 Publications

Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.

Disease descriptionA condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate.

See also OMIM:604370
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti10 – 101E → K in BC and BROVCA1. 1 Publication
VAR_020679
Natural varianti23 – 231E → K in BC and BROVCA1. 1 Publication
VAR_020680
Natural varianti835 – 8351H → Y in BROVCA1; unknown pathological significance. 1 Publication
VAR_020684
Natural varianti841 – 8411R → W in BROVCA1; unknown pathological significance. 2 Publications
Corresponds to variant rs1800709 [ dbSNP | Ensembl ].
VAR_007773
Natural varianti1187 – 11871S → I in BC and BROVCA1. 1 Publication
VAR_020690
Natural varianti1200 – 12001Q → H in BC and BROVCA1. 1 Publication
Corresponds to variant rs56214134 [ dbSNP | Ensembl ].
VAR_020691
Natural varianti1217 – 12171S → Y in BC and BROVCA1. 1 Publication
VAR_020695
Natural varianti1226 – 12261F → L in BROVCA1. 1 Publication
VAR_020696
Natural varianti1243 – 12431R → G in BROVCA1. 1 Publication
VAR_020697
Natural varianti1786 – 17861L → P in BROVCA1; unknown pathological significance. 1 Publication
VAR_020704
Ovarian cancer (OC)3 Publications

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionThe term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.

See also OMIM:167000
Pancreatic cancer 4 (PNCA4)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.

See also OMIM:614320

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi26 – 261I → A: Disrupts the interaction with E2 enzymes, thereby abolishing the E3 ubiquitin-protein ligase activity. 2 Publications
Mutagenesisi26 – 261I → E: No ubiquitination of RBBP8. No restoration RBBP8-mediated focus formation or G2/M checkpoint control upon DNA damage. 2 Publications
Mutagenesisi71 – 711R → G: No effect on interaction with BAP1. 1 Publication
Mutagenesisi308 – 3081S → N: Abolishes phosphorylation by AURKA and interferes with cell cycle progression from G2 to mitosis. 1 Publication
Mutagenesisi1143 – 11431S → A: Reduces in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1239 – 12391S → A: No effect on in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1280 – 12801S → A: Reduces in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1298 – 12981S → A: No effect on in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1330 – 13301S → A: No effect on in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1387 – 13871S → A: Loss of IR-induced S-phase checkpoint. Reduces in vitro phosphorylation by ATR. 2 Publications
Mutagenesisi1394 – 13941T → A: Reduces in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1423 – 14231S → A: Inhibition of the infrared-induced G2 arrest. Reduces phosphorylation by ATR. 2 Publications
Mutagenesisi1457 – 14571S → A: Reduces in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1466 – 14661S → A: No effect on in vitro phosphorylation by ATR. 1 Publication
Mutagenesisi1524 – 15241S → A: No change in infrared S-phase delay; when associated with A-1387. No effect on in vitro phosphorylation by ATR. 2 Publications
Mutagenesisi1655 – 16551S → A: Abolishes interaction with BRIP1. 1 Publication
Mutagenesisi1702 – 17021K → M: Abolishes interaction with BRIP1. 1 Publication
Mutagenesisi1738 – 17381G → E: Abolishes interaction with BRIP1. 1 Publication
Mutagenesisi1755 – 17551S → A: No effect on in vitro phosphorylation by ATR. 1 Publication

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

MIMi114480. phenotype.
167000. phenotype.
604370. phenotype.
614320. phenotype.
Orphaneti1333. Familial pancreatic carcinoma.
1331. Familial prostate cancer.
145. Hereditary breast and ovarian cancer syndrome.
227535. Hereditary breast cancer.
213524. Hereditary site-specific ovarian cancer syndrome.
168829. Primary peritoneal carcinoma.
PharmGKBiPA25411.

Polymorphism and mutation databases

BioMutaiBRCA1.
DMDMi728984.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18631863Breast cancer type 1 susceptibility proteinPRO_0000055830Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei114 – 1141Phosphoserine2 Publications
Modified residuei308 – 3081Phosphoserine; by AURKA1 Publication
Modified residuei395 – 3951Phosphoserine2 Publications
Modified residuei398 – 3981Phosphoserine2 Publications
Modified residuei423 – 4231Phosphoserine1 Publication
Modified residuei694 – 6941Phosphoserine1 Publication
Modified residuei753 – 7531Phosphoserine1 Publication
Modified residuei840 – 8401PhosphoserineBy similarity
Modified residuei988 – 9881Phosphoserine; by CHEK22 Publications
Modified residuei1143 – 11431Phosphoserine; by ATR; in vitro1 Publication
Modified residuei1211 – 12111Phosphoserine1 Publication
Modified residuei1217 – 12171Phosphoserine1 Publication
Modified residuei1218 – 12181Phosphoserine2 Publications
Modified residuei1280 – 12801Phosphoserine; by ATR; in vitro1 Publication
Modified residuei1328 – 13281Phosphoserine1 Publication
Modified residuei1336 – 13361Phosphoserine3 Publications
Modified residuei1342 – 13421Phosphoserine2 Publications
Modified residuei1387 – 13871Phosphoserine; by ATM and ATR1 Publication
Modified residuei1394 – 13941Phosphothreonine; by ATR; in vitro1 Publication
Modified residuei1423 – 14231Phosphoserine; by ATM and ATR1 Publication
Modified residuei1457 – 14571Phosphoserine; by ATR; in vitro1 Publication
Modified residuei1524 – 15241Phosphoserine; by ATM1 Publication

Post-translational modificationi

Phosphorylation at Ser-308 by AURKA is required for normal cell cycle progression from G2 to mitosis. Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-988 by CHEK2 regulates mitotic spindle assembly.7 Publications
Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP38398.
PaxDbiP38398.
PRIDEiP38398.

PTM databases

PhosphoSiteiP38398.

Miscellaneous databases

PMAP-CutDBP38398.

Expressioni

Tissue specificityi

Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines.

Gene expression databases

BgeeiP38398.
CleanExiHS_BRCA1.
ExpressionAtlasiP38398. baseline and differential.
GenevisibleiP38398. HS.

Organism-specific databases

HPAiCAB001946.
CAB018369.
HPA034966.

Interactioni

Subunit structurei

Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1, BRCC3, BRE and BABAM1. Interacts (via the BRCT domains) with FAM175A. Component of the BRCA1-RBBP8 complex. Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, COBRA1, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, AURKA, UBXN1 and KIAA0101/PAF15. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AFX (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1.36 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ACACAQ130852EBI-349905,EBI-717681
BAP1Q925603EBI-349905,EBI-1791447
BARD1Q997289EBI-349905,EBI-473181
BCL2P104156EBI-349905,EBI-77694
BRAPQ7Z5693EBI-349905,EBI-349900
BRAT1Q6PJG66EBI-349905,EBI-10826195
BRIP1Q9BX6312EBI-349905,EBI-3509650
CCND1P243853EBI-349905,EBI-375001
CCNE1P248642EBI-349905,EBI-519526
CHEK1O147573EBI-349905,EBI-974488
ESR1P0337212EBI-349905,EBI-78473
Ezh2Q611885EBI-349905,EBI-904311From a different organism.
FAM175AQ6UWZ710EBI-349905,EBI-1263451
FHL2Q141926EBI-349905,EBI-701903
GTF2IP783475EBI-349905,EBI-359622
H2AFXP161044EBI-349905,EBI-494830
HSPD1P108092EBI-349905,EBI-352528
IFI16Q166669EBI-349905,EBI-2867186
KPNA2P522923EBI-349905,EBI-349938
NELFBQ8WX925EBI-349905,EBI-347721
PPP1CAP621362EBI-349905,EBI-357253
PPP1CBP621403EBI-349905,EBI-352350
PPP1CCP368732EBI-349905,EBI-356283
RBBP8Q997089EBI-349905,EBI-745715
TRRAPQ9Y4A58EBI-349905,EBI-399128
UIMC1Q96RL19EBI-349905,EBI-725300
ZCCHC8Q6NZY42EBI-349905,EBI-1263058
ZNF350Q9GZX53EBI-349905,EBI-396421

Protein-protein interaction databases

BioGridi107140. 560 interactions.
DIPiDIP-5971N.
IntActiP38398. 74 interactions.
MINTiMINT-90433.
STRINGi9606.ENSP00000418960.

Structurei

Secondary structure

1
1863
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 53Combined sources
Helixi8 – 2114Combined sources
Beta strandi25 – 273Combined sources
Helixi46 – 538Combined sources
Beta strandi54 – 585Combined sources
Turni62 – 643Combined sources
Turni70 – 723Combined sources
Beta strandi78 – 803Combined sources
Helixi81 – 9616Combined sources
Beta strandi1651 – 16566Combined sources
Helixi1659 – 167113Combined sources
Beta strandi1675 – 16795Combined sources
Beta strandi1686 – 16894Combined sources
Beta strandi1695 – 16973Combined sources
Helixi1701 – 17088Combined sources
Beta strandi1712 – 17154Combined sources
Helixi1717 – 17259Combined sources
Helixi1731 – 17344Combined sources
Turni1740 – 17423Combined sources
Beta strandi1743 – 17453Combined sources
Helixi1748 – 17547Combined sources
Turni1755 – 17573Combined sources
Turni1760 – 17634Combined sources
Beta strandi1765 – 17684Combined sources
Beta strandi1770 – 17723Combined sources
Beta strandi1773 – 17753Combined sources
Helixi1777 – 178610Combined sources
Beta strandi1790 – 17945Combined sources