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P38398 Proteins BRCT domain Repeats
Uniprot ID:P38398
Protein name: Breast cancer type 1 susceptibility protein
Gene : BRCA1 RNF53
Protein Family:
Squence Length : 1863
Sequnce
>P38398 1864 MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLQETSLSVQLSNLGTVRTLRTKQRIQPQKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSSLLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLSGERVLQTERSVESSSISLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENPKGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGGSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVSTISRNNIRENVFKEASSSNINEVGSSTNEVGSSINEIGSSDENIQAELGRNRGPKLNAMLRLGVLQPEVYKQSLPGSNCKHPEIKKQEYEEVVQTVNTDFSPYLISDNLEQPMGSSHASQVCSETPDDLLDDGEIKEDTSFAENDIKESSAVFSKSVQKGELSRSPSPFTHTHLAQGYRRGAKKLESSEENLSSEDEELPCFQHLLFGKVNNIPSQSTRHSTVATECLSKNTEENLLSLKNSLNDCSNQVILAKASQEHHLSEETKCSASLFSSQCSELEDLTANTNTQDPFLIGSSKQMRHQSESQGVGLSDKELVSDDEERGTGLEENNQEEQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRDTMQHNLIKLQQEMAELEAVLEQHGSQPSNSYPSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEYPISQNPEGLSADKFEVSADSSTSKNKEPGVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVVDVEEQQLEESGPHDLTETSYLPRQDLEGTPYLESGISLFSDDPESDPSEDRAPESARVGNIPSSTSALKVPQLKVAESAQSPAAAHTTDTAGYNAMEESVSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKMLNEHDFEVRGDVVNGRNHQGPKRARESQDRKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIPHSHY
Domains
DOMAIN 1642 1736 BRCT 1 DOMAIN 1756 1855 BRCT 2
BRCT sequence regions
1642 - 1736 ERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKMLNEHDFEVRG 1756 - 1855 RKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQ
Function
"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)"
Mutation
"26 26 I->A: Disrupts the interaction with E2 enzymes, thereby abolishing the E3 ubiquitin-protein ligase activity 26 26 I->E: No ubiquitination of RBBP8 71 71 R->G: No effect on interaction with BAP1 308 308 S->N: Abolishes phosphorylation by AURKA and interferes with cell cycle progression from G2 to mitosis 1143 1143 S->A: Reduces in vitro phosphorylation by ATR 1239 1239 S->A: No effect on in vitro phosphorylation by ATR 1280 1280 S->A: Reduces in vitro phosphorylation by ATR 1298 1298 S->A: No effect on in vitro phosphorylation by ATR 1330 1330 S->A: No effect on in vitro phosphorylation by ATR 1387 1387 S->A: Loss of IR-induced S-phase checkpoint 1394 1394 T->A: Reduces in vitro phosphorylation by ATR 1423 1423 S->A: Inhibition of the infrared-induced G2 arrest 1457 1457 S->A: Reduces in vitro phosphorylation by ATR 1466 1466 S->A: No effect on in vitro phosphorylation by ATR 1524 1524 S->A: No change in infrared S-phase delay when associated with A-1387 1655 1655 S->A: Abolishes interaction with BRIP1 1656 1656 G->D: No effect on affinity for a BRIP1 phosphopeptide 1662 1662 F->S: Does not abolish ABRAXAS1 binding, but abolishes formation of a heterotetramer with ABRAXAS1 1663 1663 M->K: Does not abolish ABRAXAS1 binding, but abolishes formation of a heterotetramer with ABRAXAS1 1666 1666 Y->A: Does not abolish ABRAXAS1 binding, but impairs formation of a heterotetramer with ABRAXAS1 1670 1670 R->E: Impairs formation of a heterotetramer with ABRAXAS1 1671 1671 K->E: Impairs formation of a heterotetramer with ABRAXAS1 1700 1700 T->A: Strongly reduces affinity for a BRIP1 phosphopeptide 1702 1702 K->M: Abolishes interaction with BRIP1 1738 1738 G->E: Abolishes interaction with BRIP1 1755 1755 S->A: No effect on in vitro phosphorylation by ATR 1835 1835 R->P: Mildly reduces affinity for a BRIP1 phosphopeptide 1836 1836 E->K: Slightly reduces affinity for a BRIP1 phosphopeptide"
Disease
"DISEASE: Breast cancer (BC) [MIM:114480]: A 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 Note=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: Breast-ovarian cancer, familial, 1 (BROVCA1) [MIM:604370]: A 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 Note=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: Ovarian cancer (OC) [MIM:167000]: The 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 Note=Disease susceptibility is associated with variations affecting the gene represented in this entry ; DISEASE: Pancreatic cancer 4 (PNCA4) [MIM:614320]: A 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 Note=Disease susceptibility is associated with variations affecting the gene represented in this entry ; DISEASE: Fanconi anemia, complementation group S (FANCS) [MIM:617883]: A form of Fanconi anemia, a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair Note=Disease susceptibility is associated with variations affecting the gene represented in this entry"