UniProtKB - Q5YLB2 (Q5YLB2_HUMAN)
Breast cancer type 1 susceptibility protein
BRCA1
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 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 appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. 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.
UniRule annotationCatalytic activityi
- S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.UniRule annotation EC:2.3.2.27
GO - Molecular functioni
- DNA binding Source: UniProtKB-KW
- ubiquitin-protein transferase activity Source: UniProtKB-UniRule
- zinc ion binding Source: InterPro
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- DNA recombination Source: UniProtKB-KW
- DNA repair Source: UniProtKB-KW
- protein autoubiquitination Source: UniProtKB-UniRule
- protein K6-linked ubiquitination Source: UniProtKB-UniRule
Keywordsi
Molecular function | ActivatorARBA annotation, DNA-bindingUniRule annotation, TransferaseARBA annotation |
Biological process | Cell cycleUniRule annotation, DNA damage, DNA recombinationUniRule annotationARBA annotation, DNA repairUniRule annotationARBA annotation, Transcription, Transcription regulationARBA annotation, Ubl conjugation pathwayUniRule annotation |
Ligand | Metal-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Breast cancer type 1 susceptibility proteinUniRule annotation (EC:2.3.2.27UniRule annotation) |
Gene namesi | Name:BRCA1Imported |
Organismi | Homo sapiens (Human)Imported |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1100, BRCA1 |
VEuPathDBi | HostDB:ENSG00000012048 |
Subcellular locationi
Nucleus
- Nucleus UniRule annotation
Other locations
- Chromosome UniRule annotation
Note: Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex.UniRule annotation
Nucleus
- BRCA1-BARD1 complex Source: UniProtKB-UniRule
- nuclear body Source: HPA
- nucleoplasm Source: HPA
Other locations
- chromosome Source: UniProtKB-SubCell
Keywords - Cellular componenti
ChromosomeUniRule annotationARBA annotation, NucleusUniRule annotationARBA annotationExpressioni
Gene expression databases
Bgeei | ENSG00000012048, Expressed in ventricular zone and 194 other tissues |
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 BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1.
Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form).
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, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF.
Interacts (via BRCT domains) with BRIP1 (phosphorylated form).
Interacts with FANCD2 (ubiquitinated form).
Interacts with H2AX (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.
Interacts with EXD2.
Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme.
UniRule annotationStructurei
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 24 – 65 | RING-typeInterPro annotationAdd BLAST | 42 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 230 – 270 | DisorderedSequence analysisAdd BLAST | 41 | |
Regioni | 306 – 338 | DisorderedSequence analysisAdd BLAST | 33 | |
Regioni | 534 – 570 | DisorderedSequence analysisAdd BLAST | 37 | |
Regioni | 654 – 709 | DisorderedSequence analysisAdd BLAST | 56 | |
Regioni | 1181 – 1216 | DisorderedSequence analysisAdd BLAST | 36 | |
Regioni | 1322 – 1362 | DisorderedSequence analysisAdd BLAST | 41 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 1253 – 1273 | Sequence analysisAdd BLAST | 21 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 230 – 248 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 324 – 338 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 534 – 569 | Polar residuesSequence analysisAdd BLAST | 36 | |
Compositional biasi | 676 – 698 | Basic and acidic residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 1181 – 1196 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 1338 – 1353 | Basic and acidic residuesSequence analysisAdd BLAST | 16 |
Keywords - Domaini
Coiled coilSequence analysis, RepeatARBA annotation, Zinc-fingerPROSITE-ProRule annotationARBA annotationPhylogenomic databases
GeneTreei | ENSGT00440000034289 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR011364, BRCA1 IPR031099, BRCA1-associated IPR025994, BRCA1_serine_dom IPR018957, Znf_C3HC4_RING-type IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD IPR017907, Znf_RING_CS |
PANTHERi | PTHR13763, PTHR13763, 1 hit |
Pfami | View protein in Pfam PF12820, BRCT_assoc, 1 hit PF00097, zf-C3HC4, 1 hit |
PIRSFi | PIRSF001734, BRCA1, 1 hit |
PRINTSi | PR00493, BRSTCANCERI |
SMARTi | View protein in SMART SM00184, RING, 1 hit |
PROSITEi | View protein in PROSITE PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 24 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK
60 70 80 90 100
LLNQKKGPSQ CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE
110 120 130 140 150
YANSYNFAKK ENNSPEHLKD EVSIIQSMGY RNRAKRLLQS EPENPSLQET
160 170 180 190 200
SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI ELGSDSSEDT VNKATYCSVG
210 220 230 240 250
DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ PSNNDLNTTE
260 270 280 290 300
KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE
310 320 330 340 350
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER
360 370 380 390 400
KEWNKQKLPC SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD
410 420 430 440 450
GESESNAKVA DVLDVLNEVD EYSGSSEKID LLASDPHEAL ICKSERVHSK
460 470 480 490 500
SVESNIEDKI FGKTYRKKAS LPNLSHVTEN LIIGAFVTEP QIIQERPLTN
510 520 530 540 550
KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE QNGQVMNITN
560 570 580 590 600
SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI
610 620 630 640 650
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI
660 670 680 690 700
KKKKYNQMPV RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL
710 720 730 740 750
KLTNAPGSFT KCSNTSELKE FVNPSLPREE KEEKLETVKV SNNAEDPKDL
760 770 780 790 800
MLSGERVLQT ERSVESSSIS LVPGTDYGTQ ESISLLEVST LGKAKTEPNK
810 820 830 840 850
CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS RETSIEMEES
860 870 880 890 900
ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT
910 920 930 940 950
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS
960 970 980 990 1000
RFCLSSQFRG NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE
1010 1020 1030 1040 1050
ENFEEHSMSP EREMGNENIP STVSTISRNN IRENVFKEAS SSNINEVGSS
1060 1070 1080 1090 1100
TNEVGSSINE IGSSDENIQA ELGRNRGPKL NAMLRLGVLQ PEVYKQSLPG
1110 1120 1130 1140 1150
SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS HASQVCSETP
1160 1170 1180 1190 1200
DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ
1210 1220 1230 1240 1250
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE
1260 1270 1280 1290 1300
CLSKNTEENL LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC
1310 1320 1330 1340 1350
SELEDLTANT NTQDPFLIGS SKQMRHQSES QGVGLSDKEL VSDDEERGTG
1360 1370 1380 1390
LEENNQEEQS MDSNLGIGTR FLCLPQSIYR SELNVYAFGE HILQISKYS
Computationally mapped potential isoform sequencesi
There are 24 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketP38398 | BRCA1_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 RNF53 | 1,863 | Annotation score: | ||
E7EUM2 | E7EUM2_HUMAN | RING-type E3 ubiquitin transferase ... | BRCA1 | 623 | Annotation score: | ||
A0A0U1RRA9 | A0A0U1RRA9_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 | 798 | Annotation score: | ||
H0Y8B8 | H0Y8B8_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 | 498 | Annotation score: | ||
A0A2R8Y7V5 | A0A2R8Y7V5_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 | 659 | Annotation score: | ||
C6YB45 | C6YB45_HUMAN | BRCA1 isoform E1aA-Delta 2-17 | BRCA1 | 173 | Annotation score: | ||
E7EWN5 | E7EWN5_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 | 649 | Annotation score: | ||
Q3B891 | Q3B891_HUMAN | BRCA1 protein | BRCA1 | 473 | Annotation score: | ||
B7ZA85 | B7ZA85_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 | 572 | Annotation score: | ||
E9PH68 | E9PH68_HUMAN | Breast cancer type 1 susceptibility... | BRCA1 | 622 | Annotation score: | ||
There are more potential isoformsShow all |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC060780 Genomic DNA No translation available. AC135721 Genomic DNA No translation available. KF456281 Genomic DNA No translation available. AY354539 mRNA Translation: AAQ92977.1 |
Genome annotation databases
Ensembli | ENST00000354071; ENSP00000326002; ENSG00000012048 |
UCSCi | uc002idd.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC060780 Genomic DNA No translation available. AC135721 Genomic DNA No translation available. KF456281 Genomic DNA No translation available. AY354539 mRNA Translation: AAQ92977.1 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Proteomic databases
ProteomicsDBi | 30151 |
Protocols and materials databases
Antibodypediai | 4527, 2257 antibodies from 44 providers |
Genome annotation databases
Ensembli | ENST00000354071; ENSP00000326002; ENSG00000012048 |
UCSCi | uc002idd.5, human |
Organism-specific databases
HGNCi | HGNC:1100, BRCA1 |
OpenTargetsi | ENSG00000012048 |
VEuPathDBi | HostDB:ENSG00000012048 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00440000034289 |
Miscellaneous databases
ChiTaRSi | BRCA1, human |
Gene expression databases
Bgeei | ENSG00000012048, Expressed in ventricular zone and 194 other tissues |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit |
InterProi | View protein in InterPro IPR011364, BRCA1 IPR031099, BRCA1-associated IPR025994, BRCA1_serine_dom IPR018957, Znf_C3HC4_RING-type IPR001841, Znf_RING IPR013083, Znf_RING/FYVE/PHD IPR017907, Znf_RING_CS |
PANTHERi | PTHR13763, PTHR13763, 1 hit |
Pfami | View protein in Pfam PF12820, BRCT_assoc, 1 hit PF00097, zf-C3HC4, 1 hit |
PIRSFi | PIRSF001734, BRCA1, 1 hit |
PRINTSi | PR00493, BRSTCANCERI |
SMARTi | View protein in SMART SM00184, RING, 1 hit |
PROSITEi | View protein in PROSITE PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | Q5YLB2_HUMAN | |
Accessioni | Q5YLB2Primary (citable) accession number: Q5YLB2 Secondary accession number(s): F8W8H7 | |
Entry historyi | Integrated into UniProtKB/TrEMBL: | November 23, 2004 |
Last sequence update: | November 23, 2004 | |
Last modified: | January 19, 2022 | |
This is version 129 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Unreviewed (UniProtKB/TrEMBL) | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |