UniProtKB - Q95153 (BRCA1_CANLF)
Breast cancer type 1 susceptibility protein homolog
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.
By similarityCatalytic 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.By similarity EC:2.3.2.27
: protein ubiquitination Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 24 – 65 | RING-typePROSITE-ProRule annotationAdd BLAST | 42 |
GO - Molecular functioni
- DNA binding Source: UniProtKB-KW
- RNA polymerase binding Source: UniProtKB
- transcription coactivator activity Source: UniProtKB
- ubiquitin-protein transferase activity Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- chordate embryonic development Source: GO_Central
- dosage compensation by inactivation of X chromosome Source: GO_Central
- double-strand break repair via homologous recombination Source: GO_Central
- fatty acid biosynthetic process Source: UniProtKB-KW
- negative regulation of fatty acid biosynthetic process Source: UniProtKB
- negative regulation of histone acetylation Source: GO_Central
- positive regulation of histone acetylation Source: GO_Central
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- protein autoubiquitination Source: UniProtKB
- protein K6-linked ubiquitination Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding, Transferase |
Biological process | Cell cycle, DNA damage, DNA recombination, DNA repair, Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Transcription, Transcription regulation, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: Breast cancer type 1 susceptibility protein homolog (EC:2.3.2.27By similarity)Alternative name(s): RING-type E3 ubiquitin transferase BRCA1Curated |
Gene namesi | Name:BRCA1 |
Organismi | Canis lupus familiaris (Dog) (Canis familiaris) |
Taxonomic identifieri | 9615 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis › |
Proteomesi |
|
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus By similarity
Other locations
- Chromosome By similarity
Note: Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex. Translocated to the cytoplasm during UV-induced apoptosis.By similarity
Nucleus
- BRCA1-A complex Source: GO_Central
- BRCA1-BARD1 complex Source: UniProtKB
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- chromosome Source: UniProtKB
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Chromosome, Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000055828 | 1 – 1878 | Breast cancer type 1 susceptibility protein homologAdd BLAST | 1878 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Cross-linki | 109 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 114 | PhosphoserineBy similarity | 1 | |
Cross-linki | 298 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 336 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 392 | PhosphoserineBy similarity | 1 | |
Modified residuei | 395 | PhosphoserineBy similarity | 1 | |
Modified residuei | 420 | PhosphoserineBy similarity | 1 | |
Modified residuei | 431 | PhosphoserineBy similarity | 1 | |
Cross-linki | 456 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 516 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 581 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 692 | PhosphoserineBy similarity | 1 | |
Modified residuei | 712 | PhosphoserineBy similarity | 1 | |
Modified residuei | 751 | PhosphoserineBy similarity | 1 | |
Modified residuei | 987 | Phosphoserine; by CHEK2By similarity | 1 | |
Modified residuei | 1008 | PhosphoserineBy similarity | 1 | |
Cross-linki | 1079 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 1144 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1190 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1192 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1212 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1218 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1219 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1281 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1331 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1344 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1391 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1398 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1427 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1460 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1527 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1545 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q95153 |
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 (By similarity).
Interacts with EXD2 (By similarity).
Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme (By similarity).
By similarityGO - Molecular functioni
- RNA polymerase binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000021534 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1652 – 1739 | BRCT 1PROSITE-ProRule annotationAdd BLAST | 88 | |
Domaini | 1764 – 1863 | BRCT 2PROSITE-ProRule annotationAdd BLAST | 100 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 303 – 329 | DisorderedSequence analysisAdd BLAST | 27 | |
Regioni | 349 – 368 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 548 – 614 | DisorderedSequence analysisAdd BLAST | 67 | |
Regioni | 1134 – 1154 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 1183 – 1221 | DisorderedSequence analysisAdd BLAST | 39 | |
Regioni | 1315 – 1401 | DisorderedSequence analysisAdd BLAST | 87 | |
Regioni | 1401 – 1428 | Interaction with PALB2By similarityAdd BLAST | 28 | |
Regioni | 1419 – 1504 | DisorderedSequence analysisAdd BLAST | 86 | |
Regioni | 1570 – 1590 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 1743 – 1764 | DisorderedSequence analysisAdd BLAST | 22 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 303 – 320 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 556 – 581 | Basic and acidic residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 582 – 603 | Polar residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 1134 – 1151 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 1183 – 1201 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 1315 – 1331 | Polar residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 1341 – 1364 | Acidic residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 1374 – 1401 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 1424 – 1504 | Polar residuesSequence analysisAdd BLAST | 81 |
Domaini
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 24 – 65 | RING-typePROSITE-ProRule annotationAdd BLAST | 42 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG4362, Eukaryota |
InParanoidi | Q95153 |
OrthoDBi | 496760at2759 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit 3.40.50.10190, 2 hits |
InterProi | View protein in InterPro IPR011364, BRCA1 IPR031099, BRCA1-associated IPR025994, BRCA1_serine_dom IPR001357, BRCT_dom IPR036420, BRCT_dom_sf 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 PF00533, BRCT, 2 hits PF12820, BRCT_assoc, 1 hit PF00097, zf-C3HC4, 1 hit |
PIRSFi | PIRSF001734, BRCA1, 1 hit |
PRINTSi | PR00493, BRSTCANCERI |
SMARTi | View protein in SMART SM00292, BRCT, 2 hits SM00184, RING, 1 hit |
SUPFAMi | SSF52113, SSF52113, 2 hits |
PROSITEi | View protein in PROSITE PS50172, BRCT, 2 hits PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MDLSADRVEE VQNVLNAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK
60 70 80 90 100
LLNQRKGPSQ CPLCKNDITK RSLQESTRFS QLVEELLKII HAFELDTGLQ
110 120 130 140 150
FADSYNFSKK ENNSPEHLKE EVSIIQSMGY RNRAKRLRQS EPENPTLETS
160 170 180 190 200
LSVQLSNLGI VRSLRTKQQI QPQNKSVYIE LGSDSSEDTV NKASSCSVGD
210 220 230 240 250
DELEITSQGA RAEASLNPAK KAACEFSGDI TNIEHHQSSN KDLTTTEKHA
260 270 280 290 300
TKKHPEKYQG ISVSNLHVEP CGTNTHASSL QHENSSLLLT KHRMNVEKAE
310 320 330 340 350
ICNNSKQPGL ARSQQSRWAE SKETCNDRQI PSTEKKVVVN ADLLCGRKEL
360 370 380 390 400
NKQKPPHSDS PRDSQDVPWI TLNSSIRKVN EWFSRSDEIL TSDDSHDRGS
410 420 430 440 450
ELNTEVGGAV EVPNEVGEYS GSSEKIDLMA SDPQDAFICE SERVHTKPVG
460 470 480 490 500
GNIEDKIFGK TYRRKASLPK VSHTTEVLTI GACAIEPQTM QTHPFMNKAE
510 520 530 540 550
HKRRTTSSLH PEDFIKKVEL GIVPKTPEKL IEGINQIKRD GHVINITNNG
560 570 580 590 600
PENETEGDYV QKEKNANPTE SLEKESAFRT KTEPMSSRIS NMELELNSSS
610 620 630 640 650
SKAPKKNRLR RKSSARHTCA LEFVVNRNLN PPDHSELQIE SCSSSEEMKK
660 670 680 690 700
QHLDQVPVRH NKTLQLMQDK EPAGRAKKSS KPGEQINKRL ASHAFPELTL
710 720 730 740 750
TNVSGFFANY SSSSKPQECI NPGLRREEIE ESRRMTQVSD STRDPKELVL
760 770 780 790 800
SGGRGLQTER SVESTSISLV LDTDYGTQDS ISLLEADTLR KAKTVSNQQA
810 820 830 840 850
NLCATIENPK EPIHGCSKDT RNDTEGFVVP LTCKDNHTQE TSIEMEESEL
860 870 880 890 900
DTQCLRNMFK VSKRQSFALF SYPRDPEEDC VTVCPRSGAF GKQGPKVTLE
910 920 930 940 950
CGQKEESQGK KESEIRHVQA VHTNAGFSAV SQKAKKPGDF AKCSIKGVSR
960 970 980 990 1000
LCLSSQFKGK ETELLIANYH GISQNPYHIP PLSPIRSCVK TLCQENLSEE
1010 1020 1030 1040 1050
KFEQHSMSPE RAVGNERVIQ STVSTISQNN IRECASKEVG SSSVNEVVSS
1060 1070 1080 1090 1100
TNEVGSSVNE VGSSGENIQA ELGRNRGPKL NAMLRLGLMQ PEVCKQSLSL
1110 1120 1130 1140 1150
SNCKHPEMKW QGQSEGAVLS VSADFSPCLI SDNPEQPMGS SRSSQVCSET
1160 1170 1180 1190 1200
PDDLLNGDKI KGKVSFAESD IKEKSAVFSK SVQSGEFSRS PSPSDHTRLA
1210 1220 1230 1240 1250
QGYQRGTKKL ESSEENMSSE EEELPCFQHL IFGKVTNMPS QSTSHNAVAA
1260 1270 1280 1290 1300
EGLSNKTEEN LDSLKNSLSD ISNQVPSAKA SQEHHLSEEA RCSGSLFSSQ
1310 1320 1330 1340 1350
CSALEDLTVN TNTQDPFSMF DPTSKQVRHQ SENLDVLNDK ELVSDDDDER
1360 1370 1380 1390 1400
EPGLEEDSPQ EEQSVDSDLG EVASGYESET SLSEDCSRLS SQSDILTTQQ
1410 1420 1430 1440 1450
RDTMQDNLIK LQQEMAELEA VLEQHESQPS NSSPSLIADS CSPEDLLNPE
1460 1470 1480 1490 1500
QNASERVLTS EKSSDSPISQ NPESLSTDKF QVFLDSSTSK NGEPGMIRSS
1510 1520 1530 1540 1550
PSQSRLLDTR WYVHSCPRSL QDTNCPSQKE LTKVVSMEEQ QPTESEARDL
1560 1570 1580 1590 1600
MEQSYLSRPD LEGAPYLESG ISLFSDDPES DPSSHRASEL AHVSSMPTST
1610 1620 1630 1640 1650
SALKLPQFQV EESAKSTAAV HIASTAGYNK SEDSVGIEKP EVISSTRGVN
1660 1670 1680 1690 1700
KRISMVASGL TPKEFMLVHK FARKHHISLT NLISEETTHV IMKTDAEFVC
1710 1720 1730 1740 1750
ERTLKYFLGI AGGKWVVSYF WVTQSIKERK ILDEHDFEVR GDVVNGRNHQ
1760 1770 1780 1790 1800
GPKRARESQD RESQDRKIFR GLEICCYGPF TNMPTDQLEW MVHLCGASVV
1810 1820 1830 1840 1850
KEPSLFTLSK GTHPVVVVQP DAWTEDSGFH AIGQMCEAPV VTREWVLDSV
1860 1870
ALYQCQELDT YLIPQIPRTA ADSSQPCV
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U50709 Genomic DNA Translation: AAC48663.1 |
RefSeqi | NP_001013434.1, NM_001013416.1 |
Genome annotation databases
GeneIDi | 403437 |
KEGGi | cfa:403437 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U50709 Genomic DNA Translation: AAC48663.1 |
RefSeqi | NP_001013434.1, NM_001013416.1 |
3D structure databases
SMRi | Q95153 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9612.ENSCAFP00000021534 |
Proteomic databases
PaxDbi | Q95153 |
Genome annotation databases
GeneIDi | 403437 |
KEGGi | cfa:403437 |
Organism-specific databases
CTDi | 672 |
Phylogenomic databases
eggNOGi | KOG4362, Eukaryota |
InParanoidi | Q95153 |
OrthoDBi | 496760at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Family and domain databases
Gene3Di | 3.30.40.10, 1 hit 3.40.50.10190, 2 hits |
InterProi | View protein in InterPro IPR011364, BRCA1 IPR031099, BRCA1-associated IPR025994, BRCA1_serine_dom IPR001357, BRCT_dom IPR036420, BRCT_dom_sf 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 PF00533, BRCT, 2 hits PF12820, BRCT_assoc, 1 hit PF00097, zf-C3HC4, 1 hit |
PIRSFi | PIRSF001734, BRCA1, 1 hit |
PRINTSi | PR00493, BRSTCANCERI |
SMARTi | View protein in SMART SM00292, BRCT, 2 hits SM00184, RING, 1 hit |
SUPFAMi | SSF52113, SSF52113, 2 hits |
PROSITEi | View protein in PROSITE PS50172, BRCT, 2 hits PS00518, ZF_RING_1, 1 hit PS50089, ZF_RING_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | BRCA1_CANLF | |
Accessioni | Q95153Primary (citable) accession number: Q95153 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | February 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 153 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways