UniProtKB - Q9GKK8 (BRCA1_PANTR)
Breast cancer type 1 susceptibility protein homolog
BRCA1
Functioni
Catalytic 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
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
- tubulin binding Source: UniProtKB
- ubiquitin-protein transferase activity Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- apoptotic process Source: UniProtKB
- cell cycle Source: UniProtKB-KW
- chordate embryonic development Source: GO_Central
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: UniProtKB
- 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 centriole replication Source: UniProtKB
- negative regulation of fatty acid biosynthetic process Source: UniProtKB
- negative regulation of histone acetylation Source: GO_Central
- positive regulation of cell cycle arrest Source: GO_Central
- positive regulation of DNA repair Source: UniProtKB
- 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 apoptotic process Source: UniProtKB
- regulation of cell population proliferation Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of transcription by RNA polymerase III 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 |
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 | Pan troglodytes (Chimpanzee) |
Taxonomic identifieri | 9598 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pan |
Proteomesi |
|
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Chromosome By similarity
- Cytoplasm 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
Cytoskeleton
- gamma-tubulin ring complex Source: UniProtKB
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_0000055833 | 1 – 1863 | Breast cancer type 1 susceptibility protein homologAdd BLAST | 1863 |
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 | 301 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 308 | Phosphoserine; by AURKABy similarity | 1 | |
Cross-linki | 339 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 395 | PhosphoserineBy similarity | 1 | |
Modified residuei | 398 | PhosphoserineBy similarity | 1 | |
Modified residuei | 423 | PhosphoserineBy similarity | 1 | |
Modified residuei | 434 | PhosphoserineBy similarity | 1 | |
Cross-linki | 443 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 459 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 519 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 551 | PhosphoserineBy similarity | 1 | |
Cross-linki | 583 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 654 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 694 | PhosphoserineBy similarity | 1 | |
Modified residuei | 708 | PhosphoserineBy similarity | 1 | |
Modified residuei | 725 | PhosphoserineBy similarity | 1 | |
Cross-linki | 734 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 739 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 753 | PhosphoserineBy similarity | 1 | |
Modified residuei | 840 | PhosphoserineBy similarity | 1 | |
Cross-linki | 918 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Cross-linki | 987 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 988 | Phosphoserine; by CHEK2By similarity | 1 | |
Modified residuei | 1009 | PhosphoserineBy similarity | 1 | |
Cross-linki | 1079 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 1143 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1189 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1191 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1211 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1217 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1218 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1280 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1328 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1336 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1342 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1387 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1394 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1423 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1457 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1524 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1542 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q9GKK8 |
PRIDEi | Q9GKK8 |
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, AURKA, UBXN1 and PCLAF.
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 (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
- tubulin binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9598.ENSPTRP00000015727 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1642 – 1736 | BRCT 1PROSITE-ProRule annotationAdd BLAST | 95 | |
Domaini | 1756 – 1855 | BRCT 2PROSITE-ProRule annotationAdd BLAST | 100 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1397 – 1424 | Interaction with PALB2By similarityAdd BLAST | 28 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 651 – 654 | Poly-Lys | 4 |
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 | ENOG410ITQ6 Eukaryota ENOG4111WR7 LUCA |
HOGENOMi | HOG000230969 |
InParanoidi | Q9GKK8 |
KOi | K10605 |
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 PTHR13763:SF0 PTHR13763:SF0, 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
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 IQPQKKSVYI ELGSDSSEDT VNKATYCSVG
210 220 230 240 250
DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ PSNNDLNTTE
260 270 280 290 300
KRATERHPEK 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
GGSESNAKVA DVLDVLNEVD EYSGSSEKID LLASDPHEAL ICKSERVHSK
460 470 480 490 500
SVESNTEDKI FGKTYRRKAS LPNLSHVTEN LIIGAFVTEP QIIQERPLTN
510 520 530 540 550
KLKRKRRATS GLHPEDFIKK ADLAVQKTPE MINQGTNQME 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 DKEPATGVKK SNKPNEQTSK RHDSDTFPEL
710 720 730 740 750
KLTNAPGSFT NCSNTSELKE FVNPSLPREE KEEKLETVKV SNNAEDPKDL
760 770 780 790 800
MLSGERVLQT ERSVESSSIS LVPGTDYGTQ ESISLLEVST LGKAKTEPNK
810 820 830 840 850
CVSQCAAFEN PKGLIHGCSK DTRNDTEGFK YPLGHEVNHS RETSIEMEES
860 870 880 890 900
ELDAQYLQNT FKVSKRQSFA LFSNPGNPEE ECATFSAHCR SLKKQSPKVT
910 920 930 940 950
FEREQKEQNQ GKNESNIKPV QTVNITAGFP VVCQKDKPVD YAKCSIKGGS
960 970 980 990 1000
RFCLSSQFRG NETGLITPNK HGLLQNPYHI PPLFPIKSFV KTKCKKNLLE
1010 1020 1030 1040 1050
ENFEEHSMSP EREMGNENIP STVSTISRNN IRENVFKEAS SSNINEVGSS
1060 1070 1080 1090 1100
TNEVGSSINE VGSSDENIQA ELGRNRGPKL NAMLRLGVLQ PEVYKQSLPG
1110 1120 1130 1140 1150
SNCKHPEIKK QEYEEVVQTV NTDFSPCLIS DNLEQPMGSS HASQVCSETP
1160 1170 1180 1190 1200
DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQRGELSRSP SPFTHTHLAQ
1210 1220 1230 1240 1250
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVSNIPSQ 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 1400
LEENNQEEQS MDSNLGEAAS GCESETSVSE DCSGLSSQSD ILTTQQRDTM
1410 1420 1430 1440 1450
QDNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE DLQNPEQSTS
1460 1470 1480 1490 1500
EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
1510 1520 1530 1540 1550
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET
1560 1570 1580 1590 1600
SYLPRQDLEG TPYLESGISL FSDDPESDPS EDKAPESAHV GNIPSSTSAL
1610 1620 1630 1640 1650
KVPQLKVAES AQSPAAAHTT NTAGYNAMEE SVSREKPELT ASTERVNKRM
1660 1670 1680 1690 1700
SMVVSGLTPE EFMLVYKFAR KHHITLTNLI TEETTHVVMK TDAEFVCERT
1710 1720 1730 1740 1750
LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV VNGRNHQGPK
1760 1770 1780 1790 1800
RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
1810 1820 1830 1840 1850
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL
1860
DTYLIPQIPH SHY
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 427 | E → K in AAR04849 (PubMed:15385441).Curated | 1 | |
Sequence conflicti | 925 | I → T in AAR04849 (PubMed:15385441).Curated | 1 | |
Sequence conflicti | 1520 | R → T in AAG43492 (Ref. 1) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018712 | 309 | K → E1 Publication | 1 | |
Natural variantiVAR_018713 | 590 | S → G1 Publication | 1 | |
Natural variantiVAR_018714 | 731 | K → E2 Publications | 1 | |
Natural variantiVAR_018715 | 1100 | G → E2 Publications | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF207822 mRNA Translation: AAG43492.1 AY365046 Genomic DNA Translation: AAR04849.1 AF019075 Genomic DNA Translation: AAC39583.1 |
RefSeqi | NP_001038958.1, NM_001045493.1 |
Genome annotation databases
GeneIDi | 449497 |
KEGGi | ptr:449497 |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF207822 mRNA Translation: AAG43492.1 AY365046 Genomic DNA Translation: AAR04849.1 AF019075 Genomic DNA Translation: AAC39583.1 |
RefSeqi | NP_001038958.1, NM_001045493.1 |
3D structure databases
SMRi | Q9GKK8 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9598.ENSPTRP00000015727 |
Proteomic databases
PaxDbi | Q9GKK8 |
PRIDEi | Q9GKK8 |
Genome annotation databases
GeneIDi | 449497 |
KEGGi | ptr:449497 |
Organism-specific databases
CTDi | 672 |
Phylogenomic databases
eggNOGi | ENOG410ITQ6 Eukaryota ENOG4111WR7 LUCA |
HOGENOMi | HOG000230969 |
InParanoidi | Q9GKK8 |
KOi | K10605 |
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 PTHR13763:SF0 PTHR13763:SF0, 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | BRCA1_PANTR | |
Accessioni | Q9GKK8Primary (citable) accession number: Q9GKK8 Secondary accession number(s): O46484 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 21, 2003 |
Last sequence update: | November 21, 2003 | |
Last modified: | July 31, 2019 | |
This is version 143 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |