BRCA1_CANLF
ID BRCA1_CANLF Reviewed; 1878 AA.
AC Q95153;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 25-MAY-2022, entry version 154.
DE RecName: Full=Breast cancer type 1 susceptibility protein homolog;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:P38398};
DE AltName: Full=RING-type E3 ubiquitin transferase BRCA1 {ECO:0000305};
GN Name=BRCA1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8872468; DOI=10.1093/hmg/5.9.1289;
RA Szabo C.I., Wagner L.A., Francisco L.V., Roach J.C., Argonza R.,
RA King M.-C., Ostrander E.A.;
RT "Human, canine and murine BRCA1 genes: sequence comparison among species.";
RL Hum. Mol. Genet. 5:1289-1298(1996).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically mediates the
CC formation of 'Lys-6'-linked polyubiquitin chains and plays a central
CC role in DNA repair by facilitating cellular responses to DNA damage. It
CC is unclear whether it also mediates the formation of other types of
CC polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse
CC range of cellular pathways such as DNA damage repair, ubiquitination
CC and transcriptional regulation to maintain genomic stability. Regulates
CC centrosomal microtubule nucleation. Required for appropriate cell cycle
CC arrests after ionizing irradiation in both the S-phase and the G2 phase
CC of the cell cycle. Required for FANCD2 targeting to sites of DNA
CC damage. Inhibits lipid synthesis by binding to inactive phosphorylated
CC ACACA and preventing its dephosphorylation. Contributes to homologous
CC recombination repair (HRR) via its direct interaction with PALB2, fine-
CC tunes recombinational repair partly through its modulatory role in the
CC PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks.
CC Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation
CC and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-
CC mediated ubiquitination of RBBP8. Acts as a transcriptional activator.
CC {ECO:0000250|UniProtKB:P38398}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:P38398};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Heterodimer with BARD1. Part of the BRCA1-associated genome
CC surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1,
CC ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This
CC association could be a dynamic process changing throughout the cell
CC cycle and within subnuclear domains. Component of the BRCA1-A complex,
CC at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36,
CC BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1
CC (phosphorylated form); this is important for recruitment to sites of
CC DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1
CC (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts
CC (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the
CC interaction ubiquitinates RBBP8, regulates CHEK1 activation, and
CC involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA
CC damage. Associates with RNA polymerase II holoenzyme. Interacts with
CC SMC1A, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and
CC PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form).
CC Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX
CC (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with
CC ACACA (phosphorylated form); the interaction prevents dephosphorylation
CC of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2.
CC Interacts directly with PALB2; the interaction is essential for its
CC function in HRR. Interacts directly with BRCA2; the interaction occurs
CC only in the presence of PALB2 which serves as the bridging protein.
CC Interacts (via the BRCT domains) with LMO4; the interaction represses
CC the transcriptional activity of BRCA1. Interacts (via the BRCT domains)
CC with CCAR2 (via N-terminus); the interaction represses the
CC transcriptional activator activity of BRCA1 (By similarity). Interacts
CC with EXD2 (By similarity). Interacts (via C-terminus) with DHX9; this
CC interaction is direct and links BRCA1 to the RNA polymerase II
CC holoenzyme (By similarity). {ECO:0000250|UniProtKB:P38398}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P38398}.
CC Chromosome {ECO:0000250|UniProtKB:P48754}. Cytoplasm
CC {ECO:0000250|UniProtKB:P38398}. Note=Localizes at sites of DNA damage
CC at double-strand breaks (DSBs); recruitment to DNA damage sites is
CC mediated by the BRCA1-A complex. Translocated to the cytoplasm during
CC UV-induced apoptosis. {ECO:0000250|UniProtKB:P38398}.
CC -!- DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF motif
CC on proteins. The interaction with the phosphorylated pSXXF motif of
CC ABRAXAS1, recruits BRCA1 at DNA damage sites (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The RING-type zinc finger domain interacts with BAP1.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated in response to IR, UV, and various stimuli that
CC cause checkpoint activation, probably by ATM or ATR. Phosphorylation at
CC Ser-987 by CHEK2 regulates mitotic spindle assembly. Phosphorylation by
CC AURKA regulates centrosomal microtubule nucleation. {ECO:0000250}.
CC -!- PTM: Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination.
CC 'Lys-6'-linked polyubiquitination does not promote degradation (By
CC similarity). {ECO:0000250}.
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DR EMBL; U50709; AAC48663.1; -; Genomic_DNA.
DR RefSeq; NP_001013434.1; NM_001013416.1.
DR AlphaFoldDB; Q95153; -.
DR SMR; Q95153; -.
DR STRING; 9612.ENSCAFP00000021534; -.
DR PaxDb; Q95153; -.
DR GeneID; 403437; -.
DR KEGG; cfa:403437; -.
DR CTD; 672; -.
DR eggNOG; KOG4362; Eukaryota.
DR InParanoid; Q95153; -.
DR OrthoDB; 496760at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0070531; C:BRCA1-A complex; IBA:GO_Central.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070063; F:RNA polymerase binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0043009; P:chordate embryonic development; IBA:GO_Central.
DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IBA:GO_Central.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0035067; P:negative regulation of histone acetylation; IBA:GO_Central.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR011364; BRCA1.
DR InterPro; IPR031099; BRCA1-associated.
DR InterPro; IPR025994; BRCA1_serine_dom.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13763; PTHR13763; 1.
DR Pfam; PF00533; BRCT; 2.
DR Pfam; PF12820; BRCT_assoc; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PIRSF; PIRSF001734; BRCA1; 1.
DR PRINTS; PR00493; BRSTCANCERI.
DR SMART; SM00292; BRCT; 2.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 3: Inferred from homology;
KW Acetylation; Activator; Cell cycle; Chromosome; Cytoplasm; DNA damage;
KW DNA recombination; DNA repair; DNA-binding; Fatty acid biosynthesis;
KW Fatty acid metabolism; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Transferase; Tumor suppressor; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..1878
FT /note="Breast cancer type 1 susceptibility protein homolog"
FT /id="PRO_0000055828"
FT DOMAIN 1652..1739
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1764..1863
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ZN_FING 24..65
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 303..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..614
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1134..1154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1183..1221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1315..1401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1401..1428
FT /note="Interaction with PALB2"
FT /evidence="ECO:0000250"
FT REGION 1419..1504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1570..1590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1743..1764
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..581
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..603
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1134..1151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1183..1201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1315..1331
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1341..1364
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1374..1401
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1424..1504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 420
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 692
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 712
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48754"
FT MOD_RES 751
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 987
FT /note="Phosphoserine; by CHEK2"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1008
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1192
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1218
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1344
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1398
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1427
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 109
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 298
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 336
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 456
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 516
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 581
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 1079
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
SQ SEQUENCE 1878 AA; 208447 MW; 4799B65030327C4F CRC64;
MDLSADRVEE VQNVLNAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQRKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII HAFELDTGLQ FADSYNFSKK ENNSPEHLKE
EVSIIQSMGY RNRAKRLRQS EPENPTLETS LSVQLSNLGI VRSLRTKQQI QPQNKSVYIE
LGSDSSEDTV NKASSCSVGD DELEITSQGA RAEASLNPAK KAACEFSGDI TNIEHHQSSN
KDLTTTEKHA TKKHPEKYQG ISVSNLHVEP CGTNTHASSL QHENSSLLLT KHRMNVEKAE
ICNNSKQPGL ARSQQSRWAE SKETCNDRQI PSTEKKVVVN ADLLCGRKEL NKQKPPHSDS
PRDSQDVPWI TLNSSIRKVN EWFSRSDEIL TSDDSHDRGS ELNTEVGGAV EVPNEVGEYS
GSSEKIDLMA SDPQDAFICE SERVHTKPVG GNIEDKIFGK TYRRKASLPK VSHTTEVLTI
GACAIEPQTM QTHPFMNKAE HKRRTTSSLH PEDFIKKVEL GIVPKTPEKL IEGINQIKRD
GHVINITNNG PENETEGDYV QKEKNANPTE SLEKESAFRT KTEPMSSRIS NMELELNSSS
SKAPKKNRLR RKSSARHTCA LEFVVNRNLN PPDHSELQIE SCSSSEEMKK QHLDQVPVRH
NKTLQLMQDK EPAGRAKKSS KPGEQINKRL ASHAFPELTL TNVSGFFANY SSSSKPQECI
NPGLRREEIE ESRRMTQVSD STRDPKELVL SGGRGLQTER SVESTSISLV LDTDYGTQDS
ISLLEADTLR KAKTVSNQQA NLCATIENPK EPIHGCSKDT RNDTEGFVVP LTCKDNHTQE
TSIEMEESEL DTQCLRNMFK VSKRQSFALF SYPRDPEEDC VTVCPRSGAF GKQGPKVTLE
CGQKEESQGK KESEIRHVQA VHTNAGFSAV SQKAKKPGDF AKCSIKGVSR LCLSSQFKGK
ETELLIANYH GISQNPYHIP PLSPIRSCVK TLCQENLSEE KFEQHSMSPE RAVGNERVIQ
STVSTISQNN IRECASKEVG SSSVNEVVSS TNEVGSSVNE VGSSGENIQA ELGRNRGPKL
NAMLRLGLMQ PEVCKQSLSL SNCKHPEMKW QGQSEGAVLS VSADFSPCLI SDNPEQPMGS
SRSSQVCSET PDDLLNGDKI KGKVSFAESD IKEKSAVFSK SVQSGEFSRS PSPSDHTRLA
QGYQRGTKKL ESSEENMSSE EEELPCFQHL IFGKVTNMPS QSTSHNAVAA EGLSNKTEEN
LDSLKNSLSD ISNQVPSAKA SQEHHLSEEA RCSGSLFSSQ CSALEDLTVN TNTQDPFSMF
DPTSKQVRHQ SENLDVLNDK ELVSDDDDER EPGLEEDSPQ EEQSVDSDLG EVASGYESET
SLSEDCSRLS SQSDILTTQQ RDTMQDNLIK LQQEMAELEA VLEQHESQPS NSSPSLIADS
CSPEDLLNPE QNASERVLTS EKSSDSPISQ NPESLSTDKF QVFLDSSTSK NGEPGMIRSS
PSQSRLLDTR WYVHSCPRSL QDTNCPSQKE LTKVVSMEEQ QPTESEARDL MEQSYLSRPD
LEGAPYLESG ISLFSDDPES DPSSHRASEL AHVSSMPTST SALKLPQFQV EESAKSTAAV
HIASTAGYNK SEDSVGIEKP EVISSTRGVN KRISMVASGL TPKEFMLVHK FARKHHISLT
NLISEETTHV IMKTDAEFVC ERTLKYFLGI AGGKWVVSYF WVTQSIKERK ILDEHDFEVR
GDVVNGRNHQ GPKRARESQD RESQDRKIFR GLEICCYGPF TNMPTDQLEW MVHLCGASVV
KEPSLFTLSK GTHPVVVVQP DAWTEDSGFH AIGQMCEAPV VTREWVLDSV ALYQCQELDT
YLIPQIPRTA ADSSQPCV
