ID G3TMB7_LOXAF Unreviewed; 1347 AA.
AC G3TMB7;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 27-MAR-2024, entry version 53.
DE RecName: Full=Breast cancer type 1 susceptibility protein homolog {ECO:0000256|PIRNR:PIRNR001734};
DE EC=2.3.2.27 {ECO:0000256|PIRNR:PIRNR001734};
GN Name=BRCA1 {ECO:0000313|Ensembl:ENSLAFP00000016250.2};
OS Loxodonta africana (African elephant).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Afrotheria; Proboscidea; Elephantidae; Loxodonta.
OX NCBI_TaxID=9785 {ECO:0000313|Ensembl:ENSLAFP00000016250.2, ECO:0000313|Proteomes:UP000007646};
RN [1] {ECO:0000313|Ensembl:ENSLAFP00000016250.2, ECO:0000313|Proteomes:UP000007646}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000016250.2,
RC ECO:0000313|Proteomes:UP000007646};
RA Di Palma F., Heiman D., Young S., Johnson J., Lander E.S., Lindblad-Toh K.;
RT "The Genome Sequence of Loxodonta africana (African elephant).";
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSLAFP00000016250.2}
RP IDENTIFICATION.
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000016250.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|PIRNR:PIRNR001734}.
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:0000256|PIRNR:PIRNR001734};
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. Interacts with EXD2.
CC Interacts (via C-terminus) with DHX9; this interaction is direct and
CC links BRCA1 to the RNA polymerase II holoenzyme.
CC {ECO:0000256|PIRNR:PIRNR001734}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|PIRNR:PIRNR001734}.
CC Chromosome {ECO:0000256|PIRNR:PIRNR001734}. Note=Localizes at sites of
CC DNA damage at double-strand breaks (DSBs); recruitment to DNA damage
CC sites is mediated by the BRCA1-A complex.
CC {ECO:0000256|PIRNR:PIRNR001734}.
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DR Ensembl; ENSLAFT00000022382.2; ENSLAFP00000016250.2; ENSLAFG00000021784.2.
DR GeneTree; ENSGT00440000034289; -.
DR Proteomes; UP000007646; Unassembled WGS sequence.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0051865; P:protein autoubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IEA:UniProtKB-UniRule.
DR CDD; cd17735; BRCT_BRCA1_rpt1; 1.
DR CDD; cd17721; BRCT_BRCA1_rpt2; 1.
DR Gene3D; 3.40.50.10190; BRCT domain; 2.
DR InterPro; IPR011364; BRCA1.
DR InterPro; IPR031099; BRCA1-associated.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR PANTHER; PTHR13763:SF0; BREAST CANCER TYPE 1 SUSCEPTIBILITY PROTEIN; 1.
DR PANTHER; PTHR13763; BREAST CANCER TYPE 1 SUSCEPTIBILITY PROTEIN BRCA1; 1.
DR Pfam; PF00533; BRCT; 2.
DR PIRSF; PIRSF001734; BRCA1; 1.
DR PRINTS; PR00493; BRSTCANCERI.
DR SMART; SM00292; BRCT; 2.
DR SUPFAM; SSF52113; BRCT domain; 2.
DR PROSITE; PS50172; BRCT; 2.
PE 4: Predicted;
KW Cell cycle {ECO:0000256|PIRNR:PIRNR001734};
KW Chromosome {ECO:0000256|PIRNR:PIRNR001734};
KW DNA damage {ECO:0000256|PIRNR:PIRNR001734};
KW DNA recombination {ECO:0000256|PIRNR:PIRNR001734};
KW DNA repair {ECO:0000256|PIRNR:PIRNR001734};
KW DNA-binding {ECO:0000256|PIRNR:PIRNR001734};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR001734};
KW Reference proteome {ECO:0000313|Proteomes:UP000007646};
KW Ubl conjugation pathway {ECO:0000256|PIRNR:PIRNR001734}.
FT DOMAIN 1133..1220
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 1240..1339
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 96..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 438..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 774..985
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1048..1131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..130
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 131..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..167
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 774..793
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 802..826
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 827..870
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 883..945
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1075..1131
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1347 AA; 149394 MW; C6D6351EE6A52140 CRC64;
KINQETDHVE QNGQVMNIAN GGRENETKGD YVQKEKNAIP TESLAKESAF RTKAEPISSS
ISNMELELNM HNSKAPKKNR LRRKSSTRHI HALELVVNRN PSPPTHTELQ IDSWSSSEET
KKKSSEQKPI RHNRNLQLMK NQETATGAKK SNKPKEQISK RHGADSYPEL HLTTTAGFIT
KCSSSDNLQE FVNPSLQGEK TEENLETIQV SNITKEPKDL VLNGGRDLQT KKSIESTNIS
VIPDTVYGTQ DSVSLLGADT PGKAKTAPNR CASQCTAIEN PSELTNSCPK DTRNDTEGFK
DLLRCEASHI QETCIEIEES ELDTQYLQST FKVSKRQSFA LFSNPEKKCA TICAHSKSLR
KQSPKVTLVC GEKEENQGNR EPKIKHEQAV HMPTGYPEAC QKEKPSDYTK YSIKGVSGLC
QSSQFRGSES ELITADGHGI SQNPDQIPSL SPTRSSVKTK CKTNLLEERF EEHTISLERA
MRNENVIQST VSTVSQNNIR ESASKEASSS SINEVCSSIN EVGSSGENIQ AEISRKRGPK
LNAVLRLGLM QPEVYKQSLP ISDCKHPGIK TQGENEGVVQ AVNTDFSPCL ISDNLEQPVG
TSRASQVCSE TPDDLLDDDE IKENISFAEN GIKERSVFIK DDQRREFRRN PSPLSHSGLA
QGCLRGAREL EPSQENISSE DEELPCFQHL LFGEVTNIPS QSTRHNADAI QCLSKNTEEN
LGSVQNSIND CSNQVTSAKA SQERHLSEEV RCSSSLFSSQ CSVMEDLATN TNTQDPFLMF
GSPSKQARHQ SENQEVVLSD EELVSDEYKR GPGLEEDNHQ DDQSVDSNLD EVASGYESES
SLSEAGSGPS SQSDILTTQQ RDTMQDNLIK LQQEMAELEA VLEQQGSQPS NSSPSLLAGS
RAPKNLLNPE QNTSEKGDIF STQEEYNMLR PQNEGSISTS EKSNEHPVSE NPEGLSADKF
RPSLDSATSK NKDPGMERSS PSKFQLLDNN RWDVHSHSRS LQNGNRLSQE ELVKIVDVEE
QQVEKSEARG LIEQPYLPLQ DLEGTPCLES GVSLFSDDPE SDPSEDRAPD PAHVCSSPAS
SSALKLPQFQ VAESASDSAD AHTNNTTAYN AREESVNKET PGVTSSAERA NRRASMVASG
LTQKEFMLVH KFARKHHCTL TNQITEETTH VIMKTDADFV CERTLKYFLG IAGGKWVVSY
FWVTQSIKER KMLDECDFEV RGDVVNGRNH QGPKRAREFQ DRKIFKGLEI CCYGPFTNMP
TDQLEWMVQL CGASVVKEPL SFTLGTGTHP IVVVQPDAWT EDSGFHAIGQ LCEAPVVTRE
WVLDSVALYQ RQELDTYLIP QIPHSHY
//
