ID G3TDF5_LOXAF Unreviewed; 1854 AA.
AC G3TDF5;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 27-MAR-2024, entry version 79.
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:ENSLAFP00000012177.3};
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:ENSLAFP00000012177.3, ECO:0000313|Proteomes:UP000007646};
RN [1] {ECO:0000313|Ensembl:ENSLAFP00000012177.3, ECO:0000313|Proteomes:UP000007646}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000012177.3,
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:ENSLAFP00000012177.3}
RP IDENTIFICATION.
RC STRAIN=Isolate ISIS603380 {ECO:0000313|Ensembl:ENSLAFP00000012177.3};
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|ARBA:ARBA00000900,
CC 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: Chromosome {ECO:0000256|ARBA:ARBA00004286,
CC ECO:0000256|PIRNR:PIRNR001734}. Cytoplasm
CC {ECO:0000256|ARBA:ARBA00004496}. Nucleus
CC {ECO:0000256|PIRNR:PIRNR001734}. 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. {ECO:0000256|PIRNR:PIRNR001734}.
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DR STRING; 9785.ENSLAFP00000012177; -.
DR Ensembl; ENSLAFT00000014535.3; ENSLAFP00000012177.3; ENSLAFG00000021784.2.
DR eggNOG; KOG4362; Eukaryota.
DR GeneTree; ENSGT00440000034289; -.
DR HOGENOM; CLU_002290_0_0_1; -.
DR InParanoid; G3TDF5; -.
DR OMA; VTECQSS; -.
DR TreeFam; TF105060; -.
DR Proteomes; UP000007646; Unassembled WGS sequence.
DR GO; GO:0070531; C:BRCA1-A complex; IEA:Ensembl.
DR GO; GO:0070532; C:BRCA1-B complex; IEA:Ensembl.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IEA:UniProtKB-UniRule.
DR GO; GO:0070533; C:BRCA1-C complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990391; C:DNA repair complex; IEA:Ensembl.
DR GO; GO:0000800; C:lateral element; IEA:Ensembl.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0001741; C:XY body; IEA:Ensembl.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0002039; F:p53 binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:Ensembl.
DR GO; GO:0070063; F:RNA polymerase binding; IEA:Ensembl.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
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:0071681; P:cellular response to indole-3-methanol; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0007098; P:centrosome cycle; IEA:Ensembl.
DR GO; GO:0043009; P:chordate embryonic development; IEA:Ensembl.
DR GO; GO:0007059; P:chromosome segregation; IEA:Ensembl.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IEA:Ensembl.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0051179; P:localization; IEA:Ensembl.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:Ensembl.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; IEA:Ensembl.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0045739; P:positive regulation of DNA repair; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IEA:Ensembl.
DR GO; GO:0006301; P:postreplication repair; IEA:Ensembl.
DR GO; GO:0051865; P:protein autoubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0060816; P:random inactivation of X chromosome; IEA:Ensembl.
DR CDD; cd17735; BRCT_BRCA1_rpt1; 1.
DR CDD; cd17721; BRCT_BRCA1_rpt2; 1.
DR CDD; cd16498; RING-HC_BRCA1; 1.
DR Gene3D; 3.40.50.10190; BRCT domain; 2.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
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: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 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; BRCT domain; 2.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 4: Predicted;
KW Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW Activator {ECO:0000256|ARBA:ARBA00023159};
KW Cell cycle {ECO:0000256|ARBA:ARBA00023306, ECO:0000256|PIRNR:PIRNR001734};
KW Chromosome {ECO:0000256|ARBA:ARBA00022454, 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|ARBA:ARBA00023125, ECO:0000256|PIRNR:PIRNR001734};
KW Fatty acid biosynthesis {ECO:0000256|ARBA:ARBA00023160};
KW Fatty acid metabolism {ECO:0000256|ARBA:ARBA00022832};
KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR001734};
KW Reference proteome {ECO:0000313|Proteomes:UP000007646};
KW Transcription {ECO:0000256|ARBA:ARBA00023163};
KW Transcription regulation {ECO:0000256|ARBA:ARBA00023015};
KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786,
KW ECO:0000256|PIRNR:PIRNR001734}; Zinc {ECO:0000256|ARBA:ARBA00022833};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771, ECO:0000256|PROSITE-
KW ProRule:PRU00175}.
FT DOMAIN 24..65
FT /note="RING-type"
FT /evidence="ECO:0000259|PROSITE:PS50089"
FT DOMAIN 1640..1727
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 1747..1846
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 304..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 619..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 963..983
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1299..1512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1555..1638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 625..639
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 640..655
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..673
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..692
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1299..1318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1327..1351
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1352..1395
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1408..1452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1582..1638
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1854 AA; 206704 MW; 4D9EB14AD2C3C2A1 CRC64;
MDFSVAHIEE VQNVLNAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNHITK RSLQESTRFS QLVEELLKII RAFELDTGLQ FANSYNFAKK ENNSPEHVKE
EVSIIQSMGY RNRAKRLRQS EPENPTLQET SLNAQLSNFG IVRSLRTKQH TQLQNKSVYI
ELGSDSSEDT VNKESYYSVV DQELLHIAPQ GAKAEASLDP TKKAACEFSE KDITNLEYRQ
SSNKDLNTIK KHAAEKHPEK YRGISVSNLN VEPCGTNTHA SSLQHKNSSL LLTKDRMNVE
KAEFCNKSKQ PGLARSQQSR WAESKETCND RQTPSTEKKV DVNADPLYER KEVNKQKPPR
SENLRDTQDI PWITLNSSIQ KVNEWFFRSD GLDVLNDEGP ESSAEVAGAL EVPNEVHSNS
SEKIDLMASD LHGALICESE RVPSKPAESN IEDKIFGKTY RRKAGMSHLS HITEDLIMGA
IASEPQIARE HPFTNKLKRK RRTSGLHPED FIKKVDLAVV QKIPEKINQE TDHVEQNGQV
MNIANGGREN ETKGDYVQKE KNAIPTESLA KESAFRTKAE PISSSISNME LELNMHNSKA
PKKNRLRRKS STRHIHALEL VVNRNPSPPT HTELQIDSWS SSEETKKKSS EQKPIRHNRN
LQLMKNQETA TGAKKSNKPK EQISKRHGAD SYPELHLTTT AGFITKCSSS DNLQEFVNPS
LQGEKTEENL ETIQVSNITK EPKDLVLNGG RDLQTKKSIE STNISVIPDT VYGTQDSVSL
LGADTPGKAK TAPNRCASQC TAIENPSELT NSCPKDTRND TEGFKDLLRC EASHIQETCI
EIEESELDTQ YLQSTFKVSK RQSFALFSNP EKKCATICAH SKSLRKQSPK VTLVCGEKEE
NQGNREPKIK HEQAVHMPTG YPEACQKEKP SDYTKYSIKG VSGLCQSSQF RGSESELITA
DGHGISQNPD QIPSLSPTRS SVKTKCKTNL LEERFEEHTI SLERAMRNEN VIQSTVSTVS
QNNIRESASK EASSSSINEV CSSINEVGSS GENIQAEISR KRGPKLNAVL RLGLMQPEVY
KQSLPISDCK HPGIKTQGEN EGVVQAVNTD FSPCLISDNL EQPVGTSRAS QVCSETPDDL
LDDDEIKENI SFAENGIKER SVFIKDDQRR EFRRNPSPLS HSGLAQGCLR GARELEPSQE
NISSEDEELP CFQHLLFGEV TNIPSQSTRH NADAIQCLSK NTEENLGSVQ NSINDCSNQV
TSAKASQERH LSEEVRCSSS LFSSQCSVME DLATNTNTQD PFLMFGSPSK QARHQSENQE
VVLSDEELVS DEYKRGPGLE EDNHQDDQSV DSNLDEVASG YESESSLSEA GSGPSSQSDI
LTTQQRDTMQ DNLIKLQQEM AELEAVLEQQ GSQPSNSSPS LLAGSRAPKN LLNPEQNTSE
KGSISTSEKS NEHPVSENPE GLSADKFRPS LDSATSKNKD PGMERSSPSK FQLLDNNRWD
VHSHSRSLQN GNRLSQEELV KIVDVEEQQV EKSEARGLIE QPYLPLQDLE GTPCLESGVS
LFSDDPESDP SEDRAPDPAH VCSSPASSSA LKLPQFQVAE SASDSADAHT NNTTAYNARE
ESVNKETPGV TSSAERANRR ASMVASGLTQ KEFMLVHKFA RKHHCTLTNQ ITEETTHVIM
KTDADFVCER TLKYFLGIAG GKWVVSYFWV TQSIKERKML DECDFEVRGD VVNGRNHQGP
KRAREFQDRK IFKGLEICCY GPFTNMPTDQ LEWMVQLCGA SVVKEPLSFT LGTGTHPIVV
VQPDAWTEDS GFHAIGQLCE APVVTREWVL DSVALYQRQE LDTYLIPQIP HSHY
//
