ID G5BN95_HETGA Unreviewed; 1856 AA.
AC G5BN95;
DT 14-DEC-2011, integrated into UniProtKB/TrEMBL.
DT 14-DEC-2011, sequence version 1.
DT 27-MAR-2024, entry version 49.
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 ORFNames=GW7_07849 {ECO:0000313|EMBL:EHB10756.1};
OS Heterocephalus glaber (Naked mole rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Bathyergidae;
OC Heterocephalus.
OX NCBI_TaxID=10181 {ECO:0000313|EMBL:EHB10756.1, ECO:0000313|Proteomes:UP000006813};
RN [1] {ECO:0000313|EMBL:EHB10756.1, ECO:0000313|Proteomes:UP000006813}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21993625; DOI=10.1038/nature10533;
RA Kim E.B., Fang X., Fushan A.A., Huang Z., Lobanov A.V., Han L.,
RA Marino S.M., Sun X., Turanov A.A., Yang P., Yim S.H., Zhao X.,
RA Kasaikina M.V., Stoletzki N., Peng C., Polak P., Xiong Z., Kiezun A.,
RA Zhu Y., Chen Y., Kryukov G.V., Zhang Q., Peshkin L., Yang L., Bronson R.T.,
RA Buffenstein R., Wang B., Han C., Li Q., Chen L., Zhao W., Sunyaev S.R.,
RA Park T.J., Zhang G., Wang J., Gladyshev V.N.;
RT "Genome sequencing reveals insights into physiology and longevity of the
RT naked mole rat.";
RL Nature 479:223-227(2011).
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: 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; JH171123; EHB10756.1; -; Genomic_DNA.
DR STRING; 10181.G5BN95; -.
DR eggNOG; KOG4362; Eukaryota.
DR InParanoid; G5BN95; -.
DR Proteomes; UP000006813; 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; 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; IPR025994; BRCA1_serine_dom.
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 Pfam; PF12820; BRCT_assoc; 1.
DR PIRSF; PIRSF001734; BRCA1; 2.
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 Coiled coil {ECO:0000256|SAM:Coils};
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:UP000006813};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786,
KW ECO:0000256|PIRNR:PIRNR001734}.
FT DOMAIN 1642..1729
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 1749..1848
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 124..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 449..737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 963..1002
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1066..1088
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1198..1217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1234..1315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1484..1585
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1599..1638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1318..1345
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 138..154
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..210
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..311
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..478
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..502
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..570
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 647..662
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..737
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 969..996
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1234..1250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1258..1274
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1291..1315
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1522..1537
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1555..1579
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1856 AA; 202406 MW; 8D5F583A5E76FD7A CRC64;
MPFSPVHAHP GLIPPGVVLR SLQESTRFSQ LVEELLKVIR AFELDSGLQV ANSYNFSKKE
INSPEHGQEE IPLIQSMGYR NRARGLRQGE PEKPSLETSL GVQLSDLGIV RSLRTKKQAQ
PQNKSVYIEL GSDSSEDASE DVANRADDHS VRDQDLLFSL QGTRAKASSH PAKQGNTPCE
ASEKGTVDSD RPHLSGEDEK PVEKRAAKRR PGKQQVGPAP DLRVEPCGTD TRASSLQCRN
SRLLLTEDRM DVEKAEFCNK SKQPGFARSQ QSRWAGSEES SDDGQTPSTE QKAEPTAAAL
CERRGKEQKP PCSETLGEAQ DVYWVTLNSR IQKVNEWFSR SDKVVASDDA CDRELEADAE
EASALEDPKG QGGFSGSLEK IAMLTNSPQS ALFCANKRVC PKAGRNDMKD KVFGKTYRRK
PSLPSFTYVA ENLTVGALVV KPQVTQEFPP TNKLKRKRRS MSCLHPEDFI KRADLPVAPK
TPEKINQGTE QMEESGQVTG TPRKSHKGDA EGAGVQRQRK PSPAQSLEKE SAARAEPQSC
SISNMGLESH ARHSEPPKKS RLRRRSSTRH VPHPSPLDHT ELQIDNSTST EEVKEKSSHQ
VLIGYSQNLY LAGEGEASIG IPESKKPAEQ VRNRPAEEAV PEPALANTPG SSANSSGPDK
ELVNPSPQRD KTEENPETVQ VSDNTRDPKG PVLSGERGLQ TERSAESTSI SLVPDTDYST
QDSFSLLEAN SLRKAQRASH QCVTQYVAVA KPKELPAHSE DTGNDTEGFN DPLRRKVSHV
QEANVEMEDS ELDTQYLQNT FQASKRQSFA LFSNPGNPEK KSTGVCAHSE FFQKRNPEVT
PECEQRENSK GKKASKIRHV QVVNATASVP VISQNDQLGV GVQCGVTGVS KLRPSSQVRG
YKTELVAADK HGISRNPCHV ASVSRIGTSV KTACKKSLSM SPKEAVESER VLQSMVSTGC
CKNSRDLAPK EASSGSGSGV GSGTNEVASS NEHMQAEWGR SRGPTLNAVL RSGLMQPKVQ
EQSLPVGDYK CPKIPQRGAS GVVAQAVHAD FSPCLIFDSV EQPMGSNPAS QICSETPDDL
LDEEDRKEDA SFAEDDIKET SAVFSKSVQR RQXXXXXXSR SPSPFTHTAL ARGHQRRVRK
LESSEENMSS EDEELPCFQH LIFGKGCTTP QSTRPSTGAT ERVSKGTEEN VVSLKDNLRG
CTSEPVSPEP RLGEDIRCSG SLFSSQCSIS EESAANTISQ DXQKGHPSGI QGASLSDKEV
VSDDEDREPS LEEGSHHGGQ SVDSPLGEAA SGYESETNPS GGFSGLSSQS SILTTQQKDT
IQDNLLRLQQ EMAQLEAVLE RHGSQCSNSS TSIVPDSCPA EDLATLGRYI PGKAPVNWVP
EVLTPAHSPG ALSSSHQCCC LPKRVEPMFP TYEERSMLEH LGWLQGDFSV FQNLVRIPVF
MLPKPDKTKK ENRCLCFFDP LKAGFTSGRS NAYPVTQSLQ ACPSSKHQVS PDCPASENKE
PGAGRSSPPE AQVADSQWSA HSQPRRLRDR GCPAPEQLEE EEELGESGPH HATALAHLPR
RELDNPEPEA SEDRAPEPAH VCRALVPTPT SALTLSPFQV AEPAGTPAAA QTSNPARGAS
KEEAVSREEP ESLSSVGGGR RRLSMVVSGL TTKESVLVQK FARKHHIGLT SLITAETTHV
VMKTDPEFVC ERTLKYFLGI AGGKWVVSYF WVTQSMQERR MLDECDFEVR GDVINGRSHQ
GPKRARESQD RKIFGGLTVC CCGPFTNMAT DQLEWMLRLC GASVVGELSA LPLSTGAQSV
VVMQPEAWTE DADFLALGQL CQVPVVTRDW VLDSVALHQR QELDAYLIPQ DPHRPR
//
