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O54952 (BRCA1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Breast cancer type 1 susceptibility protein homolog

EC=6.3.2.-
Gene names
Name:Brca1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1817 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 By similarity.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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 the BRCA1, BARD1, UIMC1, BRCC3, BRE and BABAM1. Interacts (via the BRCT domains) with FAM175A. 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, COBRA1, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, AURKA, UBXN1 and KIAA0101/PAF15. 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 By similarity.

Subcellular location

Nucleus By similarity. Chromosome 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 By similarity.

Domain

The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of FAM175A/Abraxas, recruits BRCA1 at DNA damage sites By similarity.

The RING-type zinc finger domain interacts with BAP1 By similarity.

Post-translational modification

Phosphorylation at Ser-306 by AURKA is required for normal cell cycle progression from G2 to mitosis. Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-975 by CHEK2 regulates mitotic spindle assembly By similarity.

Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation By similarity.

Sequence similarities

Contains 2 BRCT domains.

Contains 1 RING-type zinc finger.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
DNA recombination
DNA repair
Fatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Ubl conjugation pathway
   Cellular componentChromosome
Nucleus
   DiseaseTumor suppressor
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionLigase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA recombination

Inferred from electronic annotation. Source: UniProtKB-KW

DNA repair

Traceable author statement Ref.3. Source: RGD

brain development

Inferred from expression pattern PubMed 12605402. Source: RGD

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of fatty acid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein K6-linked ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein autoubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

response to estradiol

Inferred from expression pattern PubMed 14729590. Source: RGD

response to lipid

Inferred from expression pattern PubMed 17342305. Source: RGD

response to nutrient

Inferred from expression pattern PubMed 17044772. Source: RGD

response to organic substance

Inferred from expression pattern PubMed 14729590. Source: RGD

   Cellular_componentBRCA1-BARD1 complex

Inferred from sequence or structural similarity. Source: UniProtKB

chromosome

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrial matrix

Inferred from direct assay PubMed 15591126. Source: RGD

   Molecular_functiondamaged DNA binding

Traceable author statement Ref.3. Source: RGD

ubiquitin-protein transferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 18171817Breast cancer type 1 susceptibility protein homolog
PRO_0000055835

Regions

Domain1588 – 168295BRCT 1
Domain1701 – 1800100BRCT 2
Zinc finger24 – 6542RING-type
Region1354 – 138128Interaction with PALB2 By similarity
Motif497 – 5037Nuclear localization signal Potential

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue1141Phosphoserine By similarity
Modified residue3061Phosphoserine; by AURKA By similarity
Modified residue3931Phosphoserine By similarity
Modified residue6861Phosphoserine By similarity
Modified residue9751Phosphoserine; by CHEK2 By similarity
Modified residue11811Phosphoserine By similarity
Modified residue12421Phosphoserine By similarity
Modified residue12981Phosphoserine By similarity
Modified residue13041Phosphoserine By similarity
Modified residue13441Phosphoserine By similarity
Modified residue13511Phosphothreonine By similarity
Modified residue13801Phosphoserine By similarity
Modified residue14141Phosphoserine By similarity
Modified residue14821Phosphoserine By similarity

Experimental info

Sequence conflict381Q → K in AAB40387. Ref.2
Sequence conflict381Q → K in AAB37501. Ref.2
Sequence conflict1921A → M in AAB40387. Ref.2
Sequence conflict1921A → M in AAB37501. Ref.2

Secondary structure

............................................ 1817
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O54952 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: C0B4760F0E349A01

FASTA1,817199,879
        10         20         30         40         50         60 
MDLSAVRIQE VQNVLHAMQK ILECPICLEL IKEPVSTQCD HIFCKFCMLK LLNQKKGPSQ 

        70         80         90        100        110        120 
CPLCKNEITK RSLQGSARFS QLVEELLKII DAFELDTGMQ CANGFSFSKK KNSSSELLNE 

       130        140        150        160        170        180 
DASIIQSVGY RNRVKKLQQI ESGSATLKDS LSVQLSNLGI VRSMKKNRQT QPQNKSVYIA 

       190        200        210        220        230        240 
LESDSSEERV NAPDGCSVRD QELFQIAPGG AGDEGKLNSA KKAACDFSEG IRNIEHHQCS 

       250        260        270        280        290        300 
DKDLNPTENH ATERHPEKCP RISVANVHVE PCGTDARASS LQRGTRSLLF TEDRLDAEKA 

       310        320        330        340        350        360 
EFCDRSKQSG AAVSQQSRWA DSKETCNGRP VPRTEGKADP NVDSLCGRKQ WNHPKSLCPE 

       370        380        390        400        410        420 
NSGATTDVPW ITLNSSIQKV NEWFSRTGEM LTSDNASDRR PASNAEAAVV LEVSNEVDGC 

       430        440        450        460        470        480 
FSSSKKIDLV APDPDNAVMC TSGRDFSKPV ENIINDKIFG KTYQRKGSRP HLNHVTEIIG 

       490        500        510        520        530        540 
TFTTEPQIIQ EQPFTNKLKR KRSTCLHPED FIKKADLTVV QRISENLNQG TDQMEPNDQA 

       550        560        570        580        590        600 
MSITSNGQEN RATGNDLQRG RNAHPIESLR KEPAFTAKAK SISNSISDLE VELNVHSSKA 

       610        620        630        640        650        660 
PKKNRLRRKS TRCVLPLEPI SRNPSPPTCA ELQIESCGSS EETKKNNSNQ TPAGHIREPQ 

       670        680        690        700        710        720 
LIEDTEPAAD AKKNEPNEHI RKRSASDAFP EEKLMNKAGL LTSCSSPRKP QGPVNPSPER 

       730        740        750        760        770        780 
KGIEQLEMCQ MPDNNKELGD LVLGGEPSGK PTEPSEESTS VSLVPDTDYD TQNSVSILEA 

       790        800        810        820        830        840 
NTVRYARTGS VQCMTQFVAS ENPKELVHGS NNAGSGSECF KHPLRHELNH NQETIEMEDS 

       850        860        870        880        890        900 
ELDTQYLQNT FQVSKRQSFA LFSKLRSPQK DCTLVGARSV PSREPSPKVT SRGEQKERQG 

       910        920        930        940        950        960 
QEESEISHVQ AVTVTVGLPV PCQEGKPGAV TMCADVSRLC PSSHYRSCEN GLNTTDKSGI 

       970        980        990       1000       1010       1020 
SQNSHFRQSV SPLRSSIKTD NRKTLTEGRF EKHTERGMGN ETAVQSTIHT ISLNNRGDAC 

      1030       1040       1050       1060       1070       1080 
LEASSGSVIE VHSTGENVQG QLDRNRGPKV NTVSLLDSTQ PGVSKQSAPV SDKYLEIKQE 

      1090       1100       1110       1120       1130       1140 
SKAVSADFSP CLFSDHLEKP MRSDKTFQVC SETPDDLLDD VEIQENASFG EGGITEKSAI 

      1150       1160       1170       1180       1190       1200 
FNGSVLRRES SRSPSPVTHA SKSRSLHRGS RKLEFSEESD STEDEDLPCF QHLLSRVSST 

      1210       1220       1230       1240       1250       1260 
PELTRCSSVV TQRVPEKAKG TQAPRKSSIS DCNNEVILGE ASQEYQFSED AKCSGSMFSS 

      1270       1280       1290       1300       1310       1320 
QHSAALGSPA NALSQDPDFN PPSKQRRHQA ENEEAFLSDK ELISDHEDMA ACLEEASDQE 

      1330       1340       1350       1360       1370       1380 
EDSIIPDSVA SGYESEANLS EDCSQSDILT TQQRATMKDN LIKLQQEMAQ LEAVLEQHGS 

      1390       1400       1410       1420       1430       1440 
QPSGHPPCLP ADPCALEDLP DPEQNRSGTA ILTSKNINEN PVSQNPKRAC DDKSQPQPPD 

      1450       1460       1470       1480       1490       1500 
GLPSGDKESG MRRPSPFKSP LTSSRCSARG HSRSLQNRNS TSQEELLQPA XLEKSCEPHN 

      1510       1520       1530       1540       1550       1560 
LTGRSCLPRQ DLEGTPYPES GIRLVSSRDP DSESPKVSAL VCTAPASTSA LKISQGQVAG 

      1570       1580       1590       1600       1610       1620 
SCRSPAAGGA DTAVVEIVSK IKPEVTSPKE RAERDISMVV SGLTPKEVMI VQKFAEKYRL 

      1630       1640       1650       1660       1670       1680 
ALTDVITEET THVIIKTDAE FVCERTLKYF LGIAGGKWIV SYSWVIKSIQ ERKLLSVHEF 

      1690       1700       1710       1720       1730       1740 
EVKGDVVTGS NHQGPRRSRE SQEKLFEGLQ IYCCEPFTNM PKDELERMLQ LCGASVVKEL 

      1750       1760       1770       1780       1790       1800 
PLLTRDTGAH PIVLVQPSAW TEDNDCPDIG QLCKGRLVMW DWVLDSISVY RCRDLDAYLV 

      1810 
QNITCGRDGS EPQDSND 

« Hide

References

[1]"Sequence analysis of the rat brca1 homolog and its promoter region."
Bennett L.M., Brownlee H.A., Hagavik S., Wiseman R.W.
Mamm. Genome 10:19-25(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
[2]"Cloning, genetic mapping and expression studies of the rat Brca1 gene."
Chen K.S., Shepel L.A., Haag J.D., Heil G.M., Gould M.N.
Carcinogenesis 17:1561-1566(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 8-222.
Strain: Wistar Kyoto.
Tissue: Spleen.
[3]"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure."
Joo W.S., Jeffrey P.D., Cantor S.B., Finnin M.S., Livingston D.M., Pavletich N.P.
Genes Dev. 16:583-593(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1589-1817.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF036760 mRNA. Translation: AAC36493.1.
S82504 Genomic DNA. No translation available.
S82502 Genomic DNA. No translation available.
U60523 mRNA. Translation: AAB40387.1.
S82500 Genomic DNA. Translation: AAB37501.1.
RefSeqNP_036646.1. NM_012514.1.
UniGeneRn.217584.
Rn.48840.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1L0BX-ray2.30A1589-1817[»]
ProteinModelPortalO54952.
SMRO54952. Positions 1-103, 1591-1801.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteO54952.

Proteomic databases

PRIDEO54952.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID497672.
KEGGrno:497672.
UCSCRGD:2218. rat.

Organism-specific databases

CTD672.
RGD2218. Brca1.

Phylogenomic databases

eggNOGNOG274496.
HOGENOMHOG000230969.
HOVERGENHBG050730.
InParanoidO54952.
KOK10605.
PhylomeDBO54952.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

GenevestigatorO54952.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
3.40.50.10190. 2 hits.
InterProIPR011364. BRCA1.
IPR025994. BRCA1_serine_dom.
IPR001357. BRCT_dom.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERPTHR13763. PTHR13763. 1 hit.
PfamPF00533. BRCT. 2 hits.
PF12820. BRCT_assoc. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
PIRSFPIRSF001734. BRCA1. 1 hit.
PRINTSPR00493. BRSTCANCERI.
SMARTSM00292. BRCT. 2 hits.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF52113. SSF52113. 2 hits.
PROSITEPS50172. BRCT. 2 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO54952.
NextBio697729.
PROO54952.

Entry information

Entry nameBRCA1_RAT
AccessionPrimary (citable) accession number: O54952
Secondary accession number(s): P97951
Entry history
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: June 1, 1998
Last modified: April 16, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways