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O54952

- BRCA1_RAT

UniProt

O54952 - BRCA1_RAT

Protein

Breast cancer type 1 susceptibility protein homolog

Gene

Brca1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Jun 1998)
      Previous versions | rss
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    Functioni

    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.By similarity

    Pathwayi

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri24 – 6542RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. damaged DNA binding Source: RGD
    2. ligase activity Source: UniProtKB-KW
    3. ubiquitin-protein transferase activity Source: UniProtKB
    4. zinc ion binding Source: InterPro

    GO - Biological processi

    1. brain development Source: RGD
    2. cell cycle Source: UniProtKB-KW
    3. DNA recombination Source: UniProtKB-KW
    4. DNA repair Source: RGD
    5. fatty acid biosynthetic process Source: UniProtKB-KW
    6. negative regulation of fatty acid biosynthetic process Source: UniProtKB
    7. protein autoubiquitination Source: UniProtKB
    8. protein K6-linked ubiquitination Source: UniProtKB
    9. response to estradiol Source: RGD
    10. response to lipid Source: RGD
    11. response to nutrient Source: RGD
    12. response to organic substance Source: RGD

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Cell cycle, DNA damage, DNA recombination, DNA repair, Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Ubl conjugation pathway

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Breast cancer type 1 susceptibility protein homolog (EC:6.3.2.-)
    Gene namesi
    Name:Brca1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2218. Brca1.

    Subcellular locationi

    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

    GO - Cellular componenti

    1. BRCA1-BARD1 complex Source: UniProtKB
    2. chromosome Source: UniProtKB
    3. mitochondrial matrix Source: RGD

    Keywords - Cellular componenti

    Chromosome, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Tumor suppressor

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 18171817Breast cancer type 1 susceptibility protein homologPRO_0000055835Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei114 – 1141PhosphoserineBy similarity
    Modified residuei306 – 3061Phosphoserine; by AURKABy similarity
    Modified residuei393 – 3931PhosphoserineBy similarity
    Modified residuei686 – 6861PhosphoserineBy similarity
    Modified residuei975 – 9751Phosphoserine; by CHEK2By similarity
    Modified residuei1181 – 11811PhosphoserineBy similarity
    Modified residuei1242 – 12421PhosphoserineBy similarity
    Modified residuei1298 – 12981PhosphoserineBy similarity
    Modified residuei1304 – 13041PhosphoserineBy similarity
    Modified residuei1344 – 13441PhosphoserineBy similarity
    Modified residuei1351 – 13511PhosphothreonineBy similarity
    Modified residuei1380 – 13801PhosphoserineBy similarity
    Modified residuei1414 – 14141PhosphoserineBy similarity
    Modified residuei1482 – 14821PhosphoserineBy similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiO54952.

    PTM databases

    PhosphoSiteiO54952.

    Expressioni

    Gene expression databases

    GenevestigatoriO54952.

    Interactioni

    Subunit structurei

    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.By similarity

    Structurei

    Secondary structure

    1
    1817
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi1597 – 16026
    Helixi1605 – 161713
    Beta strandi1632 – 16354
    Beta strandi1641 – 16433
    Helixi1647 – 16548
    Beta strandi1658 – 16614
    Helixi1663 – 16697
    Turni1670 – 16723
    Helixi1678 – 16803
    Turni1686 – 16883
    Beta strandi1690 – 16923
    Helixi1694 – 17018
    Beta strandi1710 – 17134
    Beta strandi1718 – 17203
    Helixi1722 – 173110
    Beta strandi1735 – 17373
    Beta strandi1739 – 17413
    Helixi1743 – 17453
    Beta strandi1752 – 17554
    Beta strandi1777 – 17793
    Helixi1781 – 17888
    Helixi1795 – 17984

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1L0BX-ray2.30A1589-1817[»]
    ProteinModelPortaliO54952.
    SMRiO54952. Positions 1-103, 1591-1801.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO54952.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1588 – 168295BRCT 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini1701 – 1800100BRCT 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1354 – 138128Interaction with PALB2By similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi497 – 5037Nuclear localization signalSequence Analysis

    Domaini

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

    Sequence similaritiesi

    Contains 2 BRCT domains.PROSITE-ProRule annotation
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri24 – 6542RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG274496.
    HOGENOMiHOG000230969.
    HOVERGENiHBG050730.
    InParanoidiO54952.
    KOiK10605.
    PhylomeDBiO54952.

    Family and domain databases

    Gene3Di3.30.40.10. 1 hit.
    3.40.50.10190. 2 hits.
    InterProiIPR011364. 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]
    PANTHERiPTHR13763. PTHR13763. 1 hit.
    PfamiPF00533. BRCT. 2 hits.
    PF12820. BRCT_assoc. 1 hit.
    PF00097. zf-C3HC4. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001734. BRCA1. 1 hit.
    PRINTSiPR00493. BRSTCANCERI.
    SMARTiSM00292. BRCT. 2 hits.
    SM00184. RING. 1 hit.
    [Graphical view]
    SUPFAMiSSF52113. SSF52113. 2 hits.
    PROSITEiPS50172. BRCT. 2 hits.
    PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O54952-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDLSAVRIQE VQNVLHAMQK ILECPICLEL IKEPVSTQCD HIFCKFCMLK     50
    LLNQKKGPSQ CPLCKNEITK RSLQGSARFS QLVEELLKII DAFELDTGMQ 100
    CANGFSFSKK KNSSSELLNE DASIIQSVGY RNRVKKLQQI ESGSATLKDS 150
    LSVQLSNLGI VRSMKKNRQT QPQNKSVYIA LESDSSEERV NAPDGCSVRD 200
    QELFQIAPGG AGDEGKLNSA KKAACDFSEG IRNIEHHQCS DKDLNPTENH 250
    ATERHPEKCP RISVANVHVE PCGTDARASS LQRGTRSLLF TEDRLDAEKA 300
    EFCDRSKQSG AAVSQQSRWA DSKETCNGRP VPRTEGKADP NVDSLCGRKQ 350
    WNHPKSLCPE NSGATTDVPW ITLNSSIQKV NEWFSRTGEM LTSDNASDRR 400
    PASNAEAAVV LEVSNEVDGC FSSSKKIDLV APDPDNAVMC TSGRDFSKPV 450
    ENIINDKIFG KTYQRKGSRP HLNHVTEIIG TFTTEPQIIQ EQPFTNKLKR 500
    KRSTCLHPED FIKKADLTVV QRISENLNQG TDQMEPNDQA MSITSNGQEN 550
    RATGNDLQRG RNAHPIESLR KEPAFTAKAK SISNSISDLE VELNVHSSKA 600
    PKKNRLRRKS TRCVLPLEPI SRNPSPPTCA ELQIESCGSS EETKKNNSNQ 650
    TPAGHIREPQ LIEDTEPAAD AKKNEPNEHI RKRSASDAFP EEKLMNKAGL 700
    LTSCSSPRKP QGPVNPSPER KGIEQLEMCQ MPDNNKELGD LVLGGEPSGK 750
    PTEPSEESTS VSLVPDTDYD TQNSVSILEA NTVRYARTGS VQCMTQFVAS 800
    ENPKELVHGS NNAGSGSECF KHPLRHELNH NQETIEMEDS ELDTQYLQNT 850
    FQVSKRQSFA LFSKLRSPQK DCTLVGARSV PSREPSPKVT SRGEQKERQG 900
    QEESEISHVQ AVTVTVGLPV PCQEGKPGAV TMCADVSRLC PSSHYRSCEN 950
    GLNTTDKSGI SQNSHFRQSV SPLRSSIKTD NRKTLTEGRF EKHTERGMGN 1000
    ETAVQSTIHT ISLNNRGDAC LEASSGSVIE VHSTGENVQG QLDRNRGPKV 1050
    NTVSLLDSTQ PGVSKQSAPV SDKYLEIKQE SKAVSADFSP CLFSDHLEKP 1100
    MRSDKTFQVC SETPDDLLDD VEIQENASFG EGGITEKSAI FNGSVLRRES 1150
    SRSPSPVTHA SKSRSLHRGS RKLEFSEESD STEDEDLPCF QHLLSRVSST 1200
    PELTRCSSVV TQRVPEKAKG TQAPRKSSIS DCNNEVILGE ASQEYQFSED 1250
    AKCSGSMFSS QHSAALGSPA NALSQDPDFN PPSKQRRHQA ENEEAFLSDK 1300
    ELISDHEDMA ACLEEASDQE EDSIIPDSVA SGYESEANLS EDCSQSDILT 1350
    TQQRATMKDN LIKLQQEMAQ LEAVLEQHGS QPSGHPPCLP ADPCALEDLP 1400
    DPEQNRSGTA ILTSKNINEN PVSQNPKRAC DDKSQPQPPD GLPSGDKESG 1450
    MRRPSPFKSP LTSSRCSARG HSRSLQNRNS TSQEELLQPA XLEKSCEPHN 1500
    LTGRSCLPRQ DLEGTPYPES GIRLVSSRDP DSESPKVSAL VCTAPASTSA 1550
    LKISQGQVAG SCRSPAAGGA DTAVVEIVSK IKPEVTSPKE RAERDISMVV 1600
    SGLTPKEVMI VQKFAEKYRL ALTDVITEET THVIIKTDAE FVCERTLKYF 1650
    LGIAGGKWIV SYSWVIKSIQ ERKLLSVHEF EVKGDVVTGS NHQGPRRSRE 1700
    SQEKLFEGLQ IYCCEPFTNM PKDELERMLQ LCGASVVKEL PLLTRDTGAH 1750
    PIVLVQPSAW TEDNDCPDIG QLCKGRLVMW DWVLDSISVY RCRDLDAYLV 1800
    QNITCGRDGS EPQDSND 1817
    Length:1,817
    Mass (Da):199,879
    Last modified:June 1, 1998 - v1
    Checksum:iC0B4760F0E349A01
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti38 – 381Q → K in AAB40387. (PubMed:8761410)Curated
    Sequence conflicti38 – 381Q → K in AAB37501. (PubMed:8761410)Curated
    Sequence conflicti192 – 1921A → M in AAB40387. (PubMed:8761410)Curated
    Sequence conflicti192 – 1921A → M in AAB37501. (PubMed:8761410)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    RefSeqiNP_036646.1. NM_012514.1.
    UniGeneiRn.217584.
    Rn.48840.

    Genome annotation databases

    GeneIDi497672.
    KEGGirno:497672.
    UCSCiRGD:2218. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    RefSeqi NP_036646.1. NM_012514.1.
    UniGenei Rn.217584.
    Rn.48840.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1L0B X-ray 2.30 A 1589-1817 [» ]
    ProteinModelPortali O54952.
    SMRi O54952. Positions 1-103, 1591-1801.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei O54952.

    Proteomic databases

    PRIDEi O54952.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 497672.
    KEGGi rno:497672.
    UCSCi RGD:2218. rat.

    Organism-specific databases

    CTDi 672.
    RGDi 2218. Brca1.

    Phylogenomic databases

    eggNOGi NOG274496.
    HOGENOMi HOG000230969.
    HOVERGENi HBG050730.
    InParanoidi O54952.
    KOi K10605.
    PhylomeDBi O54952.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .

    Miscellaneous databases

    EvolutionaryTracei O54952.
    NextBioi 697729.
    PROi O54952.

    Gene expression databases

    Genevestigatori O54952.

    Family and domain databases

    Gene3Di 3.30.40.10. 1 hit.
    3.40.50.10190. 2 hits.
    InterProi IPR011364. 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 ]
    PANTHERi PTHR13763. PTHR13763. 1 hit.
    Pfami PF00533. BRCT. 2 hits.
    PF12820. BRCT_assoc. 1 hit.
    PF00097. zf-C3HC4. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001734. BRCA1. 1 hit.
    PRINTSi PR00493. BRSTCANCERI.
    SMARTi SM00292. BRCT. 2 hits.
    SM00184. RING. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52113. SSF52113. 2 hits.
    PROSITEi PS50172. BRCT. 2 hits.
    PS00518. ZF_RING_1. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiBRCA1_RAT
    AccessioniPrimary (citable) accession number: O54952
    Secondary accession number(s): P97951
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 2, 2004
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3