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Brca1

Protein FULL name:

breast cancer type 1 susceptibility protein homolog [Mus musculus].


Brca1 (Mus musculus) is product of expression of Brca1 gene.






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 (By similarity).

PATHWAY: Protein modification; protein ubiquitination.

SUBUNIT: Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein 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/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1. Interacts (via BRCT domains) with FAM175A/Abraxas and RBBP8. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A and COBRA1/NELFB. Interacts (via BRCT domains) with phosphorylated BRIP1. Interacts with FANCD2 (ubiquitinated). Interacts with BAP1. Interacts with DCLRE1C/Artemis and CLSPN. Interacts with H2AFX (phosphorylated on 'Ser-140'). Interacts with CHEK1/CHK1. Interacts with BRCC3. Interacts (via BRCT domains) with ACACA (phosphorylated); the interaction prevents dephosphorylation of ACACA. Interacts with STK6/AURKA. Interacts with UBXN1 (By similarity).

SUBCELLULAR LOCATION: Nucleus (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).

TISSUE SPECIFICITY: In the embryo, expressed in otic vesicles at day 9.5. At day 10.5, this expression decreases and high levels are found in the neuroectoderm. At days 11-12.5, high levels in differentiating keratinocytes and whisker pad primordia. At days 14-17, expression also observed in kidney epithelial cells. In the adult, highest levels found in spleen, thymus, lymph nodes, epithelial organs, and alveolar and ductal epithelial cells of the mammary gland. Very low levels in brain, kidney, and skin. No expression in heart, liver or lung.

DEVELOPMENTAL STAGE: In the mammary gland, expression increases dramatically during pregnancy. Levels fall during lactation and increase again during post-lactational regression of the mammary gland.

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).

DOMAIN: The RING-type zinc finger domain interacts with BAP1 (By similarity).

PTM: Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR.

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

SIMILARITY: Contains 2 BRCT domains.

SIMILARITY: Contains 1 RING-type zinc finger.


NCBI GenPept GI number(s): 161016835
Species: Mus musculus

Links to other databases:

Database ID Link
Uniprot P48754 P48754
PFAM: - P48754 (Link - using uniprot id)
InterPro: - P48754 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MDLSAVQIQEVQNVLHAMQKILECPICLELIKEPVSTKCDHIFCKFCMLK
LLNQKKGPSQCPLCKNEITKRSLQGSTRFSQLAEELLRIMAAFELDTGMQ
LTNGFSFSKKRNNSCERLNEEASIIQSVGYRNRVRRLPQVEPGNATLKDS
LGVQLSNLGIVRSVKKNRQTQPRKKSVYIELDSDSSEETVTKPGDCSVRD
QELLQTAPQEAGDEGKLHSAEEAACEFSEGIRNIEHHQCSDDLNPTENHA
TERHPEKCQSISISNVCVEPCGTDAHASSLQPETSSLLLIEDRMNAEKAE
FCNKSKQPGIAVSQQSRWAASKGTCNDRQVPSTGEKVGPNADSLSDREKW
THPQSLCPENSGATTDVPWITLNSSVQKVNEWFSRTGEMLTSDSASARRH
ESNAEAAVVLEVSNEVDGGFSSSRKTDLVTPDPHHTLMCKSGRDFSKPVE
DNISDKIFGKSYQRKGSRPHLNHVTEIIGTFITEPQITQEQPFTNKLKRK
RSTSLQPEDFIKKADSAGVQRTPDNINQGTDLMEPNEQAVSTTSNCQENK
IAGSNLQKEKSAHPTESLRKEPASTAGAKSISNSVSDLEVELNVHSSKAP
KKNRLRRKSSIRCALPLEPISRNPSPPTCAELQIDSCGSSEETKKNHSNQ
QPAGHLREPQLIEDTEPAADAKKNEPNEHIRKRRASDAFPEEKLMNKAGL
LTSCSSPRKSQGPVNPSPQRTGTEQLETRQMSDSAKELGDRVLGGEPSGK
TTDRSEESTSVSLVSDTDYDTQNSVSVLDAHTVRYARTGSAQCMTQFVAS
ENPKELVHGSNNAGSGTEGLKPPLRHALNLSQEKVEMEDSELDTQYLQNT
FQVSKRQSFALFSKPRSPQKDCAHSVPSKELSPKVTAKGKQKERQGQEEF
EISHVQAVAATVGLPVPCQEGKLAADTMCDRGCRLCPSSHYRSGENGLSA
TGKSGISQNSHFKQSVSPIRSSIKTDNRKPLTEGRFERHTSSTEMAVGNE
NILQSTVHTVSLNNRGNACQEAGSGSIHEVCSTGDSFPGQLGRNRGPKVN
TVPPLDSMQPGVCQQSVPVSDKYLEIKKQEGEAVCADFSPCLFSDHLEQS
MSGKVFQVCSETPDDLLDDVEIQGHTSFGEGDIMERSAVFNGSILRRESS
RSPSPVTHASKSQSLHRASRKLESSEESDSTEDEDLPCFQHLLSRISNTP
ELTRCSSAVTQRMPEKAEGTQAPWKGSSSDCNNEVIMIEASQEHQFSEDP
RCSGSMFSSQHSAAQGSTANANSQDSNFIPPSKQRSHQCGNEEAFLSDKE
LISDNEEMATCLEEDNDQEEDSIIPDSEASGYESETNLSEDCSQSDILTT
QQRATMKYNLIKLQQEMAHLEAVLEQRGNQPSGHSPSLLADPCALEDLPD
LEPNMSGAAILTSKNINENPVSQNLKSACDDKFQLQHLEGPTSGDDESGM
GRPSPFKSPLAGSRGSAHGCSRHLQKRNSPSQEELLQPAGSEASSEPHNS
TGQSCLPRRELEGTPYLGSGISLFSSRDPESESPKEPAHIGTTPASTSAL
KIPQGQVAFRSAAAAGADKAVVGIVSKIKPELTSSEERADRDISMVVSGL
TPKEVMTVQKFAEKYRLTLTDAITEETTHVIIKTDAEFVCERTLKYFLGI
AGGKWIVSYSWVVRSIQERRLLNVHEFEVKGDVVTGRNHQGPRRSRESRE
KLFKGLQVYCCEPFTNMPKDELERMLQLCGASVVKELPSLTHDTGAHLVV
IVQPSAWTEDSNCPDIGQLCKARLVMWDWVLDSLSSYRCRDLDAYLVQNI
TCDSSEPQDSND

Brca1 (Mus musculus) belongs to following protein families:
References:

Title Authors Journal
The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues. Marquis ST, Rajan JV, Wynshaw-Boris A, Xu J, Yin GY, Abel KJ, Weber BL, Chodosh LA Nat Genet Sept. 1, 1995
Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome 11. Bennett LM, Haugen-Strano A, Cochran C, Brownlee HA, Fiedorek FT Jr, Wiseman RW Genomics Oct. 10, 1995
Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice. Lane TF, Deng C, Elson A, Lyu MS, Kozak CA, Leder P Genes Dev Nov. 1, 1995
Mouse Brca1: localization sequence analysis and identification of evolutionarily conserved domains. Abel KJ, Xu J, Yin GY, Lyons RH, Meisler MH, Weber BL Hum Mol Genet Dec. 1, 1995
Murine Brca1: sequence and significance for human missense mutations. Sharan SK, Wims M, Bradley A Hum Mol Genet Dec. 1, 1995
The murine homolog of the human breast and ovarian cancer susceptibility gene Brca1 maps to mouse chromosome 11D. Schrock E, Badger P, Larson D, Erdos M, Wynshaw-Boris A, Ried T, Brody L Hum Genet Jan. 1, 1996
BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains. Magnard C, Bachelier R, Vincent A, Jaquinod M, Kieffer S, Lenoir GM, Venezia ND Oncogene Oct. 3, 2002
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science May 25, 2007


Last modification of this entry: Oct. 6, 2010.

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