P48754 (BRCA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Breast cancer type 1 susceptibility protein homolog
EC=6.3.2.-

Gene names

Name:

Brca1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1812 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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 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 BABAM1/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 and CHEK2. Interacts with BRCC3. Interacts (via BRCT domains) with ACACA (phosphorylated); the interaction prevents dephosphorylation of ACACA. Interacts with AURKA. Interacts with UBXN1. Part of a trimeric complex containing BRCA1, BRCA2 and PALB2. Interacts with PALB2 and this interaction is essential for its function in HRR. Interacts with BRCA2 only in the presence of PALB2 which serves as the bridging protein By similarity. Ref.7
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. The RING-type zinc finger domain interacts with BAP1 By similarity.
Post-translational modification	Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-971 by CHEK2 regulates mitotic spindle assembly By similarity. Ref.8 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 process	Cell cycle DNA damage DNA recombination DNA repair Fatty acid biosynthesis Lipid synthesis Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Tumor suppressor
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA repair Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Inferred from mutant phenotype. Source: MGI centrosome duplication Traceable author statement. Source: UniProtKB chordate embryonic development Inferred from mutant phenotype. Source: MGI dosage compensation, by inactivation of X chromosome Inferred from direct assay. Source: MGI 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 negative regulation of histone H3-K4 methylation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of histone H3-K9 methylation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of histone acetylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of histone H3-K4 methylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of histone H3-K9 acetylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of histone H3-K9 methylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of histone H4-K16 acetylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of histone H4-K20 methylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: BHF-UCL protein K6-linked ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB protein autoubiquitination Inferred from sequence or structural similarity. Source: UniProtKB regulation of DNA methylation Inferred from mutant phenotype. Source: BHF-UCL regulation of gene expression by genetic imprinting Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	BRCA1-BARD1 complex Inferred from sequence or structural similarity. Source: UniProtKB centrosome Traceable author statement. Source: UniProtKB condensed nuclear chromosome Inferred from direct assay. Source: MGI nucleoplasm Traceable author statement. Source: Reactome
Molecular function	damaged DNA binding Inferred from direct assay. Source: MGI transcription regulatory region DNA binding Inferred from direct assay. Source: BHF-UCL ubiquitin-protein ligase 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1812	1812	Breast cancer type 1 susceptibility protein homolog		PRO_0000055832
Regions
	Domain	1585 – 1679	95	BRCT 1
	Domain	1698 – 1797	100	BRCT 2
	Zinc finger	24 – 65	42	RING-type
	Region	1353 – 1380	28	Interaction with PALB2 By similarity
	Compositional bias	1562 – 1567	6	Poly-Ala
Amino acid modifications
	Modified residue	392	1	Phosphoserine By similarity
	Modified residue	831	1	Phosphoserine Ref.8
	Modified residue	957	1	Phosphoserine Ref.8
	Modified residue	971	1	Phosphoserine; by CHEK2 By similarity
	Modified residue	1174	1	Phosphoserine By similarity
	Modified residue	1175	1	Phosphoserine By similarity
	Modified residue	1180	1	Phosphoserine By similarity
	Modified residue	1206	1	Phosphoserine By similarity
	Modified residue	1297	1	Phosphoserine By similarity
	Modified residue	1303	1	Phosphoserine By similarity
	Modified residue	1343	1	Phosphoserine By similarity
	Modified residue	1422	1	Phosphoserine By similarity
	Modified residue	1481	1	Phosphoserine By similarity
	Modified residue	1495	1	Phosphoserine By similarity
	Modified residue	1643	1	Phosphothreonine By similarity
Natural variations
	Natural variant	93	1	F → L in strain: 129/SvJ.
	Natural variant	305	1	T → S in strain: 129/SvJ.
	Natural variant	319	1	P → A in strain: 129/SvJ.
	Natural variant	377	1	Q → E in strain: 129/SvJ.
	Natural variant	550	1	K → Q in strain: 129/SvJ.
	Natural variant	652	1	A → P in strain: 129/SvJ.
	Natural variant	765	1	S → P in strain: 129/SvJ.
	Natural variant	917	1	P → L in strain: 129/SvJ.
	Natural variant	933	1	C → S in strain: 129/SvJ.
	Natural variant	1122	1	K → I in strain: 129/SvJ.
	Natural variant	1206	1	S → R in strain: 129/SvJ.
	Natural variant	1212 – 1213	2	RM → GI in strain: 129/SvJ.
	Natural variant	1255	1	S → R in strain: 129/SvJ.
	Natural variant	1261	1	H → N in strain: 129/SvJ.
	Natural variant	1264	1	V → A in strain: 129/SvJ.
	Natural variant	1269	1	P → A in strain: 129/SvJ.
	Natural variant	1283	1	T → K in strain: 129/SvJ.
	Natural variant	1337	1	T → N in strain: 129/SvJ.
	Natural variant	1349	1	P → T in strain: 129/SvJ.
	Natural variant	1352 – 1353	2	EG → QR in strain: 129/SvJ.
	Natural variant	1381	1	S → P in strain: 129/SvJ.
	Natural variant	1390	1	G → A in strain: 129/SvJ.
	Natural variant	1400	1	V → D in strain: 129/SvJ.
	Natural variant	1503	1	E → Q in strain: 129/SvJ.
	Natural variant	1549	1	V → A in strain: 129/SvJ.
	Natural variant	1680	1	T → K in strain: 129/SvJ.
	Natural variant	1712	1	D → E in strain: 129/SvJ.
	Natural variant	1721	1	D → E in strain: 129/SvJ.

Sequences

	Sequence		Length	Mass (Da)
	P48754 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 2291EA74150BB86A	FASTA	1,812	198,670
	10 20 30 40 50 60 MDLSAVQIQE VQNVLHAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ 70 80 90 100 110 120 CPLCKNEITK RSLQGSTRFS QLAEELLRIM AAFELDTGMQ LTNGFSFSKK RNNSCERLNE 130 140 150 160 170 180 EASIIQSVGY RNRVRRLPQV EPGNATLKDS LGVQLSNLGI VRSVKKNRQT QPRKKSVYIE 190 200 210 220 230 240 LDSDSSEETV TKPGDCSVRD QELLQTAPQE AGDEGKLHSA EEAACEFSEG IRNIEHHQCS 250 260 270 280 290 300 DDLNPTENHA TERHPEKCQS ISISNVCVEP CGTDAHASSL QPETSSLLLI EDRMNAEKAE 310 320 330 340 350 360 FCNKTKQPGI AVSQQSRWPA SKGTCNDRQV PSTGEKVGPN ADSLSDREKW THPQSLCPEN 370 380 390 400 410 420 SGATTDVPWI TLNSSVQKVN EWFSRTGEML TSDSASARRH ESNAEAAVVL EVSNEVDGGF 430 440 450 460 470 480 SSSRKTDLVT PDPHHTLMCK SGRDFSKPVE DNISDKIFGK SYQRKGSRPH LNHVTEIIGT 490 500 510 520 530 540 FITEPQITQE QPFTNKLKRK RSTSLQPEDF IKKADSAGVQ RTPDNINQGT DLMEPNEQAV 550 560 570 580 590 600 STTSNCQENK IAGSNLQKEK SAHPTESLRK EPASTAGAKS ISNSVSDLEV ELNVHSSKAP 610 620 630 640 650 660 KKNRLRRKSS IRCALPLEPI SRNPSPPTCA ELQIDSCGSS EETKKNHSNQ QAAGHLREPQ 670 680 690 700 710 720 LIEDTEPAAD AKKNEPNEHI RKRRASDAFP EEKLMNKAGL LTSCSSPRKS QGPVNPSPQR 730 740 750 760 770 780 TGTEQLETRQ MSDSAKELGD RVLGGEPSGK TTDRSEESTS VSLVSDTDYD TQNSVSVLDA 790 800 810 820 830 840 HTVRYARTGS AQCMTQFVAS ENPKELVHGS NNAGSGTEGL KPPLRHALNL SQEKVEMEDS 850 860 870 880 890 900 ELDTQYLQNT FQVSKRQSFA LFSKPRSPQK DCAHSVPSKE LSPKVTAKGK QKERQGQEEF 910 920 930 940 950 960 EISHVQAVAA TVGLPVPCQE GKLAADTMCD RGCRLCPSSH YRSGENGLSA TGKSGISQNS 970 980 990 1000 1010 1020 HFKQSVSPIR SSIKTDNRKP LTEGRFERHT SSTEMAVGNE NILQSTVHTV SLNNRGNACQ 1030 1040 1050 1060 1070 1080 EAGSGSIHEV CSTGDSFPGQ LGRNRGPKVN TVPPLDSMQP GVCQQSVPVS DKYLEIKKQE 1090 1100 1110 1120 1130 1140 GEAVCADFSP CLFSDHLEQS MSGKVFQVCS ETPDDLLDDV EKQGHTSFGE GDIMERSAVF 1150 1160 1170 1180 1190 1200 NGSILRRESS RSPSPVTHAS KSQSLHRASR KLESSEESDS TEDEDLPCFQ HLLSRISNTP 1210 1220 1230 1240 1250 1260 ELTRCSSAVT QRMPEKAEGT QAPWKGSSSD CNNEVIMIEA SQEHQFSEDP RCSGSMFSSQ 1270 1280 1290 1300 1310 1320 HSAVQGSTPN ANSQDSNFIP PSTQRSHQCG NEEAFLSDKE LISDNEEMAT CLEEDNDQEE 1330 1340 1350 1360 1370 1380 DSIIPDSEAS GYESETTLSE DCSQSDILPT QEGATMKYNL IKLQQEMAHL EAVLEQRGNQ 1390 1400 1410 1420 1430 1440 SSGHSPSLLG DPCALEDLPV LEPNMSGAAI LTSKNINENP VSQNLKSACD DKFQLQHLEG 1450 1460 1470 1480 1490 1500 PTSGDDESGM GRPSPFKSPL AGSRGSAHGC SRHLQKRNSP SQEELLQPAG SEASSEPHNS 1510 1520 1530 1540 1550 1560 TGESCLPRRE LEGTPYLGSG ISLFSSRDPE SESPKEPAHI GTTPASTSVL KIPQGQVAFR 1570 1580 1590 1600 1610 1620 SAAAAGADKA VVGIVSKIKP ELTSSEERAD RDISMVVSGL TPKEVMTVQK FAEKYRLTLT 1630 1640 1650 1660 1670 1680 DAITEETTHV IIKTDAEFVC ERTLKYFLGI AGGKWIVSYS WVVRSIQERR LLNVHEFEVT 1690 1700 1710 1720 1730 1740 GDVVTGRNHQ GPRRSRESRE KLFKGLQVYC CDPFTNMPKD DLERMLQLCG ASVVKELPSL 1750 1760 1770 1780 1790 1800 THDTGAHLVV IVQPSAWTED SNCPDIGQLC KARLVMWDWV LDSLSSYRCR DLDAYLVQNI 1810 TCDSSEPQDS ND

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse Brca1: localization sequence analysis and identification of evolutionarily conserved domains." Abel K.J., Xy J., Yin G.Y., Lyons R.H., Meisler M.H., Weber B.L. Hum. Mol. Genet. 4:2265-2273(1995) [PubMed: 8634697] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Embryo.
[2]	"Murine Brca1: sequence and significance for human missense mutations." Sharan S.K., Wims M., Bradley A. Hum. Mol. Genet. 4:2275-2278(1995) [PubMed: 8634698] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6.
[3]	"Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse chromosome 11." Bennett L.M., Haugen-Strano A., Cochran C., Brownlee H.A., Fiedorek F.T. Jr., Wiseman R.W. Genomics 29:576-581(1995) [PubMed: 8575748] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 129/SvJ.
[4]	"Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice." Lane T.F., Deng C., Elson A., Lyu M.S., Kozak C.A., Leder P. Genes Dev. 9:2712-2722(1995) [PubMed: 7590247] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 129/SvJ. Tissue: Embryo.
[5]	"The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues." Marquis S.T., Rajan J.V., Wynshaw-Boris A., Xu J., Yin G.Y., Abel K.J., Weber B.L., Chodosh L.A. Nat. Genet. 11:17-26(1995) [PubMed: 7550308] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 727-1111. Strain: C57BL/6. Tissue: Embryo.
[6]	"The murine homolog of the human breast and ovarian cancer susceptibility gene Brca1 maps to mouse chromosome 11D." Schroeck E., Badger P., Larson D., Erdos M., Wynshaw-Boris A., Ried T., Brody L. Hum. Genet. 97:256-259(1996) [PubMed: 8566965] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 789-1250. Strain: 129/SvJ.
[7]	"BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT domains." Magnard C., Bachelier R., Vincent A., Jaquinod M., Kieffer S., Lenoir G.M., Venezia N.D. Oncogene 21:6729-6739(2002) [PubMed: 12360400] [Abstract] Cited for: INTERACTION WITH ACACA.
[8]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-831 AND SER-957, MASS SPECTROMETRY. Tissue: Embryonic kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U31625 mRNA. Translation: AAB17114.1. U35641 mRNA. Translation: AAB17113.1. U32446 mRNA. Translation: AAA96393.1. U36475 mRNA. Translation: AAC52323.1. U33835 Genomic DNA. Translation: AAA99742.1.
IPI	IPI00331711.
PIR	I49350.
RefSeq	NP_033894.3. NM_009764.3.
UniGene	Mm.244975.
3D structure databases
ProteinModelPortal	P48754.
SMR	P48754. Positions 1-103, 1588-1798.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-41981N.
STRING	P48754.
Proteomic databases
PRIDE	P48754.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	12189.
KEGG	mmu:12189.
Organism-specific databases
CTD	672.
MGI	MGI:104537. Brca1.
Phylogenomic databases
HOGENOM	HBG127296.
HOVERGEN	HBG050730.
InParanoid	P48754.
OrthoDB	EOG42RD7C.
Enzyme and pathway databases
Reactome	REACT_27235. Meiotic Recombination (mouse). REACT_75800. Meiotic Synapsis (mouse).
Gene expression databases
ArrayExpress	P48754.
Bgee	P48754.
CleanEx	MM_BRCA1.
Genevestigator	P48754.
GermOnline	ENSMUSG00000017146. Mus musculus.
Family and domain databases
InterPro	IPR011364. BRCA1. IPR001357. BRCT. IPR002378. Brst_cancerI. IPR018957. Znf_C3HC4_RING-type. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
KO	K10605.
PANTHER	PTHR13763. BRCA1. 1 hit.
Pfam	PF00533. BRCT. 2 hits. PF00097. zf-C3HC4. 1 hit. [Graphical view]
PIRSF	PIRSF001734. BRCA1. 1 hit.
PRINTS	PR00493. BRSTCANCERI.
SMART	SM00292. BRCT. 2 hits. SM00184. RING. 1 hit. [Graphical view]
SUPFAM	SSF52113. BRCT. 2 hits.
PROSITE	PS50172. BRCT. 2 hits. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

BRCA1_MOUSE

Accession

Primary (citable) accession number: P48754
Secondary accession number(s): Q60957, Q60983

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	November 1, 1997
Last modified:	November 16, 2011
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program