O54952 (BRCA1_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1817 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. 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. 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 and COBRA1. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with BAP1. Interacts with DCLRE1C and CLSPN. Interacts with H2AFX (phosphorylated on 'Ser-140'). Interacts with CHEK1 and CHEK2. Interacts with BRCC3. Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Interacts with AURKA. Interacts with UBXN1. Part of a trimeric 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. Interacts with KIAA0101/PAF15 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 process	Cell cycle DNA damage DNA recombination DNA repair Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Ubl conjugation pathway
Cellular component	Chromosome Nucleus
Disease	Tumor suppressor
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA 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 stimulus Inferred from expression pattern PubMed 14729590. Source: RGD response to nutrient Inferred from expression pattern PubMed 17044772. Source: RGD
Cellular_component	BRCA1-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_function	damaged DNA binding Traceable author statement Ref.3. Source: RGD 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 – 1817

1817

Breast cancer type 1 susceptibility protein homolog

PRO_0000055835

Regions

Domain

1588 – 1682

95

BRCT 1

Domain

1701 – 1800

100

BRCT 2

Zinc finger

24 – 65

42

RING-type

Region

1354 – 1381

28

Interaction with PALB2 By similarity

Motif

497 – 503

7

Nuclear localization signal Potential

Amino acid modifications

Modified residue

114

1

Phosphoserine By similarity

Modified residue

306

1

Phosphoserine; by AURKA By similarity

Modified residue

393

1

Phosphoserine By similarity

Modified residue

686

1

Phosphoserine By similarity

Modified residue

961

1

Phosphoserine By similarity

Modified residue

975

1

Phosphoserine; by CHEK2 By similarity

Modified residue

1181

1

Phosphoserine By similarity

Modified residue

1242

1

Phosphoserine By similarity

Modified residue

1298

1

Phosphoserine By similarity

Modified residue

1344

1

Phosphoserine By similarity

Modified residue

1351

1

Phosphothreonine By similarity

Modified residue

1380

1

Phosphoserine By similarity

Modified residue

1414

1

Phosphoserine By similarity

Modified residue

1482

1

Phosphoserine By similarity

Experimental info

Sequence conflict

38

1

Q → K in AAB40387. Ref.2

Sequence conflict

38

1

Q → K in AAB37501. Ref.2

Sequence conflict

192

1

A → M in AAB40387. Ref.2

Sequence conflict

192

1

A → M in AAB37501. Ref.2

Secondary structure

1

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1817

Helix Strand Turn

Details...

Beta strand

1597 – 1602

6

Helix

1605 – 1617

13

Beta strand

1632 – 1635

4

Beta strand

1641 – 1643

3

Helix

1647 – 1654

8

Beta strand

1658 – 1661

4

Helix

1663 – 1669

7

Turn

1670 – 1672

3

Helix

1678 – 1680

3

Turn

1686 – 1688

3

Beta strand

1690 – 1692

3

Helix

1694 – 1701

8

Beta strand

1710 – 1713

4

Beta strand

1718 – 1720

3

Helix

1722 – 1731

10

Beta strand

1735 – 1737

3

Beta strand

1739 – 1741

3

Helix

1743 – 1745

3

Beta strand

1752 – 1755

4

Beta strand

1777 – 1779

3

Helix

1781 – 1788

8

Helix

1795 – 1798

4

Sequences

	Sequence		Length	Mass (Da)
	O54952 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: C0B4760F0E349A01	FASTA	1,817	199,879
	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

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.

IPI

IPI00202716.

RefSeq

NP_036646.1. NM_012514.1.

UniGene

Rn.217584.
Rn.48840.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L0B	X-ray	2.30	A	1589-1817	[»]

ProteinModelPortal

O54952.

SMR

O54952. Positions 1-103, 1591-1801.

ModBase

Search...

PTM databases

PhosphoSite

O54952.

Proteomic databases

PRIDE

O54952.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

497672.

KEGG

rno:497672.

UCSC

RGD:2218. rat.

Organism-specific databases

CTD

672.

RGD

2218. Brca1.

Phylogenomic databases

eggNOG

NOG274496.

HOGENOM

HOG000230969.

HOVERGEN

HBG050730.

InParanoid

O54952.

KO

K10605.

OrthoDB

EOG42RD7C.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

Genevestigator

O54952.

GermOnline

ENSRNOG00000020701. Rattus norvegicus.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR011364. BRCA1.
IPR025994. BRCA1_serine_dom.
IPR001357. BRCT_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]

PANTHER

PTHR13763. PTHR13763. 1 hit.

Pfam

PF00533. BRCT. 2 hits.
PF12820. BRCT_assoc. 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

EvolutionaryTrace

O54952.

NextBio

697729.

Entry information

Entry name

BRCA1_RAT

Accession

Primary (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 3, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program