Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

O54952

- BRCA1_RAT

UniProt

O54952 - BRCA1_RAT

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

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

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
Complete GO annotation...

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
Complete GO annotation...

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 – 16026Combined sources
Helixi1605 – 161713Combined sources
Beta strandi1632 – 16354Combined sources
Beta strandi1641 – 16433Combined sources
Helixi1647 – 16548Combined sources
Beta strandi1658 – 16614Combined sources
Helixi1663 – 16697Combined sources
Turni1670 – 16723Combined sources
Helixi1678 – 16803Combined sources
Turni1686 – 16883Combined sources
Beta strandi1690 – 16923Combined sources
Helixi1694 – 17018Combined sources
Beta strandi1710 – 17134Combined sources
Beta strandi1718 – 17203Combined sources
Helixi1722 – 173110Combined sources
Beta strandi1735 – 17373Combined sources
Beta strandi1739 – 17413Combined sources
Helixi1743 – 17453Combined sources
Beta strandi1752 – 17554Combined sources
Beta strandi1777 – 17793Combined sources
Helixi1781 – 17888Combined sources
Helixi1795 – 17984Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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

        10         20         30         40         50
MDLSAVRIQE VQNVLHAMQK ILECPICLEL IKEPVSTQCD HIFCKFCMLK
60 70 80 90 100
LLNQKKGPSQ CPLCKNEITK RSLQGSARFS QLVEELLKII DAFELDTGMQ
110 120 130 140 150
CANGFSFSKK KNSSSELLNE DASIIQSVGY RNRVKKLQQI ESGSATLKDS
160 170 180 190 200
LSVQLSNLGI VRSMKKNRQT QPQNKSVYIA LESDSSEERV NAPDGCSVRD
210 220 230 240 250
QELFQIAPGG AGDEGKLNSA KKAACDFSEG IRNIEHHQCS DKDLNPTENH
260 270 280 290 300
ATERHPEKCP RISVANVHVE PCGTDARASS LQRGTRSLLF TEDRLDAEKA
310 320 330 340 350
EFCDRSKQSG AAVSQQSRWA DSKETCNGRP VPRTEGKADP NVDSLCGRKQ
360 370 380 390 400
WNHPKSLCPE NSGATTDVPW ITLNSSIQKV NEWFSRTGEM LTSDNASDRR
410 420 430 440 450
PASNAEAAVV LEVSNEVDGC FSSSKKIDLV APDPDNAVMC TSGRDFSKPV
460 470 480 490 500
ENIINDKIFG KTYQRKGSRP HLNHVTEIIG TFTTEPQIIQ EQPFTNKLKR
510 520 530 540 550
KRSTCLHPED FIKKADLTVV QRISENLNQG TDQMEPNDQA MSITSNGQEN
560 570 580 590 600
RATGNDLQRG RNAHPIESLR KEPAFTAKAK SISNSISDLE VELNVHSSKA
610 620 630 640 650
PKKNRLRRKS TRCVLPLEPI SRNPSPPTCA ELQIESCGSS EETKKNNSNQ
660 670 680 690 700
TPAGHIREPQ LIEDTEPAAD AKKNEPNEHI RKRSASDAFP EEKLMNKAGL
710 720 730 740 750
LTSCSSPRKP QGPVNPSPER KGIEQLEMCQ MPDNNKELGD LVLGGEPSGK
760 770 780 790 800
PTEPSEESTS VSLVPDTDYD TQNSVSILEA NTVRYARTGS VQCMTQFVAS
810 820 830 840 850
ENPKELVHGS NNAGSGSECF KHPLRHELNH NQETIEMEDS ELDTQYLQNT
860 870 880 890 900
FQVSKRQSFA LFSKLRSPQK DCTLVGARSV PSREPSPKVT SRGEQKERQG
910 920 930 940 950
QEESEISHVQ AVTVTVGLPV PCQEGKPGAV TMCADVSRLC PSSHYRSCEN
960 970 980 990 1000
GLNTTDKSGI SQNSHFRQSV SPLRSSIKTD NRKTLTEGRF EKHTERGMGN
1010 1020 1030 1040 1050
ETAVQSTIHT ISLNNRGDAC LEASSGSVIE VHSTGENVQG QLDRNRGPKV
1060 1070 1080 1090 1100
NTVSLLDSTQ PGVSKQSAPV SDKYLEIKQE SKAVSADFSP CLFSDHLEKP
1110 1120 1130 1140 1150
MRSDKTFQVC SETPDDLLDD VEIQENASFG EGGITEKSAI FNGSVLRRES
1160 1170 1180 1190 1200
SRSPSPVTHA SKSRSLHRGS RKLEFSEESD STEDEDLPCF QHLLSRVSST
1210 1220 1230 1240 1250
PELTRCSSVV TQRVPEKAKG TQAPRKSSIS DCNNEVILGE ASQEYQFSED
1260 1270 1280 1290 1300
AKCSGSMFSS QHSAALGSPA NALSQDPDFN PPSKQRRHQA ENEEAFLSDK
1310 1320 1330 1340 1350
ELISDHEDMA ACLEEASDQE EDSIIPDSVA SGYESEANLS EDCSQSDILT
1360 1370 1380 1390 1400
TQQRATMKDN LIKLQQEMAQ LEAVLEQHGS QPSGHPPCLP ADPCALEDLP
1410 1420 1430 1440 1450
DPEQNRSGTA ILTSKNINEN PVSQNPKRAC DDKSQPQPPD GLPSGDKESG
1460 1470 1480 1490 1500
MRRPSPFKSP LTSSRCSARG HSRSLQNRNS TSQEELLQPA XLEKSCEPHN
1510 1520 1530 1540 1550
LTGRSCLPRQ DLEGTPYPES GIRLVSSRDP DSESPKVSAL VCTAPASTSA
1560 1570 1580 1590 1600
LKISQGQVAG SCRSPAAGGA DTAVVEIVSK IKPEVTSPKE RAERDISMVV
1610 1620 1630 1640 1650
SGLTPKEVMI VQKFAEKYRL ALTDVITEET THVIIKTDAE FVCERTLKYF
1660 1670 1680 1690 1700
LGIAGGKWIV SYSWVIKSIQ ERKLLSVHEF EVKGDVVTGS NHQGPRRSRE
1710 1720 1730 1740 1750
SQEKLFEGLQ IYCCEPFTNM PKDELERMLQ LCGASVVKEL PLLTRDTGAH
1760 1770 1780 1790 1800
PIVLVQPSAW TEDNDCPDIG QLCKGRLVMW DWVLDSISVY RCRDLDAYLV
1810
QNITCGRDGS EPQDSND
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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: November 26, 2014
This is version 120 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