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Protein

Breast cancer type 1 susceptibility protein homolog

Gene

Brca1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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. Acts as a transcriptional activator (By similarity).By similarity

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri24 – 65RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Transferase

Keywords - Biological processi

Cell cycle, DNA damage, DNA recombination, DNA repair, Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Transcription, Transcription regulation, 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:2.3.2.27By similarity)
Alternative name(s):
RING-type E3 ubiquitin transferase BRCA1Curated
Gene namesi
Name:Brca1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2218. Brca1.

Subcellular locationi

  • Nucleus By similarity
  • Chromosome By similarity
  • Cytoplasm 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. Translocated to the cytoplasm during UV-induced apoptosis.By similarity

GO - Cellular componenti

  • BRCA1-A complex Source: GO_Central
  • BRCA1-BARD1 complex Source: UniProtKB
  • chromosome Source: UniProtKB
  • mitochondrial matrix Source: RGD
  • nucleus Source: UniProtKB
  • plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000558351 – 1817Breast cancer type 1 susceptibility protein homologAdd BLAST1817

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei114PhosphoserineBy similarity1
Modified residuei306Phosphoserine; by AURKABy similarity1
Cross-linki337Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei393PhosphoserineBy similarity1
Cross-linki457Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki578Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei686PhosphoserineBy similarity1
Modified residuei706PhosphoserineBy similarity1
Modified residuei717PhosphoserineBy similarity1
Modified residuei975Phosphoserine; by CHEK2By similarity1
Modified residuei1153PhosphoserineBy similarity1
Modified residuei1155PhosphoserineBy similarity1
Modified residuei1181PhosphoserineBy similarity1
Modified residuei1242PhosphoserineBy similarity1
Modified residuei1298PhosphoserineBy similarity1
Modified residuei1304PhosphoserineBy similarity1
Modified residuei1344PhosphoserineBy similarity1
Modified residuei1351PhosphothreonineBy similarity1
Modified residuei1380PhosphoserineBy similarity1
Modified residuei1414PhosphoserineBy similarity1
Modified residuei1482PhosphoserineBy similarity1

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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO54952.
PRIDEiO54952.

PTM databases

iPTMnetiO54952.
PhosphoSitePlusiO54952.

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 BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. Interacts (via the BRCT domains) with FAM175A (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of FAM175A (phosphorylated form). 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. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1 (By similarity). Interacts with EXD2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000028109.

Structurei

Secondary structure

11817
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1597 – 1602Combined sources6
Helixi1605 – 1617Combined sources13
Beta strandi1632 – 1635Combined sources4
Beta strandi1641 – 1643Combined sources3
Helixi1647 – 1654Combined sources8
Beta strandi1658 – 1661Combined sources4
Helixi1663 – 1669Combined sources7
Turni1670 – 1672Combined sources3
Helixi1678 – 1680Combined sources3
Turni1686 – 1688Combined sources3
Beta strandi1690 – 1692Combined sources3
Helixi1694 – 1701Combined sources8
Beta strandi1710 – 1713Combined sources4
Beta strandi1718 – 1720Combined sources3
Helixi1722 – 1731Combined sources10
Beta strandi1735 – 1737Combined sources3
Beta strandi1739 – 1741Combined sources3
Helixi1743 – 1745Combined sources3
Beta strandi1752 – 1755Combined sources4
Beta strandi1777 – 1779Combined sources3
Helixi1781 – 1788Combined sources8
Helixi1795 – 1798Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1L0BX-ray2.30A1589-1817[»]
ProteinModelPortaliO54952.
SMRiO54952.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO54952.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1588 – 1682BRCT 1PROSITE-ProRule annotationAdd BLAST95
Domaini1701 – 1800BRCT 2PROSITE-ProRule annotationAdd BLAST100

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1354 – 1381Interaction with PALB2By similarityAdd BLAST28

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi497 – 503Nuclear localization signalSequence analysis7

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
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)DescriptionActionsGraphical viewLength
Zinc fingeri24 – 65RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITQ6. Eukaryota.
ENOG4111WR7. LUCA.
HOGENOMiHOG000230969.
HOVERGENiHBG050730.
InParanoidiO54952.
KOiK10605.
PhylomeDBiO54952.

Family and domain databases

CDDicd00027. BRCT. 2 hits.
Gene3Di3.30.40.10. 1 hit.
3.40.50.10190. 2 hits.
InterProiIPR011364. BRCA1.
IPR031099. BRCA1-associated.
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.
PTHR13763:SF0. PTHR13763:SF0. 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)DescriptionActionsGraphical viewLength
Sequence conflicti38Q → K in AAB40387 (PubMed:8761410).Curated1
Sequence conflicti38Q → K in AAB37501 (PubMed:8761410).Curated1
Sequence conflicti192A → M in AAB40387 (PubMed:8761410).Curated1
Sequence conflicti192A → M in AAB37501 (PubMed:8761410).Curated1

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.
RefSeqiNP_036646.1. NM_012514.1.
UniGeneiRn.217584.
Rn.48840.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1L0BX-ray2.30A1589-1817[»]
ProteinModelPortaliO54952.
SMRiO54952.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000028109.

PTM databases

iPTMnetiO54952.
PhosphoSitePlusiO54952.

Proteomic databases

PaxDbiO54952.
PRIDEiO54952.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi672.
RGDi2218. Brca1.

Phylogenomic databases

eggNOGiENOG410ITQ6. Eukaryota.
ENOG4111WR7. LUCA.
HOGENOMiHOG000230969.
HOVERGENiHBG050730.
InParanoidiO54952.
KOiK10605.
PhylomeDBiO54952.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

EvolutionaryTraceiO54952.
PROiO54952.

Family and domain databases

CDDicd00027. BRCT. 2 hits.
Gene3Di3.30.40.10. 1 hit.
3.40.50.10190. 2 hits.
InterProiIPR011364. BRCA1.
IPR031099. BRCA1-associated.
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.
PTHR13763:SF0. PTHR13763:SF0. 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]
ProtoNetiSearch...

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 30, 2016
This is version 137 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.