CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006929
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Breast cancer type 1 susceptibility protein 
Protein Synonyms/Alias
 RING finger protein 53 
Gene Name
 BRCA1 
Gene Synonyms/Alias
 RNF53 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
32PICLELIKEPVSTKCsumoylation[1]
50FCKFCMLKLLNQKKGubiquitination[2]
109ANSYNFAKKENNSPEsumoylation[3]
119NNSPEHLKDEVSIIQsumoylation[4]
987IPPLFPIKSFVKTKCubiquitination[2]
1667EEFMLVYKFARKHHIubiquitination[5]
1690ETTHVVMKTDAEFVCsumoylation[1]
Reference
 [1] Cell cycle-dependent conjugation of endogenous BRCA1 protein with SUMO-2/3.
 Vialter A, Vincent A, Demidem A, Morvan D, Stepien G, Venezia ND, Rio PG.
 Biochim Biophys Acta. 2011 Apr;1810(4):432-8. [PMID: 21147198]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] A novel mechanism whereby BRCA1/1a/1b fine tunes the dynamic complex interplay between SUMO-dependent/independent activities of Ubc9 on E2-induced ERalpha activation/repression and degradation in breast cancer cells.
 Xu J, Watkins T, Reddy A, Reddy ES, Rao VN.
 Int J Oncol. 2009 Apr;34(4):939-49. [PMID: 19287951]
 [4] The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.
 Morris JR, Boutell C, Keppler M, Densham R, Weekes D, Alamshah A, Butler L, Galanty Y, Pangon L, Kiuchi T, Ng T, Solomon E.
 Nature. 2009 Dec 17;462(7275):886-90. [PMID: 20016594]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 1642 1736 BRCT 1.
 DOMAIN 1756 1855 BRCT 2.
 ZN_FING 24 65 RING-type.
 REGION 1397 1424 Interaction with PALB2.
 MOD_RES 114 114 Phosphoserine.
 MOD_RES 308 308 Phosphoserine; by AURKA.
 MOD_RES 395 395 Phosphoserine.
 MOD_RES 398 398 Phosphoserine.
 MOD_RES 423 423 Phosphoserine.
 MOD_RES 694 694 Phosphoserine.
 MOD_RES 753 753 Phosphoserine.
 MOD_RES 988 988 Phosphoserine; by CHEK2.
 MOD_RES 1143 1143 Phosphoserine; by ATR; in vitro.
 MOD_RES 1211 1211 Phosphoserine.
 MOD_RES 1217 1217 Phosphoserine.
 MOD_RES 1218 1218 Phosphoserine.
 MOD_RES 1280 1280 Phosphoserine; by ATR; in vitro.
 MOD_RES 1328 1328 Phosphoserine.
 MOD_RES 1336 1336 Phosphoserine.
 MOD_RES 1342 1342 Phosphoserine.
 MOD_RES 1387 1387 Phosphoserine; by ATM and ATR.
 MOD_RES 1394 1394 Phosphothreonine; by ATR; in vitro.
 MOD_RES 1423 1423 Phosphoserine; by ATM and ATR.
 MOD_RES 1457 1457 Phosphoserine; by ATR; in vitro.
 MOD_RES 1524 1524 Phosphoserine; by ATM.  
Keyword
 3D-structure; Alternative initiation; Alternative splicing; Cell cycle; Chromosome; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; DNA damage; DNA recombination; DNA repair; DNA-binding; Fatty acid biosynthesis; Fatty acid metabolism; Ligase; Lipid biosynthesis; Lipid metabolism; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Tumor suppressor; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1863 AA 
Protein Sequence
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ 60
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD 120
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI 180
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ 240
PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE 300
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC 360
SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD 420
EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN 480
LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE 540
QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI 600
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV 660
RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE 720
FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ 780
ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS 840
RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT 900
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG 960
NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP 1020
STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL 1080
NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS 1140
HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ 1200
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL 1260
LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS 1320
SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE 1380
DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE 1440
DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK 1500
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG 1560
TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT 1620
DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI 1680
TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV 1740
VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL 1800
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH 1860
SHY 1863 
Gene Ontology
 GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
 GO:0031436; C:BRCA1-BARD1 complex; IDA:UniProtKB.
 GO:0005694; C:chromosome; ISS:UniProtKB.
 GO:0008274; C:gamma-tubulin ring complex; NAS:UniProtKB.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; IDA:BHF-UCL.
 GO:0030529; C:ribonucleoprotein complex; IDA:MGI.
 GO:0001726; C:ruffle; IDA:BHF-UCL.
 GO:0050681; F:androgen receptor binding; NAS:UniProtKB.
 GO:0003723; F:RNA binding; IDA:MGI.
 GO:0003713; F:transcription coactivator activity; NAS:UniProtKB.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
 GO:0015631; F:tubulin binding; NAS:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; TAS:ProtInc.
 GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB.
 GO:0007059; P:chromosome segregation; IMP:UniProtKB.
 GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; TAS:UniProtKB.
 GO:0000724; P:double-strand break repair via homologous recombination; IDA:HGNC.
 GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
 GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:MGI.
 GO:0046600; P:negative regulation of centriole replication; NAS:UniProtKB.
 GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:UniProtKB.
 GO:0051573; P:negative regulation of histone H3-K9 methylation; IDA:BHF-UCL.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0071158; P:positive regulation of cell cycle arrest; IDA:BHF-UCL.
 GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
 GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:BHF-UCL.
 GO:2000617; P:positive regulation of histone H3-K9 acetylation; IDA:BHF-UCL.
 GO:2000620; P:positive regulation of histone H4-K16 acetylation; IDA:BHF-UCL.
 GO:0070512; P:positive regulation of histone H4-K20 methylation; IDA:BHF-UCL.
 GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0006301; P:postreplication repair; IDA:HGNC.
 GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
 GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
 GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
 GO:2000145; P:regulation of cell motility; IDA:BHF-UCL.
 GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB.
 GO:0006359; P:regulation of transcription from RNA polymerase III promoter; TAS:UniProtKB.
 GO:0043627; P:response to estrogen stimulus; IDA:UniProtKB.
 GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
 GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:BHF-UCL. 
Interpro
 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. 
Pfam
 PF00533; BRCT
 PF12820; BRCT_assoc
 PF00097; zf-C3HC4 
SMART
 SM00292; BRCT
 SM00184; RING 
PROSITE
 PS50172; BRCT
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS
 PR00493; BRSTCANCERI.