CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-017121
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase RNF168 
Protein Synonyms/Alias
 hRNF168; RING finger protein 168 
Gene Name
 RNF168 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
112QPVRLLSKPGELRREubiquitination[1, 2]
126EYEEEISKVAAERRAubiquitination[1]
158AEEEEEEKRQAEKRRubiquitination[1, 2]
173RAMEEQLKSDEELARubiquitination[1]
181SDEELARKLSIDINNubiquitination[1]
203ASPLNSRKSDPVTPKubiquitination[1]
227RNTGDIQKYLTPKSQubiquitination[1, 2, 3, 4, 5]
232IQKYLTPKSQFGSASubiquitination[1, 2, 3, 4, 5, 6, 7, 8, 9]
254VRKDSVSKDIDSSDRubiquitination[1, 2]
334VLSHERPKTRVPYSKubiquitination[1, 2]
341KTRVPYSKETAVMPCubiquitination[1, 2, 4, 7, 8]
383ESCLLISKEISKRKNubiquitination[1, 7]
387LISKEISKRKNQESSubiquitination[1]
389SKEISKRKNQESSFEubiquitination[1, 2]
399ESSFEAVKDPCFSAKubiquitination[1, 2, 4]
406KDPCFSAKRRKVSPEubiquitination[1, 2]
409CFSAKRRKVSPESSPubiquitination[1, 2, 3]
441HLLFERHKQEEQDRLubiquitination[1]
455LLALQLQKEVDKEQMubiquitination[1, 2, 6, 9]
459QLQKEVDKEQMVPNRubiquitination[1, 2]
468QMVPNRQKGSPDEYHubiquitination[1, 2, 3, 5, 7]
485ATSSPPDKVLNGQRKubiquitination[1, 2]
524KNRQVSLKMQLKQSVubiquitination[1]
528VSLKMQLKQSVNRRKubiquitination[1, 2, 7]
548RDHCKVSKSAHSLQPubiquitination[1, 2, 4]
560LQPSISQKSVFQMFQubiquitination[1, 2, 5, 7]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] 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]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] 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]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8- dependent H2A ubiquitination, promoting the formation of 'Lys-63'- linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively). 
Sequence Annotation
 ZN_FING 16 55 RING-type.
 MOTIF 110 128 LR motif 1.
 MOTIF 143 151 UMI motif.
 MOTIF 168 191 MIU motif 1.
 MOTIF 439 462 MIU motif 2.
 MOTIF 466 477 LR motif 2.
 MOD_RES 362 362 Phosphothreonine (By similarity).
 MOD_RES 411 411 Phosphoserine.
 MOD_RES 414 414 Phosphoserine.
 MOD_RES 415 415 Phosphoserine.  
Keyword
 3D-structure; Chromatin regulator; Complete proteome; DNA damage; DNA repair; Ligase; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 571 AA 
Protein Sequence
MALPKDAIPS LSECQCGICM EILVEPVTLP CNHTLCKPCF QSTVEKASLC CPFCRRRVSS 60
WTRYHTRRNS LVNVELWTII QKHYPRECKL RASGQESEEV ADDYQPVRLL SKPGELRREY 120
EEEISKVAAE RRASEEEENK ASEEYIQRLL AEEEEEEKRQ AEKRRRAMEE QLKSDEELAR 180
KLSIDINNFC EGSISASPLN SRKSDPVTPK SEKKSKNKQR NTGDIQKYLT PKSQFGSASH 240
SEAVQEVRKD SVSKDIDSSD RKSPTGQDTE IEDMPTLSPQ ISLGVGEQGA DSSIESPMPW 300
LCACGAEWYH EGNVKTRPSN HGKELCVLSH ERPKTRVPYS KETAVMPCGR TESGCAPTSG 360
VTQTNGNNTG ETENEESCLL ISKEISKRKN QESSFEAVKD PCFSAKRRKV SPESSPDQEE 420
TEINFTQKLI DLEHLLFERH KQEEQDRLLA LQLQKEVDKE QMVPNRQKGS PDEYHLRATS 480
SPPDKVLNGQ RKNPKDGNFK RQTHTKHPTP ERGSRDKNRQ VSLKMQLKQS VNRRKMPNST 540
RDHCKVSKSA HSLQPSISQK SVFQMFQRCT K 571 
Gene Ontology
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0035861; C:site of double-strand break; IDA:UniProtKB.
 GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
 GO:0042393; F:histone binding; IDA:UniProtKB.
 GO:0070530; F:K63-linked polyubiquitin binding; IDA:UniProtKB.
 GO:0031491; F:nucleosome binding; IDA:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006302; P:double-strand break repair; IDA:UniProtKB.
 GO:0070535; P:histone H2A K63-linked ubiquitination; IDA:UniProtKB.
 GO:0035518; P:histone H2A monoubiquitination; IDA:UniProtKB.
 GO:0036351; P:histone H2A-K13 ubiquitination; IDA:UniProtKB.
 GO:0036352; P:histone H2A-K15 ubiquitination; IDA:UniProtKB.
 GO:0036297; P:interstrand cross-link repair; TAS:UniProtKB.
 GO:0045190; P:isotype switching; ISS:UniProtKB.
 GO:0045900; P:negative regulation of translational elongation; IMP:UniProtKB.
 GO:0045739; P:positive regulation of DNA repair; IDA:UniProtKB.
 GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. 
Interpro
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD. 
Pfam
  
SMART
 SM00184; RING 
PROSITE
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS