E3 ubiquitin-protein ligase RNF168 (hRNF168) (EC 2.3.2.27) (RING finger protein 168) (RING-type E3 ubiquitin transferase RNF168)
1_MALPK 6_ DAIPS 11_ LSECQ 16_ CGICM 21_ EILVE 26_ PVTLP 31_ CNHTL 36_ CKPCF 41_ QSTVE 46_ KASLC 51_ CPFCR 56_ RRVSS 61_ WTRYH 66_ TRRNS 71_ LVNVE 76_ LWTII 81_ QKHYP 86_ RECKL 91_ RASGQ 96_ ESEEV 101_ ADDYQ 106_ PVRLL 111_ SKPGE 116_ LRREY 121_ EEEIS 126_ KVAAE 131_ RRASE 136_ EEENK 141_ ASEEY 146_ IQRLL 151_ AEEEE 156_ EEKRQ 161_ AEKRR 166_ RAMEE 171_ QLKSD 176_ EELAR 181_ KLSID 186_ INNFC 191_ EGSIS 196_ ASPLN 201_ SRKSD 206_ PVTPK 211_ SEKKS 216_ KNKQR 221_ NTGDI 226_ QKYLT 231_ PKSQF 236_ GSASH 241_ SEAVQ 246_ EVRKD 251_ SVSKD 256_ IDSSD 261_ RKSPT 266_ GQDTE 271_ IEDMP 276_ TLSPQ 281_ ISLGV 286_ GEQGA 291_ DSSIE 296_ SPMPW 301_ LCACG 306_ AEWYH 311_ EGNVK 316_ TRPSN 321_ HGKEL 326_ CVLSH 331_ ERPKT 336_ RVPYS 341_ KETAV 346_ MPCGR 351_ TESGC 356_ APTSG 361_ VTQTN 366_ GNNTG 371_ ETENE 376_ ESCLL 381_ ISKEI 386_ SKRKN 391_ QESSF 396_ EAVKD 401_ PCFSA 406_ KRRKV 411_ SPESS 416_ PDQEE 421_ TEINF 426_ TQKLI 431_ DLEHL 436_ LFERH 441_ KQEEQ 446_ DRLLA 451_ LQLQK 456_ EVDKE 461_ QMVPN 466_ RQKGS 471_ PDEYH 476_ LRATS 481_ SPPDK 486_ VLNGQ 491_ RKNPK 496_ DGNFK 501_ RQTHT 506_ KHPTP 511_ ERGSR 516_ DKNRQ 521_ VSLKM 526_ QLKQS 531_ VNRRK 536_ MPNST 541_ RDHCK 546_ VSKSA 551_ HSLQP 556_ SISQK 561_ SVFQM 566_FQRCT
1: 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)