Tripartite motif-containing protein 65
1_MAAQL 6_ LEEKL 11_ TCAIC 16_ LGLYQ 21_ DPVTL 26_ PCGHN 31_ FCGAC 36_ IRDWW 41_ DRCGK 46_ ACPEC 51_ REPFP 56_ DGAEL 61_ RRNVA 66_ LSGVL 71_ EVVRA 76_ GPARD 81_ PGPDP 86_ GPGPD 91_ PAARC 96_ PRHGR 101_ PLELF 106_ CRTEG 111_ RCVCS 116_ VCTVR 121_ ECRLH 126_ ERALL 131_ DAERL 136_ KREAQ 141_ LRASL 146_ EVTQQ 151_ QATQA 156_ EGQLL 161_ ELRKQ 166_ SSQIQ 171_ NSACI 176_ LASWV 181_ SGKFS 186_ SLLQA 191_ LEIQH 196_ TTALR 201_ SIEVA 206_ KTQAL 211_ AQARD 216_ EEQRL 221_ RVHLE 226_ AVARH 231_ GCRIR 236_ ELLEQ 241_ VDEQT 246_ FLQES 251_ QLLQP 256_ PGPLG 261_ PLTPL 266_ QWDED 271_ QQLGD 276_ LKQLL 281_ SRLCG 286_ LLLEE 291_ GSHPG 296_ APAKP 301_ VDLAP 306_ VEAPG 311_ PLAPV 316_ PSTVC 321_ PLRRK 326_ LWQNY 331_ RNLTF 336_ DPVSA 341_ NRHFY 346_ LSRQD 351_ QQVKH 356_ CRQSR 361_ GPGGP 366_ GSFEL 371_ WQVQC 376_ AQSFQ 381_ AGHHY 386_ WEVRA 391_ SDHSV 396_ TLGVS 401_ YPQLP 406_ RCRLG 411_ PHTDN 416_ IGRGP 421_ CSWGL 426_ CVQED 431_ SLQAW 436_ HNGEA 441_ QRLPG 446_ VSGRL 451_ LGMDL 456_ DLASG 461_ CLTFY 466_ SLEPQ 471_ TQPLY 476_ TFHAL 481_ FNQPL 486_ TPVFW 491_ LLEGR 496_ TLTLC 501_ HQPGA 506_ VFPLG 511_PQEEV
1: E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:28594402, PubMed:34512673). Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252). This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576). Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402). Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584). Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649). In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673)