E3 ubiquitin-protein ligase MARCHF8 (EC 2.3.2.27) (Cellular modulator of immune recognition) (c-MIR) (Membrane-associated RING finger protein 8) (Membrane-associated RING-CH protein VIII) (MARCH-VIII) (RING finger protein 178) (RING-type E3 ubiquitin transferase MARCHF8)
1_MSMPL 6_ HQISA 11_ IPSQD 16_ AISAR 21_ VYRSK 26_ TKEKE 31_ REEQN 36_ EKTLG 41_ HFMSH 46_ SSNIS 51_ KAGSP 56_ PSASA 61_ PAPVS 66_ SFSRT 71_ SITPS 76_ SQDIC 81_ RICHC 86_ EGDDE 91_ SPLIT 96_ PCHCT 101_ GSLHF 106_ VHQAC 111_ LQQWI 116_ KSSDT 121_ RCCEL 126_ CKYEF 131_ IMETK 136_ LKPLR 141_ KWEKL 146_ QMTSS 151_ ERRKI 156_ MCSVT 161_ FHVIA 166_ ITCVV 171_ WSLYV 176_ LIDRT 181_ AEEIK 186_ QGQAT 191_ GILEW 196_ PFWTK 201_ LVVVA 206_ IGFTG 211_ GLLFM 216_ YVQCK 221_ VYVQL 226_ WKRLK 231_ AYNRV 236_ IYVQN 241_ CPETS 246_ KKNIF 251_ EKSPL 256_ TEPNF 261_ ENKHG 266_ YGICH 271_ SDTNS 276_ SCCTE 281_ PEDTG 286_AEIIH
1: E3 ubiquitin-protein ligase that plays several important roles in innate immunity and adaptive immunity (PubMed:34285233, PubMed:35019698, PubMed:35503863). Mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies (PubMed:19117940, PubMed:19566897). Possesses a very broad antiviral activity by specifically inactivating different viral fusion proteins (PubMed:32934085). Targets and ubiquitinates cytoplasmic lysine residues of viral envelope glycoproteins with single transmembrane domains leading to their lysosomal degradation (PubMed:35019698). Therefore, shows broad-spectrum inhibition against many viruses including retroviruses, rhabdoviruses, arenaviruses, sarbecoviruses or influenzaviruses (PubMed:34285233, PubMed:35019698). Strongly blocks human immunodeficiency virus type 1 envelope glycoprotein incorporation into virions by down-regulating its cell surface expression. Also blocks ebola virus glycoprotein/GP incorporation via surface down-regulation (PubMed:32934085). Mediates 'Lys-63'-linked polyubiquitination of influenza M2 to target it to lysosome for degradation (PubMed:34285233). Mediates the regulation of constitutive ubiquitination and trafficking of the viral restriction factor BST2 within the endocytic pathway (PubMed:28320822). Plays a role in maintenance of immune tolerance to self by promoting the turnover and proteasomal degradation of PD-L1/CD274 via ubiquitination (PubMed:34183449). Catalyzes the 'Lys-63'-linked polyubiquitylation of cGAS thereby inhibiting its DNA binding ability and impairing its antiviral innate immunity (PubMed:35503863). Negatively regulates IL7-mediated T-cell homeostasis by mediating 'Lys-27'-linked polyubiquitination of IL7R, leading to its lysosomal degradation (PubMed:39311660)
2: (Microbial infection) Mediates 'Lys-63'-linked polyubiquitination of hepatitis C virus/HCV protein NS2 which allows its binding to HGS, an ESCRT-0 complex component, and this interaction is essential for HCV envelopment