2d8s

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Current revision (18:38, 29 May 2024) (edit) (undo)
 
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== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/MARH8_HUMAN MARH8_HUMAN] 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:35019698, PubMed:34285233). Strongly blocks human immunodeficiency virus type 1 envelope glycoprotein incorporation into virions by down-regulating its cell surface expression. Blocks also 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).<ref>PMID:12582153</ref> <ref>PMID:14722266</ref> <ref>PMID:18389477</ref> <ref>PMID:19117940</ref> <ref>PMID:19566897</ref> <ref>PMID:28320822</ref> <ref>PMID:32934085</ref> <ref>PMID:34183449</ref> <ref>PMID:34285233</ref> <ref>PMID:35019698</ref> <ref>PMID:35503863</ref> (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.<ref>PMID:30759391</ref>
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[https://www.uniprot.org/uniprot/MARH8_HUMAN MARH8_HUMAN] 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. Blocks also 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).<ref>PMID:12582153</ref> <ref>PMID:14722266</ref> <ref>PMID:18389477</ref> <ref>PMID:19117940</ref> <ref>PMID:19566897</ref> <ref>PMID:28320822</ref> <ref>PMID:32934085</ref> <ref>PMID:34183449</ref> <ref>PMID:34285233</ref> <ref>PMID:35019698</ref> <ref>PMID:35503863</ref> (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.<ref>PMID:30759391</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]

Current revision

Solution structure of the RING domain of the human cellular modulator of immune recognition protein

PDB ID 2d8s

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