MIR1_MHV68
ID MIR1_MHV68 Reviewed; 201 AA.
AC O41933;
DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=E3 ubiquitin-protein ligase MIR1;
DE EC=2.3.2.36 {ECO:0000250|UniProtKB:P90495};
DE AltName: Full=MK3;
DE AltName: Full=Modulator of immune recognition 1 homolog;
DE AltName: Full=ORF K3;
DE AltName: Full=RING-type E3 ubiquitin transferase MIR1 {ECO:0000305};
GN Name=K3;
OS Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=33708;
OH NCBI_TaxID=10129; Apodemus sylvaticus (European woodmouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate g2.4, and Isolate WUMS;
RX PubMed=9223479; DOI=10.1128/jvi.71.8.5894-5904.1997;
RA Virgin H.W., Latreille P., Wamsley P., Hallsworth K., Weck K.E.,
RA Dal Canto A.J., Speck S.H.;
RT "Complete sequence and genomic analysis of murine gammaherpesvirus 68.";
RL J. Virol. 71:5894-5904(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Isolate g2.4;
RX PubMed=2351958; DOI=10.1099/0022-1317-71-6-1355;
RA Efstathiou S., Ho Y.M., Minson A.C.;
RT "Cloning and molecular characterization of the murine herpesvirus 68
RT genome.";
RL J. Gen. Virol. 71:1355-1364(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHV76;
RX PubMed=11333912; DOI=10.1128/jvi.75.11.5315-5327.2001;
RA Macrae A.I., Dutia B.M., Milligan S., Brownstein D.G., Allen D.J.,
RA Mistrikova J., Davison A.J., Nash A.A., Stewart J.P.;
RT "Analysis of a novel strain of murine gammaherpesvirus reveals a genomic
RT locus important for acute pathogenesis.";
RL J. Virol. 75:5315-5327(2001).
RN [4]
RP FUNCTION.
RX PubMed=10890918; DOI=10.1073/pnas.150240097;
RA Stevenson P.G., Efstathiou S., Doherty P.C., Lehner P.J.;
RT "Inhibition of MHC class I-restricted antigen presentation by gamma 2-
RT herpesviruses.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8455-8460(2000).
RN [5]
RP FUNCTION, DOMAIN RING-CH-TYPE ZINC-FINGER, AND SUBCELLULAR LOCATION.
RX PubMed=11672544; DOI=10.1016/s1074-7613(01)00213-8;
RA Boname J.M., Stevenson P.G.;
RT "MHC class I ubiquitination by a viral PHD/LAP finger protein.";
RL Immunity 15:627-636(2001).
RN [6]
RP DOMAIN RING-CH-TYPE ZINC-FINGER.
RX PubMed=12695663; DOI=10.4161/cc.2.2.335;
RA Aravind L., Iyer L.M., Koonin E.V.;
RT "Scores of RINGS but no PHDs in ubiquitin signaling.";
RL Cell Cycle 2:123-126(2003).
RN [7]
RP FUNCTION, DOMAIN DIRT, AND MUTAGENESIS OF TRP-9.
RX PubMed=17502423; DOI=10.1083/jcb.200611063;
RA Wang X., Herr R.A., Chua W.J., Lybarger L., Wiertz E.J., Hansen T.H.;
RT "Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic
RT tail can induce ERAD of MHC-I by viral E3 ligase mK3.";
RL J. Cell Biol. 177:613-624(2007).
RN [8]
RP FUNCTION.
RX PubMed=19531064; DOI=10.1111/j.1600-0854.2009.00946.x;
RA Herr R.A., Harris J., Fang S., Wang X., Hansen T.H.;
RT "Role of the RING-CH domain of viral ligase mK3 in ubiquitination of non-
RT lysine and lysine MHC I residues.";
RL Traffic 10:1301-1317(2009).
RN [9]
RP FUNCTION, AND INTERACTION WITH HOST UBE2J2.
RX PubMed=19951915; DOI=10.1083/jcb.200908036;
RA Wang X., Herr R.A., Rabelink M., Hoeben R.C., Wiertz E.J., Hansen T.H.;
RT "Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation
RT substrates.";
RL J. Cell Biol. 187:655-668(2009).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of
CC host surface class I (MHC-I) H-2D(b)/H2-D1 and H-2K(b)/H2-K1 molecules
CC before they exit the endoplasmic reticulum, leading to their
CC degradation by the endoplasmic reticulum-associated degradation (ERAD)
CC system, thus blocking the immune detection of virus-infected cells.
CC Mediates ubiquitination of lysine, as well as serine and threonine
CC residues present in the cytoplasmic tail of surface class I molecules.
CC Promotes ubiquitination of hydroxylated serine or threonine residues
CC via ester bonds instead of the classical isopeptide linkage.
CC {ECO:0000269|PubMed:10890918, ECO:0000269|PubMed:11672544,
CC ECO:0000269|PubMed:17502423, ECO:0000269|PubMed:19531064,
CC ECO:0000269|PubMed:19951915}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine.; EC=2.3.2.36;
CC Evidence={ECO:0000250|UniProtKB:P90495};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with host UBE2J2. {ECO:0000269|PubMed:19951915}.
CC -!- SUBCELLULAR LOCATION: Host endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11672544}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:11672544}.
CC -!- DOMAIN: The DIRT (domain in between the RING-CH-type and the first
CC transmembrane) region is essential to determine substrate residues that
CC can be ubiquitinated.
CC -!- DOMAIN: The RING-CH-type zinc finger (also named RINGV-type zinc-
CC finger) mediates the E3 ubiquitin ligase activity.
CC -!- MISCELLANEOUS: Murine herpesvirus 76 (MHV76) is identical to murine
CC herpesvirus 68 except for a large deletion at the genome left end of
CC the unique region.
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DR EMBL; U97553; AAB66429.1; -; Genomic_DNA.
DR EMBL; AF105037; AAF19280.1; -; Genomic_DNA.
DR EMBL; AF324455; AAK16705.1; -; Genomic_DNA.
DR RefSeq; NP_044852.1; NC_001826.2.
DR SMR; O41933; -.
DR GeneID; 1497186; -.
DR KEGG; vg:1497186; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000099649; Genome.
DR Proteomes; UP000175018; Genome.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011016; Znf_RING-CH.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF12906; RINGv; 1.
DR SMART; SM00744; RINGv; 1.
DR PROSITE; PS51292; ZF_RING_CH; 1.
PE 1: Evidence at protein level;
KW Early protein; Host endoplasmic reticulum; Host membrane;
KW Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host MHC class I molecule presentation by virus; Membrane;
KW Metal-binding; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation pathway; Viral immunoevasion; Zinc;
KW Zinc-finger.
FT CHAIN 1..201
FT /note="E3 ubiquitin-protein ligase MIR1"
FT /id="PRO_0000221391"
FT TOPO_DOM 1..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 114..134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 135..201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ZN_FING 1..58
FT /note="RING-CH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT REGION 52..79
FT /note="DIRT"
FT BINDING 8
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 11
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 22
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 32
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 35
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 48
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT BINDING 51
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00623"
FT MUTAGEN 9
FT /note="W->R: Abolishes E3 ligase activity."
FT /evidence="ECO:0000269|PubMed:17502423"
SQ SEQUENCE 201 AA; 22214 MW; 0953B5BDACDF8367 CRC64;
MDSTGEFCWI CHQPEGPLKR FCGCKGSCAV SHQDCLRGWL ETSRRQTCAL CGTPYSMKWK
TKPLREWTWG EEEVLAAMEA CLPLVLIPLA VLMIVMGTWL LVNHNGFLSP RMQVVLVVIV
LLAMIVFSAS ASYVMVEGPG CLDTCTAKNS TVTVNSIDEA IATQQPTKTD LGLARETLST
RFRRGKCRSC CRLGCVRLCC V
