UL42_HCMVT
ID UL42_HCMVT Reviewed; 122 AA.
AC D5LX53;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 1.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Protein UL42;
GN Name=UL42;
OS Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10363;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CINCY/Towne {ECO:0000312|EMBL:ADE88049.1};
RA Davison A.J.;
RT "Human cytomegalovirus RL11 gene family: variation, recombination and
RT transcription.";
RL Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INTERACTION WITH HOST ITCH, DOMAIN, AND MUTAGENESIS OF TYR-19 AND TYR-45.
RX PubMed=29535361; DOI=10.1038/s41598-018-22682-2;
RA Koshizuka T., Kobayashi T., Ishioka K., Suzutani T.;
RT "Herpesviruses possess conserved proteins for interaction with Nedd4 family
RT ubiquitin E3 ligases.";
RL Sci. Rep. 8:4447-4447(2018).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=34260096; DOI=10.1111/1348-0421.12932;
RA Koshizuka T., Kondo H., Kato H., Takahashi K.;
RT "Human cytomegalovirus UL42 protein inhibits the degradation of
RT glycoprotein B through inhibition of Nedd4 family ubiquitin E3 ligases.";
RL Microbiol. Immunol. 65:472-480(2021).
CC -!- FUNCTION: Plays a role in the inhibition of host innate immune response
CC to promote latent infection. Mechanistically, suppresses viral DNA-
CC triggered signaling by impairing DNA binding and oligomerization of
CC CGAS. Impairs also the translocation of host STING1 from the
CC endoplasmic reticulum to perinuclear punctate structures which is an
CC essential step for its activation (By similarity). Regulates the
CC function of host NEDD4 family ubiquitin E3 ligases through its PPxY
CC motif and thereby prevents the excessive ubiquitination of gB and its
CC degradation by inhibiting these E3 ligases (PubMed:34260096).
CC {ECO:0000250|UniProtKB:P16815, ECO:0000269|PubMed:34260096}.
CC -!- SUBUNIT: Interacts with host ITCH; this interaction induces the
CC ubiquitination and subsequent degradation of ITCH (PubMed:29535361).
CC Interacts with host STING1 (By similarity). Interacts with CGAS (By
CC similarity). {ECO:0000250|UniProtKB:P16815,
CC ECO:0000269|PubMed:29535361}.
CC -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000250|UniProtKB:F5HHZ3};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:F5HHZ3}. Host
CC cytoplasm {ECO:0000250|UniProtKB:F5HHZ3}. Note=Accumulates in the
CC perinuclear region of the host cytoplasm, with some dispersal into the
CC cytoplasm in a fine-speckled pattern. {ECO:0000250|UniProtKB:F5HHZ3}.
CC -!- DOMAIN: Late-budding domains (L domains) are short sequence motifs
CC essential for viral particle budding. They recruit proteins of the host
CC ESCRT machinery (Endosomal Sorting Complex Required for Transport) or
CC ESCRT-associated proteins. Contains one L domain: a PPXY motif which is
CC involved in the interaction with Itch, a member of the Nedd4 family.
CC {ECO:0000269|PubMed:29535361}.
CC -!- DISRUPTION PHENOTYPE: In the absence of functional UL42, a significant
CC amount of gB interacts with host ITCH leading to gB ubiquitination and
CC degradation. {ECO:0000269|PubMed:34260096}.
CC -!- SIMILARITY: Belongs to the Cytomegalovirus UL42 protein family.
CC {ECO:0000305}.
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DR EMBL; GU980198; ADE88049.1; -; Genomic_DNA.
DR SMR; D5LX53; -.
DR Proteomes; UP000149703; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR035110; UL42.
DR Pfam; PF17638; UL42; 1.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Membrane;
KW Transmembrane; Transmembrane helix; Viral immunoevasion.
FT CHAIN 1..122
FT /note="Protein UL42"
FT /id="PRO_0000448382"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 16..19
FT /note="PPXY motif"
FT /evidence="ECO:0000269|PubMed:29535361"
FT MOTIF 42..45
FT /note="PPXY motif"
FT /evidence="ECO:0000269|PubMed:29535361"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..47
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 19
FT /note="Y->A: Complete loss of interaction with host ITCH;
FT when associated with A-45."
FT /evidence="ECO:0000269|PubMed:29535361"
FT MUTAGEN 45
FT /note="Y->A: Complete loss of interaction with host ITCH;
FT when associated with A-19."
FT /evidence="ECO:0000269|PubMed:29535361"
SQ SEQUENCE 122 AA; 13355 MW; 31E331C2AFCD12BB CRC64;
MEPTPMLRDR DHDDAPPTYE QAMGLCPTTV STPPPPPPDC SPPPYRPPYC LVSSPSPRHT
FDMDMMEMPA TMHPTTGAYF DNGWKWTFAL LVVAILGIIF LAVVFTVVIN RDNSTATGTS
SG
