ID   UL42_HCMVM              Reviewed;         125 AA.
AC   F5HHZ3;
DT   11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 1.
DT   03-AUG-2022, entry version 28.
DE   RecName: Full=Protein UL42;
GN   Name=UL42;
OS   Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX   NCBI_TaxID=295027;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15105547; DOI=10.1099/vir.0.79888-0;
RA   Dolan A., Cunningham C., Hector R.D., Hassan-Walker A.F., Lee L.,
RA   Addison C., Dargan D.J., McGeoch D.J., Gatherer D., Emery V.C.,
RA   Griffiths P.D., Sinzger C., McSharry B.P., Wilkinson G.W.G., Davison A.J.;
RT   "Genetic content of wild-type human cytomegalovirus.";
RL   J. Gen. Virol. 85:1301-1312(2004).
RN   [2]
RP   FUNCTION, INTERACTION WITH HOST ITCH, AND SUBCELLULAR LOCATION.
RX   PubMed=26555021; DOI=10.1099/jgv.0.000336;
RA   Koshizuka T., Tanaka K., Suzutani T.;
RT   "Degradation of host ubiquitin E3 ligase Itch by human cytomegalovirus
RT   UL42.";
RL   J. Gen. Virol. 97:196-208(2016).
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 (By similarity).
CC       {ECO:0000250|UniProtKB:D5LX53, ECO:0000250|UniProtKB:P16815}.
CC   -!- SUBUNIT: Interacts with host ITCH; this interaction induces the
CC       ubiquitination and subsequent degradation of ITCH (By similarity).
CC       Interacts with host STING1. Interacts with CGAS (By similarity).
CC       {ECO:0000250|UniProtKB:D5LX53, ECO:0000250|UniProtKB:P16815}.
CC   -!- SUBCELLULAR LOCATION: Host membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}. Host cytoplasm {ECO:0000269|PubMed:26555021}.
CC       Note=Accumulates in the perinuclear region of the host cytoplasm, with
CC       some dispersal into the cytoplasm in a fine-speckled pattern.
CC       {ECO:0000269|PubMed:26555021}.
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:0000250|UniProtKB:D5LX53}.
CC   -!- SIMILARITY: Belongs to the Cytomegalovirus UL42 protein family.
CC       {ECO:0000305}.
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DR   EMBL; AY446894; AAR31606.1; -; Genomic_DNA.
DR   RefSeq; YP_081500.1; NC_006273.2.
DR   SMR; F5HHZ3; -.
DR   BioGRID; 1677993; 1.
DR   PRIDE; F5HHZ3; -.
DR   DNASU; 3077440; -.
DR   GeneID; 3077440; -.
DR   KEGG; vg:3077440; -.
DR   Proteomes; UP000000938; 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   Reference proteome; Transmembrane; Transmembrane helix;
KW   Viral immunoevasion.
FT   CHAIN           1..125
FT                   /note="Protein UL42"
FT                   /id="PRO_0000418316"
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:0000250|UniProtKB:D5LX53"
FT   MOTIF           42..45
FT                   /note="PPXY motif"
FT                   /evidence="ECO:0000250|UniProtKB:D5LX53"
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"
SQ   SEQUENCE   125 AA;  13668 MW;  79870B50807CCB66 CRC64;
     MEPTPMLRDR DHDDAPPTYE QAMGLCPTTV STPPPPPPDC SPPPYRPPYC LVSSPSPRHT
     FDMDMMEMPA TMHPTTGAYF DNGWKWTFAL LVVAILGIIF LAVVFTVVIN RDSANITTGT
     QASSG