TRS1_HCMVA
ID TRS1_HCMVA Reviewed; 788 AA.
AC P09695; Q7M6U0;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 23-FEB-2022, entry version 79.
DE RecName: Full=Protein HHLF1;
GN Name=TRS1;
OS Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10360;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3031311; DOI=10.1016/0022-2836(86)90359-1;
RA Weston K.M., Barrell B.G.;
RT "Sequence of the short unique region, short repeats, and part of the long
RT repeats of human cytomegalovirus.";
RL J. Mol. Biol. 192:177-208(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
RA Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
RA Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
RA Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
RT "Analysis of the protein-coding content of the sequence of human
RT cytomegalovirus strain AD169.";
RL Curr. Top. Microbiol. Immunol. 154:125-169(1990).
RN [3]
RP GENOME REANNOTATION.
RX PubMed=12533697; DOI=10.1099/vir.0.18606-0;
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RT "The human cytomegalovirus genome revisited: comparison with the chimpanzee
RT cytomegalovirus genome.";
RL J. Gen. Virol. 84:17-28(2003).
RN [4]
RP ERRATUM OF PUBMED:12533697.
RA Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
RA McGeoch D.J., Hayward G.S.;
RL J. Gen. Virol. 84:1053-1053(2003).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=8995674; DOI=10.1128/jvi.71.2.1485-1496.1997;
RA Romanowski M.J., Shenk T.;
RT "Characterization of the human cytomegalovirus irs1 and trs1 genes: a
RT second immediate-early transcription unit within irs1 whose product
RT antagonizes transcriptional activation.";
RL J. Virol. 71:1485-1496(1997).
RN [6]
RP IDENTIFICATION.
RX PubMed=15452216; DOI=10.1128/jvi.78.20.10960-10966.2004;
RA Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA Shenk T., Smith R.D., Nelson J.A.;
RT "Identification of proteins in human cytomegalovirus (HCMV) particles: the
RT HCMV proteome.";
RL J. Virol. 78:10960-10966(2004).
RN [7]
RP ERRATUM OF PUBMED:15452216.
RA Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
RA Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
RA Shenk T., Smith R.D., Nelson J.A.;
RL J. Virol. 78:13395-13395(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST EIF2AK2.
RC STRAIN=rTowne-1;
RX PubMed=16987971; DOI=10.1128/jvi.00957-06;
RA Hakki M., Marshall E.E., De Niro K.L., Geballe A.P.;
RT "Binding and nuclear relocalization of protein kinase R by human
RT cytomegalovirus TRS1.";
RL J. Virol. 80:11817-11826(2006).
RN [9]
RP INTERACTION WITH HOST HSPA5.
RC STRAIN=Towne;
RX PubMed=19741001; DOI=10.1128/jvi.00762-09;
RA Buchkovich N.J., Maguire T.G., Paton A.W., Paton J.C., Alwine J.C.;
RT "The endoplasmic reticulum chaperone BiP/GRP78 is important in the
RT structure and function of the human cytomegalovirus assembly compartment.";
RL J. Virol. 83:11421-11428(2009).
RN [10]
RP FUNCTION, AND INTERACTION WITH UL44.
RX PubMed=20444996; DOI=10.1099/vir.0.022640-0;
RA Strang B.L., Geballe A.P., Coen D.M.;
RT "Association of human cytomegalovirus proteins IRS1 and TRS1 with the viral
RT DNA polymerase accessory subunit UL44.";
RL J. Gen. Virol. 91:2167-2175(2010).
RN [11]
RP FUNCTION, AND INTERACTION WITH HOST BECN1.
RX PubMed=22205736; DOI=10.1128/jvi.05746-11;
RA Chaumorcel M., Lussignol M., Mouna L., Cavignac Y., Fahie K.,
RA Cotte-Laffitte J., Geballe A., Brune W., Beau I., Codogno P., Esclatine A.;
RT "The human cytomegalovirus protein TRS1 inhibits autophagy via its
RT interaction with Beclin 1.";
RL J. Virol. 86:2571-2584(2012).
CC -!- FUNCTION: Inhibits the establishment of the antiviral state in the
CC infected cell. Prevents the phosphorylation of the host eukaryotic
CC translation initiation factor eIF-2alpha/EIF2S1 and thus the shutoff of
CC viral and cellular protein synthesis by directly interacting with
CC EIF2AK2/PKR. Also inhibits host autophagy by interacting with host
CC Beclin-1/BECN1. {ECO:0000269|PubMed:16987971,
CC ECO:0000269|PubMed:20444996, ECO:0000269|PubMed:22205736}.
CC -!- SUBUNIT: Interacts with host EIF2AK2/PKR; this interaction retains
CC EIF2AK2 to the host nucleus and prevents its activation. Interaction
CC (via N-terminus) with host BECN1; this interaction inhibits host
CC autophagy. Interacts with the viral DNA polymerase accessory subunit
CC UL44. Interacts with host HSPA5. {ECO:0000269|PubMed:16987971,
CC ECO:0000269|PubMed:19741001, ECO:0000269|PubMed:20444996,
CC ECO:0000269|PubMed:22205736}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:8995674}. Host
CC cytoplasm {ECO:0000269|PubMed:8995674}. Host nucleus
CC {ECO:0000269|PubMed:8995674}.
CC -!- SIMILARITY: Belongs to the herpesviridae US22 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X17403; CAA35269.1; -; Genomic_DNA.
DR EMBL; X04650; CAB37121.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00094.1; -; Genomic_DNA.
DR PIR; C27349; QQBEE3.
DR Proteomes; UP000008991; Genome.
DR Proteomes; UP000008992; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0039521; P:suppression by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR003360; US22-like.
DR Pfam; PF02393; US22; 2.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host autophagy by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host PKR by virus; Reference proteome; Viral immunoevasion;
KW Virion.
FT CHAIN 1..788
FT /note="Protein HHLF1"
FT /id="PRO_0000115266"
FT REGION 1..82
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 609..633
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 648..663
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 788 AA; 83982 MW; 604BC69C4472BC7A CRC64;
MAQRNGMSPR PPPLGRGRGA GGPSGVGSSP PSSCVPMGAP STAGTGASAA ATTTPGHGVH
RVEPRGPPGA PPSSGNNSNF WHGPERLLLS QIPVERQALT ELEYQAMGAV WRAAFLANST
GRAMRKWSQR DAGTLLPLGR PYGFYARVTP RSQMNGVGAT DLRQLSPRDA WIVLVATVVH
EVDPAADPTL GDKAGHPEGL CAQDGLYLAL GAGFRVFVYD LANNTLILAA RDADEWFRHG
AGEVVRLYRC NRLGVGTPRA TLLPQPALRQ TLLRAEEATA LGRELRRRWA GTTVALQTPG
RRLQPMVLLG AWQELAQYEP FASAPHPASL LTAVRRHLNQ RLCCGWLALG AVLPARWLGC
AAGPATGTAA GTTSPPAASG TETEAAGGDA PCAIAGAVGS AVPVPPQPYG AAGGGAICVP
NADAHAVVGA DAAAAAAPTV MVGSTAMAGP AASGTVPRAM LVVLLDELGA VFGYCPLDGH
VYPLAAELSH FLRAGVLGAL ALGRESAPAA EAARRLLPEL DREQWERPRW DALHLHPRAA
LWAREPHGQL AFLLRPGRGE AEVLTLATKH PAICANVEDY LQDARRRADA QALGLDLATV
VMEAGGQMIH KKTKKPKGKE DESLMKGKHS RYTRPTEPPL TPQASLGRAL RRDDEDWKPS
RLPGEDSWYD LDETFWVLGS NRKNDVYQRR WKKTVLRCGL EIDRPMPTVP KGCRPQTFTH
EGIQLMGGAT QEPLDTGLYA PSHVTSAFVP SVYMPPTVPY PDPAARLCRD MRRVTFSNIA
THYHYNAQ
