IRS1_HCMVA
ID IRS1_HCMVA Reviewed; 846 AA.
AC P09715; Q7M6U2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 23-FEB-2022, entry version 80.
DE RecName: Full=Protein IRS1;
DE AltName: Full=HQRF1;
GN Name=IRS1;
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 ISOFORM IRS1-263, AND 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 [5]
RP ERRATUM OF PUBMED:8995674.
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 [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.
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 FUNCTION.
RX PubMed=19211736; DOI=10.1128/jvi.02489-08;
RA Marshall E.E., Bierle C.J., Brune W., Geballe A.P.;
RT "Essential role for either TRS1 or IRS1 in human cytomegalovirus
RT replication.";
RL J. Virol. 83:4112-4120(2009).
RN [10]
RP 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).
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 and thus the shutoff of viral
CC and cellular protein synthesis by directly interacting with
CC EIF2AK2/PKR. May also participate in viral DNA replication by
CC interacting with the DNA polymerase accessory protein and the lytic
CC origin of replication, oriLyt. {ECO:0000269|PubMed:16987971,
CC ECO:0000269|PubMed:19211736}.
CC -!- SUBUNIT: Interacts (via N-terminus) with the viral DNA polymerase
CC accessory subunit UL44. Interacts (via C-terminus) with host
CC EIF2AK2/PKR. {ECO:0000269|PubMed:16987971,
CC ECO:0000269|PubMed:20444996}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:8995674}. Host
CC cytoplasm {ECO:0000269|PubMed:8995674}. Host nucleus
CC {ECO:0000269|PubMed:8995674}. Note=Isoform IRS1-263 is predominantly
CC nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=IRS1;
CC IsoId=P09715-1; Sequence=Displayed;
CC Name=IRS1-263;
CC IsoId=P09715-2; Sequence=VSP_043923;
CC -!- SIMILARITY: Belongs to the herpesviridae US22 family. {ECO:0000305}.
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DR EMBL; X17403; CAA35311.1; -; Genomic_DNA.
DR EMBL; X04650; CAA28312.1; -; Genomic_DNA.
DR EMBL; BK000394; DAA00089.1; -; Genomic_DNA.
DR PIR; C26078; QQBEC3.
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:0039686; P:bidirectional double-stranded viral DNA replication; IDA:UniProtKB.
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 Alternative initiation; Early protein; Host cytoplasm; Host nucleus;
KW Host-virus interaction; 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; Transcription;
KW Viral immunoevasion; Virion.
FT CHAIN 1..846
FT /note="Protein IRS1"
FT /id="PRO_0000115262"
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 606..626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 714..846
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 606..621
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 733..750
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..766
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..583
FT /note="Missing (in isoform IRS1-263)"
FT /evidence="ECO:0000305"
FT /id="VSP_043923"
SQ SEQUENCE 846 AA; 91048 MW; 622B6CFE211674BD CRC64;
MAQRNGMSPR PPPLGRGRGA GGPSGVGSSP PSSCVPMGAP STAGTGASAA ATTTPGHGVH
RVEPRGPPGA PPSSGNNSNF WHGPERLLLS QIPVERQALT ELEYQAMGAV WRAAFLANST
GRAMRKWSQR DAGTLLPLGR PYGFYARVTP RSQMNGVGAT DLRQLSPRDA WIVLVATVVH
EVDPAADPTV 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
LWAREPHGQW EFMFREQRGD PINDPLAFRL SDARTLGLDL TTVMTERQSQ LPEKYIGFYQ
IRKPPWLMEQ PPPPSRQTKP DAATMPPPLS AQASVSYALR YDDESWRPLS TVDDHKAWLD
LDESHWVLGD SRPDDIKQRR LLKATQRRGA EIDRPMPVVP EECYDQRFTT EGHQVIPLCA
SEPEDDDEDP TYDELPSRPP QKHKPPDKPP RLCKTGPGPP PLPPKQRHGS TDGKVSAPRQ
SEHHKRQTRP PRPPPPKFGD RTAAHLSQNM RDMYLDMCTS SGHRPRPPAP PRPKKCQTHA
PHHVHH
