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Protein IRS1 (HQRF1)

 IRS1_HCMVA              Reviewed;         846 AA.
P09715; Q7M6U2;
01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
01-JUL-1989, sequence version 1.
22-APR-2020, entry version 75.
RecName: Full=Protein IRS1;
AltName: Full=HQRF1;
Name=IRS1;
Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5).
Viruses; Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
NCBI_TaxID=10360;
NCBI_TaxID=9606; Homo sapiens (Human).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=3031311; DOI=10.1016/0022-2836(86)90359-1;
Weston K.M., Barrell B.G.;
"Sequence of the short unique region, short repeats, and part of the long
repeats of human cytomegalovirus.";
J. Mol. Biol. 192:177-208(1986).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=2161319; DOI=10.1007/978-3-642-74980-3_6;
Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R.,
Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A.,
Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.;
"Analysis of the protein-coding content of the sequence of human
cytomegalovirus strain AD169.";
Curr. Top. Microbiol. Immunol. 154:125-169(1990).
[3]
GENOME REANNOTATION.
PubMed=12533697; DOI=10.1099/vir.0.18606-0;
Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
McGeoch D.J., Hayward G.S.;
"The human cytomegalovirus genome revisited: comparison with the chimpanzee
cytomegalovirus genome.";
J. Gen. Virol. 84:17-28(2003).
[4]
ISOFORM IRS1-263, AND SUBCELLULAR LOCATION.
PubMed=8995674;
Romanowski M.J., Shenk T.;
"Characterization of the human cytomegalovirus irs1 and trs1 genes: a
second immediate-early transcription unit within irs1 whose product
antagonizes transcriptional activation.";
J. Virol. 71:1485-1496(1997).
[5]
ERRATUM OF PUBMED:8995674.
Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J.,
McGeoch D.J., Hayward G.S.;
J. Gen. Virol. 84:1053-1053(2003).
[6]
IDENTIFICATION.
PubMed=15452216; DOI=10.1128/jvi.78.20.10960-10966.2004;
Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
Shenk T., Smith R.D., Nelson J.A.;
"Identification of proteins in human cytomegalovirus (HCMV) particles: the
HCMV proteome.";
J. Virol. 78:10960-10966(2004).
[7]
ERRATUM OF PUBMED:15452216.
Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J.,
Pasa-Tolic L., Wang D., Camp D.G. II, Rodland K., Wiley S., Britt W.,
Shenk T., Smith R.D., Nelson J.A.;
J. Virol. 78:13395-13395(2004).
[8]
FUNCTION, AND INTERACTION WITH HOST EIF2AK2.
PubMed=16987971; DOI=10.1128/jvi.00957-06;
Hakki M., Marshall E.E., De Niro K.L., Geballe A.P.;
"Binding and nuclear relocalization of protein kinase R by human
cytomegalovirus TRS1.";
J. Virol. 80:11817-11826(2006).
[9]
FUNCTION.
PubMed=19211736; DOI=10.1128/jvi.02489-08;
Marshall E.E., Bierle C.J., Brune W., Geballe A.P.;
"Essential role for either TRS1 or IRS1 in human cytomegalovirus
replication.";
J. Virol. 83:4112-4120(2009).
[10]
INTERACTION WITH UL44.
PubMed=20444996; DOI=10.1099/vir.0.022640-0;
Strang B.L., Geballe A.P., Coen D.M.;
"Association of human cytomegalovirus proteins IRS1 and TRS1 with the viral
DNA polymerase accessory subunit UL44.";
J. Gen. Virol. 91:2167-2175(2010).
-!- FUNCTION: Inhibits the establishment of the antiviral state in the
infected cell. Prevents the phosphorylation of the host eukaryotic
translation initiation factor eIF-2alpha and thus the shutoff of viral
and cellular protein synthesis by directly interacting with
EIF2AK2/PKR. May also participate in viral DNA replication by
interacting with the DNA polymerase accessory protein and the lytic
origin of replication, oriLyt. {ECO:0000269|PubMed:16987971,
ECO:0000269|PubMed:19211736}.
-!- SUBUNIT: Interacts (via N-terminus) with the viral DNA polymerase
accessory subunit UL44. Interacts (via C-terminus) with host
EIF2AK2/PKR. {ECO:0000269|PubMed:16987971,
ECO:0000269|PubMed:20444996}.
-!- SUBCELLULAR LOCATION: Virion {ECO:0000269|PubMed:8995674}. Host
cytoplasm {ECO:0000269|PubMed:8995674}. Host nucleus
{ECO:0000269|PubMed:8995674}. Note=Isoform IRS1-263 is predominantly
nuclear.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative initiation; Named isoforms=2;
Name=IRS1;
IsoId=P09715-1; Sequence=Displayed;
Name=IRS1-263;
IsoId=P09715-2; Sequence=VSP_043923;
-!- SIMILARITY: Belongs to the herpesviridae US22 family. {ECO:0000305}.
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EMBL; X17403; CAA35311.1; -; Genomic_DNA.
EMBL; X04650; CAA28312.1; -; Genomic_DNA.
EMBL; BK000394; DAA00089.1; -; Genomic_DNA.
PIR; C26078; QQBEC3.
PRIDE; P09715; -.
Proteomes; UP000008991; Genome.
Proteomes; UP000008992; Genome.
GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
GO; GO:0019012; C:virion; IEA:UniProtKB-SubCell.
GO; GO:0039686; P:bidirectional double-stranded viral DNA replication; IDA:UniProtKB.
GO; GO:0039580; P:suppression by virus of host PKR activity; IEA:UniProtKB-KW.
GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
InterPro; IPR003360; US22-like.
Pfam; PF02393; US22; 2.
1: Evidence at protein level;
Alternative initiation; Early protein; Host cytoplasm; Host nucleus;
Host-virus interaction; Inhibition of host innate immune response by virus;
Inhibition of host interferon signaling pathway by virus;
Inhibition of host PKR by virus; Reference proteome; Transcription;
Viral immunoevasion; Virion.
CHAIN 1..846
/note="Protein IRS1"
/id="PRO_0000115262"
COMPBIAS 430..437
/note="Poly-Ala"
COMPBIAS 611..614
/note="Poly-Pro"
COMPBIAS 790..796
/note="Poly-Pro"
COMPBIAS 839..846
/note="His-rich"
VAR_SEQ 1..583
/note="Missing (in isoform IRS1-263)"
/evidence="ECO:0000305"
/id="VSP_043923"
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


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Catalog number Product name Quantity
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Pathways :
WP10: IL-9 Signaling Pathway
WP1654: gamma-Hexachlorocyclohexane degradation
WP2261: Signaling Pathways in Glioblastoma
WP781: IL-7 Signaling Pathway
WP1249: EPO Receptor Signaling
WP1694: Pyrimidine metabolism
WP488: Alpha6-Beta4 Integrin Signaling Pathway
WP966: Insulin Signaling
WP1438: Influenza A virus infection
WP1714: Tyrosine metabolism
WP569: IL-2 Signaling Pathway
WP985: Alpha6-Beta4 Integrin Signaling Pathway
WP1052: Id Signaling Pathway
WP1661: Glyoxylate and dicarboxylate metabolism
WP232: G Protein Signaling Pathways
WP815: Id Signaling Pathway
WP1672: Mismatch repair
WP2371: Parkinsons Disease Pathway
WP855: IL-2 Signaling Pathway
WP1502: Mitochondrial biogenesis
WP1892: Protein folding
WP65: Insulin Signaling
WP1091: IL-2 Signaling Pathway
WP1984: Integrated Breast Cancer Pathway
WP731: Sterol regulatory element binding protein related

Related Genes :
[IRS1] Protein IRS1 (HQRF1)
[Irs1 Irs-1] Insulin receptor substrate 1 (IRS-1) (pp185)
[Irs1 Irs-1] Insulin receptor substrate 1 (IRS-1)
[IRS1] Insulin receptor substrate 1 (IRS-1)
[KRT71 K6IRS1 KB34 KRT6IRS1] Keratin, type II cytoskeletal 71 (Cytokeratin-71) (CK-71) (Keratin-71) (K71) (Type II inner root sheath-specific keratin-K6irs1) (Keratin 6 irs) (hK6irs) (hK6irs1) (Type-II keratin Kb34)
[Krt71 K6irs1 Kb34 Krt2-6g Krt6g] Keratin, type II cytoskeletal 71 (Cytokeratin-6G) (CK-6G) (Cytokeratin-71) (CK-71) (Keratin-6G) (K6G) (Keratin-71) (K71) (Type II inner root sheath-specific keratin-K6irs1) (mK6irs) (mK6irs1/Krt2-6g) (Type-II keratin Kb34)
[irs1-a] Insulin receptor substrate 1-A (IRS1-A) (xIRS-1-A) (XIRS-L)
[IRS1] Insulin receptor substrate 1 (IRS-1)
[irs1] Insulin receptor substrate 1 (IRS-1)
[irs1-b] Insulin receptor substrate 1-B (IRS1-B) (xIRS-1-B) (XIRS-L')
[Sh2b1 Sh2bpsm1] SH2B adapter protein 1 (Pro-rich, PH and SH2 domain-containing signaling mediator) (PSM) (SH2 domain-containing protein 1B) (SH2-B PH domain-containing signaling mediator 1)
[INSR] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[SOCS7 NAP4 SOCS6] Suppressor of cytokine signaling 7 (SOCS-7) (Nck, Ash and phospholipase C gamma-binding protein) (Nck-associated protein 4) (NAP-4)
[EIF2AK2 PKR PRKR] Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase)
[Sh2b1 Sh2-b Sh2bpsm1] SH2B adapter protein 1 (FceRI gamma-chain-interacting protein SH2-B) (SH2 domain-containing protein 1B) (SH2-B PH domain-containing signaling mediator 1)
[Eif2ak2 Pkr Prkr Tik] Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Serine/threonine-protein kinase TIK) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase)
[SH2B1 KIAA1299 SH2B] SH2B adapter protein 1 (Pro-rich, PH and SH2 domain-containing signaling mediator) (PSM) (SH2 domain-containing protein 1B)
[IL4R IL4RA 582J2.1] Interleukin-4 receptor subunit alpha (IL-4 receptor subunit alpha) (IL-4R subunit alpha) (IL-4R-alpha) (IL-4RA) (CD antigen CD124) [Cleaved into: Soluble interleukin-4 receptor subunit alpha (Soluble IL-4 receptor subunit alpha) (Soluble IL-4R-alpha) (sIL4Ralpha/prot) (IL-4-binding protein) (IL4-BP)]
[GRB2 ASH] Growth factor receptor-bound protein 2 (Adapter protein GRB2) (Protein Ash) (SH2/SH3 adapter GRB2)
[Prkaa1 Ampk1] 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (EC 2.7.11.27) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26)
[PRKCQ PRKCT] Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)
[FBXW8 FBW6 FBW8 FBX29 FBXO29 FBXW6] F-box/WD repeat-containing protein 8 (F-box and WD-40 domain-containing protein 8) (F-box only protein 29)
[PIK3R1 GRB1] Phosphatidylinositol 3-kinase regulatory subunit alpha (PI3-kinase regulatory subunit alpha) (PI3K regulatory subunit alpha) (PtdIns-3-kinase regulatory subunit alpha) (Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha) (PI3-kinase subunit p85-alpha) (PtdIns-3-kinase regulatory subunit p85-alpha)
[Insr] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[Prkaa2 Ampk Ampk2] 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK subunit alpha-2) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (EC 2.7.11.27) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31)
[IGF1R] Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain]
[Insr] Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta]
[Eif2ak2 Prkr] Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2)
[PTPN11 PTP2C SHPTP2] Tyrosine-protein phosphatase non-receptor type 11 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1D) (PTP-1D) (Protein-tyrosine phosphatase 2C) (PTP-2C) (SH-PTP2) (SHP-2) (Shp2) (SH-PTP3)
[PIK3CA] Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PI3-kinase subunit alpha) (PI3K-alpha) (PI3Kalpha) (PtdIns-3-kinase subunit alpha) (EC 2.7.1.153) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha) (PtdIns-3-kinase subunit p110-alpha) (p110alpha) (Phosphoinositide-3-kinase catalytic alpha polypeptide) (Serine/threonine protein kinase PIK3CA) (EC 2.7.11.1)

Bibliography :