ICP47_HHV11
ID ICP47_HHV11 Reviewed; 88 AA.
AC P03170; Q99BW2; Q9E0N0; Q9E0N1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 23-FEB-2022, entry version 103.
DE RecName: Full=ICP47 protein;
DE AltName: Full=Immediate-early protein IE12;
DE AltName: Full=Immediate-early-5;
DE AltName: Full=Infected cell protein 47;
DE AltName: Full=US12 protein;
DE AltName: Full=Vmw12;
GN Name=US12;
OS Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6278443; DOI=10.1093/nar/10.3.979;
RA Watson R.J., Vande Woude G.F.;
RT "DNA sequence of an immediate-early gene (IEmRNA-5) of herpes simplex virus
RT type I.";
RL Nucleic Acids Res. 10:979-991(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6290591; DOI=10.1099/0022-1317-62-1-1;
RA Murchie M.-J., McGeoch D.J.;
RT "DNA sequence analysis of an immediate-early gene region of the herpes
RT simplex virus type 1 genome (map coordinates 0.950 to 0.978).";
RL J. Gen. Virol. 62:1-15(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6324121; DOI=10.1093/nar/12.5.2473;
RA Rixon F.J., McGeoch D.J.;
RT "A 3' co-terminal family of mRNAs from the herpes simplex virus type 1
RT short region: two overlapping reading frames encode unrelated polypeptide
RT one of which has highly reiterated amino acid sequence.";
RL Nucleic Acids Res. 12:2473-2487(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2984429; DOI=10.1016/0022-2836(85)90320-1;
RA McGeoch D.J., Dolan A., Donald S., Rixon F.J.;
RT "Sequence determination and genetic content of the short unique region in
RT the genome of herpes simplex virus type 1.";
RL J. Mol. Biol. 181:1-13(1985).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2846760; DOI=10.1099/0022-1317-69-11-2831;
RA Perry L.J., McGeoch D.J.;
RT "The DNA sequences of the long repeat region and adjoining parts of the
RT long unique region in the genome of herpes simplex virus type 1.";
RL J. Gen. Virol. 69:2831-2846(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-55.
RX PubMed=6272198; DOI=10.1093/nar/9.16.4189;
RA Watson R.J., Umene K., Enquist L.W.;
RT "Reiterated sequences within the intron of an immediate-early gene of
RT herpes simplex virus type 1.";
RL Nucleic Acids Res. 9:4189-4199(1981).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
RX PubMed=11117552;
RX DOI=10.1002/1531-8249(200012)48:6<936::aid-ana16>3.0.co;2-7;
RA Maertzdorf J., Van der Lelij A., Baarsma G.S., Osterhaus A.D.M.E.,
RA Verjans G.M.G.M.;
RT "Herpes simplex virus type 1 (HSV-1)-induced retinitis following herpes
RT simplex encephalitis: indications for brain-to-eye transmission of HSV-1.";
RL Ann. Neurol. 48:936-939(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
RC STRAIN=Isolates D, and R;
RX PubMed=11273067; DOI=10.1016/s0140-6736(00)04011-3;
RA Remeijer L., Maertzdorf J., Doornenbal P., Verjans G.M.G.M.,
RA Osterhaus A.D.M.E.;
RT "Herpes simplex virus type 1 transmission through corneal
RT transplantation.";
RL Lancet 357:442-442(2001).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8187174; DOI=10.1016/0092-8674(94)90215-1;
RA York I.A., Roop C., Andrews D.W., Riddell S.R., Graham F.L., Johnson D.C.;
RT "A cytosolic herpes simplex virus protein inhibits antigen presentation to
RT CD8+ T lymphocytes.";
RL Cell 77:525-535(1994).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST TAP1 AND TAP2.
RC STRAIN=Strain F;
RX PubMed=7760936; DOI=10.1038/375415a0;
RA Frueh K., Ahn K., Djaballah H., Sempe P., van Endert P.M., Tampe R.,
RA Peterson P.A., Yang Y.;
RT "A viral inhibitor of peptide transporters for antigen presentation.";
RL Nature 375:415-418(1995).
RN [11]
RP FUNCTION.
RC STRAIN=Strain F;
RX PubMed=8670825; DOI=10.1002/j.1460-2075.1996.tb00689.x;
RA Ahn K., Meyer T.H., Uebel S., Sempe P., Djaballah H., Yang Y.,
RA Peterson P.A., Frueh K., Tampe R.;
RT "Molecular mechanism and species specificity of TAP inhibition by herpes
RT simplex virus ICP47.";
RL EMBO J. 15:3247-3255(1996).
RN [12]
RP ACTIVE DOMAIN, AND MUTAGENESIS.
RC STRAIN=Strain F;
RX PubMed=9325106; DOI=10.1006/jmbi.1997.1282;
RA Neumann L., Kraas W., Uebel S., Jung G., Tampe R.;
RT "The active domain of the herpes simplex virus protein ICP47: a potent
RT inhibitor of the transporter associated with antigen processing (TAP).";
RL J. Mol. Biol. 272:484-492(1997).
RN [13]
RP FUNCTION.
RC STRAIN=Strain F;
RX PubMed=11254939; DOI=10.1016/s0165-0378(00)00088-7;
RA Easterfield A.J., Austen B.M., Westwood O.M.R.;
RT "Inhibition of antigen transport by expression of infected cell peptide 47
RT (ICP47) prevents cell surface expression of HLA in choriocarcinoma cell
RT lines.";
RL J. Reprod. Immunol. 50:19-40(2001).
RN [14]
RP STRUCTURE BY NMR OF 2-34.
RX PubMed=10521276; DOI=10.1021/bi9909647;
RA Pfaender R., Neumann L., Zweckstetter M., Seger C., Holak T.A., Tampe R.;
RT "Structure of the active domain of the herpes simplex virus protein ICP47
RT in water/sodium dodecyl sulfate solution determined by nuclear magnetic
RT resonance spectroscopy.";
RL Biochemistry 38:13692-13698(1999).
CC -!- FUNCTION: Plays a role in the inhibition of host immune response. Binds
CC specifically to transporters associated with antigen processing (TAP),
CC thereby blocking peptide-binding and translocation by TAP as well as
CC subsequent loading of peptides onto MHC class I molecules. Empty MHC I
CC molecules are retained in the endoplasmic reticulum and ultimately
CC directed to proteasomal degradation. In consequence, infected cells are
CC masked for immune recognition by cytotoxic T-lymphocytes.
CC {ECO:0000269|PubMed:11254939, ECO:0000269|PubMed:7760936,
CC ECO:0000269|PubMed:8187174, ECO:0000269|PubMed:8670825}.
CC -!- SUBUNIT: Interacts with host TAP1 and TAP2; these interactions inhibit
CC the loading of peptides onto MHC class I molecules.
CC {ECO:0000269|PubMed:7760936}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:8187174}. Host
CC nucleus {ECO:0000269|PubMed:8187174}.
CC -!- DOMAIN: The N-terminal active domain blocks peptide binding to and
CC peptide transport by TAP. {ECO:0000250|UniProtKB:P14345}.
CC -!- SIMILARITY: Belongs to the herpesviridae US12 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; J02220; AAA45795.1; -; Genomic_DNA.
DR EMBL; L00036; AAA96676.1; -; Genomic_DNA.
DR EMBL; X00428; CAA25124.1; -; Genomic_RNA.
DR EMBL; X02138; CAA26066.1; -; Genomic_DNA.
DR EMBL; X14112; CAA32277.1; -; Genomic_DNA.
DR EMBL; V00462; CAA23737.1; -; Genomic_DNA.
DR EMBL; AF290017; AAG33133.1; -; Genomic_DNA.
DR EMBL; AF290018; AAG33134.1; -; Genomic_DNA.
DR EMBL; AF324428; AAK12110.1; -; Genomic_DNA.
DR PIR; A93454; EDBE51.
DR RefSeq; YP_009137148.1; NC_001806.2.
DR PDB; 1QLO; NMR; -; A=1-34.
DR PDBsum; 1QLO; -.
DR BMRB; P03170; -.
DR SMR; P03170; -.
DR DIP; DIP-61932N; -.
DR IntAct; P03170; 2.
DR TCDB; 8.A.72.1.1; the immune evasion protein, icp47 (icp47) family.
DR PRIDE; P03170; -.
DR DNASU; 2703441; -.
DR GeneID; 2703441; -.
DR KEGG; vg:2703441; -.
DR EvolutionaryTrace; P03170; -.
DR Proteomes; UP000009294; 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:0039588; P:suppression by virus of host antigen processing and presentation; IEA:UniProtKB-KW.
DR InterPro; IPR008026; Herpes_ICP47.
DR Pfam; PF05363; Herpes_US12; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Early protein; Host cytoplasm; Host nucleus;
KW Host-virus interaction;
KW Inhibition of host adaptive immune response by virus;
KW Inhibition of host TAP by virus; Reference proteome; Viral immunoevasion.
FT CHAIN 1..88
FT /note="ICP47 protein"
FT /id="PRO_0000115810"
FT REGION 2..35
FT /note="Active domain"
FT /evidence="ECO:0000250|UniProtKB:P14345"
FT REGION 33..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..48
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 22
FT /note="Binding to TAP1 subunit"
FT /evidence="ECO:0000250|UniProtKB:P14345"
FT MUTAGEN 24
FT /note="D->G: Reduced ability to inhibit peptide-binding to
FT TAP."
FT /evidence="ECO:0000269|PubMed:9325106"
FT MUTAGEN 31
FT /note="K->G: Reduced ability to inhibit peptide-binding to
FT TAP."
FT /evidence="ECO:0000269|PubMed:9325106"
FT MUTAGEN 32
FT /note="R->G: Reduced ability to inhibit peptide-binding to
FT TAP."
FT /evidence="ECO:0000269|PubMed:9325106"
FT CONFLICT 14
FT /note="T -> N (in Ref. 1 and 7)"
FT /evidence="ECO:0000305"
FT HELIX 5..13
FT /evidence="ECO:0007829|PDB:1QLO"
FT STRAND 16..18
FT /evidence="ECO:0007829|PDB:1QLO"
FT HELIX 22..31
FT /evidence="ECO:0007829|PDB:1QLO"
SQ SEQUENCE 88 AA; 9793 MW; C5D2EA8C35006612 CRC64;
MSWALEMADT FLDTMRVGPR TYADVRDEIN KRGREDREAA RTAVHDPERP LLRSPGLLPE
IAPNASLGVA HRRTGGTVTD SPRNPVTR
