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 24-JAN-2024, entry version 107. 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; Orthoherpesviridae; Alphaherpesvirinae; Simplexvirus; OC Simplexvirus humanalpha1; Human herpesvirus 1. 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>3.3.co;2-z; 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 DNASU; 2703441; -. DR GeneID; 2703441; -. DR KEGG; vg:2703441; -. DR EvolutionaryTrace; P03170; -. DR Proteomes; UP000009294; Genome. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IC:UniProt. 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:0140313; F:molecular sequestering activity; IDA:UniProt. DR GO; GO:0046776; P:suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I; IDA:UniProt. 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 //