ID   GP42_EBVB9              Reviewed;         223 AA.
AC   P03205; Q777E6;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   24-JAN-2024, entry version 120.
DE   RecName: Full=Glycoprotein 42;
DE            Short=gp42;
DE   Contains:
DE     RecName: Full=Soluble gp42;
GN   ORFNames=BZLF2;
OS   Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4).
OC   Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC   Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Lymphocryptovirus;
OC   Lymphocryptovirus humangamma4; Epstein-Barr virus (strain GD1).
OX   NCBI_TaxID=10377;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=6087149; DOI=10.1038/310207a0;
RA   Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J.,
RA   Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C.,
RA   Tuffnell P.S., Barrell B.G.;
RT   "DNA sequence and expression of the B95-8 Epstein-Barr virus genome.";
RL   Nature 310:207-211(1984).
RN   [2]
RP   GENOME REANNOTATION.
RX   PubMed=12771413; DOI=10.1099/vir.0.19054-0;
RA   de Jesus O., Smith P.R., Spender L.C., Elgueta Karstegl C., Niller H.H.,
RA   Huang D., Farrell P.J.;
RT   "Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter
RT   for the BART (CST, BARF0) RNAs of EBV.";
RL   Virology 84:1443-1450(2003).
RN   [3]
RP   INTERACTION WITH GP25 AND GP85.
RX   PubMed=9621012; DOI=10.1128/jvi.72.7.5552-5558.1998;
RA   Wang X., Kenyon W.J., Li Q., Mullberg J., Hutt-Fletcher L.M.;
RT   "Epstein-Barr virus uses different complexes of glycoproteins gH and gL to
RT   infect B lymphocytes and epithelial cells.";
RL   J. Virol. 72:5552-5558(1998).
RN   [4]
RP   INTERACTION WITH HUMAN HLA-DRA, AND FUNCTION.
RX   PubMed=9151859; DOI=10.1128/jvi.71.6.4657-4662.1997;
RA   Li Q., Spriggs M.K., Kovats S., Turk S.M., Comeau M.R., Nepom B.,
RA   Hutt-Fletcher L.M.;
RT   "Epstein-Barr virus uses HLA class II as a cofactor for infection of B
RT   lymphocytes.";
RL   J. Virol. 71:4657-4662(1997).
RN   [5]
RP   FUNCTION.
RX   PubMed=12042810; DOI=10.1038/nm0602-594;
RA   Borza C.M., Hutt-Fletcher L.M.;
RT   "Alternate replication in B cells and epithelial cells switches tropism of
RT   Epstein-Barr virus.";
RL   Nat. Med. 8:594-599(2002).
RN   [6]
RP   MUTAGENESIS OF TYR-107; TRP-125; GLU-160; PHE-210 AND ARG-220.
RX   PubMed=15140992; DOI=10.1128/jvi.78.11.5946-5956.2004;
RA   Silva A.L., Omerovic J., Jardetzky T.S., Longnecker R.;
RT   "Mutational analyses of Epstein-Barr virus glycoprotein 42 reveal
RT   functional domains not involved in receptor binding but required for
RT   membrane fusion.";
RL   J. Virol. 78:5946-5956(2004).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15534216; DOI=10.1073/pnas.0407320101;
RA   Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E.,
RA   Illanes D., Sarracino D., Kieff E.;
RT   "Proteins of purified Epstein-Barr virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004).
RN   [8]
RP   FUNCTION, AND SOLUBLE FORM.
RX   PubMed=15613312; DOI=10.1128/jvi.79.2.841-852.2005;
RA   Ressing M.E., van Leeuwen D., Verreck F.A., Keating S., Gomez R.,
RA   Franken K.L., Ottenhoff T.H., Spriggs M., Schumacher T.N.,
RA   Hutt-Fletcher L.M., Rowe M., Wiertz E.J.;
RT   "Epstein-Barr virus gp42 is posttranslationally modified to produce soluble
RT   gp42 that mediates HLA class II immune evasion.";
RL   J. Virol. 79:841-852(2005).
RN   [9]
RP   INTERACTION WITH GP25 AND GP85.
RX   PubMed=17581996; DOI=10.1128/jvi.00575-07;
RA   Kirschner A.N., Lowrey A.S., Longnecker R., Jardetzky T.S.;
RT   "Binding-site interactions between Epstein-Barr virus fusion proteins gp42
RT   and gH/gL reveal a peptide that inhibits both epithelial and B-cell
RT   membrane fusion.";
RL   J. Virol. 81:9216-9229(2007).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 86-221, AND INTERACTION WITH
RP   HUMAN HLA-DRA AND HLA-DRB1.
RX   PubMed=11864610; DOI=10.1016/s1097-2765(02)00465-3;
RA   Mullen M.M., Haan K.M., Longnecker R., Jardetzky T.S.;
RT   "Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II
RT   receptor HLA-DR1.";
RL   Mol. Cell 9:375-385(2002).
CC   -!- FUNCTION: Plays a role in virion attachment to host B-lymphocytes,
CC       through binding to leukocyte antigen (HLA) class II and subsequently
CC       participates in fusion of the virion with host membranes. May act as a
CC       tropism switch that directs fusion with B-lymphocytes and inhibits
CC       fusion with epithelial cells. Additionally, hampers T-cell recognition
CC       via HLA class II molecules through steric hindrance of T-cell receptor-
CC       class II-peptide interaction. {ECO:0000269|PubMed:12042810,
CC       ECO:0000269|PubMed:15613312, ECO:0000269|PubMed:9151859}.
CC   -!- FUNCTION: Soluble gp42 inhibits HLA class II-restricted antigen
CC       presentation to T-cells through binding to immature and mature HLA
CC       class II complexes. {ECO:0000269|PubMed:15613312}.
CC   -!- SUBUNIT: Forms a complex with gp25 and gp85 via its N-terminus; this
CC       complex is used for invasion of B-lymphocytes. Interacts with human
CC       HLA-DRA and HLA-DRB1. {ECO:0000269|PubMed:11864610,
CC       ECO:0000269|PubMed:17581996, ECO:0000269|PubMed:9151859,
CC       ECO:0000269|PubMed:9621012}.
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000269|PubMed:15534216}.
CC       Host membrane {ECO:0000305}; Single-pass membrane protein
CC       {ECO:0000255}. Note=virions synthesized in B-lymphocytes contain a
CC       lower amount of gp42 due to sequestration by cellular HLA class II
CC       protein, whereas virions made from epithelial cells has a higher amount
CC       of gp42. {ECO:0000305}.
CC   -!- DOMAIN: The C-lectin type domain is essential for virion-induced
CC       membrane fusion.
CC   -!- SIMILARITY: Belongs to the epstein barr virus gp42 family.
CC       {ECO:0000305}.
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DR   EMBL; V01555; CAA24860.1; -; Genomic_DNA.
DR   EMBL; AJ507799; CAD53422.1; -; Genomic_DNA.
DR   PIR; F43042; QQBE26.
DR   RefSeq; YP_401672.1; NC_007605.1.
DR   PDB; 1KG0; X-ray; 2.65 A; C=86-221.
DR   PDB; 3FD4; X-ray; 2.40 A; A/B=33-223.
DR   PDB; 5W0K; X-ray; 3.10 A; X/Y=47-81.
DR   PDBsum; 1KG0; -.
DR   PDBsum; 3FD4; -.
DR   PDBsum; 5W0K; -.
DR   SMR; P03205; -.
DR   BioGRID; 971787; 1.
DR   IntAct; P03205; 1.
DR   MINT; P03205; -.
DR   TCDB; 1.G.21.1.1; the epstein barr virus (human herpes virus 4) gp42 (gp42) family.
DR   DNASU; 3783745; -.
DR   GeneID; 3783745; -.
DR   KEGG; vg:3783745; -.
DR   SIGNOR; P03205; -.
DR   EvolutionaryTrace; P03205; -.
DR   Proteomes; UP000153037; Segment.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR   Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 1.
DR   InterPro; IPR016186; C-type_lectin-like/link_sf.
DR   InterPro; IPR016187; CTDL_fold.
DR   SUPFAM; SSF56436; C-type lectin-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Host membrane; Host-virus interaction;
KW   Lectin; Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW   Virion.
FT   CHAIN           1..223
FT                   /note="Glycoprotein 42"
FT                   /id="PRO_0000116279"
FT   CHAIN           34..223
FT                   /note="Soluble gp42"
FT                   /id="PRO_0000433226"
FT   TOPO_DOM        1..8
FT                   /note="Intravirion"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        9..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        30..223
FT                   /note="Virion surface"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          111..217
FT                   /note="C-type lectin"
FT   SITE            33..34
FT                   /note="Potential cleavage"
FT                   /evidence="ECO:0000305"
FT   DISULFID        99..138
FT   DISULFID        102..115
FT   DISULFID        128..214
FT   DISULFID        132..216
FT   DISULFID        192..208
FT   MUTAGEN         107
FT                   /note="Y->A: Loss of HLA class II binding and fusion
FT                   competence."
FT                   /evidence="ECO:0000269|PubMed:15140992"
FT   MUTAGEN         125
FT                   /note="W->G: Loss of HLA class II binding and fusion
FT                   competence."
FT                   /evidence="ECO:0000269|PubMed:15140992"
FT   MUTAGEN         160
FT                   /note="E->A: Loss of HLA class II binding and fusion
FT                   competence."
FT                   /evidence="ECO:0000269|PubMed:15140992"
FT   MUTAGEN         210
FT                   /note="F->A: Binds to HLA class II but unable to mediate
FT                   fusion."
FT                   /evidence="ECO:0000269|PubMed:15140992"
FT   MUTAGEN         220
FT                   /note="R->A: Loss of HLA class II binding and fusion
FT                   competence."
FT                   /evidence="ECO:0000269|PubMed:15140992"
FT   TURN            66..70
FT                   /evidence="ECO:0007829|PDB:5W0K"
FT   TURN            104..106
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          108..111
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          114..118
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   HELIX           127..135
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          139..141
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   TURN            146..148
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   HELIX           149..153
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          161..164
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          174..176
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          179..182
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          187..191
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          193..198
FT                   /evidence="ECO:0007829|PDB:3FD4"
FT   STRAND          214..219
FT                   /evidence="ECO:0007829|PDB:3FD4"
SQ   SEQUENCE   223 AA;  25257 MW;  F87541F6CEC26D74 CRC64;
     MVSFKQVRVP LFTAIALVIV LLLAYFLPPR VRGGGRVAAA AITWVPKPNV EVWPVDPPPP
     VNFNKTAEQE YGDKEVKLPH WTPTLHTFQV PQNYTKANCT YCNTREYTFS YKGCCFYFTK
     KKHTWNGCFQ ACAELYPCTY FYGPTPDILP VVTRNLNAIE SLWVGVYRVG EGNWTSLDGG
     TFKVYQIFGS HCTYVSKFST VPVSHHECSF LKPCLCVSQR SNS
//