GP42_EBVB9
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 23-FEB-2022, entry version 114.
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; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
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 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 [3]
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 [4]
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
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 PRIDE; P03205; -.
DR DNASU; 3783745; -.
DR GeneID; 3783745; -.
DR KEGG; vg:3783745; -.
DR SIGNOR; P03205; -.
DR EvolutionaryTrace; P03205; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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; -; 1.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
DR SUPFAM; SSF56436; SSF56436; 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
