GH_EBVB9
ID GH_EBVB9 Reviewed; 706 AA.
AC P03231; Q6LBU6; Q777C0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 113.
DE RecName: Full=Envelope glycoprotein H {ECO:0000255|HAMAP-Rule:MF_04033};
DE Short=gH {ECO:0000255|HAMAP-Rule:MF_04033};
DE Flags: Precursor;
GN Name=gH {ECO:0000255|HAMAP-Rule:MF_04033}; ORFNames=BXLF2;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-116.
RX PubMed=6092825;
RA Bankier A.T., Deininger P.L., Farrell P.J., Barrell B.G.;
RT "Sequence analysis of the 17,166 base-pair EcoRI fragment C of B95-8
RT Epstein-Barr virus.";
RL Mol. Biol. Med. 1:21-45(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 338-389.
RX PubMed=2835748; DOI=10.1093/nar/16.7.2859;
RA Walls D., Perricaudet M., Gannon F.;
RT "The analysis of EBV proteins which are antigenic in vivo.";
RL Nucleic Acids Res. 16:2859-2872(1988).
RN [4]
RP CHARACTERIZATION.
RX PubMed=2831372; DOI=10.1128/jvi.62.4.1101-1107.1988;
RA Heineman T., Gong M., Sample J., Kieff E.;
RT "Identification of the Epstein-Barr virus gp85 gene.";
RL J. Virol. 62:1101-1107(1988).
RN [5]
RP INTERACTION WITH GP25 AND GP42.
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 [6]
RP FUNCTION.
RX PubMed=11021994; DOI=10.1006/viro.2000.0531;
RA Oda T., Imai S., Chiba S., Takada K.;
RT "Epstein-Barr virus lacking glycoprotein gp85 cannot infect B cells and
RT epithelial cells.";
RL Virology 276:52-58(2000).
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 INTERACTION WITH HOST EPHA2.
RX PubMed=29292383; DOI=10.1038/s41564-017-0080-8;
RA Zhang H., Li Y., Wang H.B., Zhang A., Chen M.L., Fang Z.X., Dong X.D.,
RA Li S.B., Du Y., Xiong D., He J.Y., Li M.Z., Liu Y.M., Zhou A.J., Zhong Q.,
RA Zeng Y.X., Kieff E., Zhang Z., Gewurz B.E., Zhao B., Zeng M.S.;
RT "Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus
RT entry.";
RL Nat. Microbiol. 3:1-8(2018).
RN [9]
RP FUNCTION, AND INTERACTION WITH HOST EPHA2.
RX PubMed=29292384; DOI=10.1038/s41564-017-0081-7;
RA Chen J., Sathiyamoorthy K., Zhang X., Schaller S., Perez White B.E.,
RA Jardetzky T.S., Longnecker R.;
RT "Ephrin receptor A2 is a functional entry receptor for Epstein-Barr
RT virus.";
RL Nat. Microbiol. 3:172-180(2018).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.58 ANGSTROMS) OF 20-672, DISULFIDE BOND, AND
RP GLYCOSYLATION AT ASN-60; ASN-435; ASN-549; ASN-604 AND ASN-664.
RX PubMed=21149717; DOI=10.1073/pnas.1011806108;
RA Matsuura H., Kirschner A.N., Longnecker R., Jardetzky T.S.;
RT "Crystal structure of the Epstein-Barr virus (EBV) glycoprotein
RT H/glycoprotein L (gH/gL) complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:22641-22646(2010).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 20-674, GLYCOSYLATION AT ASN-60,
RP AND INTERACTION WITH GLYCOPROTEIN 42/BZLF2.
RX PubMed=27929061; DOI=10.1038/ncomms13557;
RA Sathiyamoorthy K., Hu Y.X., Moehl B.S., Chen J., Longnecker R.,
RA Jardetzky T.S.;
RT "Structural basis for Epstein-Barr virus host cell tropism mediated by gp42
RT and gHgL entry glycoproteins.";
RL Nat. Commun. 7:13557-13557(2016).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 20-679.
RX PubMed=28939750; DOI=10.1073/pnas.1704661114;
RA Sathiyamoorthy K., Jiang J., Moehl B.S., Chen J., Zhou Z.H., Longnecker R.,
RA Jardetzky T.S.;
RT "Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:703-710(2017).
CC -!- FUNCTION: The heterodimer glycoprotein H-glycoprotein L is required for
CC the fusion of viral and plasma membranes leading to virus entry into
CC the host cell. Following initial binding to host receptor, membrane
CC fusion is mediated by the fusion machinery composed of gB and the
CC heterodimer gH/gL. May also be involved in the fusion between the
CC virion envelope and the outer nuclear membrane during virion
CC morphogenesis. The heterodimer gH/gL targets also host EPHA2 to promote
CC viral entry. {ECO:0000255|HAMAP-Rule:MF_04033,
CC ECO:0000269|PubMed:11021994, ECO:0000269|PubMed:29292383,
CC ECO:0000269|PubMed:29292384}.
CC -!- SUBUNIT: Interacts with glycoprotein L (gL); this interaction is
CC necessary for the correct processing and cell surface expression of gH.
CC The heterodimer gH/gL seems to interact with gB trimers during fusion.
CC The heterodimer gH/gL interacts with host EPHA2 to facilitate virus
CC internalization and fusion (PubMed:29292384). Interacts with
CC glycoprotein 42/BZLF2 (PubMed:27929061). {ECO:0000255|HAMAP-
CC Rule:MF_04033, ECO:0000269|PubMed:27929061,
CC ECO:0000269|PubMed:29292384}.
CC -!- INTERACTION:
CC P03231; P03212: gL; NbExp=3; IntAct=EBI-15815779, EBI-15897767;
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04033}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04033}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04033};
CC Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04033}.
CC Host endosome membrane {ECO:0000255|HAMAP-Rule:MF_04033}; Single-pass
CC type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04033}. Note=During
CC virion morphogenesis, this protein probably accumulates in the
CC endosomes and trans-Golgi where secondary envelopment occurs. It is
CC probably transported to the cell surface from where it is endocytosed
CC and directed to the trans-Golgi network (TGN). {ECO:0000255|HAMAP-
CC Rule:MF_04033}.
CC -!- PTM: N-glycosylated, O-glycosylated, and sialylated.
CC {ECO:0000255|HAMAP-Rule:MF_04033}.
CC -!- SIMILARITY: Belongs to the herpesviridae glycoprotein H family.
CC {ECO:0000255|HAMAP-Rule:MF_04033}.
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DR EMBL; V01555; CAA24797.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53450.1; -; Genomic_DNA.
DR EMBL; X07532; CAE82041.1; -; Genomic_DNA.
DR PIR; A93065; QQBE6L.
DR PIR; S00736; S00736.
DR RefSeq; YP_401700.1; NC_007605.1.
DR PDB; 3PHF; X-ray; 3.58 A; 1/3/5/A/C/E/G/I/K/M/O/Q/S/U/W/Y=20-672.
DR PDB; 5T1D; X-ray; 3.10 A; A=20-674.
DR PDB; 5W0K; X-ray; 3.10 A; A/C=20-679.
DR PDB; 7CZE; X-ray; 3.00 A; A/C/E/G=18-674.
DR PDBsum; 3PHF; -.
DR PDBsum; 5T1D; -.
DR PDBsum; 5W0K; -.
DR PDBsum; 7CZE; -.
DR SMR; P03231; -.
DR DIP; DIP-49016N; -.
DR IntAct; P03231; 2.
DR iPTMnet; P03231; -.
DR PRIDE; P03231; -.
DR ABCD; P03231; 3 sequenced antibodies.
DR DNASU; 3783742; -.
DR GeneID; 3783742; -.
DR KEGG; vg:3783742; -.
DR SIGNOR; P03231; -.
DR EvolutionaryTrace; P03231; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.3190; -; 1.
DR HAMAP; MF_04033; HSV_GH; 1.
DR InterPro; IPR003493; Herpes_gH.
DR InterPro; IPR035305; Herpes_glycoH_C.
DR InterPro; IPR038172; Herpes_glycoH_C_sf.
DR Pfam; PF17488; Herpes_glycoH_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond;
KW Fusion of virus membrane with host cell membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host endosome; Host membrane; Membrane;
KW Reference proteome; Sialic acid; Signal; Transmembrane;
KW Transmembrane helix; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT SIGNAL 1..18
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CHAIN 19..706
FT /note="Envelope glycoprotein H"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT /id="PRO_0000436649"
FT TOPO_DOM 19..682
FT /note="Virion surface"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT TRANSMEM 683..703
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT TOPO_DOM 704..706
FT /note="Intravirion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT REGION 165..229
FT /note="Interaction with gL"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033,
FT ECO:0000269|PubMed:21149717"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033,
FT ECO:0000269|PubMed:21149717"
FT CARBOHYD 549
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033,
FT ECO:0000269|PubMed:21149717"
FT CARBOHYD 604
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033,
FT ECO:0000269|PubMed:21149717"
FT CARBOHYD 664
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04033,
FT ECO:0000269|PubMed:21149717"
FT DISULFID 120..312
FT /evidence="ECO:0000269|PubMed:21149717"
FT DISULFID 278..335
FT /evidence="ECO:0000269|PubMed:21149717"
FT DISULFID 454..478
FT /evidence="ECO:0000269|PubMed:21149717"
FT DISULFID 534..587
FT /evidence="ECO:0000269|PubMed:21149717"
FT DISULFID 612..615
FT /evidence="ECO:0000269|PubMed:21149717"
FT CONFLICT 380..389
FT /note="TVGYPKAGVY -> GAPGGRAGPP (in Ref. 3; CAE82041)"
FT /evidence="ECO:0000305"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 40..46
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 52..58
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 65..72
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 123..130
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 142..147
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 156..162
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 163..166
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 175..185
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 191..200
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 213..216
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 232..239
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 246..255
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 258..274
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 275..279
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 285..306
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 315..335
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 346..356
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 371..381
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 392..405
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 415..432
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:5T1D"
FT HELIX 440..453
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 456..468
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 471..473
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 477..480
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:5T1D"
FT HELIX 488..492
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 499..501
FT /evidence="ECO:0007829|PDB:5T1D"
FT HELIX 503..515
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 520..522
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 524..527
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 530..533
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 540..547
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 550..556
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 572..575
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 578..583
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 613..616
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 618..623
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 624..626
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 627..633
FT /evidence="ECO:0007829|PDB:7CZE"
FT HELIX 637..645
FT /evidence="ECO:0007829|PDB:7CZE"
FT TURN 646..648
FT /evidence="ECO:0007829|PDB:5T1D"
FT STRAND 656..661
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 663..665
FT /evidence="ECO:0007829|PDB:7CZE"
FT STRAND 667..670
FT /evidence="ECO:0007829|PDB:7CZE"
SQ SEQUENCE 706 AA; 78322 MW; A1006BDA6633B1D9 CRC64;
MQLLCVFCLV LLWEVGAASL SEVKLHLDIE GHASHYTIPW TELMAKVPGL SPEALWREAN
VTEDLASMLN RYKLIYKTSG TLGIALAEPV DIPAVSEGSM QVDASKVHPG VISGLNSPAC
MLSAPLEKQL FYYIGTMLPN TRPHSYVFYQ LRCHLSYVAL SINGDKFQYT GAMTSKFLMG
TYKRVTEKGD EHVLSLVFGK TKDLPDLRGP FSYPSLTSAQ SGDYSLVIVT TFVHYANFHN
YFVPNLKDMF SRAVTMTAAS YARYVLQKLV LLEMKGGCRE PELDTETLTT MFEVSVAFFK
VGHAVGETGN GCVDLRWLAK SFFELTVLKD IIGICYGATV KGMQSYGLER LAAMLMATVK
MEELGHLTTE KQEYALRLAT VGYPKAGVYS GLIGGATSVL LSAYNRHPLF QPLHTVMRET
LFIGSHVVLR ELRLNVTTQG PNLALYQLLS TALCSALEIG EVLRGLALGT ESGLFSPCYL
SLRFDLTRDK LLSMAPQEAT LDQAAVSNAV DGFLGRLSLE REDRDAWHLP AYKCVDRLDK
VLMIIPLINV TFIISSDREV RGSALYEAST TYLSSSLFLS PVIMNKCSQG AVAGEPRQIP
KIQNFTRTQK SCIFCGFALL SYDEKEGLET TTYITSQEVQ NSILSSNYFD FDNLHVHYLL
LTTNGTVMEI AGLYEERAHV VLAIILYFIA FALGIFLVHK IVMFFL
