Reviewed, UniProtKB/Swiss-Prot P57083 (GD_HHV1P)

Names and origin

Protein names

Recommended name:
    Envelope glycoprotein D
      Short name=gD

Gene names

Name:	gD
Synonyms:	US6

Organism

Human herpesvirus 1 (strain Patton) (HHV-1) (Human herpes simplex virus 1)

Taxonomic identifier

10308 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	394 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Envelope glycoprotein that binds to the potential host cell entry receptors TNFRSF14/HVEM, PVRL1 and 3-O-sulfated heparan sulfate. May trigger fusion with host membrane, by recruiting the fusion machinery composed of gB and gH/gL By similarity.
Subunit structure	Homodimer By similarity. Interacts with host receptor TNFRSF14. Interacts with host receptor PVRL1. Interacts (via profusion domain) with gB; this interaction occurs in the absence of gH/gL. Interacts (via profusion domain) with gH/gL heterodimer; this interaction occurs in the absence of gB. Associates with the gB-gH/gL-gD complex. Interacts (via C-terminus) with UL11 tegument protein By similarity.
Subcellular location	Virion membrane; Single-pass type I membrane protein By similarity. Note: During virion morphogenesis, this protein probably accumulates in the endosomes and trans-Golgi where secondary envelopment occurs By similarity.
Sequence similarities	Belongs to the herpesviridae glycoprotein D family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Envelope protein Membrane Virion
Domain	Signal Transmembrane
Ligand	Metal-binding Zinc
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell virion Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein binding Ref.2 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFRSF14	Q92956	1	EBI-1031723,EBI-1056653	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Chain

26 – 394

369

Envelope glycoprotein D

PRO_0000038214

Regions

Topological domain

26 – 339

314

Extracellular Potential

Transmembrane

340 – 364

25

Potential

Topological domain

365 – 394

30

Cytoplasmic Potential

Region

25 – 57

33

Interaction with TNFRSF14

Region

261 – 305

45

Profusion By similarity

Compositional bias

365 – 381

17

Arg/Lys-rich (highly basic; probably serves to anchor the glycoprotein in the membrane)

Sites

Metal binding

64

1

Zinc 1; shared with dimeric partner

Metal binding

240

1

Zinc 1; shared with dimeric partner

Amino acid modifications

Glycosylation

119

1

N-linked (GlcNAc...); by host

Glycosylation

146

1

N-linked (GlcNAc...); by host Potential

Glycosylation

287

1

N-linked (GlcNAc...); by host Potential

Disulfide bond

91 ↔ 214

Ref.3

Disulfide bond

131 ↔ 227

Ref.3

Disulfide bond

143 ↔ 152

Ref.3

Experimental info

Mutagenesis

62

1

V → C: Impaired virus entry into host cell; when associated with C-327. Inability of the corresponding soluble gD to bind TNFRSF14 and PVRL1. Ref.3

Mutagenesis

319

1

W → A: Impaired virus entry into host cell. Ref.3

Mutagenesis

327

1

A → C: Impaired virus entry into host cell; when associated with C-62. Inability of the corresponding soluble gD to bind TNFRSF14 and PVRL1. Ref.3

Secondary structure

1

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394

Helix Strand Turn

Details...

Helix

44 – 46

3

Beta strand

60 – 63

4

Beta strand

65 – 68

4

Beta strand

82 – 87

6

Beta strand

92 – 97

6

Helix

103 – 107

5

Helix

111 – 114

4

Beta strand

118 – 128

11

Beta strand

131 – 143

13

Beta strand

153 – 156

4

Beta strand

166 – 169

4

Beta strand

171 – 180

10

Helix

183 – 185

3

Beta strand

187 – 195

9

Beta strand

198 – 208

11

Beta strand

210 – 212

3

Helix

224 – 226

3

Helix

230 – 235

6

Turn

239 – 243

5

Helix

250 – 256

7

Helix

259 – 263

5

Beta strand

275 – 277

3

Beta strand

306 – 308

3

Sequences

	Sequence		Length	Mass (Da)
	P57083-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 052ABB5F53033D5E	FASTA	394	43,347
	10 20 30 40 50 60 MGGTAARLGA VILFVVIVGL HGVRGKYALA DASLKMADPN RFRGKDLPVL DQLTDPPGVR 70 80 90 100 110 120 RVYHIQAGLP DPFQPPSLPI TVYYAVLERA CRSVLLNAPS EAPQIVRGAS EDVRKQPYNL 130 140 150 160 170 180 TIAWFRMGGN CAIPITVMEY TECSYNKSLG ACPIRTQPRW NYYDSFSAVS EDNLGFLMHA 190 200 210 220 230 240 PAFETAGTYL RLVKINDWTE ITQFILEHRA KGSCKYALPL RIPPSACLSP QAYQQGVTVD 250 260 270 280 290 300 SIGMLPRFIP ENQRTVAVYS LKIAGWHGPK APYTSTLLPP ELSETPNATQ PELAPEDPED 310 320 330 340 350 360 SALLEDPVGT VAPQIPPNWH IPSIQDAATP YHPPATPNNM GLIAGAVGGS LLAALVICGI 370 380 390 VYWMHRRTRK APKRIRLPHI REDDQPSSHQ PLFY

References

[1]	"Herpes simplex virus type-1 glycoprotein D gene: nucleotide sequence and expression in Escherichia coli." Watson R.J., Weis J.H., Salstrom J.S., Enquist L.W. Science 218:381-384(1982) [PubMed: 6289440] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Herpes simplex virus glycoprotein D bound to the human receptor HveA." Carfi A., Willis S.H., Whitbeck J.C., Krummenacher C., Cohen G.H., Eisenberg R.J., Wiley D.C. Mol. Cell 8:169-179(2001) [PubMed: 11511370] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 26-310 IN COMPLEX WITH TNFRSF14.
[3]	"Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry." Krummenacher C., Supekar V.M., Whitbeck J.C., Lazear E., Connolly S.A., Eisenberg R.J., Cohen G.H., Wiley D.C., Carfi A. EMBO J. 24:4144-4153(2005) [PubMed: 16292345] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 48-331, DISULFIDE BONDS, ZINC-BINDING, MUTAGENESIS OF VAL-62; TRP-319 AND ALA-327.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X02138 Genomic DNA. Translation: CAA26060.1.
J02217 Genomic DNA. Translation: AAA45785.1.

PIR

VGBED1. A94268.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JMA	X-ray	2.65	A	26-310	[»]
1L2G	X-ray	2.85	A/B/C/D	26-310	[»]
2C36	X-ray	2.11	A/B	48-331	[»]
2C3A	X-ray	2.50	A/B	47-332	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P57083. 1 interaction.

Family and domain databases

InterPro

IPR002896. Herpes_gD.
[Graphical view]

Pfam

PF01537. Herpes_glycop_D. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

GD_HHV1P

Accession

Primary (citable) accession number: P57083
Secondary accession number(s): P03171

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	November 3, 2009
This is version 49 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)