A1Z0Q5 (GD_HHV1K) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Envelope glycoprotein D
Short name=gD

Gene names

Name:	gD
ORF Names:	US6

Organism

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

Taxonomic identifier

10306 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Alphaherpesvirinae › Simplexvirus › Human herpesvirus 1

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. Mutant Rid1 interacts with host receptor PVRL2. 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. Interacts (via C-terminus) with VP22 tegument protein; this interaction might be very weak By similarity. Ref.3 Ref.5
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 Viral attachment to host cell Virus entry into host cell
Cellular component	Membrane Viral envelope protein Virion
Domain	Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological_process	viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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_5000142086
Regions
	Topological domain	26 – 340	315	Virion surface Potential
	Transmembrane	341 – 361	21	Helical; Potential
	Topological domain	362 – 394	33	Intravirion Potential
	Region	26 – 57	32	Interaction with TNFRSF14
	Region	261 – 305	45	Profusion By similarity
	Compositional bias	269 – 337	69	Pro-rich
	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 By similarity
	Metal binding	240	1	Zinc 1; shared with dimeric partner By similarity
Amino acid modifications
	Glycosylation	119	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	146	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	287	1	N-linked (GlcNAc...); by host Potential
	Disulfide bond	91 ↔ 214		By similarity
	Disulfide bond	131 ↔ 227		By similarity
	Disulfide bond	143 ↔ 152		By similarity
Natural variations
	Natural variant	52	1	Q → P in strain: Mutant rid1 and Isolate KOSc(AC3,AC6); interference resistant.
	Natural variant	52	1	Q → R in strain: Mutant rid2; interference resistant.
Experimental info
	Sequence conflict	30	1	A → V in AAA19630. Ref.1
	Sequence conflict	30	1	A → V in ABM52980. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	A1Z0Q5 [UniParc]. Last modified September 22, 2009. Version 2. Checksum: 905A0F0F1953CB7F	FASTA	394	43,317
	10 20 30 40 50 60 MGGAAARLGA 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]	"Molecular basis for resistance of herpes simplex virus type 1 mutants to the sulfated oligosaccharide inhibitor PI-88." Ekblad M., Adamiak B., Bergefall K., Nenonen H., Roth A., Bergstrom T., Ferro V., Trybala E. Virology 367:244-252(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Isolate KOSc, Isolate KOSc(AC3,AC6) and Isolate KOSc(AC4).
[2]	"Single amino acid substitutions in glycoprotein D of herpes simplex virus type 1 that confer resistance to gD-mediated interference also alter virus infectivity." Dean H.J., Terhune S.S., Shieh M.-T., Spear P.G. Virology 199:67-80(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: KOS, Mutant Rid1 and Mutant Rid2.
[3]	"Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry." Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W., Lambris J.D., Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J. J. Virol. 72:7064-7074(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN RECEPTORS PVRL1 AND TNFRSF14.
[4]	"A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry." Shukla D., Liu J., Blaiklock P., Shworak N.W., Bai X., Esko J.D., Cohen G.H., Eisenberg R.J., Rosenberg R.D., Spear P.G. Cell 99:13-22(1999) [PubMed] [Europe PMC] [Abstract] Cited for: BINDING TO 3-O-SULFATED HEPARAN SULFATE.
[5]	"Structural features of nectin-2 (HveB) required for herpes simplex virus entry." Martinez W.M., Spear P.G. J. Virol. 75:11185-11195(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION OF MUTANT RID1 WITH HUMAN PVRL2. Strain: Mutant Rid1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L09243 Unassigned DNA. Translation: AAA19629.1. L09244 Unassigned DNA. Translation: AAA19631.1. L09245 Unassigned DNA. Translation: AAA19630.1. EF157319 Genomic DNA. Translation: ABM52978.1. EF157320 Genomic DNA. Translation: ABM52979.1. EF157321 Genomic DNA. Translation: ABM52980.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-237377.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR002896. Herpes_glycop_dom. [Graphical view]
Pfam	PF01537. Herpes_glycop_D. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

GD_HHV1K

Accession

Primary (citable) accession number: A1Z0Q5
Secondary accession number(s): Q05060, Q69081, Q69082

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 22, 2009
Last sequence update:	September 22, 2009
Last modified:	May 1, 2013
This is version 28 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program