P14334 (US06_HCMVA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Unique short US6 glycoprotein

Alternative name(s):
Protein HXLF6
gpUS6

Gene names

Name:

US6

Organism

Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) [Complete proteome]

Taxonomic identifier

10360 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Betaherpesvirinae › Cytomegalovirus › Human cytomegalovirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	183 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	Inhibits peptide loading of MHC class I molecules by transporters associated with antigen processing (TAP). Does not prevent peptide binding to TAP, but binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1, but not TAP2. Also prevents the conformational rearrangement of TAP induced by peptide binding. In consequence, infected cells are masked for immune recognition by cytotoxic T-lymphocytes. Ref.5 Ref.6
Subunit structure	Interacts with UL18. Ref.7
Subcellular location	Host endoplasmic reticulum membrane; Single-pass type I membrane protein Ref.5.
Developmental stage	Expressed at early period of virus infection.
Domain	The ER-lumenal domain is responsible for TAP inhibition. It is sufficient to inhibit ATP binding to TAP.
Sequence similarities	Belongs to the cytomegalovirus US6 family. Contains 1 Ig-like H-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Host-virus interaction Inhibition of host TAP by virus Inhibition of host adaptive immune response by virus Viral immunoevasion
Cellular component	Host endoplasmic reticulum Host membrane Membrane
Developmental stage	Early protein
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	suppression by virus of host TAP complex Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane 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 – 19	19	Potential
	Chain	20 – 183	164	Unique short US6 glycoprotein		PRO_0000037438
Regions
	Topological domain	20 – 144	125	Lumenal Potential
	Transmembrane	145 – 165	21	Helical; Potential
	Topological domain	166 – 183	18	Cytoplasmic Potential
	Domain	30 – 131	102	Ig-like H-type
Amino acid modifications
	Glycosylation	52	1	N-linked (GlcNAc...); by host Potential
	Disulfide bond	39 ↔ 127		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P14334 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: C3722E9F011C0023	FASTA	183	20,639
	10 20 30 40 50 60 MDLLIRLGFL LMCALPTPGE RSSRDPKTLL SLSPRQQACV PRTKSHRPVC YNDTGDCTDA 70 80 90 100 110 120 DDSWKQLGED FAHQCLQAAK KRPKTHKSRP NDRNLEGRLT CQRVRRLLPC DLDIHPSHRL 130 140 150 160 170 180 LTLMNNCVCD GAVWNAFRLI ERHGFFAVTL YLCCGITLLV VILALLCSIT YESTGRGIRR CGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the short unique region, short repeats, and part of the long repeats of human cytomegalovirus." Weston K.M., Barrell B.G. J. Mol. Biol. 192:177-208(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169." Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R., Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A., Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G. Curr. Top. Microbiol. Immunol. 154:125-169(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome." Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J., McGeoch D.J., Hayward G.S. J. Gen. Virol. 84:17-28(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION.
[4]	Erratum Davison A.J., Dolan A., Akter P., Addison C., Dargan D.J., Alcendor D.J., McGeoch D.J., Hayward G.S. J. Gen. Virol. 84:1053-1053(2003)
[5]	"The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP." Ahn K., Gruhler A., Galocha B., Jones T.R., Wiertz E.J.H.J., Ploegh H.L., Peterson P.A., Yang Y., Frueh K. Immunity 6:613-621(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"The human cytomegalovirus gene product US6 inhibits ATP binding by TAP." Hewitt E.W., Gupta S.S., Lehner P.J. EMBO J. 20:387-396(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Human cytomegalovirus UL18 utilizes US6 for evading the NK and T-cell responses." Kim Y., Park B., Cho S., Shin J., Cho K., Jun Y., Ahn K. PLoS Pathog. 4:E1000123-E1000123(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UL18.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X17403 Genomic DNA. Translation: CAA35273.1. X04650 Genomic DNA. Translation: CAB37098.1. BK000394 Genomic DNA. Translation: DAA00223.1.
PIR	QQBEC7. G26078.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
PROSITE	PS50835. IG_LIKE. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

US06_HCMVA

Accession

Primary (citable) accession number: P14334
Secondary accession number(s): Q7M6G5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	April 3, 2013
This is version 61 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program