P05919 (VPU_HV1H2) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein Vpu

Alternative name(s):
U ORF protein
Viral protein U

Gene names

Name:

vpu

Organism

Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)

Taxonomic identifier

11706 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Lentivirus › Primate lentivirus group

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	81 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

General annotation (Comments)

Function	Enhances virion budding, by targeting human CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its receptor human CD4 in the endoplasmic reticulum. Degradation of antiretroviral protein Tetherin/BST2 is important for virion budding, as BST2 tethers new viral particles to the host cell membrane. Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, induces their ubiquitination and subsequent proteasomal degradation. The alteration of the E3 ligase specificity by Vpu seems to interfere with the degradation of host IKBKB, leading to NF-kappa-B down-regulation and subsequent apoptosis. Ion channel activity has also been suggested, however, formation of cation-selective channel has been reconstituted ex-vivo in lipid bilayers. It is thus unsure that this activity plays a role in vivo By similarity. Ref.2
Enzyme regulation	Ion channel activity is inhibited by hexamethylene amiloride in vitro By similarity.
Subunit structure	May form pentamers or hexamers. Forms ternary complexes, by interacting with human CD4 and BTRC, and with human BST2 and BTRC.
Subcellular location	Host membrane; Single-pass type I membrane protein By similarity.
Domain	The N-terminal and transmembrane domains are required for proper virion budding, whereas the cytoplasmic domain is required for CD4 degradation. The cytoplasmic domain is composed of 2 amphipathic alpha helix By similarity.
Post-translational modification	Phosphorylated by host CK2. This phosphorylation is necessary for interaction with human BTRC and degradation of CD4 By similarity.
Miscellaneous	HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).
Sequence similarities	Belongs to the HIV-1 VPU protein family.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Inhibition of host tetherin by virus Ion transport Transport Viral immunoevasion
Cellular component	Host membrane Membrane
Disease	AIDS
Domain	Transmembrane Transmembrane helix
Molecular function	Ionic channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	RNA-dependent DNA replication Traceable author statement. Source: Reactome apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW entry into host cell Traceable author statement. Source: Reactome evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW provirus integration Traceable author statement. Source: Reactome release of virus from host Inferred from electronic annotation. Source: InterPro uncoating of virus Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome host cell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleoplasm Traceable author statement. Source: Reactome
Molecular function	ion channel activity 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
	Chain	1 – 81	81	Protein Vpu		PRO_0000085433
Regions
	Topological domain	1 – 6	6	Extracellular Potential
	Transmembrane	7 – 27	21	Helical; Potential
	Topological domain	28 – 81	54	Cytoplasmic Potential
Amino acid modifications
	Modified residue	52	1	Phosphoserine; by host CK2 By similarity
	Modified residue	56	1	Phosphoserine; by host CK2 By similarity

Sequences

	Sequence		Length	Mass (Da)
	P05919 [UniParc]. Last modified November 1, 1988. Version 1. Checksum: 53A951D6240556EA	FASTA	81	9,111
	10 20 30 40 50 60 QPIPIVAIVA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE DSGNESEGEI 70 80 SALVEMGVEM GHHAPWDVDD L

References

[1]	"Complete nucleotide sequences of functional clones of the AIDS virus." Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C., Wong-Staal F. AIDS Res. Hum. Retroviruses 3:57-69(1987) [PubMed: 3040055] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels." Ewart G.D., Sutherland T., Gage P.W., Cox G.B. J. Virol. 70:7108-7115(1996) [PubMed: 8794357] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

BioAfrica HIV proteomics resource

Vpu entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	K03455 Genomic RNA. No translation available.
3D structure databases
ProteinModelPortal	P05919.
SMR	P05919. Positions 37-81.
ModBase	Search...
Protein family/group databases
TCDB	1.A.40.1.1. human immunodeficiency virus type I, HIV-1 (Retrovirdiac) vpu channel (Vpu-C) family.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Enzyme and pathway databases
Reactome	REACT_6185. HIV Infection.
Family and domain databases
InterPro	IPR008187. Vpu. IPR009032. Vpu_cyt. [Graphical view]
Gene3D	G3DSA:1.10.195.10. Vpu_cyt. 1 hit.
Pfam	PF00558. Vpu. 1 hit. [Graphical view]
SUPFAM	SSF57647. Vpu_cyt. 1 hit.
ProtoNet	Search...

Entry information

Entry name

VPU_HV1H2

Accession

Primary (citable) accession number: P05919

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1988
Last sequence update:	November 1, 1988
Last modified:	October 19, 2011
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program