VPU - Viral Protein U

HIV VPU acts in the degradation of CD4 in the endoplasmic reticulum and the enhancement of virion release from the plasma membrane.




PDB-1VPU: HIV-1 (isolate SF_162) Vpu cytoplasmic domain fragment (residues 39-81) with R37L and K38Q mutations - produced using SwissModel/SPDBV/POVray
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ViralZone:HIV-1
PDB: 1VPU (HIV-1 Vpu)
SwissProt: P05919 (HIV-1 HXB2 Vpu)
Chime Tutorial:  not available
Los Alamos HIV structure DB: not available
EMBL: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Vpu Protein Data Mining Tool


Isoforms:

  • p16 (81 amino acids)

Localization:

  • Cell internal membranes of the cell (Ref. #3)
  • Cell nucleus

Function:

  • promotes extracellular release of viral particles
  • down-modulation of CD4 in Endoplasmic Reticulum
  • involved in Env maturation, and is not found in virion

Additional Information:

  • Vpu is unique to HIV/SIVcpz viruses
  • The formation of Env-CD4 complexes interfers with virion assembly.
  • Vpu triggers ubiquitin-mediated degradation of CD4 molecules, reducing the interference. (Ref. #6)
  • Large numbers of virions remain attached to the surface of infected cells that lack Vpu. (Ref. #7)
  • Vpu increases susceptibility of HIV-1 infected cells to Fas killing.
  • CD4 down-regulation and increased virion release are genetically distinct, are relate to different domains (Ref. #5)

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2):

          10         20         30         40         50         60         70
| | | | | | |
QPIPIVAIVA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE DSGNESEGEI SALVEMGVEM
80
|
GHHAPWDVDD L
[download in fasta format]

Length: 81 amino acids
Molecular Weight: 9111 Da
Theoretical pI: 4.69
Gene Description: Vpu translation initiation codon is not efficient. (Ref. #4)


Protein Domains/Folds/Motifs: [TOP]

InterPro:

VPU Protein - IPR008187


VPU ORF (N-terminal domain) - IPR008188

  • acts as a hydrophobic membrane anchor.



VPU Protein (C-terminal cytoplasmic domain) - IPR009032

  • is responsible for direct interaction with and degradation of the CD4 receptor.
  • encompasses the C-terminal half of the protein.
  • contains a few helical turns.
  • does not contain an apparent hydrophobic core.

Secondary Structure prediction:

Transmembrane Regions - tmhmm:


Low Complexity Regions - seg:


Antigenic Sites - EMBOSS:

Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Arginine-rich Region:
Isoleucine-rich Region:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Protein-Protein Interactions: [TOP]

  • casein kinase II phosphorylation at positions Ser52 and Ser56.
  • Vpu binds CD4, facilitating the release of gp160, while still retaining CD4 within the ER.
  • Vpu targets CD4 for degradation by binding to hβTrCp, which is a component of the ubiquitin mediated protein degradation pathway.
  • Vpu binds a cellular protein UBP, which helps facilitate virus particle assembly and release.
  • There is either a direct interaction between Vpu and Gag, or an indirect interaction through UBP


Primary & Secondary Database Entries:[TOP]

Identifiers:

ViralZone: HIV-1
PDB/MMDB: Search for HIV-1 & VPU

SwissProt: P05919 (HIV-1 HXB2 Vpu)
EMBL: K03455; CDS Not Annotated [EMBL/GenBank/DDBJ]

PIR: UNKNOWN
HIV: K03455; VPU$HXB2
InterPro: IPR008187 Vpu / IPR008188 Vpu_N / IPR009032 Vpu_cyt
Pfam: PF00558
Prints: none
ProDom: PD449486 (residues 33 - 59) / PD000399 (residues 34 - 81)
SCOP: SSF57647 HIV-1 VPU cytoplasmic domain
BLOCKS: P05919
Prosite: P05919
ProtoNet: P05919
ProtoMap: P05919
PRESAGE: P05919
Database of Interacting Proteins: P05919
ModBase: P05919
Swiss-2DPAGE: 2D gel

BioAfrica Tools:
- Vpu Protein Data Mining Tool provides real-time analysis of HIV-1 Vpu isolates
- HIV Structure BLAST searches for similar HIV sequences that have known structures
- HIV Proteomics Resource contains protein sequence and structure analysis tools
Reviews and References: [TOP]

Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - Identification and localization of vpr gene product of human immunodeficiency virus type 1.
Sato A, Igarashi H, Adachi A.
Virus Genes 4: 303-312 (1990) [pubmed: 2149621]
4 - Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple
bicistronic mRNAs.
Schwartz S, Felber BK, Fenyo EM, Pavlakis GN.
J Virol 64: 5448-5456 (1990) [pubmed: 2214021]
5 - The two biological activities of human immunodeficiency virus type 1 Vpu protein involve
two separable structural domains.
Schubert U, Bour S, Ferrer-Montiel AV.
J Virol 70: 809-819 (1996) [pubmed: 8551619]
6 - Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4.
Willey RL, Maldarelli F, Martin MA.
J Virol 66(12): 7193-7200 (1992) [pubmed: 1433512]
7 - The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus
maturation and release.
Klimkait T, Strebel K, Hoggan MD.
J Virol 64: 621-629 (1990) [pubmed: 2404139]





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