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.
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[animated gif: 320x240 ]
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Isoforms:
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Localization:
- Internal membranes of the cell (Ref. #3)
- nucleus
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Function:
- accessory protein
- promotes extracellular release of viral particles
- down-modulation of CD4 in Endoplasmic Reticulum
- involved in Env maturation, and is not found in virion
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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)
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Genomic Location: [TOP]
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Reference
Sequences:
HIV-1
(HXB2):
10 20 30 40 50 60 70
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QPIPIVAIVA LVVAIIIAIV VWSIVIIEYR KILRQRKIDR LIDRLIERAE DSGNESEGEI SALVEMGVEM
80
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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)
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Protein Domains/Folds/Motifs: [TOP]
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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.
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Secondary Structure prediction:
Transmembrane Regions - tmhmm:
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N-glycosylation:
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N-myristoylation:
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Amidation:
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Protein kinase C:
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Casein kinase II:
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Tyrosine kinase:
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cAMP / cGMP kinase:
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Cell attachment motif:
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Asp Protease motif:
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Asp Prot Retro motif:
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Arginine-rich Region:
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Isoleucine-rich Region:
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Cysteine-rich Region:
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Tryptophan-rich Region:
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Zinc-finger CCHC motif:
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Leucine Zipper motif:
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Protein-Protein Interactions: [TOP]
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- 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
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Primary & Secondary Database Entries:[TOP]
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Identifiers:
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
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Reviews and References: [TOP]
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- 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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