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P03274 (CAP6_ADE02) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Pre-protein VI

Short name=pVI

Cleaved into the following 2 chains:

  1. Endosome lysis protein
  2. Protease cofactor
    Alternative name(s):
    pVI-C
Gene names
ORF Names:L3
OrganismHuman adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2) [Reference proteome]
Taxonomic identifier10515 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageAdenoviridaeMastadenovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length250 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Pre-protein VI: During virus assembly, promotes hexon trimers nuclear import through nuclear pore complexes via an importin alpha/beta-dependent mechanism. By analogy to herpesviruses capsid assembly, might act as a scaffold protein to promote the formation of the icosahedral capsid. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Endosome lysis protein: Structural component of the virion that provides increased stability to the particle shell through its interaction with the core-capsid bridging protein. Fibers shedding during virus entry into host cell allows the endosome lysis protein to be exposed as a membrane-lytic peptide. Exhibits pH-independent membrane fragmentation activity and probably mediates viral rapid escape from host endosome via organellar membrane lysis. It is not clear if it then remains partially associated with the capsid and involved in the intracellular microtubule-dependent transport of capsid to the nucleus, or if it is lost during endosomal penetration. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Protease cofactor: Cofactor that activates the viral protease. Binds to viral protease in a 1:1 ratio. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Subunit structure

Pre-protein VI: Interacts with hexon protein; this interaction allows nuclear import of hexon trimers and possibly pre-capsid assembly. Interacts (via C-terminal NLS) with importin alpha/beta. Endosome lysis protein: Interacts (via PPxY motif) with host NEDD4 ubiquitine ligase; this interaction might play a role in virus intracellular transport during entry. Protease cofactor: Homodimer; disulfide-linked. Interacts with the viral protease. Ref.5 Ref.6 Ref.7 Ref.8 Ref.10

Subcellular location

Pre-protein VI: Host nucleus Probable Ref.8.

Endosome lysis protein: Virion. Host nucleus. Host cytoplasm. Note: Located inside the capsid underneath the 12 vertices. Present in around 360 copies per virion. Shuttles between host cytoplasm and nucleus. Ref.8

Induction

Expressed in the late phase of the viral replicative cycle.

Domain

N-terminal amphipathic alpha-helix domain is essential for the membrane lytic activity.

Late-budding domains (L domains) are short sequence motifs essential for viral particle release. They can occur individually or in close proximity within structural proteins. They interacts with sorting cellular proteins of the multivesicular body (MVB) pathway. Most of these proteins are class E vacuolar protein sorting factors belonging to ESCRT-I, ESCRT-II or ESCRT-III complexes. Minor capsid protein 6 contains one L domain: a PPXY motif which binds to the WW domains of HECT (homologous to E6-AP C-terminus) E3 ubiquitin ligases, like NEDD4. In adenoviruses, this motif seems to play a role in microtubule-dependent intracellular trafficking toward the nucleus during virus entry into host cell and in suppression of DAXX-mediated repression of the immediate early E1A promoter.

Post-translational modification

Ubiquitinated by Nedd4 following partial capsid disassembly; which might play a role in intracellular virus movement during entry. Ref.10

Protease cofactor: Contains the major nuclear import and export signals. Proteolytically removed during virion maturation. The processing of the C-terminus turns the precursor into a mature viral structural protein and abrogates its ability to promote hexon import and act as a potential scaffold protein.

Miscellaneous

All late proteins expressed from the major late promoter are produced by alternative splicing and alternative polyadenylation of the same gene giving rise to non-overlapping ORFs. A leader sequence is present in the N-terminus of all these mRNAs and is recognized by the viral shutoff protein to provide expression although conventional translation via ribosome scanning from the cap has been shut off in the host cell.

Sequence similarities

Belongs to the adenoviridae protein VI family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 250250Pre-protein VI
PRO_0000421078
Propeptide1 – 3333
PRO_0000036543
Chain34 – 239206Endosome lysis protein
PRO_0000036544
Peptide240 – 25011Protease cofactor
PRO_0000036545

Regions

Region34 – 5421Amphipathic alpha-helix essential for membrane lytic activity
Region48 – 7427Interaction with hexon protein
Region105 – 225121Disordered Potential
Region233 – 2397Interaction with hexon protein
Region240 – 25011Binds to importin alpha/beta, involved in hexon nuclear import
Motif67 – 7610Nuclear export signal By similarity
Motif131 – 1355Nuclear localization signal Potential
Motif148 – 1514PPXY motif By similarity
Motif231 – 24212Nuclear export signal By similarity
Motif245 – 2484Nuclear localization signal Potential

Sites

Site33 – 342Cleavage; by viral protease
Site239 – 2402Cleavage; by viral protease

Amino acid modifications

Modified residue1241Phosphoserine; by host Ref.2
Modified residue1431Phosphothreonine; by host Ref.2
Disulfide bond249Interchain (with C-104 in Adenovirus protease) Ref.7

Experimental info

Mutagenesis401L → Q: Impaired endosome penetration and reduces infectivity. Ref.12
Mutagenesis481G → C: Decreased infectivity and endosomal membrane disruption activity. Ref.14

Secondary structure

... 250
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03274 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 4CACF18014647328

FASTA25027,014
        10         20         30         40         50         60 
MEDINFASLA PRHGSRPFMG NWQDIGTSNM SGGAFSWGSL WSGIKNFGST IKNYGSKAWN 

        70         80         90        100        110        120 
SSTGQMLRDK LKEQNFQQKV VDGLASGISG VVDLANQAVQ NKINSKLDPR PPVEEPPPAV 

       130        140        150        160        170        180 
ETVSPEGRGE KRPRPDREET LVTQIDEPPS YEEALKQGLP TTRPIAPMAT GVLGQHTPVT 

       190        200        210        220        230        240 
LDLPPPADTQ QKPVLPGPSA VVVTRPSRAS LRRAASGPRS MRPVASGNWQ STLNSIVGLG 

       250 
VQSLKRRRCF 

« Hide

References

[1]"Gene and mRNA for precursor polypeptide VI from adenovirus type 2."
Akusjaervi G., Persson H.
J. Virol. 38:469-482(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The phosphoproteome of the adenovirus type 2 virion."
Bergstrom Lind S., Artemenko K.A., Elfineh L., Zhao Y., Bergquist J., Pettersson U.
Virology 433:253-261(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 107-128 AND 138-156, PHOSPHORYLATION AT SER-124 AND THR-143.
[3]"Nucleic acid-binding properties of adenovirus structural polypeptides."
Russell W.C., Precious B.
J. Gen. Virol. 63:69-79(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING.
Strain: Human adenovirus C serotype 5.
[4]"The adenovirus protease is activated by a virus-coded disulphide-linked peptide."
Webster A., Hay R.T., Kemp G.
Cell 72:97-104(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF PROTEASE COFACTOR.
[5]"Adenovirus protein-protein interactions: molecular parameters governing the binding of protein VI to hexon and the activation of the adenovirus 23K protease."
Matthews D.A., Russell W.C.
J. Gen. Virol. 76:1959-1969(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF PRE-PROTEIN VI WITH HEXON PROTEIN.
[6]"Interaction of the human adenovirus proteinase with its 11-amino acid cofactor pVIc."
Baniecki M.L., McGrath W.J., McWhirter S.M., Li C., Toledo D.L., Pellicena P., Barnard D.L., Thorn K.S., Mangel W.F.
Biochemistry 40:12349-12356(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION OF PROTEASE COFACTOR WITH VIRAL PROTEASE.
[7]"In the virion, the 11-amino-acid peptide cofactor pVIc is covalently linked to the adenovirus proteinase."
McGrath W.J., Aherne K.S., Mangel W.F.
Virology 296:234-240(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERCHAIN DISULFIDE BOND WITH VIRAL PROTEASE.
[8]"Switch from capsid protein import to adenovirus assembly by cleavage of nuclear transport signals."
Wodrich H., Guan T., Cingolani G., Von Seggern D., Nemerow G., Gerace L.
EMBO J. 22:6245-6255(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION OF PRE-PROTEIN VI, NUCLEAR LOCALIZATION SIGNALS, NUCLEAR EXPORT SIGNALS, INTERACTION OF PRE-PROTEIN VI WITH IMPORTIN ALPHA/BETA, INTERACTION OF PRE-PROTEIN VI WITH HEXON PROTEIN.
Strain: Human adenovirus C serotype 5.
[9]"Adenovirus protein VI mediates membrane disruption following capsid disassembly."
Wiethoff C.M., Wodrich H., Gerace L., Nemerow G.R.
J. Virol. 79:1992-2000(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF ENDOSOME LYSIS PROTEIN.
Strain: Human adenovirus C serotype 5.
[10]"A capsid-encoded PPxY-motif facilitates adenovirus entry."
Wodrich H., Henaff D., Jammart B., Segura-Morales C., Seelmeir S., Coux O., Ruzsics Z., Wiethoff C.M., Kremer E.J.
PLoS Pathog. 6:E1000808-E1000808(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, INTERACTION WITH HOST NEDD4.
Strain: Human adenovirus C serotype 5.
[11]"An N-terminal domain of adenovirus protein VI fragments membranes by inducing positive membrane curvature."
Maier O., Galan D.L., Wodrich H., Wiethoff C.M.
Virology 402:11-19(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF ENDOSOME LYSIS PROTEIN.
Strain: Human adenovirus C serotype 5.
[12]"Functional genetic and biophysical analyses of membrane disruption by human adenovirus."
Moyer C.L., Wiethoff C.M., Maier O., Smith J.G., Nemerow G.R.
J. Virol. 85:2631-2641(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF ENDOSOME LYSIS PROTEIN, MUTAGENESIS OF LEU-40.
Strain: Human adenovirus C serotype 5.
[13]"Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure."
Burckhardt C.J., Suomalainen M., Schoenenberger P., Boucke K., Hemmi S., Greber U.F.
Cell Host Microbe 10:105-117(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF ENDOSOME LYSIS PROTEIN.
[14]"Disulfide-bond formation by a single cysteine mutation in adenovirus protein VI impairs capsid release and membrane lysis."
Moyer C.L., Nemerow G.R.
Virology 428:41-47(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF ENDOSOME LYSIS PROTEIN, MUTAGENESIS OF GLY-48.
Strain: Human adenovirus C serotype 5.
[15]"Latest insights on adenovirus structure and assembly."
San Martin C.
Viruses 4:847-877(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[16]"Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor."
Ding J., McGrath W.J., Sweet R.M., Mangel W.F.
EMBO J. 15:1778-1783(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 240-250 IN COMPLEX WITH VIRAL PROTEASE.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J01917 Genomic DNA. Translation: AAA92214.1.
PIRQ5ADB2. A03844.
RefSeqAP_000174.1. AC_000007.1.
NP_040524.1. NC_001405.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AVPX-ray2.60B240-250[»]
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2652998.

Phylogenomic databases

ProtClustDBCLSP2513899.

Family and domain databases

InterProIPR004243. McpVI.
[Graphical view]
PfamPF02993. MCPVI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP03274.
PMAP-CutDBP03274.

Entry information

Entry nameCAP6_ADE02
AccessionPrimary (citable) accession number: P03274
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: February 19, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references