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P03274

- CAP6_ADE02

UniProt

P03274 - CAP6_ADE02

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Protein

Pre-protein VI

Gene

L3

Organism
Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.
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.
Protease cofactor: Cofactor that activates the viral protease. Binds to viral protease in a 1:1 ratio.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei33 – 342Cleavage; by viral protease
Sitei239 – 2402Cleavage; by viral protease

GO - Biological processi

  1. lysis of host organelle involved in viral entry into host cell Source: UniProtKB-KW
  2. microtubule-dependent intracellular transport of viral material towards nucleus Source: UniProtKB-KW
  3. viral release from host cell Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Cytoplasmic inwards viral transport, Host-virus interaction, Microtubular inwards viral transport, Viral capsid assembly, Viral penetration into host cytoplasm, Viral penetration via lysis of host organellar membrane, Virus entry into host cell, Virus exit from host cell

Names & Taxonomyi

Protein namesi
Recommended name:
Pre-protein VI
Short name:
pVI
Cleaved into the following 2 chains:
Gene namesi
ORF Names:L3
OrganismiHuman adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2)
Taxonomic identifieri10515 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageAdenoviridaeMastadenovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000008167: Genome

Subcellular locationi

Chain 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.

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell nucleus Source: UniProtKB-KW
  3. intracellular Source: GOC
  4. viral capsid Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Capsid protein, Host cytoplasm, Host nucleus, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi40 – 401L → Q: Impaired endosome penetration and reduces infectivity. 1 Publication
Mutagenesisi48 – 481G → C: Decreased infectivity and endosomal membrane disruption activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 250250Pre-protein VIPRO_0000421078Add
BLAST
Propeptidei1 – 3333PRO_0000036543Add
BLAST
Chaini34 – 239206Endosome lysis proteinPRO_0000036544Add
BLAST
Peptidei240 – 25011Protease cofactorPRO_0000036545Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei124 – 1241Phosphoserine; by host1 Publication
Modified residuei143 – 1431Phosphothreonine; by host1 Publication
Disulfide bondi249 – 249Interchain (with C-104 in Adenovirus protease)

Post-translational modificationi

Ubiquitinated by Nedd4 following partial capsid disassembly; which might play a role in intracellular virus movement during entry.1 Publication
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.

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Miscellaneous databases

PMAP-CutDBP03274.

Expressioni

Inductioni

Expressed in the late phase of the viral replicative cycle.

Keywords - Developmental stagei

Late protein

Interactioni

Subunit structurei

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.5 Publications

Structurei

Secondary structure

1
250
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi243 – 2497

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AVPX-ray2.60B240-250[»]
1NLNX-ray1.60B240-250[»]
4PIDX-ray1.59B240-250[»]
4PIEX-ray1.94B240-250[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03274.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni34 – 5421Amphipathic alpha-helix essential for membrane lytic activityAdd
BLAST
Regioni48 – 7427Interaction with hexon proteinAdd
BLAST
Regioni105 – 225121DisorderedSequence AnalysisAdd
BLAST
Regioni233 – 2397Interaction with hexon protein
Regioni240 – 25011Binds to importin alpha/beta, involved in hexon nuclear importAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi67 – 7610Nuclear export signalBy similarity
Motifi131 – 1355Nuclear localization signalSequence Analysis
Motifi148 – 1514PPXY motifBy similarity
Motifi231 – 24212Nuclear export signalBy similarityAdd
BLAST
Motifi245 – 2484Nuclear localization signalSequence Analysis

Domaini

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.

Sequence similaritiesi

Belongs to the adenoviridae protein VI family.Curated

Family and domain databases

InterProiIPR004243. McpVI.
[Graphical view]
PfamiPF02993. MCPVI. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P03274-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MEDINFASLA PRHGSRPFMG NWQDIGTSNM SGGAFSWGSL WSGIKNFGST
60 70 80 90 100
IKNYGSKAWN SSTGQMLRDK LKEQNFQQKV VDGLASGISG VVDLANQAVQ
110 120 130 140 150
NKINSKLDPR PPVEEPPPAV ETVSPEGRGE KRPRPDREET LVTQIDEPPS
160 170 180 190 200
YEEALKQGLP TTRPIAPMAT GVLGQHTPVT LDLPPPADTQ QKPVLPGPSA
210 220 230 240 250
VVVTRPSRAS LRRAASGPRS MRPVASGNWQ STLNSIVGLG VQSLKRRRCF
Length:250
Mass (Da):27,014
Last modified:July 21, 1986 - v1
Checksum:i4CACF18014647328
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J01917 Genomic DNA. Translation: AAA92214.1.
PIRiA03844. Q5ADB2.
RefSeqiAP_000174.1. AC_000007.1.
NP_040524.1. NC_001405.1.

Genome annotation databases

GeneIDi2652998.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
J01917 Genomic DNA. Translation: AAA92214.1 .
PIRi A03844. Q5ADB2.
RefSeqi AP_000174.1. AC_000007.1.
NP_040524.1. NC_001405.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1AVP X-ray 2.60 B 240-250 [» ]
1NLN X-ray 1.60 B 240-250 [» ]
4PID X-ray 1.59 B 240-250 [» ]
4PIE X-ray 1.94 B 240-250 [» ]
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 2652998.

Miscellaneous databases

EvolutionaryTracei P03274.
PMAP-CutDB P03274.

Family and domain databases

InterProi IPR004243. McpVI.
[Graphical view ]
Pfami PF02993. MCPVI. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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. 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.

Entry informationi

Entry nameiCAP6_ADE02
AccessioniPrimary (citable) accession number: P03274
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 29, 2014
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3