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Annotation rule MF_04048
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General rule information [?]

Accession MF_04048
Dates 23-FEB-2017 (Created)
20-NOV-2019 (Last updated, Version 6)
Viruses; Adenoviridae
Template P24937 (CAP6_ADE05)

Propagated annotation [?]

Identifier, protein and gene names [?]

Protein name
RecName: Full=Pre-protein VI;
RecName: Full=Endosome lysis protein;
RecName: Full=Protease cofactor;
AltName: Full=pVI-C;
Gene name

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 chaperone 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 and the hexon-linking protein VIII. 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.
Subunit [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. Part of a complex composed of the core-capsid bridging protein, the endosome lysis protein VI and the hexon-linking protein VIII; these interactions bridge the virus core to the capsid. Interacts with peripentonal hexons; this interaction stabilizes the capsid by gluing two peripentonal hexons together and joining them with an adjacent group-of-nine hexon.
[Protease cofactor]: Heterodimer with the viral protease; disulfide-linked. Interacts with the viral protease.
Subcellular location Pre-protein VI: Host nucleus. Host cytoplasm. Note=Shuttles between host cytoplasm and nucleus.
Endosome lysis protein: Virion. Note=Associates with the base of each peripentonal hexon on the capsid interior. Present in around 360 copies per virion.
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.
Ptm Ubiquitinated by Nedd4 following partial capsid disassembly; which might play a role in intracellular virus movement during entry.
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 chaperone 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.
Similarity Belongs to the adenoviridae protein VI family.

Keywords [?]

Gene Ontology [?]

GO:0030430; Cellular component: host cell cytoplasm.
GO:0042025; Cellular component: host cell nucleus.
GO:0019028; Cellular component: viral capsid.
GO:0046729; Cellular component: viral procapsid.
GO:0019012; Cellular component: virion.
GO:0039664; Biological process: lysis of host organelle involved in viral entry into host cell.
GO:0075521; Biological process: microtubule-dependent intracellular transport of viral material towards nucleus.
GO:0019076; Biological process: viral release from host cell.

Cross-references [?]

Pfam PF02993; MCPVI; 1;

Features [?]

From: CAP6_ADE05 (P24937)
Key     From     To       Description   Tag   Condition   FTGroup
CHAIN     Nter     Cter       Pre-protein VI        
PROPEP     Nter     33                
CHAIN     34     239       Endosome lysis protein        
CHAIN     240     250       Protease cofactor        
REGION     34     54       Amphipathic alpha-helix essential for membrane lytic activity        
REGION     36     53       Involved in endosomal membrane lysis        
REGION     48     74       Interaction with hexon protein        
REGION     105     225       Disordered        
REGION     233     239       Interaction with hexon protein        
REGION     240     250       Binds to importin alpha/beta, involved in hexon nuclear import        
MOTIF     67     76       Nuclear export signal        
MOTIF     131     135       Nuclear localization signal     [KR]-[KR]-x-[KR]-x  
MOTIF     148     151       PPXY motif     P-P-x-Y  
MOTIF     231     242       Nuclear export signal        
MOTIF     245     248       Nuclear localization signal     [KR]-[KR]-[KR]-[KR]  
SITE     33     34       Cleavage; by viral protease        
SITE     239     240       Cleavage; by viral protease        
MOD_RES     124     124       Phosphoserine; by host     S  
MOD_RES     143     143       Phosphothreonine; by host     T  
DISULFID     249     249       Interchain (with Adenovirus protease)     C  

Additional information [?]

Size range 223-267 amino acids
Related rules None
Fusion None