HAMAP rule MF

Accession	MF_04048
Dates	23-FEB-2017 (Created) 15-OCT-2021 (Last updated, Version 9)

Name

ADV_CAP6

Scope

Viruses; Adenoviridae

Template

P24937 (CAP6_ADE05)

Triggered by

HAMAP; MF_04048 (Get profile general information and statistics)

Identifier

CAP6

Protein name

RecName:		Full=Pre-protein VI;
		Short=pVI;
Contains:
	RecName:		Full=Endosome lysis protein;
Contains:
	RecName:		Full=Protease cofactor;
	AltName:		Full=pVI-C;

Gene name

L3

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.

Capsid protein
Cytoplasmic inwards viral transport
Disulfide bond
Host cytoplasm
Host nucleus
Host-virus interaction
Late protein
Microtubular inwards viral transport
Phosphoprotein
Ubl conjugation
Viral capsid assembly
Viral penetration into host cytoplasm
Viral penetration via lysis of host organellar membrane
Virion
Virus entry into host cell
Viral release from host cell

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: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.

Pfam	PF02993; MCPVI; 1;

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 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

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

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HAMAP rule MF_04048