L3 - Pre-protein VI - Human adenovirus C serotype 5 (HAdV-5)

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 chaperone to promote the formation of the icosahedral capsid.UniRule annotation1 Publication

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 (PubMed:25071205). Fibers shedding during virus entry into host cell allows the endosome lysis protein to be exposed as a membrane-lytic peptide (By similarity). Exhibits pH-independent membrane fragmentation activity and probably mediates viral rapid escape from host endosome via organellar membrane lysis (PubMed:15681401, PubMed:21209115, PubMed:20409568, PubMed:22516138). 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 (PubMed:20333243).UniRule annotationBy similarity6 Publications

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

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.UniRule annotation

GO - Biological processⁱ

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	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, Viral release from host cell, Virus entry into host cell

Biological process

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, Viral release from host cell, Virus entry into host cell

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Pre-protein VIUniRule annotation Short name: pVIUniRule annotation Cleaved into the following 2 chains: Endosome lysis proteinUniRule annotation Protease cofactorUniRule annotation Alternative name(s): pVI-CUniRule annotation
Gene namesⁱ	Name:L3UniRule annotation
Organismⁱ	Human adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5)
Taxonomic identifierⁱ	28285 [NCBI]
Taxonomic lineageⁱ	Viruses › dsDNA viruses, no RNA stage › Adenoviridae › Mastadenovirus › Human mastadenovirus C
Virus hostⁱ	Homo sapiens (Human) [TaxID: 9606]
Proteomesⁱ	UP000004992 Componentⁱ: Genome

Subcellular locationⁱ

Pre-protein VI :

Note:

Shuttles between host cytoplasm and nucleus.UniRule annotation1 Publication

Endosome lysis protein :

Virion
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04048
1 Publication
Manual assertion based on experiment inⁱ
- Ref.10
  "Structures and organization of adenovirus cement proteins provide insights into the role of capsid maturation in virus entry and infection."
  Reddy V.S., Nemerow G.R.
  Proc. Natl. Acad. Sci. U.S.A. 111:11715-11720(2014) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS), INTERACTION WITH THE HEXON PROTEIN, IDENTIFICATION IN A COMPLEX WITH THE CORE-CAPSID BRIDGING PROTEIN AND THE HEXON-LINKING PROTEIN VIII, SUBCELLULAR LOCATION, FUNCTION.

Note:

Associates with the base of each peripentonal hexon on the capsid interior. Present in around 360 copies per virion.UniRule annotation1 Publication

GO - Cellular componentⁱ

host cell cytoplasm
Source: UniProtKB
Inferred from direct assayⁱ
- 14633984
host cell nucleus
Source: UniProtKB
Inferred from direct assayⁱ
- 14633984
viral capsid Source: UniProtKB-KW
viral procapsid
Source: CACAO
Inferred from direct assayⁱ
- 19782383
virion
Source: UniProtKB
Inferred from direct assayⁱ
- 25071205

View the complete GO annotation on QuickGO ...

Keywords - Cellular componentⁱ

Capsid protein, Host cytoplasm, Host nucleus, Virion

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	40	L → Q: Impaired endosome penetration and reduces infectivity. 1 Publication	1
Mutagenesisⁱ	48	G → C: Decreased infectivity and endosomal membrane disruption activity. 1 Publication	1
Mutagenesisⁱ	149 – 151	PSY → GAA: No effect on endosomal escape; defective in microtubule-dependent trafficking toward the nucleus. 1 Publication	3

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Length
ChainⁱPRO_0000421133	1 – 250	Pre-protein VIUniRule annotationAdd BLAST	250
PropeptideⁱPRO_0000036546	1 – 33	UniRule annotationAdd BLAST	33
ChainⁱPRO_0000036547	34 – 239	Endosome lysis proteinUniRule annotationAdd BLAST	206
ChainⁱPRO_0000439553	240 – 250	Protease cofactorUniRule annotationAdd BLAST	11
PeptideⁱPRO_0000036548	240 – 250	Protease cofactorAdd BLAST	11

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	124	Phosphoserine; by hostUniRule annotation	1
Modified residueⁱ	143	Phosphothreonine; by hostUniRule annotation	1
Disulfide bondⁱ	249	Interchain (with Adenovirus protease)UniRule annotation

Post-translational modificationⁱ

Ubiquitinated by Nedd4 following partial capsid disassembly; which might play a role in intracellular virus movement during entry.UniRule annotation1 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 chaperone protein.UniRule annotation1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	33 – 34	Cleavage; by viral proteaseUniRule annotation		2
Siteⁱ	239 – 240	Cleavage; by viral proteaseUniRule annotation		2

Keywords - PTMⁱ

Disulfide bond, Phosphoprotein, Ubl conjugation

Miscellaneous databases

PMAP-CutDBⁱ	P24937

PMAP-CutDBⁱ

P24937

Expressionⁱ

Inductionⁱ

Expressed in the late phase of the viral replicative cycle.UniRule annotation

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 (PubMed:14633984). Pre-protein VI: Interacts (via C-terminal NLS) with importin alpha/beta (PubMed:14633984). Endosome lysis protein: Interacts (via PPxY motif) with host NEDD4 ubiquitine ligase; this interaction might play a role in virus intracellular transport during entry (PubMed:20333243). Endosome lysis protein: 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 (PubMed:25071205). Endosome lysis protein: 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 (PubMed:25071205). Protease cofactor: Heterodimer with the viral protease; disulfide-linked (By similarity). Interacts with the viral protease (By similarity).UniRule annotationBy similarity3 Publications

Structureⁱ

3D structure databases

Database of protein disorder More...DisProtⁱ	DP00808
ProteinModelPortalⁱ	P24937
SMRⁱ	P24937
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P24937

EvolutionaryTraceⁱ

P24937

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	34 – 54	Amphipathic alpha-helix essential for membrane lytic activityUniRule annotationAdd BLAST	21
Regionⁱ	36 – 53	Involved in endosomal membrane lysisUniRule annotationAdd BLAST	18
Regionⁱ	48 – 74	Interaction with hexon proteinUniRule annotationAdd BLAST	27
Regionⁱ	105 – 225	DisorderedUniRule annotationAdd BLAST	121
Regionⁱ	233 – 239	Interaction with hexon proteinUniRule annotation	7
Regionⁱ	240 – 250	Binds to importin alpha/beta, involved in hexon nuclear importUniRule annotationAdd BLAST	11

Motif

Feature key	Position(s)	DescriptionActions	Length
Motifⁱ	67 – 76	Nuclear export signalUniRule annotation	10
Motifⁱ	131 – 135	Nuclear localization signalUniRule annotation	5
Motifⁱ	148 – 151	PPXY motifUniRule annotation	4
Motifⁱ	231 – 242	Nuclear export signalUniRule annotationAdd BLAST	12
Motifⁱ	245 – 248	Nuclear localization signalUniRule annotation	4

Domainⁱ

N-terminal amphipathic alpha-helix domain is essential for the membrane lytic activity.UniRule annotation1 Publication

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.UniRule annotation1 Publication

Sequence similaritiesⁱ

Belongs to the adenoviridae protein VI family.UniRule annotationCurated

Phylogenomic databases

Database of Orthologous Groups More...OrthoDBⁱ	VOG0900020I

OrthoDBⁱ

VOG0900020I

Family and domain databases

HAMAPⁱ	MF_04048 ADV_CAP6, 1 hit
InterProⁱ	View protein in InterPro IPR004243 McpVI
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02993 MCPVI, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

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

P24937-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MEDINFASLA PRHGSRPFMG NWQDIGTSNM SGGAFSWGSL WSGIKNFGST 
        60         70         80         90        100
VKNYGSKAWN SSTGQMLRDK LKEQNFQQKV VDGLASGISG VVDLANQAVQ 
       110        120        130        140        150
NKINSKLDPR PPVEEPPPAV ETVSPEGRGE KRPRPDREET LVTQIDEPPS 
       160        170        180        190        200
YEEALKQGLP TTRPIAPMAT GVLGQHTPVT LDLPPPADTQ QKPVLPGPTA 
       210        220        230        240        250
VVVTRPSRAS LRRAASGPRS LRPVASGNWQ STLNSIVGLG VQSLKRRRCF

Length:250

Mass (Da):26,996

Last modified:March 1, 1992 - v1

Checksum:ⁱ7BD1283743167EC0

GO

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M73260 Genomic DNA Translation: AAA96411.1
PIRⁱ	D39449 Q5ADB5
NCBI Reference Sequences More...RefSeqⁱ	AP_000210.1, AC_000008.1

Protein	Similar proteins		Species	Score	Length	Source
P24937	Pre-protein VI		Human mastadenovirus C		250	UniRef100_P24937
Pre-protein VI		ADE05		250
Adenovirus type 5 hexon, 23k, 100k and dna binding protein (coordinates 50.88% to 71.91% as measured by ad2-) (Fragment)		ADE05		45
UPI000BBB67A6		ADE05		217

Protein	Similar proteins		Species	Score	Length	Source
P24937	Pre-protein VI	)	ADE02		250	UniRef90_P24937
Pre-protein VI		Human mastadenovirus C		250
Pre-protein VI		ADE05		250
Pre-protein VI		AD01A		250
Pre-protein VI		ADE06		250
+15

Protein	Similar proteins		Species	Score	Length	Source
P24937	Pre-protein VI	)	ADE02		250	UniRef50_P24937
Pre-protein VI		Human mastadenovirus C		250
Pre-protein VI		ADE05		250
Pre-protein VI		ADE06		250
Pre-protein VI		AD01A		250
+102

Entry informationⁱ

Entry nameⁱ	CAP6_ADE05
Accessionⁱ	P24937Primary (citable) accession number: P24937
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
	Last sequence update:	March 1, 1992
	Last modified:	June 20, 2018
	This is version 92 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Viral Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P24937 (CAP6_ADE05)

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Pre-protein VI

L3

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Sites

Keywords - PTMi

Miscellaneous databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Keywords - Developmental stagei

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Sequence databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Keywords - Developmental stageⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ