CAP6_ADE05
ID CAP6_ADE05 Reviewed; 250 AA.
AC P24937;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 25-MAY-2022, entry version 110.
DE RecName: Full=Pre-protein VI {ECO:0000255|HAMAP-Rule:MF_04048};
DE Short=pVI {ECO:0000255|HAMAP-Rule:MF_04048};
DE Contains:
DE RecName: Full=Endosome lysis protein {ECO:0000255|HAMAP-Rule:MF_04048};
DE Contains:
DE RecName: Full=Protease cofactor {ECO:0000255|HAMAP-Rule:MF_04048};
DE AltName: Full=pVI-C {ECO:0000255|HAMAP-Rule:MF_04048};
GN Name=L3 {ECO:0000255|HAMAP-Rule:MF_04048};
OS Human adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5).
OC Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; Adenoviridae; Mastadenovirus.
OX NCBI_TaxID=28285;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1727603; DOI=10.1016/0042-6822(92)90082-z;
RA Chroboczek J., Bieber F., Jacrot B.;
RT "The sequence of the genome of adenovirus type 5 and its comparison with
RT the genome of adenovirus type 2.";
RL Virology 186:280-285(1992).
RN [2]
RP DNA-BINDING.
RX PubMed=7175505; DOI=10.1099/0022-1317-63-1-69;
RA Russell W.C., Precious B.;
RT "Nucleic acid-binding properties of adenovirus structural polypeptides.";
RL J. Gen. Virol. 63:69-79(1982).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION OF PRE-PROTEIN VI, NUCLEAR LOCALIZATION
RP SIGNALS, NUCLEAR EXPORT SIGNALS, INTERACTION OF PRE-PROTEIN VI WITH
RP IMPORTIN ALPHA/BETA, INTERACTION OF PRE-PROTEIN VI WITH HEXON PROTEIN, AND
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=14633984; DOI=10.1093/emboj/cdg614;
RA Wodrich H., Guan T., Cingolani G., Von Seggern D., Nemerow G., Gerace L.;
RT "Switch from capsid protein import to adenovirus assembly by cleavage of
RT nuclear transport signals.";
RL EMBO J. 22:6245-6255(2003).
RN [4]
RP FUNCTION OF ENDOSOME LYSIS PROTEIN, AND DOMAIN.
RX PubMed=15681401; DOI=10.1128/jvi.79.4.1992-2000.2005;
RA Wiethoff C.M., Wodrich H., Gerace L., Nemerow G.R.;
RT "Adenovirus protein VI mediates membrane disruption following capsid
RT disassembly.";
RL J. Virol. 79:1992-2000(2005).
RN [5]
RP FUNCTION, UBIQUITINATION, INTERACTION WITH HOST NEDD4, MUTAGENESIS OF
RP 149-PRO--TYR-151, AND DOMAIN.
RX PubMed=20333243; DOI=10.1371/journal.ppat.1000808;
RA Wodrich H., Henaff D., Jammart B., Segura-Morales C., Seelmeir S., Coux O.,
RA Ruzsics Z., Wiethoff C.M., Kremer E.J.;
RT "A capsid-encoded PPxY-motif facilitates adenovirus entry.";
RL PLoS Pathog. 6:E1000808-E1000808(2010).
RN [6]
RP FUNCTION OF ENDOSOME LYSIS PROTEIN.
RX PubMed=20409568; DOI=10.1016/j.virol.2010.03.043;
RA Maier O., Galan D.L., Wodrich H., Wiethoff C.M.;
RT "An N-terminal domain of adenovirus protein VI fragments membranes by
RT inducing positive membrane curvature.";
RL Virology 402:11-19(2010).
RN [7]
RP FUNCTION OF ENDOSOME LYSIS PROTEIN, AND MUTAGENESIS OF LEU-40.
RX PubMed=21209115; DOI=10.1128/jvi.02321-10;
RA Moyer C.L., Wiethoff C.M., Maier O., Smith J.G., Nemerow G.R.;
RT "Functional genetic and biophysical analyses of membrane disruption by
RT human adenovirus.";
RL J. Virol. 85:2631-2641(2011).
RN [8]
RP CHARACTERIZATION OF ENDOSOME LYSIS PROTEIN, MUTAGENESIS OF GLY-48, AND
RP FUNCTION.
RX PubMed=22516138; DOI=10.1016/j.virol.2012.03.024;
RA Moyer C.L., Nemerow G.R.;
RT "Disulfide-bond formation by a single cysteine mutation in adenovirus
RT protein VI impairs capsid release and membrane lysis.";
RL Virology 428:41-47(2012).
RN [9]
RP REVIEW.
RX PubMed=22754652; DOI=10.3390/v4050847;
RA San Martin C.;
RT "Latest insights on adenovirus structure and assembly.";
RL Viruses 4:847-877(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS), INTERACTION WITH THE HEXON PROTEIN,
RP IDENTIFICATION IN A COMPLEX WITH THE CORE-CAPSID BRIDGING PROTEIN AND THE
RP HEXON-LINKING PROTEIN VIII, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=25071205; DOI=10.1073/pnas.1408462111;
RA Reddy V.S., Nemerow G.R.;
RT "Structures and organization of adenovirus cement proteins provide insights
RT into the role of capsid maturation in virus entry and infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:11715-11720(2014).
CC -!- FUNCTION: [Pre-protein VI]: During virus assembly, promotes hexon
CC trimers nuclear import through nuclear pore complexes via an importin
CC alpha/beta-dependent mechanism. By analogy to herpesviruses capsid
CC assembly, might act as a chaperone to promote the formation of the
CC icosahedral capsid. {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000269|PubMed:14633984}.
CC -!- FUNCTION: [Endosome lysis protein]: Structural component of the virion
CC that provides increased stability to the particle shell through its
CC interaction with the core-capsid bridging protein and the hexon-linking
CC protein VIII (PubMed:25071205). Fibers shedding during virus entry into
CC host cell allows the endosome lysis protein to be exposed as a
CC membrane-lytic peptide (By similarity). Exhibits pH-independent
CC membrane fragmentation activity and probably mediates viral rapid
CC escape from host endosome via organellar membrane lysis
CC (PubMed:15681401, PubMed:21209115, PubMed:20409568, PubMed:22516138).
CC It is not clear if it then remains partially associated with the capsid
CC and involved in the intracellular microtubule-dependent transport of
CC capsid to the nucleus, or if it is lost during endosomal penetration
CC (PubMed:20333243). {ECO:0000250|UniProtKB:P03274, ECO:0000255|HAMAP-
CC Rule:MF_04048, ECO:0000269|PubMed:15681401,
CC ECO:0000269|PubMed:20333243, ECO:0000269|PubMed:20409568,
CC ECO:0000269|PubMed:21209115, ECO:0000269|PubMed:22516138,
CC ECO:0000269|PubMed:25071205}.
CC -!- FUNCTION: [Protease cofactor]: Cofactor that activates the viral
CC protease. Binds to viral protease in a 1:1 ratio. {ECO:0000255|HAMAP-
CC Rule:MF_04048}.
CC -!- SUBUNIT: [Pre-protein VI]: Interacts with hexon protein; this
CC interaction allows nuclear import of hexon trimers and possibly pre-
CC capsid assembly (PubMed:14633984). Interacts (via C-terminal NLS) with
CC importin alpha/beta (PubMed:14633984). {ECO:0000255|HAMAP-
CC Rule:MF_04048, ECO:0000269|PubMed:14633984}.
CC -!- SUBUNIT: [Endosome lysis protein]: Interacts (via PPxY motif) with host
CC NEDD4 ubiquitine ligase; this interaction might play a role in virus
CC intracellular transport during entry (PubMed:20333243). Part of a
CC complex composed of the core-capsid bridging protein, the endosome
CC lysis protein VI and the hexon-linking protein VIII; these interactions
CC bridge the virus core to the capsid (PubMed:25071205). Interacts with
CC peripentonal hexons; this interaction stabilizes the capsid by gluing
CC two peripentonal hexons together and joining them with an adjacent
CC group-of-nine hexon (PubMed:25071205). {ECO:0000255|HAMAP-
CC Rule:MF_04048, ECO:0000269|PubMed:20333243,
CC ECO:0000269|PubMed:25071205}.
CC -!- SUBUNIT: [Protease cofactor]: Heterodimer with the viral protease;
CC disulfide-linked. Interacts with the viral protease.
CC {ECO:0000255|HAMAP-Rule:MF_04048}.
CC -!- SUBCELLULAR LOCATION: [Pre-protein VI]: Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04048, ECO:0000269|PubMed:14633984}. Host
CC cytoplasm {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000269|PubMed:14633984}. Note=Shuttles between host cytoplasm and
CC nucleus. {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000269|PubMed:14633984}.
CC -!- SUBCELLULAR LOCATION: [Endosome lysis protein]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04048, ECO:0000269|PubMed:25071205}.
CC Note=Associates with the base of each peripentonal hexon on the capsid
CC interior. Present in around 360 copies per virion. {ECO:0000255|HAMAP-
CC Rule:MF_04048, ECO:0000269|PubMed:25071205}.
CC -!- INDUCTION: Expressed in the late phase of the viral replicative cycle.
CC {ECO:0000255|HAMAP-Rule:MF_04048}.
CC -!- DOMAIN: N-terminal amphipathic alpha-helix domain is essential for the
CC membrane lytic activity. {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000269|PubMed:20409568}.
CC -!- DOMAIN: Late-budding domains (L domains) are short sequence motifs
CC essential for viral particle release. They can occur individually or in
CC close proximity within structural proteins. They interacts with sorting
CC cellular proteins of the multivesicular body (MVB) pathway. Most of
CC these proteins are class E vacuolar protein sorting factors belonging
CC to ESCRT-I, ESCRT-II or ESCRT-III complexes. Minor capsid protein 6
CC contains one L domain: a PPXY motif which binds to the WW domains of
CC HECT (homologous to E6-AP C-terminus) E3 ubiquitin ligases, like NEDD4.
CC In adenoviruses, this motif seems to play a role in microtubule-
CC dependent intracellular trafficking toward the nucleus during virus
CC entry into host cell and in suppression of DAXX-mediated repression of
CC the immediate early E1A promoter. {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000305|PubMed:20333243}.
CC -!- PTM: Ubiquitinated by Nedd4 following partial capsid disassembly; which
CC might play a role in intracellular virus movement during entry.
CC {ECO:0000255|HAMAP-Rule:MF_04048, ECO:0000269|PubMed:20333243}.
CC -!- PTM: [Protease cofactor]: Contains the major nuclear import and export
CC signals. Proteolytically removed during virion maturation. The
CC processing of the C-terminus turns the precursor into a mature viral
CC structural protein and abrogates its ability to promote hexon import
CC and act as a potential chaperone protein. {ECO:0000255|HAMAP-
CC Rule:MF_04048, ECO:0000269|PubMed:14633984}.
CC -!- MISCELLANEOUS: All late proteins expressed from the major late promoter
CC are produced by alternative splicing and alternative polyadenylation of
CC the same gene giving rise to non-overlapping ORFs. A leader sequence is
CC present in the N-terminus of all these mRNAs and is recognized by the
CC viral shutoff protein to provide expression although conventional
CC translation via ribosome scanning from the cap has been shut off in the
CC host cell. {ECO:0000255|HAMAP-Rule:MF_04048}.
CC -!- SIMILARITY: Belongs to the adenoviridae protein VI family.
CC {ECO:0000255|HAMAP-Rule:MF_04048, ECO:0000305}.
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DR EMBL; M73260; AAA96411.1; -; Genomic_DNA.
DR PIR; D39449; Q5ADB5.
DR RefSeq; AP_000210.1; AC_000008.1.
DR PDB; 6CGV; X-ray; 3.80 A; W=6-29.
DR PDB; 7S78; EM; 3.72 A; 0/1/2/3/4/W/X/Y/Z=1-250.
DR PDBsum; 6CGV; -.
DR PDBsum; 7S78; -.
DR SMR; P24937; -.
DR EvolutionaryTrace; P24937; -.
DR Proteomes; UP000004992; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0046729; C:viral procapsid; IDA:CACAO.
DR GO; GO:0039664; P:lysis of host organelle involved in viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0075521; P:microtubule-dependent intracellular transport of viral material towards nucleus; IEA:UniProtKB-UniRule.
DR GO; GO:0019076; P:viral release from host cell; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04048; ADV_CAP6; 1.
DR InterPro; IPR004243; McpVI.
DR Pfam; PF02993; MCPVI; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Capsid protein; Cytoplasmic inwards viral transport;
KW Disulfide bond; Host cytoplasm; Host nucleus; Host-virus interaction;
KW Late protein; Microtubular inwards viral transport; Phosphoprotein;
KW Ubl conjugation; Viral capsid assembly;
KW Viral penetration into host cytoplasm;
KW Viral penetration via lysis of host organellar membrane;
KW Viral release from host cell; Virion; Virus entry into host cell.
FT CHAIN 1..250
FT /note="Pre-protein VI"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000421133"
FT PROPEP 1..33
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000036546"
FT CHAIN 34..239
FT /note="Endosome lysis protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000036547"
FT PEPTIDE 240..250
FT /note="Protease cofactor"
FT /id="PRO_0000036548"
FT CHAIN 240..250
FT /note="Protease cofactor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000439553"
FT REGION 34..54
FT /note="Amphipathic alpha-helix essential for membrane lytic
FT activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT REGION 36..53
FT /note="Involved in endosomal membrane lysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT REGION 48..74
FT /note="Interaction with hexon protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT REGION 103..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 233..239
FT /note="Interaction with hexon protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT REGION 240..250
FT /note="Binds to importin alpha/beta, involved in hexon
FT nuclear import"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOTIF 67..76
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOTIF 131..135
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOTIF 148..151
FT /note="PPXY motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOTIF 231..242
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOTIF 245..248
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT COMPBIAS 125..143
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 33..34
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT SITE 239..240
FT /note="Cleavage; by viral protease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOD_RES 124
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MOD_RES 143
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT DISULFID 249
FT /note="Interchain (with Adenovirus protease)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT MUTAGEN 40
FT /note="L->Q: Impaired endosome penetration and reduces
FT infectivity."
FT /evidence="ECO:0000269|PubMed:21209115"
FT MUTAGEN 48
FT /note="G->C: Decreased infectivity and endosomal membrane
FT disruption activity."
FT /evidence="ECO:0000269|PubMed:22516138"
FT MUTAGEN 149..151
FT /note="PSY->GAA: No effect on endosomal escape; defective
FT in microtubule-dependent trafficking toward the nucleus."
FT /evidence="ECO:0000269|PubMed:20333243"
SQ SEQUENCE 250 AA; 26996 MW; 7BD1283743167EC0 CRC64;
MEDINFASLA PRHGSRPFMG NWQDIGTSNM SGGAFSWGSL WSGIKNFGST VKNYGSKAWN
SSTGQMLRDK LKEQNFQQKV VDGLASGISG VVDLANQAVQ NKINSKLDPR PPVEEPPPAV
ETVSPEGRGE KRPRPDREET LVTQIDEPPS YEEALKQGLP TTRPIAPMAT GVLGQHTPVT
LDLPPPADTQ QKPVLPGPTA VVVTRPSRAS LRRAASGPRS LRPVASGNWQ STLNSIVGLG
VQSLKRRRCF
