CAP6_ADE02
ID CAP6_ADE02 Reviewed; 250 AA.
AC P03274;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 02-JUN-2021, entry version 114.
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 2 (HAdV-2) (Human adenovirus 2).
OC Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; Adenoviridae; Mastadenovirus.
OX NCBI_TaxID=10515;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6985479; DOI=10.1128/jvi.38.2.469-482.1981;
RA Akusjaervi G., Persson H.;
RT "Gene and mRNA for precursor polypeptide VI from adenovirus type 2.";
RL J. Virol. 38:469-482(1981).
RN [2]
RP PROTEIN SEQUENCE OF 107-128 AND 138-156, AND PHOSPHORYLATION AT SER-124 AND
RP THR-143.
RX PubMed=22939182; DOI=10.1016/j.virol.2012.08.012;
RA Bergstrom Lind S., Artemenko K.A., Elfineh L., Zhao Y., Bergquist J.,
RA Pettersson U.;
RT "The phosphoproteome of the adenovirus type 2 virion.";
RL Virology 433:253-261(2012).
RN [3]
RP DNA-BINDING.
RC STRAIN=Human adenovirus C serotype 5;
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 [4]
RP INTERCHAIN DISULFIDE BOND WITH VIRAL PROTEASE (PROTEASE COFACTOR), SUBUNIT
RP (PROTEASE COFACTOR), AND INTERACTION OF PROTEASE COFACTOR WITH VIRAL
RP PROTEASE.
RX PubMed=8422686; DOI=10.1016/0092-8674(93)90053-s;
RA Webster A., Hay R.T., Kemp G.;
RT "The adenovirus protease is activated by a virus-coded disulphide-linked
RT peptide.";
RL Cell 72:97-104(1993).
RN [5]
RP INTERACTION OF PRE-PROTEIN VI WITH HEXON PROTEIN.
RX PubMed=7636476; DOI=10.1099/0022-1317-76-8-1959;
RA Matthews D.A., Russell W.C.;
RT "Adenovirus protein-protein interactions: molecular parameters governing
RT the binding of protein VI to hexon and the activation of the adenovirus 23K
RT protease.";
RL J. Gen. Virol. 76:1959-1969(1995).
RN [6]
RP INTERACTION WITH VIRAL PROTEASE (PROTEASE COFACTOR).
RX PubMed=11591154; DOI=10.1021/bi0109008;
RA Baniecki M.L., McGrath W.J., McWhirter S.M., Li C., Toledo D.L.,
RA Pellicena P., Barnard D.L., Thorn K.S., Mangel W.F.;
RT "Interaction of the human adenovirus proteinase with its 11-amino acid
RT cofactor pVIc.";
RL Biochemistry 40:12349-12356(2001).
RN [7]
RP INTERCHAIN DISULFIDE BOND WITH VIRAL PROTEASE (PROTEASE COFACTOR).
RX PubMed=12069522; DOI=10.1006/viro.2002.1394;
RA McGrath W.J., Aherne K.S., Mangel W.F.;
RT "In the virion, the 11-amino-acid peptide cofactor pVIc is covalently
RT linked to the adenovirus proteinase.";
RL Virology 296:234-240(2002).
RN [8]
RP FUNCTION (ENDOSOME LYSIS PROTEIN).
RX PubMed=21843868; DOI=10.1016/j.chom.2011.07.006;
RA Burckhardt C.J., Suomalainen M., Schoenenberger P., Boucke K., Hemmi S.,
RA Greber U.F.;
RT "Drifting motions of the adenovirus receptor CAR and immobile integrins
RT initiate virus uncoating and membrane lytic protein exposure.";
RL Cell Host Microbe 10:105-117(2011).
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 (2.6 ANGSTROMS) OF 240-250 IN COMPLEX WITH VIRAL
RP PROTEASE.
RX PubMed=8617222; DOI=10.1002/j.1460-2075.1996.tb00526.x;
RA Ding J., McGrath W.J., Sweet R.M., Mangel W.F.;
RT "Crystal structure of the human adenovirus proteinase with its 11 amino
RT acid cofactor.";
RL EMBO J. 15:1778-1783(1996).
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 -!- 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. Fibers shedding during virus entry into host cell allows
CC the endosome lysis protein to be exposed as a membrane-lytic peptide.
CC Exhibits pH-independent membrane fragmentation activity and probably
CC mediates viral rapid escape from host endosome via organellar membrane
CC lysis. It is not clear if it then remains partially associated with the
CC capsid and involved in the intracellular microtubule-dependent
CC transport of capsid to the nucleus, or if it is lost during endosomal
CC penetration. {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000269|PubMed:21843868}.
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:7636476). Interacts (via C-terminal NLS) with
CC importin alpha/beta. {ECO:0000255|HAMAP-Rule:MF_04048,
CC ECO:0000269|PubMed:7636476}.
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. Part of a complex composed of the
CC core-capsid bridging protein, the endosome lysis protein VI and the
CC hexon-linking protein VIII; these interactions bridge the virus core to
CC the capsid. Interacts with peripentonal hexons; this interaction
CC stabilizes the capsid by gluing two peripentonal hexons together and
CC joining them with an adjacent group-of-nine hexon. {ECO:0000255|HAMAP-
CC Rule:MF_04048}.
CC -!- SUBUNIT: [Protease cofactor]: Heterodimer with the viral protease;
CC disulfide-linked (PubMed:8422686, PubMed:12069522). Interacts with the
CC viral protease (PubMed:11591154, PubMed:8617222). {ECO:0000255|HAMAP-
CC Rule:MF_04048, ECO:0000269|PubMed:11591154, ECO:0000269|PubMed:8422686,
CC ECO:0000269|PubMed:8617222}.
CC -!- SUBCELLULAR LOCATION: [Pre-protein VI]: Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04048}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04048}. Note=Shuttles between host cytoplasm and nucleus.
CC {ECO:0000255|HAMAP-Rule:MF_04048}.
CC -!- SUBCELLULAR LOCATION: [Endosome lysis protein]: Virion
CC {ECO:0000255|HAMAP-Rule:MF_04048}. Note=Associates with the base of
CC each peripentonal hexon on the capsid interior. Present in around 360
CC copies per virion. {ECO:0000255|HAMAP-Rule:MF_04048}.
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 -!- 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 -!- 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}.
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}.
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}.
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DR EMBL; J01917; AAA92214.1; -; Genomic_DNA.
DR PIR; A03844; Q5ADB2.
DR RefSeq; AP_000174.1; AC_000007.1.
DR RefSeq; NP_040524.1; NC_001405.1.
DR PDB; 1AVP; X-ray; 2.60 A; B=240-250.
DR PDB; 1NLN; X-ray; 1.60 A; B=240-250.
DR PDB; 4PID; X-ray; 1.59 A; B=240-250.
DR PDB; 4PIE; X-ray; 1.94 A; B=240-250.
DR PDB; 5FGY; X-ray; 2.10 A; B=240-250.
DR PDBsum; 1AVP; -.
DR PDBsum; 1NLN; -.
DR PDBsum; 4PID; -.
DR PDBsum; 4PIE; -.
DR PDBsum; 5FGY; -.
DR SMR; P03274; -.
DR iPTMnet; P03274; -.
DR GeneID; 2652998; -.
DR EvolutionaryTrace; P03274; -.
DR Proteomes; UP000008167; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019028; C:viral capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0046729; C:viral procapsid; IEA:UniProtKB-UniRule.
DR GO; GO:0039664; P:lysis of host organelle involved in viral entry into host cell; IEA:UniProtKB-UniRule.
DR GO; GO:0075521; P:microtubule-dependent intracellular transport of viral material towards nucleus; IEA:UniProtKB-UniRule.
DR GO; GO:0039708; P:nuclear capsid assembly; IDA:UniProtKB.
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 Direct protein sequencing; Disulfide bond; Host cytoplasm; Host nucleus;
KW Host-virus interaction; Late protein; Microtubular inwards viral transport;
KW Phosphoprotein; Reference proteome; 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_0000421078"
FT PROPEP 1..33
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000036543"
FT CHAIN 34..239
FT /note="Endosome lysis protein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000036544"
FT PEPTIDE 240..250
FT /note="Protease cofactor"
FT /id="PRO_0000036545"
FT CHAIN 240..250
FT /note="Protease cofactor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT /id="PRO_0000439552"
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..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..226
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 ECO:0000269|PubMed:22939182"
FT MOD_RES 143
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048,
FT ECO:0000269|PubMed:22939182"
FT DISULFID 249
FT /note="Interchain (with Adenovirus protease)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04048"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:4PID"
SQ SEQUENCE 250 AA; 27014 MW; 4CACF18014647328 CRC64;
MEDINFASLA PRHGSRPFMG NWQDIGTSNM SGGAFSWGSL WSGIKNFGST IKNYGSKAWN
SSTGQMLRDK LKEQNFQQKV VDGLASGISG VVDLANQAVQ NKINSKLDPR PPVEEPPPAV
ETVSPEGRGE KRPRPDREET LVTQIDEPPS YEEALKQGLP TTRPIAPMAT GVLGQHTPVT
LDLPPPADTQ QKPVLPGPSA VVVTRPSRAS LRRAASGPRS MRPVASGNWQ STLNSIVGLG
VQSLKRRRCF