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   08-NOV-2023, entry version 115.
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; Human mastadenovirus C.
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
//