PRO_ADE02
ID PRO_ADE02 Reviewed; 204 AA.
AC P03252;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Protease {ECO:0000255|HAMAP-Rule:MF_04059};
DE EC=3.4.22.39 {ECO:0000255|HAMAP-Rule:MF_04059};
DE AltName: Full=Adenain {ECO:0000255|HAMAP-Rule:MF_04059};
DE AltName: Full=Adenovirus protease {ECO:0000255|HAMAP-Rule:MF_04059};
DE Short=AVP {ECO:0000255|HAMAP-Rule:MF_04059};
DE AltName: Full=Adenovirus proteinase {ECO:0000255|HAMAP-Rule:MF_04059};
DE AltName: Full=Endoprotease {ECO:0000255|HAMAP-Rule:MF_04059};
GN Name=L3 {ECO:0000255|HAMAP-Rule:MF_04059};
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=6259616; DOI=10.1093/nar/9.1.1;
RA Akusjaervi G., Zabielski J., Perricaudet M., Pettersson U.;
RT "The sequence of the 3' non-coding region of the hexon mRNA discloses a
RT novel adenovirus gene.";
RL Nucleic Acids Res. 9:1-17(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 167-204.
RX PubMed=6258984; DOI=10.1016/0014-5793(80)80464-9;
RA Buttner W., Veres-Molnar Z.;
RT "Localization of the 3'-terminal end of the EcoRI B fragment-specific early
RT mRNA of adenovirus type 2.";
RL FEBS Lett. 122:317-321(1980).
RN [3]
RP SUBCELLULAR LOCATION.
RC STRAIN=Human adenovirus C serotype 5;
RX PubMed=12645618; DOI=10.1021/pr025528c;
RA Chelius D., Huhmer A.F., Shieh C.H., Lehmberg E., Traina J.A.,
RA Slattery T.K., Pungor E. Jr.;
RT "Analysis of the adenovirus type 5 proteome by liquid chromatography and
RT tandem mass spectrometry methods.";
RL J. Proteome Res. 1:501-513(2002).
RN [4]
RP DNA-BINDING.
RX PubMed=11683632; DOI=10.1021/bi0111653;
RA McGrath W.J., Baniecki M.L., Li C., McWhirter S.M., Brown M.T.,
RA Toledo D.L., Mangel W.F.;
RT "Human adenovirus proteinase: DNA binding and stimulation of proteinase
RT activity by DNA.";
RL Biochemistry 40:13237-13245(2001).
RN [5]
RP INTERACTION WITH PROTEASE COFACTOR, AND ACTIVITY REGULATION.
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 [6]
RP INTERCHAIN DISULFIDE BOND WITH PROTEASE COFACTOR, AND ACTIVITY REGULATION.
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 [7]
RP CHARACTERIZATION.
RX PubMed=12367749; DOI=10.1016/s0168-1702(02)00111-9;
RA Ruzindana-Umunyana A., Imbeault L., Weber J.M.;
RT "Substrate specificity of adenovirus protease.";
RL Virus Res. 89:41-52(2002).
RN [8]
RP MUTAGENESIS OF PRO-137.
RC STRAIN=Mutant ts-1;
RX PubMed=19860872; DOI=10.1186/1743-422x-6-174;
RA Imelli N., Ruzsics Z., Puntener D., Gastaldelli M., Greber U.F.;
RT "Genetic reconstitution of the human adenovirus type 2 temperature-
RT sensitive 1 mutant defective in endosomal escape.";
RL Virol. J. 6:174-174(2009).
RN [9]
RP FUNCTION.
RX PubMed=22791715; DOI=10.1074/jbc.m112.389957;
RA Perez-Berna A.J., Ortega-Esteban A., Menendez-Conejero R., Winkler D.C.,
RA Menendez M., Steven A.C., Flint S.J., de Pablo P.J., San Martin C.;
RT "The role of capsid maturation on adenovirus priming for sequential
RT uncoating.";
RL J. Biol. Chem. 287:31582-31595(2012).
RN [10]
RP CHARACTERIZATION.
RX PubMed=23043138; DOI=10.1074/jbc.m112.407460;
RA Blainey P.C., Graziano V., Perez-Berna A.J., McGrath W.J., Flint S.J.,
RA San Martin C., Xie X.S., Mangel W.F.;
RT "Regulation of a viral proteinase by a peptide and DNA in one-dimensional
RT space. IV. viral proteinase slides along DNA to locate and process its
RT substrates.";
RL J. Biol. Chem. 288:2092-2102(2013).
RN [11]
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 [12]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH PROTEASE COFACTOR,
RP DISULFIDE BOND, ACTIVE SITE, AND ACTIVITY REGULATION.
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: Cleaves viral precursor proteins (pTP, pIIIa, pVI, pVII,
CC pVIII, and pX) inside newly assembled particles giving rise to mature
CC virions. Protease complexed to its cofactor slides along the viral DNA
CC to specifically locate and cleave the viral precursors. Mature virions
CC have a weakened organization compared to the unmature virions, thereby
CC facilitating subsequent uncoating. Without maturation, the particle
CC lacks infectivity and is unable to uncoat. Late in adenovirus
CC infection, in the cytoplasm, may participate in the cytoskeleton
CC destruction. Cleaves host cell cytoskeletal keratins K7 and K18.
CC {ECO:0000255|HAMAP-Rule:MF_04059, ECO:0000269|PubMed:22791715}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves proteins of the adenovirus and its host cell at two
CC consensus sites: -Yaa-Xaa-Gly-Gly-|-Xaa- and -Yaa-Xaa-Gly-Xaa-|-
CC Gly- (in which Yaa is Met, Ile or Leu, and Xaa is any amino acid).;
CC EC=3.4.22.39; Evidence={ECO:0000255|HAMAP-Rule:MF_04059};
CC -!- ACTIVITY REGULATION: Requires DNA and protease cofactor for maximal
CC activation. Inside nascent virions, becomes partially activated by
CC binding to the viral DNA, allowing it to cleave the cofactor that binds
CC to the protease and fully activates it. Actin, like the viral protease
CC cofactor, seems to act as a cofactor in the cleavage of cytokeratin 18
CC and of actin itself. {ECO:0000255|HAMAP-Rule:MF_04059,
CC ECO:0000269|PubMed:11591154, ECO:0000269|PubMed:12069522,
CC ECO:0000269|PubMed:8617222}.
CC -!- SUBUNIT: Interacts with protease cofactor pVI-C; this interaction is
CC necessary for protease activation. {ECO:0000255|HAMAP-Rule:MF_04059,
CC ECO:0000269|PubMed:11591154, ECO:0000269|PubMed:8617222}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04059,
CC ECO:0000269|PubMed:12645618}. Host nucleus {ECO:0000255|HAMAP-
CC Rule:MF_04059, ECO:0000305|PubMed:12645618}. Note=Present in about 10
CC copies per virion. {ECO:0000255|HAMAP-Rule:MF_04059}.
CC -!- INDUCTION: Expressed in the late phase of the viral replicative cycle.
CC {ECO:0000255|HAMAP-Rule:MF_04059}.
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_04059}.
CC -!- SIMILARITY: Belongs to the peptidase C5 family. {ECO:0000255|HAMAP-
CC Rule:MF_04059, ECO:0000305}.
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DR EMBL; J01917; AAA92216.1; -; Genomic_DNA.
DR PIR; A03823; W2AD35.
DR RefSeq; AP_000176.1; AC_000007.1.
DR RefSeq; NP_040526.1; NC_001405.1.
DR PDB; 1AVP; X-ray; 2.60 A; A=1-204.
DR PDB; 1NLN; X-ray; 1.60 A; A=1-204.
DR PDB; 4EKF; X-ray; 0.98 A; A=1-204.
DR PDB; 4PID; X-ray; 1.59 A; A=1-204.
DR PDB; 4PIE; X-ray; 1.94 A; A=1-204.
DR PDB; 5FGY; X-ray; 2.10 A; A=1-204.
DR PDBsum; 1AVP; -.
DR PDBsum; 1NLN; -.
DR PDBsum; 4EKF; -.
DR PDBsum; 4PID; -.
DR PDBsum; 4PIE; -.
DR PDBsum; 5FGY; -.
DR SMR; P03252; -.
DR MEROPS; C05.001; -.
DR PRIDE; P03252; -.
DR GeneID; 2652998; -.
DR EvolutionaryTrace; P03252; -.
DR Proteomes; UP000008167; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:CACAO.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR HAMAP; MF_04059; ADV_PRO; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000855; Peptidase_C5.
DR Pfam; PF00770; Peptidase_C5; 1.
DR PIRSF; PIRSF001218; Protease_ADV; 1.
DR PRINTS; PR00703; ADVENDOPTASE.
DR SUPFAM; SSF54001; SSF54001; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Disulfide bond; DNA-binding;
KW Host nucleus; Hydrolase; Late protein; Protease; Reference proteome;
KW Thiol protease; Virion.
FT CHAIN 1..204
FT /note="Protease"
FT /id="PRO_0000218023"
FT ACT_SITE 54
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04059,
FT ECO:0000269|PubMed:8617222"
FT ACT_SITE 71
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04059,
FT ECO:0000269|PubMed:8617222"
FT ACT_SITE 122
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04059,
FT ECO:0000269|PubMed:8617222"
FT SITE 51..52
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04059"
FT DISULFID 104
FT /note="Interchain (with C-10 in cleaved protease cofactor
FT pVI-C)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04059,
FT ECO:0000269|PubMed:8617222"
FT MUTAGEN 137
FT /note="P->L: Loss of activity; gives rise to unprocessed
FT capsids defective in endosomal escape."
FT /evidence="ECO:0000269|PubMed:19860872"
FT HELIX 5..14
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:4EKF"
FT STRAND 21..28
FT /evidence="ECO:0007829|PDB:4EKF"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:5FGY"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:4PID"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:4EKF"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:4EKF"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 78..95
FT /evidence="ECO:0007829|PDB:4EKF"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 122..135
FT /evidence="ECO:0007829|PDB:4EKF"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 164..181
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:4EKF"
FT HELIX 189..195
FT /evidence="ECO:0007829|PDB:4EKF"
FT TURN 198..201
FT /evidence="ECO:0007829|PDB:4EKF"
SQ SEQUENCE 204 AA; 23087 MW; E43C7DDF14A589A2 CRC64;
MGSSEQELKA IVKDLGCGPY FLGTYDKRFP GFVSPHKLAC AIVNTAGRET GGVHWMAFAW
NPRSKTCYLF EPFGFSDQRL KQVYQFEYES LLRRSAIASS PDRCITLEKS TQSVQGPNSA
ACGLFCCMFL HAFANWPQTP MDHNPTMNLI TGVPNSMLNS PQVQPTLRRN QEQLYSFLER
HSPYFRSHSA QIRSATSFCH LKNM
