P03252 (PRO_ADE02) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protease
EC=3.4.22.39

Alternative name(s):
Adenain
Adenovirus protease
Short name=AVP
Adenovirus proteinase
Endoprotease

Gene names

ORF Names:

L3

Organism

Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2) [Reference proteome]

Taxonomic identifier

10515 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Adenoviridae › Mastadenovirus › Human adenovirus C

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	204 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cleaves viral precursor proteins (pTP, pIIIa, pVI, pVII, pVIII, and pX) inside newly assembled particles giving rise to mature virions. Protease complexed to its cofactor slides along the viral DNA to specifically locate and cleave the viral precursors. Mature virions have a weakened organization compared to the unmature virions, thereby facilitating subsequent uncoating. Without maturation, the particle lacks infectivity and is unable to uncoat. Late in adenovirus infection, in the cytoplasm, may participate to the cytoskeleton destruction. Cleaves host cells cytoskeletal keratins K7 and K18. Ref.9
Catalytic activity	Cleaves proteins of the adenovirus and its host cell at two consensus sites: -Yaa-Xaa-Gly-Gly-|-Xaa- and -Yaa-Xaa-Gly-Xaa-|-Gly- (in which Yaa is Met, Ile or Leu, and Xaa is any amino acid).
Enzyme regulation	Requires DNA and protease cofactor for maximal activation. Inside nascent virions, becomes partially activated by binding to the viral DNA, allowing it to cleave the cofactor that binds to the protease and fully activates it. Actin, like the viral protease cofactor, seems to act as a cofactor in the cleavage of cytokeratin 18 and of actin itself. Ref.5 Ref.6 Ref.12
Subunit structure	Interacts with protease cofactor pVI-C; this interaction is necessary for protease activation. Ref.5
Subcellular location	Virion. Host nucleus Probable. Note: Present in about 10 copies per virion. Ref.3
Induction	Expressed in the late phase of the viral replicative cycle. Ref.5 Ref.6 Ref.12
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.
Sequence similarities	Belongs to the peptidase C5 family.

Ontologies

Keywords
Cellular component	Host nucleus Virion
Developmental stage	Late protein
Ligand	DNA-binding
Molecular function	Hydrolase Protease Thiol protease
PTM	Autocatalytic cleavage Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 204

204

Protease

PRO_0000218023

Sites

Active site

54

1

Ref.12

Active site

71

1

Ref.12

Active site

122

1

Ref.12

Site

46 – 47

2

Cleavage; by autolysis Potential

Amino acid modifications

Disulfide bond

104

Interchain (with C-10 in cleaved protease cofactor pVI-C) Ref.6 Ref.12

Experimental info

Mutagenesis

137

1

P → L: Loss of activity; gives rise to unprocessed capsids defective in endosomal escape. Ref.8

Secondary structure

1

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204

Helix Strand Turn

Details...

Helix

5 – 14

10

Helix

18 – 20

3

Beta strand

21 – 28

8

Beta strand

35 – 37

3

Beta strand

39 – 45

7

Turn

48 – 50

3

Beta strand

55 – 61

7

Turn

62 – 65

4

Beta strand

66 – 70

5

Helix

78 – 95

18

Beta strand

106 – 109

4

Helix

122 – 135

14

Beta strand

141 – 144

4

Helix

147 – 149

3

Helix

155 – 157

3

Helix

161 – 163

3

Helix

164 – 181

18

Helix

183 – 187

5

Helix

189 – 195

7

Turn

198 – 201

4

Sequences

	Sequence		Length	Mass (Da)
	P03252 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: E43C7DDF14A589A2	FASTA	204	23,087
	10 20 30 40 50 60 MGSSEQELKA IVKDLGCGPY FLGTYDKRFP GFVSPHKLAC AIVNTAGRET GGVHWMAFAW 70 80 90 100 110 120 NPRSKTCYLF EPFGFSDQRL KQVYQFEYES LLRRSAIASS PDRCITLEKS TQSVQGPNSA 130 140 150 160 170 180 ACGLFCCMFL HAFANWPQTP MDHNPTMNLI TGVPNSMLNS PQVQPTLRRN QEQLYSFLER 190 200 HSPYFRSHSA QIRSATSFCH LKNM

References

[1]	"The sequence of the 3' non-coding region of the hexon mRNA discloses a novel adenovirus gene." Akusjaervi G., Zabielski J., Perricaudet M., Pettersson U. Nucleic Acids Res. 9:1-17(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Localization of the 3'-terminal end of the EcoRI B fragment-specific early mRNA of adenovirus type 2." Buttner W., Veres-Molnar Z. FEBS Lett. 122:317-321(1980) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 167-204.
[3]	"Analysis of the adenovirus type 5 proteome by liquid chromatography and tandem mass spectrometry methods." Chelius D., Huhmer A.F., Shieh C.H., Lehmberg E., Traina J.A., Slattery T.K., Pungor E. Jr. J. Proteome Res. 1:501-513(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION. Strain: Human adenovirus C serotype 5.
[4]	"Human adenovirus proteinase: DNA binding and stimulation of proteinase activity by DNA." McGrath W.J., Baniecki M.L., Li C., McWhirter S.M., Brown M.T., Toledo D.L., Mangel W.F. Biochemistry 40:13237-13245(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING.
[5]	"Interaction of the human adenovirus proteinase with its 11-amino acid cofactor pVIc." Baniecki M.L., McGrath W.J., McWhirter S.M., Li C., Toledo D.L., Pellicena P., Barnard D.L., Thorn K.S., Mangel W.F. Biochemistry 40:12349-12356(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PROTEASE COFACTOR, ENZYME REGULATION.
[6]	"In the virion, the 11-amino-acid peptide cofactor pVIc is covalently linked to the adenovirus proteinase." McGrath W.J., Aherne K.S., Mangel W.F. Virology 296:234-240(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERCHAIN DISULFIDE BOND WITH PROTEASE COFACTOR, ENZYME REGULATION.
[7]	"Substrate specificity of adenovirus protease." Ruzindana-Umunyana A., Imbeault L., Weber J.M. Virus Res. 89:41-52(2002) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Genetic reconstitution of the human adenovirus type 2 temperature-sensitive 1 mutant defective in endosomal escape." Imelli N., Ruzsics Z., Puntener D., Gastaldelli M., Greber U.F. Virol. J. 6:174-174(2009) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF PRO-137. Strain: Mutant ts-1.
[9]	"The role of capsid maturation on adenovirus priming for sequential uncoating." Perez-Berna A.J., Ortega-Esteban A., Menendez-Conejero R., Winkler D.C., Menendez M., Steven A.C., Flint S.J., de Pablo P.J., San Martin C. J. Biol. Chem. 287:31582-31595(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Regulation of a viral proteinase by a peptide and DNA in one-dimensional space. IV. viral proteinase slides along DNA to locate and process its substrates." Blainey P.C., Graziano V., Perez-Berna A.J., McGrath W.J., Flint S.J., San Martin C., Xie X.S., Mangel W.F. J. Biol. Chem. 288:2092-2102(2013) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[11]	"Latest insights on adenovirus structure and assembly." San Martin C. Viruses 4:847-877(2012) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor." Ding J., McGrath W.J., Sweet R.M., Mangel W.F. EMBO J. 15:1778-1783(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH PROTEASE COFACTOR, DISULFIDE BOND, ACTIVE SITE, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J01917 Genomic DNA. Translation: AAA92216.1.

PIR

W2AD35. A03823.

RefSeq

AP_000176.1. AC_000007.1.
NP_040526.1. NC_001405.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AVP	X-ray	2.60	A	1-204	[»]
1NLN	X-ray	1.60	A	1-204	[»]
4EKF	X-ray	0.98	A	1-204	[»]

ProteinModelPortal

P03252.

SMR

P03252. Positions 1-204.

ModBase

Search...

Protein family/group databases

MEROPS

C05.001.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

2652998.

Phylogenomic databases

ProtClustDB

CLSP2513881.

Family and domain databases

Gene3D

3.40.395.10. 1 hit.

InterPro

IPR000855. Peptidase_C5.
[Graphical view]

Pfam

PF00770. Peptidase_C5. 1 hit.
[Graphical view]

PIRSF

PIRSF001218. Protease_ADV. 1 hit.

PRINTS

PR00703. ADVENDOPTASE.

ProDom

PD003705. Peptidase_C5. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other

EvolutionaryTrace

P03252.

Entry information

Entry name

PRO_ADE02

Accession

Primary (citable) accession number: P03252

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program