O41965 (DEN_MHV68) Reviewed, UniProtKB/Swiss-Prot
Last modified
April 3, 2013.
Version 36.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Deneddylase ORF64 EC=3.4.19.12 EC=3.4.22.- Alternative name(s): Tegument protein VP1-2 Tegument protein VP1/2 | ||
| Gene names |
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| Organism | Murid herpesvirus 4 (MuHV-4) (Murine gammaherpesvirus 68) | ||
| Taxonomic identifier | 33708 [NCBI] | ||
| Taxonomic lineage | Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Gammaherpesvirinae › Rhadinovirus | ||
| Virus host | Apodemus sylvaticus (European woodmouse) [TaxID: 10129] |
Protein attributes
| Sequence length | 2457 AA. |
| Sequence status | Complete. |
| Protein existence | Inferred from homology |
General annotation (Comments)
| Function | Deneddylase that deregulates the host cell cycle S phase to create a favorable environment allowing efficient viral genome replication. Interacts with and deneddylates host cullins including CUL1 and CUL4A, thereby reducing their E3 ubiquitin ligase activity. Inhibition of cullins leads to the stabilization of cullin-RING ligase substrates such as host CDN1A/p21, CDKN1B/p27kip and CDC25A, preventing S phase progression. Additionally, acts as a deubiquitinase and cleaves both 'Lys-48' and 'Lys-63'-linked ubiquitin chains By similarity. Ref.2 |
| Catalytic activity | Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). |
| Subunit structure | Interacts with host CUL1 and CUL4A; these interactions inhibit the E3 ligase activity of cullins By similarity. |
| Subcellular location | Virion tegument. Host cytoplasm. Host nucleus By similarity. Note: Tightly associated with the capsid By similarity. |
| Sequence similarities | Belongs to the herpesviridae large tegument protein family. Contains 8 LRR (leucine-rich) repeats. Contains 1 peptidase C76 domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Host-virus interaction Modulation of host ubiquitin pathway by viral deubiquitinase Modulation of host ubiquitin pathway by virus Ubl conjugation pathway |
| Cellular component | Host cytoplasm Host nucleus Virion Virion tegument |
| Domain | Coiled coil Leucine-rich repeat Repeat |
| Molecular function | Hydrolase Protease Thiol protease |
| Gene Ontology (GO) | |
| Biological_process | modulation by virus of host protein ubiquitination Inferred from electronic annotation. Source: UniProtKB-KW proteolysisInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular_component | host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleusInferred from electronic annotation. Source: UniProtKB-SubCell viral tegumentInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular_function | cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2457 | 2457 | Deneddylase ORF64 | PRO_0000406915 | |||||
Regions | |||||||||
| Domain | 13 – 224 | 212 | Peptidase C76 | ||||||
| Repeat | 426 – 449 | 24 | LRR 1 | ||||||
| Repeat | 1017 – 1042 | 26 | LRR 2 | ||||||
| Repeat | 1254 – 1277 | 24 | LRR 3 | ||||||
| Repeat | 1662 – 1685 | 24 | LRR 4 | ||||||
| Repeat | 1699 – 1721 | 23 | LRR 5 | ||||||
| Repeat | 1740 – 1763 | 24 | LRR 6 | ||||||
| Repeat | 1801 – 1827 | 27 | LRR 7 | ||||||
| Repeat | 2046 – 2071 | 26 | LRR 8 | ||||||
Sites | |||||||||
| Active site | 33 | 1 | By similarity | ||||||
| Active site | 163 | 1 | By similarity | ||||||
| Active site | 165 | 1 | By similarity | ||||||
| Site | 20 | 1 | Important for catalytic activity By similarity | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Complete sequence and genomic analysis of murine gammaherpesvirus 68." Virgin H.W. IV, Latreille P., Wamsley P., Hallsworth K., Weck K.E., Dal Canto A.J., Speck S.H. J. Virol. 71:5894-5904(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: G2.4 and WUMS. |
| [2] | "A functional ubiquitin-specific protease embedded in the large tegument protein (ORF64) of murine gammaherpesvirus 68 is active during the course of infection." Gredmark S., Schlieker C., Quesada V., Spooner E., Ploegh H.L. J. Virol. 81:10300-10309(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U97553 Genomic DNA. Translation: AAB66417.1. AF105037 Genomic DNA. Translation: AAF19328.1. |
| RefSeq | NP_044902.1. NC_001826.2. |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-47224N. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| GeneID | 1497174. |
Phylogenomic databases | |
| ProtClustDB | CLSP2509700. |
Family and domain databases | |
| InterPro | IPR006928. Pept_C76_UL36-USP. [Graphical view] |
| Pfam | PF04843. Herpes_teg_N. 1 hit. [Graphical view] |
| PROSITE | PS51521. HTUSP. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | DEN_MHV68 | ||||||||
| Accession | Primary (citable) accession number: O41965 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Viral Protein Annotation Program | ||||||||
Relevant documents
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |