D5LX59 (DEN_HCMVT) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 9, 2013.
Version 8.
History...
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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 UL48 EC=3.4.19.12 EC=3.4.22.- Alternative name(s): Tegument protein VP1-2 Tegument protein VP1/2 | ||
| Gene names |
| ||
| Organism | Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5) | ||
| Taxonomic identifier | 10363 [NCBI] | ||
| Taxonomic lineage | Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Betaherpesvirinae › Cytomegalovirus ›  | ||
| Virus host | Homo sapiens (Human) [TaxID: 9606] |
Protein attributes
| Sequence length | 2242 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
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 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 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 – 2242 | 2242 | Deneddylase UL48 | PRO_0000406913 | |||||
Regions | |||||||||
| Domain | 4 – 226 | 223 | Peptidase C76 | ||||||
| Coiled coil | 545 – 572 | 28 | Potential | ||||||
| Coiled coil | 766 – 793 | 28 | Potential | ||||||
| Coiled coil | 1168 – 1201 | 34 | Potential | ||||||
| Coiled coil | 1241 – 1273 | 33 | Potential | ||||||
| Compositional bias | 244 – 247 | 4 | Poly-Thr | ||||||
| Compositional bias | 315 – 320 | 6 | Poly-Ser | ||||||
| Compositional bias | 326 – 329 | 4 | Poly-Ser | ||||||
| Compositional bias | 786 – 790 | 5 | Poly-Glu | ||||||
| Compositional bias | 1922 – 1931 | 10 | Poly-Thr | ||||||
| Compositional bias | 2134 – 2138 | 5 | Poly-Ala | ||||||
Sites | |||||||||
| Active site | 24 | 1 | By similarity | ||||||
| Active site | 160 | 1 | By similarity | ||||||
| Active site | 162 | 1 | By similarity | ||||||
Experimental info | |||||||||
| Mutagenesis | 24 | 1 | C → S: Complete loss of DUB activity. Ref.2 | ||||||
| Mutagenesis | 162 | 1 | H → A: Complete loss of DUB activity. Ref.2 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human cytomegalovirus RL11 gene family: variation, recombination and transcription." Davison A.J. Submitted (MAR-2010) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CINCY+Towne. |
| [2] | "Cleavage specificity of the UL48 deubiquitinating protease activity of human cytomegalovirus and the growth of an active-site mutant virus in cultured cells." Kim E.T., Oh S.E., Lee Y.O., Gibson W., Ahn J.H. J. Virol. 83:12046-12056(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-24 AND HIS-162. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | GU980198 Genomic DNA. Translation: ADE88055.1. |
3D structure databases | |
| ModBase | Search... |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
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_HCMVT | ||||||||
| Accession | Primary (citable) accession number: D5LX59 | ||||||||
| 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 |