Tbio ISG15 Ubiquitin-like protein ISG15

Protein Summary

Description

Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade therby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The protein encoded by this gene is a ubiquitin-like protein that is conjugated to intracellular target proteins upon activation by interferon-alpha and interferon-beta. Several functions have been ascribed to the encoded protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes secreted. [provided by RefSeq, Dec 2012]

Uniprot Accession IDs

• P05161
• Q5SVA4
• Q7Z2G2
• Q96GF0

Gene Name

• ISG15

Ensembl ID

• ENST00000379389
• ENSP00000368699
• ENSG00000187608
• ENST00000649529
• ENSP00000496832

Symbol

• G1P2
• UCRP
• G1P2
• IP17
• UCRP
• IFI15
• IMD38
• hUCRP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	1
PubMedID	0.96
small molecule perturbation	0.88
transcription factor perturbation	0.8
biological term	0.78

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Ribosomal Protein / Ubiquitin-like Protein Isg15

DTO Classes

Protein / Nucleic Acid Binding / Rna Binding Protein / Ribosomal Protein / Ubiquitin-like Protein Isg15

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 667.25   (req: < 5)

Gene RIFs: 182   (req: <= 3)

Antibodies: 525   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 667.25   (req: >= 5)

Gene RIFs: 182   (req: > 3)

Antibodies: 525   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0