Antibody-points Bulletin: ISG15

BOLO:

Name: Ubiquitin-like protein ISG15

PID: P05161

GID: 9626

Nicknames: ISG15

AKA: G1P2, IP17, UCRP, IFI15, IMD38, hUCR

Vitals:

   Origins: 1p36.33
   DNA: NG_03303 1074 bp, (5001..6074)
   RNA: NM_005101.3 685 bp
   Exons: 2
   Protein: 165 aa, 17.8 kDa

Description:

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.

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.

Protein of Interest in the Following Cases:

Source: Open Targets Platform

Last Known Addresses:

  •  Cytoplasm
  •  Secreted

Known Hangouts:

Source: NCBI

Known Associates:

Source: BioGrid

Gang Associations:

  •  Defense Response To Virus
  •  Isg15-Protein Conjugation
  •  Modification-Dependent Protein Catabolic Process
  •  Negative Regulation Of Protein Ubiquitination
  •  Negative Regulation Of Type I Interferon Production
  •  Negative Regulation Of Viral Genome Replication
  •  Positive Regulation Of Bone Mineralization
  •  Positive Regulation Of Erythrocyte Differentiation
  •  Regulation Of Interferon-Gamma Production
  •  Response To Type I Interferon
  •  Translesion Synthesis
  •  Type I Interferon Signaling Pathway
  •  Viral Process

Known Weaknesses: Unknown

Reported Sightings:

Source: Pubmed

Means of Capture: