|Description:||Rabbit polyclonal antibody to ISG15.|
|Immunogen:||A synthetic peptide of human ISG15|
|Formulation:||PBS with 0.02% sodium azide, 50% glycerol, pH7.3.|
|Synonyms:||G1P2; IP17; UCRP; IFI15; hUCRP|
|Background:||ISG15 is a ubiquitin-like protein that becomes conjugated to many cellular proteins upon activation by interferon-alpha (IFNA) and -beta (IFNB). ISG15 forms covalent conjugates with its target proteins in a process called ISGylation, which in mammals is known to play a role in antiviral immunity. ISG15 proteins possess two ubiquitin-like (UBL) domains and a highly conserved C-terminal LRGG sequence, the latter being known as the ubiquitin conjugation motif. Intracellular ISG15 are conjugated, via the LRGG motif, to target proteins through a process called ISGylation, which resembles largely ubiquitination, the process of formation of ubiquitin conjugates. Unconjugated extracellular ISG15, which are released from several types of human and murine cells, are known to possess cytokine-like activity.|
|Storage:||Store at 4℃. Avoid freeze / thaw cycles.|
|Recommended Dilutions:||WB 1:500 - 1:2000, IHC 1:50 - 1:200|
Target (Information from UniProt)
|Function:||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.|
|Tissue Specificity:||Detected in lymphoid cells, striated and smooth muscle, several epithelia and neurons. Expressed in neutrophils, monocytes and lymphocytes. Enhanced expression seen in pancreatic adenocarcinoma, endometrial cancer, and bladder cancer, as compared to non-cancerous tissue. In bladder cancer, the increase in expression exhibits a striking positive correlation with more advanced stages of the disease.|
|Involvement in Disease:||Immunodeficiency 38, with basal ganglia calcification: A primary immunodeficiency predisposing individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines. Patients are also susceptible to Salmonella and Mycobacterium tubercolosis infections. Affected individuals have intracranial calcification.|
|Post-Translational Modification:||S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins.|
|Cellular Location:||Cytoplasm. Secreted.
Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins.
Western blot analysis of extracts of HeLa cell line, using ISG15 antibody.