Recombinant Bovine Ubiquitin-like protein ISG15 (ISG15)

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. Exhibits antiviral activity towards both DNA and RNA viruses. The secreted form of ISG15 can: induce natural killer cell proliferation, augment lymphokine-activated-killer (LAK) activity, induce dendritic cell maturation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity (By similarity). The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (By similarity). In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (PubMed:9546718)

Subcellular Location

Cytoplasm; Secreted

Tissue Specificity

Expressed in endometrium and uterine flushings of pregnant cow. Also secreted. Not detected in spleen, liver, corpus luteum or muscle

Subunit

Homodimer; disulfide-linked (By similarity). Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) (By similarity). Interacts with NEDD4 (By similarity). Interacts with PARP12; this interaction inhibits PINK1/Parkin-dependent mitophagy (By similarity)

• Austin K.J. et al. Complementary deoxyribonucleic acid sequence encoding bovine ubiquitin cross-reactive protein: a comparison with ubiquitin and a 15-kDa ubiquitin homolog. — Endocrine (1996)
• Perry D.J. et al. Cloning of interferon-stimulated gene 17: the promoter and nuclear proteins that regulate transcription. — Mol. Endocrinol. (1999)
• PubMed: CI-BB3I87URM95J3 (AUG-)
• Austin K.J. et al. Ubiquitin cross-reactive protein is released by the bovine uterus in response to interferon during early pregnancy. — Biol. Reprod. (1996)
• Hansen T.R. et al. Transient ubiquitin cross-reactive protein gene expression in the bovine endometrium. — Endocrinology (1997)
• Johnson G.A. et al. Pregnancy and interferon-tau induce conjugation of bovine ubiquitin cross-reactive protein to cytosolic uterine proteins. — Biol. Reprod. (1998)