interferon a-6

SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK STAT pathway. Through binding to JAKs and IFNGR1, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival. Probable substrate recognition component of an ECS (Elongin BC-CUL2 5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize JAK2. SOCS1 appears to be a negative regulator in IGF1R signaling pathway.

PSME2, also known as PA28b, is a subunit of proteasome. The 26S proteasome multicatalytic proteinase complex has a highly ordered structure composed of 2 complexes, a 2S core and a 19S regulator. The 2S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 1 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. PSME2 gene encodes the beta subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three beta and three alpha subunits combine to form a heterohexameric ring.

Interferon α-6 (IFN-α6) is a secreted protein which belongs to the α β interferon family. IFN-α6 is produced by macrophages, expressed at low level, only 1.0% of the average gene in this release. IFN-α6 contains interferon alpha, beta and delta domain. IFN-α has antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.

PA28A, also known as PSME1, is a subunit of proteasome. The 26S proteasome multicatalytic proteinase complex has a highly ordered structure composed of 2 complexes, a 2S core and a 19S regulator. The 2S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 1 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. The immunoproteasome contains an alternate regulator, referred to as the 11S regulator or PA28, that replaces the 19S regulator. Three subunits (alpha, beta and gamma) of the 11S regulator have been identified. PSME1 gene encodes the alpha subunit of the 11S regulator, one of the two 11S subunits that is induced by gamma-interferon. Three alpha and three beta subunits combine to form a heterohexameric ring.

SECTM1A (secreted and transmembrane 1A), is 192 amino acid (aa) protein, appears to share structural and functional characteristics with other SECTM1 proteins. Human SECTM1 can be found either found as an approximately 27 kDa intracellular type I transmembrane protein that shows a perinuclear, Golgi like staining pattern, or as a 20 kDa soluble, secreted form, and is produced by some myeloid cells and by thymic epithelia and fibroblasts. Stimulation with IFN gamma is often necessary to detect human SECTM1 expression, and it is thought to be an interferon early response gene. Mouse SECTM1A cDNA encodes a signal sequence, an extracellular domain with four potential N linked glycosylation sites, a transmembrane sequence, and a very short (approximately 6 aa) cytoplasmic sequence. SECTM1 proteins from human and mouse show species specific binding of CD7 and co stimulation of T cells, including enhancement of CD3 induced proliferation.