IFNGR1

This gene (IFNGR1) encodes the ligand-binding chain (alpha) of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. A genetic variation in IFNGR1 is associated with susceptibility to Helicobacter pylori infection. In addition, defects in IFNGR1 are a cause of mendelian susceptibility to mycobacterial disease, also known as familial disseminated atypical mycobacterial infection.

interferon gamma receptor 1

CD119; IFNGR; IMD27A; IMD27B

Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:20015550).

Associates with transmembrane accessory factor IFNGR2 to form a functional receptor (PubMed:7615558, PubMed:2971451, PubMed:7617032, PubMed:10986460, PubMed:7673114).

Upon ligand binding, the intracellular domain of IFNGR1 opens out to allow association of downstream signaling components JAK1 and JAK2. In turn, activated JAK1 phosphorylates IFNGR1 to form a docking site for STAT1. Subsequent phosphorylation of STAT1 leads to dimerization, translocation to the nucleus, and stimulation of target gene transcription (PubMed:28883123).

STAT3 can also be activated in a similar manner although activation seems weaker. IFNGR1 intracellular domain phosphorylation also provides a docking site for SOCS1 that regulates the JAK-STAT pathway by competing with STAT1 binding to IFNGR1 (By similarity).

Astrocyte activation Source: ARUK-UCL
Cytokine-mediated signaling pathway Source: GO_Central
Defense response to virus Source: Ensembl
Microglial cell activation Source: ARUK-UCL
Negative regulation of amyloid-beta clearance Source: ARUK-UCL
Positive regulation of amyloid-beta formation Source: ARUK-UCL
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of tumor necrosis factor production Source: ARUK-UCL
Response to virus Source: ProtInc
Signal transduction Source: ProtInc

Cell membrane

Immunodeficiency 27A (IMD27A):
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas.
Immunodeficiency 27B (IMD27B):
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD27B commonly presents with recurrent, moderately severe infections with environmental mycobacteria or BCG. Salmonellosis is present in about 5% of patients.

Extracellular: 18-245
Helical: 246-266
Cytoplasmic: 267-489

Phosphorylated at Ser/Thr residues. Phosphorylation of Tyr-457 is required for IFNG receptor signal transduction (PubMed:8156998). Influenza virus infection leads to phosphorylation in a CSNK1A1-dependent manner (PubMed:29343571).
Ubiquitinated after phosphorylation in a CSNK1A1-dependent manner, leading to the lysosome-dependent degradation (PubMed:29343571). Proteasomally degraded through 'Lys-48'-mediated ubiquitination (PubMed:28883123). Ubiquitination is necessary for efficient IFNGR1 signaling (PubMed:28883123).