Interferon-gamma receptor

protein
Name= interferon gamma receptor 1
caption=


width=
HGNCid=5439
Symbol=IFNGR1
AltSymbols=IFNGR
EntrezGene=3459
OMIM=107470
RefSeq=NM_000416
UniProt=P15260
PDB=
ECnumber=
Chromosome=6
Arm=q
Band=23
LocusSupplementaryData=-q24protein
Name=interferon gamma receptor 2 (interferon gamma transducer 1)
caption=


width=
HGNCid=5440
Symbol=IFNGR2
AltSymbols=IFNGT1
EntrezGene=3460
OMIM=147569
RefSeq=NM_005534
UniProt=P38484
PDB=
ECnumber=
Chromosome=21
Arm=q
Band=22.1
LocusSupplementaryData=The interferon-gamma receptor (IFNGR) is a receptor which binds interferon-γ, the sole member of interferon type II.

tructure and function

The human interferon-gamma receptor complex consists the heterodimer of two chains: IFNGR1 and IFNGR2.cite journal | author = Bach EA, Aguet M, Schreiber RD | title = The IFN gamma receptor: a paradigm for cytokine receptor signaling | journal = Annu. Rev. Immunol. | volume = 15 | issue = | pages = 563–91 | year = 1997 | pmid = 9143700 | doi = 10.1146/annurev.immunol.15.1.563 | issn = ] cite journal | author = Pestka S, Kotenko SV, Muthukumaran G, Izotova LS, Cook JR, Garotta G | title = The interferon gamma (IFN-gamma) receptor: a paradigm for the multichain cytokine receptor | journal = Cytokine Growth Factor Rev. | volume = 8 | issue = 3 | pages = 189–206 | year = 1997 | pmid = 9462485 | doi = 10.1016/S1359-6101(97)00009-9 | issn = ] In unstimulated cells, these subunits are not preassociated with each other but rather associate through their intracellular domains with inactive forms of specific Janus family kinases ( Jak1 and Jak2). Jak1 and Jak2 constitutively associate with IFNGR1 and IFNGR2, respectively. Binding of IFN-γ to IFNGR1 induces the rapid dimerization of IFNGR1 chains, thereby forming a site that is recognized by the extracellular domain of IFNGR2. The ligand-induced assembly of the complete receptor complex contains two IFNGR1 and two IFNGR2 subunits which bring into close juxtaposition the intracellular domains of these proteins together with the inactive Jak1 and Jak2 kinases that they associate with. In this complex, Jak1 and Jak2 transactivate one another and then phosphorylate IFNGR1, thereby forming a paired set of Stat1 docking sites on the ligated receptor. Two Stat1 molecules then associate with the paired docking sites, are brought into close proximity with receptor-associated activated JAK kinases, and are activated by phosphorylation of the Stat1. Tyrosine-phosphorylated Stat1 molecules dissociate from their receptor tether and form homodimeric complexes. Activated Stat1 translocates to the nucleus and, after binding to a specific sequence in the promoter region of immediate-early IFN-γ-inducible genes, effects gene transcription.

Disease linkage

IFNGR1 deficiency is associated with the increased susceptibility to certain infectious diseases in patients.cite journal | author = Jouanguy E, Lamhamedi-Cherradi S, Lammas D, Dorman SE, Fondanèche MC, Dupuis S, Döffinger R, Altare F, Girdlestone J, Emile JF, Ducoulombier H, Edgar D, Clarke J, Oxelius VA, Brai M, Novelli V, Heyne K, Fischer A, Holland SM, Kumararatne DS, Schreiber RD, Casanova JL | title = A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection | journal = Nat. Genet. | volume = 21 | issue = 4 | pages = 370–8 | year = 1999 | pmid = 10192386 | doi = 10.1038/7701 | issn = ] cite journal | author = Levin M, Newport MJ, D'Souza S, Kalabalikis P, Brown IN, Lenicker HM, Agius PV, Davies EG, Thrasher A, Klein N | title = Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? | journal = Lancet | volume = 345 | issue = 8942 | pages = 79–83 | year = 1995 | pmid = 7815885 | doi = | issn = ]

References