ID IFNG_BOVIN Reviewed; 166 AA. AC P07353; A7L687; A9QWQ4; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 27-MAR-2024, entry version 179. DE RecName: Full=Interferon gamma; DE Short=BoIFNG; DE Short=IFN-gamma; DE Flags: Precursor; GN Name=IFNG; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3086437; RA Cerretti D.P., McKereghan K., Larsen A., Cosman D., Gillis S., Baker P.E.; RT "Cloning, sequence, and expression of bovine interferon-gamma."; RL J. Immunol. 136:4561-4564(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-14. RC STRAIN=Deutsche Schwarzbunte; RX PubMed=12396714; DOI=10.1089/10799900260286632; RA Schmidt P., Kuehn C., Maillard J.-C., Pitra C., Tiemann U., Weikard R., RA Schwerin M.; RT "A comprehensive survey for polymorphisms in the bovine IFN-gamma gene RT reveals a highly polymorphic intronic DNA sequence allowing improved RT genotyping of Bovinae."; RL J. Interferon Cytokine Res. 22:923-934(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-166. RA Li G., Hu Y., Ren X., Ma D., Gai R.; RT "Cloning and sequence analysis of cattle interferon gamma."; RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Belted Galloway; TISSUE=Peripheral blood; RG U.S. Veterinary Immune Reagent Network; RA Hudgens T., Tompkins D., Baldwin C.L.; RT "U.S. veterinary immune reagent network: expressed bovine gene sequences."; RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases. RN [5] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). RX PubMed=15299487; DOI=10.1107/s0907444993006924; RA Samudzi C.T., Rubin J.R.; RT "Structure of recombinant bovine interferon-gamma at 3.0-A resolution."; RL Acta Crystallogr. D 49:513-521(1993). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RX PubMed=10666622; DOI=10.1107/s0907444999014304; RA Randal M., Kossiakoff A.A.; RT "The 2.0-A structure of bovine interferon-gamma; assessment of the RT structural differences between species."; RL Acta Crystallogr. D 56:14-24(2000). CC -!- FUNCTION: Type II interferon produced by immune cells such as T-cells CC and NK cells that plays crucial roles in antimicrobial, antiviral, and CC antitumor responses by activating effector immune cells and enhancing CC antigen presentation. Primarily signals through the JAK-STAT pathway CC after interaction with its receptor IFNGR1 to affect gene regulation. CC Upon IFNG binding, IFNGR1 intracellular domain opens out to allow CC association of downstream signaling components JAK2, JAK1 and STAT1, CC leading to STAT1 activation, nuclear translocation and transcription of CC IFNG-regulated genes. Many of the induced genes are transcription CC factors such as IRF1 that are able to further drive regulation of a CC next wave of transcription. Plays a role in class I antigen CC presentation pathway by inducing a replacement of catalytic proteasome CC subunits with immunoproteasome subunits. In turn, increases the CC quantity, quality, and repertoire of peptides for class I MHC loading. CC Increases the efficiency of peptide generation also by inducing the CC expression of activator PA28 that associates with the proteasome and CC alters its proteolytic cleavage preference. Up-regulates as well MHC II CC complexes on the cell surface by promoting expression of several key CC molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (By CC similarity). Participates in the regulation of hematopoietic stem cells CC during development and under homeostatic conditions by affecting their CC development, quiescence, and differentiation (By similarity). CC {ECO:0000250|UniProtKB:P01579, ECO:0000250|UniProtKB:P01580}. CC -!- SUBUNIT: Homodimer. Interacts with IFNGR1 (via extracellular domain); CC this interaction promotes IFNGR1 dimerization. CC {ECO:0000250|UniProtKB:P01579}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01579}. CC -!- TISSUE SPECIFICITY: Released primarily from activated T lymphocytes. CC -!- SIMILARITY: Belongs to the type II (or gamma) interferon family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M29867; AAB64477.1; -; mRNA. DR EMBL; Z54144; CAA90859.1; -; Genomic_DNA. DR EMBL; EF675629; ABS11696.1; -; mRNA. DR EMBL; EU276066; ABX72064.1; -; mRNA. DR PIR; A24390; IVBOG. DR RefSeq; NP_776511.1; NM_174086.1. DR PDB; 1D9C; X-ray; 2.00 A; A/B=24-144. DR PDB; 1D9G; X-ray; 2.90 A; A/B=24-144. DR PDB; 1RFB; X-ray; 3.00 A; A/B=24-142. DR PDBsum; 1D9C; -. DR PDBsum; 1D9G; -. DR PDBsum; 1RFB; -. DR AlphaFoldDB; P07353; -. DR SMR; P07353; -. DR STRING; 9913.ENSBTAP00000016634; -. DR GlyCosmos; P07353; 2 sites, No reported glycans. DR PaxDb; 9913-ENSBTAP00000016634; -. DR Ensembl; ENSBTAT00000016634.3; ENSBTAP00000016634.2; ENSBTAG00000012529.3. DR GeneID; 281237; -. DR KEGG; bta:281237; -. DR CTD; 3458; -. DR VEuPathDB; HostDB:ENSBTAG00000012529; -. DR VGNC; VGNC:30057; IFNG. DR eggNOG; ENOG502SBGW; Eukaryota. DR GeneTree; ENSGT00390000007831; -. DR HOGENOM; CLU_135106_0_0_1; -. DR InParanoid; P07353; -. DR OMA; QIVSMYL; -. DR OrthoDB; 5314434at2759; -. DR TreeFam; TF336308; -. DR Reactome; R-BTA-877300; Interferon gamma signaling. DR Reactome; R-BTA-877312; Regulation of IFNG signaling. DR Reactome; R-BTA-9732724; IFNG signaling activates MAPKs. DR EvolutionaryTrace; P07353; -. DR Proteomes; UP000009136; Chromosome 5. DR Bgee; ENSBTAG00000012529; Expressed in mesenteric lymph node and 40 other cell types or tissues. DR GO; GO:0005615; C:extracellular space; IDA:AgBase. DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central. DR GO; GO:0005133; F:type II interferon receptor binding; IEA:InterPro. DR GO; GO:0002250; P:adaptive immune response; IBA:GO_Central. DR GO; GO:0048143; P:astrocyte activation; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0006959; P:humoral immune response; IBA:GO_Central. DR GO; GO:0002281; P:macrophage activation involved in immune response; IEA:Ensembl. DR GO; GO:0030225; P:macrophage differentiation; IEA:Ensembl. DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:Ensembl. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IEA:Ensembl. DR GO; GO:0010508; P:positive regulation of autophagy; IEA:Ensembl. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:AgBase. DR GO; GO:0032834; P:positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response; IEA:Ensembl. DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IEA:Ensembl. DR GO; GO:0060552; P:positive regulation of fructose 1,6-bisphosphate metabolic process; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl. DR GO; GO:0032747; P:positive regulation of interleukin-23 production; IEA:Ensembl. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IEA:Ensembl. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IEA:Ensembl. DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IEA:Ensembl. DR GO; GO:0090312; P:positive regulation of protein deacetylation; IEA:Ensembl. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IEA:Ensembl. DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:AgBase. DR GO; GO:2000309; P:positive regulation of tumor necrosis factor (ligand) superfamily member 11 production; IEA:Ensembl. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl. DR GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; IEA:Ensembl. DR GO; GO:0050796; P:regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0060333; P:type II interferon-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0038196; P:type III interferon-mediated signaling pathway; IEA:Ensembl. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR002069; Interferon_gamma. DR PANTHER; PTHR11419; INTERFERON GAMMA; 1. DR PANTHER; PTHR11419:SF0; INTERFERON GAMMA; 1. DR Pfam; PF00714; IFN-gamma; 1. DR PIRSF; PIRSF001936; IFN-gamma; 1. DR SUPFAM; SSF47266; 4-helical cytokines; 1. PE 1: Evidence at protein level; KW 3D-structure; Antiviral defense; Cytokine; Glycoprotein; Growth regulation; KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal. FT SIGNAL 1..23 FT /evidence="ECO:0000250" FT CHAIN 24..166 FT /note="Interferon gamma" FT /id="PRO_0000016433" FT MOD_RES 24 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000250|UniProtKB:P01579" FT CARBOHYD 39 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT VARIANT 14 FT /note="G -> V" FT /evidence="ECO:0000269|PubMed:12396714" FT VARIANT 166 FT /note="M -> T (may represent an allelic difference or a FT cloning artifact)" FT /evidence="ECO:0000269|Ref.3" FT HELIX 25..38 FT /evidence="ECO:0007829|PDB:1D9C" FT TURN 39..41 FT /evidence="ECO:0007829|PDB:1D9G" FT HELIX 43..46 FT /evidence="ECO:0007829|PDB:1D9G" FT HELIX 53..58 FT /evidence="ECO:0007829|PDB:1D9C" FT TURN 59..61 FT /evidence="ECO:0007829|PDB:1D9C" FT TURN 63..65 FT /evidence="ECO:0007829|PDB:1D9C" FT HELIX 66..81 FT /evidence="ECO:0007829|PDB:1D9C" FT TURN 82..85 FT /evidence="ECO:0007829|PDB:1D9C" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:1D9C" FT HELIX 90..104 FT /evidence="ECO:0007829|PDB:1D9C" FT HELIX 109..119 FT /evidence="ECO:0007829|PDB:1D9C" FT HELIX 126..134 FT /evidence="ECO:0007829|PDB:1D9C" FT HELIX 136..143 FT /evidence="ECO:0007829|PDB:1D9C" SQ SEQUENCE 166 AA; 19393 MW; 27B268B950BB3B1F CRC64; MKYTSYFLAL LLCGLLGFSG SYGQGQFFRE IENLKEYFNA SSPDVAKGGP LFSEILKNWK DESDKKIIQS QIVSFYFKLF ENLKDNQVIQ RSMDIIKQDM FQKFLNGSSE KLEDFKKLIQ IPVDDLQIQR KAINELIKVM NDLSPKSNLR KRKRSQNLFR GRRASM //