ID IFNG_HUMAN Reviewed; 166 AA. AC P01579; B5BU88; Q53ZV4; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 13-FEB-2019, entry version 215. DE RecName: Full=Interferon gamma; DE Short=IFN-gamma; DE AltName: Full=Immune interferon; DE Flags: Precursor; GN Name=IFNG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6180322; DOI=10.1038/298859a0; RA Gray P.W., Goeddel D.V.; RT "Structure of the human immune interferon gene."; RL Nature 298:859-863(1982). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6173769; DOI=10.1038/295503a0; RA Gray P.W., Leung D.W., Pennica D., Yelverton E., Najarian R., RA Simonsen C.C., Derynck R., Sherwood P.J., Wallace D.M., Berger S.L., RA Levinson A.D., Goeddel D.V.; RT "Expression of human immune interferon cDNA in E. coli and monkey RT cells."; RL Nature 295:503-508(1982). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2860101; RA Nishi T., Fujita T., Nishi-Takaoka C., Saito A., Matsumoto T., RA Sato M., Oka T., Itoh S., Yip Y.K., Vilcek J., Taniguchi T.; RT "Cloning and expression of a novel variant of human interferon-gamma RT cDNA."; RL J. Biochem. 97:153-159(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6329718; RA Taya Y., Devos R., Tavernier J., Cheroutre H., Engler G., Fiers W.; RT "Cloning and structure of the human immune interferon-gamma RT chromosomal gene."; RL EMBO J. 1:953-958(1982). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6176945; DOI=10.1093/nar/10.8.2487; RA Devos R., Cheroutre H., Taya Y., Degrave W., van Heuverswyn H., RA Fiers W.; RT "Molecular cloning of human immune interferon cDNA and its expression RT in eukaryotic cells."; RL Nucleic Acids Res. 10:2487-2501(1982). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-160. RA Chikara S.K., Jaiswal P., Sharma G.; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., RA Isogai T., Imai J., Watanabe S., Nomura N.; RT "Human protein factory for converting the transcriptome into an in RT vitro-expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Blood; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP PROTEIN SEQUENCE OF 24-157, PYROGLUTAMATE FORMATION AT GLN-24, AND RP GLYCOSYLATION AT ASN-48 AND ASN-120. RX PubMed=6427223; RA Rinderknecht E., O'Conner B.H., Rodriguez H.; RT "Natural human interferon-gamma. Complete amino acid sequence and RT determination of sites of glycosylation."; RL J. Biol. Chem. 259:6790-6797(1984). RN [12] RP PROTEIN SEQUENCE OF 24-161, PYROGLUTAMATE FORMATION AT GLN-24, AND RP PROTEOLYTIC PROCESSING OF THE C-TERMINUS. RX PubMed=3109913; DOI=10.1111/j.1432-1033.1987.tb13494.x; RA Pan Y.C.E., Stern A.S., Familletti P.C., Khan F.R., Chizzonite R.; RT "Structural characterization of human interferon gamma. Heterogeneity RT of the carboxyl terminus."; RL Eur. J. Biochem. 166:145-149(1987). RN [13] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=2504704; RA Yamamoto S., Hase S., Yamauchi H., Tanimoto T., Ikenaka T.; RT "Studies on the sugar chains of interferon-gamma from human RT peripheral-blood lymphocytes."; RL J. Biochem. 105:1034-1039(1989). RN [14] RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS). RX PubMed=1902591; DOI=10.1126/science.1902591; RA Ealick S.E., Cook W.J., Vijay-Kumar S., Carson M., Nagabhushan T.L., RA Trotta P.P., Bugg C.E.; RT "Three-dimensional structure of recombinant human interferon-gamma."; RL Science 252:698-702(1991). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS). RX PubMed=7617032; DOI=10.1038/376230a0; RA Walter M.R., Windsor W.T., Nagabhushan T.L., Lundell D.J., Lunn C.A., RA Zauodny P.J., Narula S.K.; RT "Crystal structure of a complex between interferon-gamma and its RT soluble high-affinity receptor."; RL Nature 376:230-235(1995). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS). RX PubMed=10860730; DOI=10.1006/jmbi.2000.3734; RA Landar A., Curry B., Parker M.H., DiGiacomo R., Indelicato S.R., RA Nagabhushan T.L., Rizzi G., Walter M.R.; RT "Design, characterization, and structure of a biologically active RT single-chain mutant of human IFN-gamma."; RL J. Mol. Biol. 299:169-179(2000). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF COMPLEX WITH RECEPTOR. RX PubMed=10986460; DOI=10.1016/S0969-2126(00)00184-2; RA Thiel D.J., le Du M.-H., Walter R.L., D'Arcy A., Chene C., RA Fountoulakis M., Garotta G., Winkler F.K., Ealick S.E.; RT "Observation of an unexpected third receptor molecule in the crystal RT structure of human interferon-gamma receptor complex."; RL Structure 8:927-936(2000). RN [18] RP STRUCTURE BY NMR. RX PubMed=1525157; DOI=10.1021/bi00150a009; RA Grzesiek S., Doebeli H., Gentz R., Garotta G., Labhardt A.M., Bax A.; RT "1H, 13C, and 15N NMR backbone assignments and secondary structure of RT human interferon-gamma."; RL Biochemistry 31:8180-8190(1992). RN [19] RP ASSOCIATION WITH APLASTIC ANEMIA. RX PubMed=15327519; DOI=10.1111/j.1365-2141.2004.05102.x; RA Dufour C., Capasso M., Svahn J., Marrone A., Haupt R., Bacigalupo A., RA Giordani L., Longoni D., Pillon M., Pistorio A., Di Michele P., RA Iori A.P., Pongiglione C., Lanciotti M., Iolascon A.; RT "Homozygosis for (12) CA repeats in the first intron of the human IFN- RT gamma gene is significantly associated with the risk of aplastic RT anaemia in Caucasian population."; RL Br. J. Haematol. 126:682-685(2004). CC -!- FUNCTION: Produced by lymphocytes activated by specific antigens CC or mitogens. IFN-gamma, in addition to having antiviral activity, CC has important immunoregulatory functions. It is a potent activator CC of macrophages, it has antiproliferative effects on transformed CC cells and it can potentiate the antiviral and antitumor effects of CC the type I interferons. CC -!- SUBUNIT: Homodimer. CC -!- INTERACTION: CC Q66793:C4R (xeno); NbExp=2; IntAct=EBI-1030767, EBI-15683787; CC P15260:IFNGR1; NbExp=2; IntAct=EBI-1030767, EBI-1030755; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Released primarily from activated T CC lymphocytes. CC -!- PTM: Proteolytic processing produces C-terminal heterogeneity, CC with proteins ending alternatively at Gly-150, Met-157 or Gly-161. CC {ECO:0000269|PubMed:3109913}. CC -!- DISEASE: Aplastic anemia (AA) [MIM:609135]: A form of anemia in CC which the bone marrow fails to produce adequate numbers of CC peripheral blood elements. It is characterized by peripheral CC pancytopenia and marrow hypoplasia. {ECO:0000269|PubMed:15327519}. CC Note=Disease susceptibility may be associated with variations CC affecting the gene represented in this entry. CC -!- PHARMACEUTICAL: Available under the name Actimmune (Genentech). CC Used for reducing the frequency and severity of serious infections CC associated with chronic granulomatous disease (CGD). CC -!- SIMILARITY: Belongs to the type II (or gamma) interferon family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interferon gamma entry; CC URL="https://en.wikipedia.org/wiki/Interferon_gamma"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/ifng/"; 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; X13274; CAA31639.1; -; mRNA. DR EMBL; J00219; AAB59534.1; -; Genomic_DNA. DR EMBL; X01992; CAA26022.1; -; mRNA. DR EMBL; V00543; CAA23804.1; -; mRNA. DR EMBL; AY255837; AAP20098.1; -; mRNA. DR EMBL; AF375790; AAK53058.1; -; Genomic_DNA. DR EMBL; AB451324; BAG70138.1; -; mRNA. DR EMBL; AB451453; BAG70267.1; -; mRNA. DR EMBL; CH471054; EAW97180.1; -; Genomic_DNA. DR EMBL; BC070256; AAH70256.1; -; mRNA. DR CCDS; CCDS8980.1; -. DR PIR; A93284; IVHUG. DR RefSeq; NP_000610.2; NM_000619.2. DR UniGene; Hs.856; -. DR PDB; 1EKU; X-ray; 2.90 A; A/B=26-161. DR PDB; 1FG9; X-ray; 2.90 A; A/B=24-156. DR PDB; 1FYH; X-ray; 2.04 A; A/D=28-156. DR PDB; 1HIG; X-ray; 3.50 A; A/B/C/D=24-161. DR PDB; 3BES; X-ray; 2.20 A; L=24-161. DR PDBsum; 1EKU; -. DR PDBsum; 1FG9; -. DR PDBsum; 1FYH; -. DR PDBsum; 1HIG; -. DR PDBsum; 3BES; -. DR ProteinModelPortal; P01579; -. DR SMR; P01579; -. DR BioGrid; 109680; 5. DR DIP; DIP-483N; -. DR IntAct; P01579; 3. DR STRING; 9606.ENSP00000229135; -. DR BindingDB; P01579; -. DR ChEMBL; CHEMBL3286073; -. DR DrugBank; DB05676; Apremilast. DR DrugBank; DB05111; Fontolizumab. DR DrugBank; DB01296; Glucosamine. DR DrugBank; DB01250; Olsalazine. DR DrugBank; DB05110; VIR201. DR GlyConnect; 287; -. DR iPTMnet; P01579; -. DR PhosphoSitePlus; P01579; -. DR UniCarbKB; P01579; -. DR BioMuta; IFNG; -. DR DMDM; 124479; -. DR EPD; P01579; -. DR PaxDb; P01579; -. DR PeptideAtlas; P01579; -. DR PRIDE; P01579; -. DR ProteomicsDB; 51389; -. DR DNASU; 3458; -. DR Ensembl; ENST00000229135; ENSP00000229135; ENSG00000111537. DR GeneID; 3458; -. DR KEGG; hsa:3458; -. DR UCSC; uc001stw.2; human. DR CTD; 3458; -. DR DisGeNET; 3458; -. DR EuPathDB; HostDB:ENSG00000111537.4; -. DR GeneCards; IFNG; -. DR HGNC; HGNC:5438; IFNG. DR HPA; CAB010344; -. DR MalaCards; IFNG; -. DR MIM; 147570; gene. DR MIM; 609135; phenotype. DR neXtProt; NX_P01579; -. DR OpenTargets; ENSG00000111537; -. DR Orphanet; 88; Idiopathic aplastic anemia. DR PharmGKB; PA29674; -. DR eggNOG; ENOG410IWSY; Eukaryota. DR eggNOG; ENOG410Z8I5; LUCA. DR GeneTree; ENSGT00390000007831; -. DR HOGENOM; HOG000254784; -. DR HOVERGEN; HBG056912; -. DR InParanoid; P01579; -. DR KO; K04687; -. DR OMA; WKEESDK; -. DR OrthoDB; 870903at2759; -. DR PhylomeDB; P01579; -. DR TreeFam; TF336308; -. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-877312; Regulation of IFNG signaling. DR Reactome; R-HSA-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs). DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation. DR SignaLink; P01579; -. DR SIGNOR; P01579; -. DR EvolutionaryTrace; P01579; -. DR GeneWiki; Interferon-gamma; -. DR GenomeRNAi; 3458; -. DR PMAP-CutDB; P01579; -. DR PRO; PR:P01579; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000111537; Expressed in 68 organ(s), highest expression level in leukocyte. DR Genevisible; P01579; HS. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central. DR GO; GO:0005133; F:interferon-gamma receptor binding; TAS:ProtInc. DR GO; GO:0002250; P:adaptive immune response; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; IGI:MGI. DR GO; GO:0007050; P:cell cycle arrest; IDA:BHF-UCL. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0006959; P:humoral immune response; IBA:GO_Central. DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; IDA:CAFA. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; TAS:Reactome. DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; ISS:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:CAFA. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB. DR GO; GO:0060559; P:positive regulation of calcidiol 1-monooxygenase activity; IDA:BHF-UCL. DR GO; GO:0032834; P:positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:1904798; P:positive regulation of core promoter binding; IDA:CAFA. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IDA:CACAO. DR GO; GO:1903543; P:positive regulation of exosomal secretion; HDA:UniProtKB. DR GO; GO:0060550; P:positive regulation of fructose 1,6-bisphosphate 1-phosphatase activity; IDA:BHF-UCL. DR GO; GO:0060552; P:positive regulation of fructose 1,6-bisphosphate metabolic process; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:UniProtKB. DR GO; GO:0032747; P:positive regulation of interleukin-23 production; IDA:BHF-UCL. DR GO; GO:0051712; P:positive regulation of killing of cells of other organism; IDA:BHF-UCL. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:BHF-UCL. DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IDA:MGI. DR GO; GO:0031334; P:positive regulation of protein complex assembly; IDA:CAFA. DR GO; GO:0090312; P:positive regulation of protein deacetylation; IDA:CAFA. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:CAFA. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; HDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:CAFA. DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:CAFA. DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IDA:BHF-UCL. DR GO; GO:2000309; P:positive regulation of tumor necrosis factor (ligand) superfamily member 11 production; IDA:BHF-UCL. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL. DR GO; GO:0060557; P:positive regulation of vitamin D biosynthetic process; IDA:BHF-UCL. DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW. DR GO; GO:0050796; P:regulation of insulin secretion; IDA:BHF-UCL. DR GO; GO:0060334; P:regulation of interferon-gamma-mediated signaling pathway; TAS:Reactome. DR GO; GO:0010835; P:regulation of protein ADP-ribosylation; IDA:CAFA. DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; TAS:Reactome. DR GO; GO:0009615; P:response to virus; IDA:MGI. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR002069; Interferon_gamma. DR PANTHER; PTHR11419; PTHR11419; 1. DR Pfam; PF00714; IFN-gamma; 1. DR PIRSF; PIRSF001936; IFN-gamma; 1. DR ProDom; PD002435; Interferon_gamma; 1. DR SUPFAM; SSF47266; SSF47266; 1. PE 1: Evidence at protein level; KW 3D-structure; Antiviral defense; Cleavage on pair of basic residues; KW Complete proteome; Cytokine; Direct protein sequencing; Glycoprotein; KW Growth regulation; Pharmaceutical; Polymorphism; KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal. FT SIGNAL 1 23 {ECO:0000269|PubMed:3109913, FT ECO:0000269|PubMed:6427223}. FT CHAIN 24 161 Interferon gamma. FT /FTId=PRO_0000016444. FT PROPEP 162 166 FT /FTId=PRO_0000259481. FT MOD_RES 24 24 Pyrrolidone carboxylic acid. FT {ECO:0000269|PubMed:3109913, FT ECO:0000269|PubMed:6427223}. FT CARBOHYD 48 48 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:6427223}. FT CARBOHYD 120 120 N-linked (GlcNAc...) asparagine; in FT dimeric form. FT {ECO:0000269|PubMed:6427223}. FT VARIANT 29 29 K -> Q. FT /FTId=VAR_004017. FT VARIANT 160 160 R -> Q (in dbSNP:rs201359065). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_004018. FT HELIX 27 38 {ECO:0000244|PDB:1FYH}. FT HELIX 43 46 {ECO:0000244|PDB:1FYH}. FT HELIX 53 58 {ECO:0000244|PDB:1FYH}. FT HELIX 62 81 {ECO:0000244|PDB:1FYH}. FT TURN 82 85 {ECO:0000244|PDB:1FYH}. FT HELIX 87 89 {ECO:0000244|PDB:1FG9}. FT HELIX 90 104 {ECO:0000244|PDB:1FYH}. FT HELIX 109 119 {ECO:0000244|PDB:1FYH}. FT HELIX 126 140 {ECO:0000244|PDB:1FYH}. FT HELIX 146 148 {ECO:0000244|PDB:3BES}. SQ SEQUENCE 166 AA; 19348 MW; 1514E8F785FD81AA CRC64; MKYTSYILAF QLCIVLGSLG CYCQDPYVKE AENLKKYFNA GHSDVADNGT LFLGILKNWK EESDRKIMQS QIVSFYFKLF KNFKDDQSIQ KSVETIKEDM NVKFFNSNKK KRDDFEKLTN YSVTDLNVQR KAIHELIQVM AELSPAAKTG KRKRSQMLFR GRRASQ //