IFNG_HUMAN
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 03-AUG-2022, entry version 237.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 cells.";
RL Nature 295:503-508(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2860101; DOI=10.1093/oxfordjournals.jbchem.a135039;
RA Nishi T., Fujita T., Nishi-Takaoka C., Saito A., Matsumoto T., Sato M.,
RA 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; DOI=10.1002/j.1460-2075.1982.tb01277.x;
RA Taya Y., Devos R., Tavernier J., Cheroutre H., Engler G., Fiers W.;
RT "Cloning and structure of the human immune interferon-gamma chromosomal
RT 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., Fiers W.;
RT "Molecular cloning of human immune interferon cDNA and its expression in
RT 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., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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; DOI=10.1016/s0021-9258(17)39797-1;
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 of
RT the carboxyl terminus.";
RL Eur. J. Biochem. 166:145-149(1987).
RN [13]
RP STRUCTURE OF CARBOHYDRATES.
RX PubMed=2504704; DOI=10.1093/oxfordjournals.jbchem.a122762;
RA Yamamoto S., Hase S., Yamauchi H., Tanimoto T., Ikenaka T.;
RT "Studies on the sugar chains of interferon-gamma from human peripheral-
RT blood lymphocytes.";
RL J. Biochem. 105:1034-1039(1989).
RN [14]
RP INTERACTION WITH IFNGR1, AND FUNCTION.
RX PubMed=8349687; DOI=10.1016/s0021-9258(17)46817-7;
RA Greenlund A.C., Schreiber R.D., Goeddel D.V., Pennica D.;
RT "Interferon-gamma induces receptor dimerization in solution and on cells.";
RL J. Biol. Chem. 268:18103-18110(1993).
RN [15]
RP FUNCTION IN IMMUNOPROTEASOME EXPRESSION.
RX PubMed=8163024; DOI=10.1016/0014-5793(94)80612-8;
RA Akiyama K., Kagawa S., Tamura T., Shimbara N., Takashina M., Kristensen P.,
RA Hendil K.B., Tanaka K., Ichihara A.;
RT "Replacement of proteasome subunits X and Y by LMP7 and LMP2 induced by
RT interferon-gamma for acquirement of the functional diversity responsible
RT for antigen processing.";
RL FEBS Lett. 343:85-88(1994).
RN [16]
RP FUNCTION IN CATHEPSIN EXPRESSION.
RX PubMed=7729559; DOI=10.1016/0014-5793(95)00287-j;
RA Lah T.T., Hawley M., Rock K.L., Goldberg A.L.;
RT "Gamma-interferon causes a selective induction of the lysosomal proteases,
RT cathepsins B and L, in macrophages.";
RL FEBS Lett. 363:85-89(1995).
RN [17]
RP FUNCTION IN IMMUNOPROTEASOME EXPRESSION.
RX PubMed=8666937; DOI=10.1084/jem.183.4.1807;
RA Hisamatsu H., Shimbara N., Saito Y., Kristensen P., Hendil K.B.,
RA Fujiwara T., Takahashi E., Tanahashi N., Tamura T., Ichihara A., Tanaka K.;
RT "Newly identified pair of proteasomal subunits regulated reciprocally by
RT interferon gamma.";
RL J. Exp. Med. 183:1807-1816(1996).
RN [18]
RP INDUCTION BY INTERLEUKIN 12.
RX PubMed=9643557; DOI=10.3109/10428199809050903;
RA Lee S.M., Suen Y., Qian J., Knoppel E., Cairo M.S.;
RT "The regulation and biological activity of interleukin 12.";
RL Leuk. Lymphoma 29:427-438(1998).
RN [19]
RP FUNCTION.
RX PubMed=11112687; DOI=10.1242/jcs.114.1.29;
RA Fabunmi R.P., Wigley W.C., Thomas P.J., DeMartino G.N.;
RT "Interferon gamma regulates accumulation of the proteasome activator PA28
RT and immunoproteasomes at nuclear PML bodies.";
RL J. Cell Sci. 114:29-36(2001).
RN [20]
RP FUNCTION.
RX PubMed=16914093;
RA El Bougrini J., Pampin M., Chelbi-Alix M.K.;
RT "Arsenic enhances the apoptosis induced by interferon gamma: key role of
RT IRF-1.";
RL Cell. Mol. Biol. 52:9-15(2006).
RN [21]
RP INVOLVEMENT IN IMD69.
RX PubMed=32163377; DOI=10.1172/jci135460;
RA Kerner G., Rosain J., Guerin A., Al-Khabaz A., Oleaga-Quintas C.,
RA Rapaport F., Massaad M.J., Ding J.Y., Khan T., Ali F.A., Rahman M.,
RA Deswarte C., Martinez-Barricarte R., Geha R.S., Jeanne-Julien V.,
RA Garcia D., Chi C.Y., Yang R., Roynard M., Fleckenstein B., Rozenberg F.,
RA Boisson-Dupuis S., Ku C.L., Seeleuthner Y., Beziat V., Marr N., Abel L.,
RA Al-Herz W., Casanova J.L., Bustamante J.;
RT "Inherited human IFN-gamma deficiency underlies mycobacterial disease.";
RL J. Clin. Invest. 130:3158-3171(2020).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS), AND SUBUNIT.
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 [23]
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 soluble
RT high-affinity receptor.";
RL Nature 376:230-235(1995).
RN [24]
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 single-
RT chain mutant of human IFN-gamma.";
RL J. Mol. Biol. 299:169-179(2000).
RN [25]
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., Fountoulakis M.,
RA 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 [26]
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 human
RT interferon-gamma.";
RL Biochemistry 31:8180-8190(1992).
RN [27]
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., Iori A.P.,
RA Pongiglione C., Lanciotti M., Iolascon A.;
RT "Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma
RT gene is significantly associated with the risk of aplastic anaemia in
RT Caucasian population.";
RL Br. J. Haematol. 126:682-685(2004).
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 (PubMed:16914093, PubMed:8666937). Primarily
CC signals through the JAK-STAT pathway after interaction with its
CC receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG
CC binding, IFNGR1 intracellular domain opens out to allow association of
CC downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1
CC activation, nuclear translocation and transcription of IFNG-regulated
CC genes. Many of the induced genes are transcription factors such as IRF1
CC that are able to further drive regulation of a next wave of
CC transcription (PubMed:16914093). Plays a role in class I antigen
CC presentation pathway by inducing a replacement of catalytic proteasome
CC subunits with immunoproteasome subunits (PubMed:8666937). In turn,
CC increases the quantity, quality, and repertoire of peptides for class I
CC MHC loading (PubMed:8163024). Increases the efficiency of peptide
CC generation also by inducing the expression of activator PA28 that
CC associates with the proteasome and alters its proteolytic cleavage
CC preference (PubMed:11112687). Up-regulates as well MHC II complexes on
CC the cell surface by promoting expression of several key molecules such
CC as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates
CC in the regulation of hematopoietic stem cells during development and
CC under homeostatic conditions by affecting their development,
CC quiescence, and differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P01580, ECO:0000269|PubMed:11112687,
CC ECO:0000269|PubMed:16914093, ECO:0000269|PubMed:7729559,
CC ECO:0000269|PubMed:8163024, ECO:0000269|PubMed:8349687,
CC ECO:0000269|PubMed:8666937}.
CC -!- SUBUNIT: Homodimer (PubMed:1902591). Interacts with IFNGR1 (via
CC extracellular domain); this interaction promotes IFNGR1 dimerization
CC (PubMed:8349687). {ECO:0000269|PubMed:1902591,
CC ECO:0000269|PubMed:8349687}.
CC -!- INTERACTION:
CC P01579; P15260: IFNGR1; NbExp=3; IntAct=EBI-1030767, EBI-1030755;
CC P01579; Q66793: C4R; Xeno; NbExp=2; IntAct=EBI-1030767, EBI-15683787;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Released primarily from activated T lymphocytes.
CC -!- INDUCTION: By cytokines, most notably interleukin IL-12, secreted by
CC professional antigen-presenting cells such as monocytes/macrophages and
CC dendritic cells. {ECO:0000269|PubMed:9643557}.
CC -!- PTM: Proteolytic processing produces C-terminal heterogeneity, with
CC 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 which
CC the bone marrow fails to produce adequate numbers of peripheral blood
CC elements. It is characterized by peripheral pancytopenia and marrow
CC hypoplasia. {ECO:0000269|PubMed:15327519}. Note=Disease susceptibility
CC may be associated with variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Immunodeficiency 69 (IMD69) [MIM:618963]: A form of Mendelian
CC susceptibility to mycobacterial disease, a rare condition caused by
CC impairment of interferon-gamma mediated immunity. It is characterized
CC by predisposition to illness caused by moderately virulent
CC mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine,
CC environmental non-tuberculous mycobacteria, and by the more virulent
CC Mycobacterium tuberculosis. Other microorganisms rarely cause severe
CC clinical disease in individuals with susceptibility to mycobacterial
CC infections. Clinical outcome severity depends on the degree of
CC impairment of interferon-gamma mediated immunity. IMD69 is an autosomal
CC recessive disorder manifesting with fever, hepatosplenomegaly,
CC leukocytosis, and thrombocytosis during the acute infection.
CC {ECO:0000269|PubMed:32163377}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- PHARMACEUTICAL: Available under the name Actimmune (Genentech). Used
CC 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/";
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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 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 PDB; 6E3K; X-ray; 3.25 A; A/B=24-156.
DR PDB; 6E3L; X-ray; 3.80 A; A/B=24-156.
DR PDBsum; 1EKU; -.
DR PDBsum; 1FG9; -.
DR PDBsum; 1FYH; -.
DR PDBsum; 1HIG; -.
DR PDBsum; 3BES; -.
DR PDBsum; 6E3K; -.
DR PDBsum; 6E3L; -.
DR AlphaFoldDB; P01579; -.
DR SMR; P01579; -.
DR BioGRID; 109680; 24.
DR ComplexPortal; CPX-6024; Interferon gamma complex.
DR DIP; DIP-483N; -.
DR IntAct; P01579; 4.
DR STRING; 9606.ENSP00000229135; -.
DR BindingDB; P01579; -.
DR ChEMBL; CHEMBL3286073; -.
DR DrugBank; DB14724; Emapalumab.
DR DrugBank; DB05111; Fontolizumab.
DR DrugBank; DB10770; Foreskin fibroblast (neonatal).
DR DrugBank; DB10772; Foreskin keratinocyte (neonatal).
DR DrugBank; DB01296; Glucosamine.
DR DrugBank; DB01250; Olsalazine.
DR DrugBank; DB05110; VIR201.
DR DrugCentral; P01579; -.
DR GlyConnect; 287; 23 N-Linked glycans.
DR GlyGen; P01579; 3 sites, 41 N-linked glycans (1 site).
DR iPTMnet; P01579; -.
DR PhosphoSitePlus; P01579; -.
DR BioMuta; IFNG; -.
DR DMDM; 124479; -.
DR MassIVE; P01579; -.
DR PaxDb; P01579; -.
DR PeptideAtlas; P01579; -.
DR PRIDE; P01579; -.
DR ABCD; P01579; 31 sequenced antibodies.
DR Antibodypedia; 4154; 3247 antibodies from 49 providers.
DR DNASU; 3458; -.
DR Ensembl; ENST00000229135.4; ENSP00000229135.3; ENSG00000111537.5.
DR GeneID; 3458; -.
DR KEGG; hsa:3458; -.
DR MANE-Select; ENST00000229135.4; ENSP00000229135.3; NM_000619.3; NP_000610.2.
DR UCSC; uc001stw.2; human.
DR CTD; 3458; -.
DR DisGeNET; 3458; -.
DR GeneCards; IFNG; -.
DR HGNC; HGNC:5438; IFNG.
DR HPA; ENSG00000111537; Group enriched (bone marrow, lymphoid tissue).
DR MalaCards; IFNG; -.
DR MIM; 147570; gene.
DR MIM; 609135; phenotype.
DR MIM; 618963; phenotype.
DR neXtProt; NX_P01579; -.
DR OpenTargets; ENSG00000111537; -.
DR Orphanet; 88; Idiopathic aplastic anemia.
DR PharmGKB; PA29674; -.
DR VEuPathDB; HostDB:ENSG00000111537; -.
DR eggNOG; ENOG502SBGW; Eukaryota.
DR GeneTree; ENSGT00390000007831; -.
DR HOGENOM; CLU_135106_0_0_1; -.
DR InParanoid; P01579; -.
DR OMA; GGPIFTE; -.
DR OrthoDB; 1382686at2759; -.
DR PhylomeDB; P01579; -.
DR TreeFam; TF336308; -.
DR PathwayCommons; P01579; -.
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 BioGRID-ORCS; 3458; 5 hits in 1037 CRISPR screens.
DR EvolutionaryTrace; P01579; -.
DR GeneWiki; Interferon-gamma; -.
DR GenomeRNAi; 3458; -.
DR Pharos; P01579; Tclin.
DR PRO; PR:P01579; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P01579; protein.
DR Bgee; ENSG00000111537; Expressed in granulocyte and 97 other tissues.
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:0048143; P:astrocyte activation; IDA:ARUK-UCL.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0098586; P:cellular response to virus; IC:ComplexPortal.
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:0002281; P:macrophage activation involved in immune response; IDA:ARUK-UCL.
DR GO; GO:0030225; P:macrophage differentiation; IDA:ARUK-UCL.
DR GO; GO:0001774; P:microglial cell activation; IGI:ARUK-UCL.
DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; ISS:ARUK-UCL.
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:1902948; P:negative regulation of tau-protein kinase activity; IGI:ARUK-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:0150076; P:neuroinflammatory response; ISS:ARUK-UCL.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IGI:ARUK-UCL.
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:1901857; P:positive regulation of cellular respiration; ISS:ARUK-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:ARUK-UCL.
DR GO; GO:1904798; P:positive regulation of core promoter binding; IDA:CAFA.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:ARUK-UCL.
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:0045821; P:positive regulation of glycolytic process; ISS:ARUK-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:ARUK-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:ARUK-UCL.
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:0032755; P:positive regulation of interleukin-6 production; IDA:ARUK-UCL.
DR GO; GO:1904440; P:positive regulation of iron ion import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IDA:BHF-UCL.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IDA:BHF-UCL.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IGI:ARUK-UCL.
DR GO; GO:1901216; P:positive regulation of neuron death; IGI:ARUK-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0051173; P:positive regulation of nitrogen compound metabolic process; IGI:ARUK-UCL.
DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; ISS:ARUK-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:0050766; P:positive regulation of phagocytosis; ISS:ARUK-UCL.
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:0031334; P:positive regulation of protein-containing complex assembly; IDA:CAFA.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISS:ARUK-UCL.
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:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-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:0007259; P:receptor signaling pathway via JAK-STAT; ISS:ARUK-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:0010835; P:regulation of protein ADP-ribosylation; IDA:CAFA.
DR GO; GO:0009615; P:response to virus; IDA:MGI.
DR Gene3D; 1.20.1250.10; -; 1.
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 SUPFAM; SSF47266; SSF47266; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Cleavage on pair of basic residues;
KW Cytokine; Direct protein sequencing; Glycoprotein; Growth regulation;
KW Pharmaceutical; Pyrrolidone carboxylic acid; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:3109913,
FT ECO:0000269|PubMed:6427223"
FT CHAIN 24..161
FT /note="Interferon gamma"
FT /id="PRO_0000016444"
FT PROPEP 162..166
FT /id="PRO_0000259481"
FT REGION 147..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 24
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:3109913,
FT ECO:0000269|PubMed:6427223"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6427223"
FT CARBOHYD 120
FT /note="N-linked (GlcNAc...) asparagine; in dimeric form"
FT /evidence="ECO:0000269|PubMed:6427223"
FT VARIANT 29
FT /note="K -> Q"
FT /id="VAR_004017"
FT VARIANT 160
FT /note="R -> Q (in dbSNP:rs201359065)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_004018"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:1FYH"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:3BES"
FT HELIX 53..58
FT /evidence="ECO:0007829|PDB:1FYH"
FT HELIX 62..81
FT /evidence="ECO:0007829|PDB:1FYH"
FT TURN 82..85
FT /evidence="ECO:0007829|PDB:1FYH"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:1FYH"
FT HELIX 90..104
FT /evidence="ECO:0007829|PDB:1FYH"
FT HELIX 109..119
FT /evidence="ECO:0007829|PDB:1FYH"
FT HELIX 126..140
FT /evidence="ECO:0007829|PDB:1FYH"
FT HELIX 146..148
FT /evidence="ECO:0007829|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
