Interferon gamma

Details

Name
Interferon gamma
Synonyms
  • IFN-gamma
  • Immune interferon
Gene Name
IFNG
UniProtKB Entry
P01579Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010663|Interferon gamma
MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK
EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN
YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ
Number of residues
166
Molecular Weight
19348.165
Theoretical pI
10.01
GO Classification
Functions
type II interferon receptor binding
Processes
astrocyte activation / cell surface receptor signaling pathway via JAK-STAT / cellular response to virus / macrophage activation involved in immune response / macrophage differentiation / microglial cell activation / negative regulation of amyloid-beta clearance / negative regulation of DNA-templated transcription / negative regulation of tau-protein kinase activity / negative regulation of transcription by RNA polymerase II / neuroinflammatory response / positive regulation of amyloid-beta formation / positive regulation of cell population proliferation / positive regulation of cellular respiration / positive regulation of chemokine production / positive regulation of core promoter binding / positive regulation of cytokine production / positive regulation of exosomal secretion / positive regulation of glycolytic process / positive regulation of inflammatory response / positive regulation of interleukin-1 beta production / positive regulation of interleukin-6 production / positive regulation of iron ion import across plasma membrane / positive regulation of killing of cells of another organism / positive regulation of neurogenesis / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of NMDA glutamate receptor activity / positive regulation of phagocytosis / positive regulation of protein deacetylation / positive regulation of protein import into nucleus / positive regulation of protein localization to plasma membrane / positive regulation of protein serine/threonine kinase activity / positive regulation of protein-containing complex assembly / positive regulation of signaling receptor activity / positive regulation of tyrosine phosphorylation of STAT protein / regulation of metabolic process / type II interferon-mediated signaling pathway / type III interferon-mediated signaling pathway
General Function
Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093). Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937). In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024). Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687). Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity)
Specific Function
Cytokine activity
Pfam Domain Function
Signal Regions
1-23
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010664|Interferon gamma (IFNG)
ATGAAATATACAAGTTATATCTTGGCTTTTCAGCTCTGCATCGTTTTGGGTTCTCTTGGC
TGTTACTGCCAGGACCCATATGTAAAAGAAGCAGAAAACCTTAAGAAATATTTTAATGCA
GGTCATTCAGATGTAGCGGATAATGGAACTCTTTTCTTAGGCATTTTGAAGAATTGGAAA
GAGGAGAGTGACAGAAAAATAATGCAGAGCCAAATTGTCTCCTTTTACTTCAAACTTTTT
AAAAACTTTAAAGATGACCAGAGCATCCAAAAGAGTGTGGAGACCATCAAGGAAGACATG
AATGTCAAGTTTTTCAATAGCAACAAAAAGAAACGAGATGACTTCGAAAAGCTGACTAAT
TATTCGGTAACTGACTTGAATGTCCAACGCAAAGCAATACATGAACTCATCCAAGTGATG
GCTGAACTGTCGCCAGCAGCTAAAACAGGGAAGCGAAAAAGGAGTCAGATGCTGTTTCGA
GGTCGAAGAGCATCCCAGTAA
Chromosome Location
12
Locus
12q15
External Identifiers
ResourceLink
UniProtKB IDP01579
UniProtKB Entry NameIFNG_HUMAN
GenBank Protein ID32692
GenBank Gene IDX13274
GeneCard IDIFNG
GenAtlas IDIFNG
HGNC IDHGNC:5438
PDB ID(s)1EKU, 1FG9, 1FYH, 1HIG, 3BES, 6E3K, 6E3L
KEGG IDhsa:3458
NCBI Gene ID3458
General References
  1. Gray PW, Goeddel DV: Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859-63. [Article]
  2. Gray PW, Leung DW, Pennica D, Yelverton E, Najarian R, Simonsen CC, Derynck R, Sherwood PJ, Wallace DM, Berger SL, Levinson AD, Goeddel DV: Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503-8. [Article]
  3. Nishi T, Fujita T, Nishi-Takaoka C, Saito A, Matsumoto T, Sato M, Oka T, Itoh S, Yip YK, Vilcek J, et al.: Cloning and expression of a novel variant of human interferon-gamma cDNA. J Biochem. 1985 Jan;97(1):153-9. [Article]
  4. Taya Y, Devos R, Tavernier J, Cheroutre H, Engler G, Fiers W: Cloning and structure of the human immune interferon-gamma chromosomal gene. EMBO J. 1982;1(8):953-8. [Article]
  5. Devos R, Cheroutre H, Taya Y, Degrave W, Van Heuverswyn H, Fiers W: Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells. Nucleic Acids Res. 1982 Apr 24;10(8):2487-501. [Article]
  6. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Rinderknecht E, O'Connor BH, Rodriguez H: Natural human interferon-gamma. Complete amino acid sequence and determination of sites of glycosylation. J Biol Chem. 1984 Jun 10;259(11):6790-7. [Article]
  9. Pan YC, Stern AS, Familletti PC, Khan FR, Chizzonite R: Structural characterization of human interferon gamma. Heterogeneity of the carboxyl terminus. Eur J Biochem. 1987 Jul 1;166(1):145-9. [Article]
  10. Yamamoto S, Hase S, Yamauchi H, Tanimoto T, Ikenaka T: Studies on the sugar chains of interferon-gamma from human peripheral-blood lymphocytes. J Biochem. 1989 Jun;105(6):1034-9. [Article]
  11. Ealick SE, Cook WJ, Vijay-Kumar S, Carson M, Nagabhushan TL, Trotta PP, Bugg CE: Three-dimensional structure of recombinant human interferon-gamma. Science. 1991 May 3;252(5006):698-702. [Article]
  12. Walter MR, Windsor WT, Nagabhushan TL, Lundell DJ, Lunn CA, Zauodny PJ, Narula SK: Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor. Nature. 1995 Jul 20;376(6537):230-5. [Article]
  13. Landar A, Curry B, Parker MH, DiGiacomo R, Indelicato SR, Nagabhushan TL, Rizzi G, Walter MR: Design, characterization, and structure of a biologically active single-chain mutant of human IFN-gamma. J Mol Biol. 2000 May 26;299(1):169-79. [Article]
  14. Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chene C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE: Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure. 2000 Sep 15;8(9):927-36. [Article]
  15. Grzesiek S, Dobeli H, Gentz R, Garotta G, Labhardt AM, Bax A: 1H, 13C, and 15N NMR backbone assignments and secondary structure of human interferon-gamma. Biochemistry. 1992 Sep 8;31(35):8180-90. [Article]
  16. Dufour C, Capasso M, Svahn J, Marrone A, Haupt R, Bacigalupo A, Giordani L, Longoni D, Pillon M, Pistorio A, Di Michele P, Iori AP, Pongiglione C, Lanciotti M, Iolascon A: Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma gene is significantly associated with the risk of aplastic anaemia in Caucasian population. Br J Haematol. 2004 Sep;126(5):682-5. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Interferon gamma (Humans)protein
primary
Drug Relations
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Emapalumabapproved, investigationalyestargetneutralizerDetails
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