P01579 (IFNG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon gamma
Short name=IFN-gamma

Alternative name(s):
Immune interferon

Gene names

Name:

IFNG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	166 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
Subunit structure	Homodimer.
Subcellular location	Secreted.
Tissue specificity	Released primarily from activated T lymphocytes.
Post-translational modification	Proteolytic processing produces C-terminal heterogeneity, with proteins ending alternatively at Gly-150, Met-157 or Gly-161.
Involvement in disease	Aplastic anemia (AA) [MIM:609135]: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Pharmaceutical use	Available under the name Actimmune (Genentech). Used for reducing the frequency and severity of serious infections associated with chronic granulomatous disease (CGD).
Sequence similarities	Belongs to the type II (or gamma) interferon family.

Ontologies

Keywords
Biological process	Antiviral defense Growth regulation
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine
PTM	Cleavage on pair of basic residues Glycoprotein Pyrrolidone carboxylic acid
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	CD8-positive, alpha-beta T cell differentiation involved in immune response Inferred from electronic annotation. Source: Compara adaptive immune response Inferred from electronic annotation. Source: Compara antigen processing and presentation Inferred from electronic annotation. Source: Compara apoptotic process Inferred from genetic interaction PubMed 7828849. Source: MGI cell cycle arrest Inferred from direct assay PubMed 16942485. Source: BHF-UCL cellular component movement Traceable author statement PubMed 10477596. Source: ProtInc cellular response to interleukin-18 Inferred from electronic annotation. Source: Compara cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara defense response to bacterium Inferred from electronic annotation. Source: Compara defense response to protozoan Inferred from electronic annotation. Source: Compara defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum unfolded protein response Inferred from electronic annotation. Source: Compara humoral immune response Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of growth of symbiont in host Inferred from electronic annotation. Source: Compara negative regulation of interleukin-17 production Inferred from direct assay PubMed 18501882. Source: BHF-UCL negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of metanephric nephron tubule epithelial cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of myelination Inferred from electronic annotation. Source: Compara negative regulation of smooth muscle cell proliferation Inferred from direct assay PubMed 16942485. Source: BHF-UCL negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL neutrophil apoptotic process Inferred from electronic annotation. Source: Compara neutrophil chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of MHC class II biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of calcidiol 1-monooxygenase activity Inferred from direct assay PubMed 9282826. Source: BHF-UCL positive regulation of cell adhesion Inferred from electronic annotation. Source: Compara positive regulation of chemokine biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of fructose 1,6-bisphosphate 1-phosphatase activity Inferred from direct assay PubMed 9282826. Source: BHF-UCL positive regulation of fructose 1,6-bisphosphate metabolic process Inferred from direct assay PubMed 9282826. Source: BHF-UCL positive regulation of interleukin-1 beta secretion Inferred from electronic annotation. Source: Compara positive regulation of interleukin-12 biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of interleukin-12 production Inferred from direct assay PubMed 7605994PubMed 8557999. Source: UniProtKB positive regulation of interleukin-23 production Inferred from direct assay PubMed 20027291. Source: BHF-UCL positive regulation of interleukin-6 biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of isotype switching to IgG isotypes Inferred from electronic annotation. Source: Compara positive regulation of killing of cells of other organism Inferred from direct assay PubMed 7544003. Source: BHF-UCL positive regulation of membrane protein ectodomain proteolysis Inferred from direct assay PubMed 18373975. Source: BHF-UCL positive regulation of mesenchymal cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of neuron differentiation Inferred from electronic annotation. Source: Compara positive regulation of nitric oxide biosynthetic process Inferred from direct assay PubMed 8383325. Source: BHF-UCL positive regulation of osteoclast differentiation Inferred from direct assay PubMed 16220542. Source: BHF-UCL positive regulation of peptidyl-serine phosphorylation of STAT protein Non-traceable author statement PubMed 21268089. Source: BHF-UCL positive regulation of smooth muscle cell apoptotic process Inferred from direct assay PubMed 16942485. Source: BHF-UCL positive regulation of synaptic transmission, cholinergic Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of tumor necrosis factor (ligand) superfamily member 11 production Inferred from direct assay PubMed 16220542. Source: BHF-UCL positive regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from direct assay PubMed 15604419. Source: BHF-UCL positive regulation of vitamin D biosynthetic process Inferred from direct assay PubMed 9282826. Source: BHF-UCL protein import into nucleus, translocation Inferred from direct assay PubMed 15604419. Source: UniProtKB regulation of insulin secretion Inferred from direct assay PubMed 8383325. Source: BHF-UCL regulation of interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome regulation of the force of heart contraction Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to virus Inferred from direct assay PubMed 16280321. Source: MGI
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular region Inferred from direct assay PubMed 20041150. Source: BHF-UCL extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	interferon-gamma receptor binding Traceable author statement PubMed 10477596. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.11 Ref.12

Chain

24 – 161

138

Interferon gamma

PRO_0000016444

Propeptide

162 – 166

5

PRO_0000259481

Amino acid modifications

Modified residue

24

1

Pyrrolidone carboxylic acid

Glycosylation

48

1

N-linked (GlcNAc...) Ref.11

Glycosylation

120

1

N-linked (GlcNAc...); in dimeric form Ref.11

Natural variations

Natural variant

29

1

K → Q.

VAR_004017

Natural variant

160

1

R → Q. Ref.6

VAR_004018

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

166

Helix Strand Turn

Details...

Helix

27 – 38

12

Turn

39 – 41

3

Helix

43 – 46

4

Helix

53 – 58

6

Helix

62 – 81

20

Turn

82 – 85

4

Helix

87 – 89

3

Helix

90 – 105

16

Helix

109 – 119

11

Helix

126 – 142

17

Helix

146 – 148

3

Sequences

	Sequence		Length	Mass (Da)
	P01579 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: 1514E8F785FD81AA	FASTA	166	19,348
	10 20 30 40 50 60 MKYTSYILAF QLCIVLGSLG CYCQDPYVKE AENLKKYFNA GHSDVADNGT LFLGILKNWK 70 80 90 100 110 120 EESDRKIMQS QIVSFYFKLF KNFKDDQSIQ KSVETIKEDM NVKFFNSNKK KRDDFEKLTN 130 140 150 160 YSVTDLNVQR KAIHELIQVM AELSPAAKTG KRKRSQMLFR GRRASQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of the human immune interferon gene." Gray P.W., Goeddel D.V. Nature 298:859-863(1982) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Expression of human immune interferon cDNA in E. coli and monkey cells." Gray P.W., Leung D.W., Pennica D., Yelverton E., Najarian R., Simonsen C.C., Derynck R., Sherwood P.J., Wallace D.M., Berger S.L., Levinson A.D., Goeddel D.V. Nature 295:503-508(1982) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning and expression of a novel variant of human interferon-gamma cDNA." Nishi T., Fujita T., Nishi-Takaoka C., Saito A., Matsumoto T., Sato M., Oka T., Itoh S., Yip Y.K., Vilcek J., Taniguchi T. J. Biochem. 97:153-159(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Cloning and structure of the human immune interferon-gamma chromosomal gene." Taya Y., Devos R., Tavernier J., Cheroutre H., Engler G., Fiers W. EMBO J. 1:953-958(1982) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Molecular cloning of human immune interferon cDNA and its expression in eukaryotic cells." Devos R., Cheroutre H., Taya Y., Degrave W., van Heuverswyn H., Fiers W. Nucleic Acids Res. 10:2487-2501(1982) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	Chikara S.K., Jaiswal P., Sharma G. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-160.
[7]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Human protein factory for converting the transcriptome into an in vitro-expressed proteome." 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. Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood.
[11]	"Natural human interferon-gamma. Complete amino acid sequence and determination of sites of glycosylation." Rinderknecht E., O'Conner B.H., Rodriguez H. J. Biol. Chem. 259:6790-6797(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-157, GLYCOSYLATION AT ASN-48 AND ASN-120.
[12]	"Structural characterization of human interferon gamma. Heterogeneity of the carboxyl terminus." Pan Y.C.E., Stern A.S., Familletti P.C., Khan F.R., Chizzonite R. Eur. J. Biochem. 166:145-149(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-161, PROTEOLYTIC PROCESSING OF THE C-TERMINUS.
[13]	"Studies on the sugar chains of interferon-gamma from human peripheral-blood lymphocytes." Yamamoto S., Hase S., Yamauchi H., Tanimoto T., Ikenaka T. J. Biochem. 105:1034-1039(1989) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATES.
[14]	"Three-dimensional structure of recombinant human interferon-gamma." Ealick S.E., Cook W.J., Vijay-Kumar S., Carson M., Nagabhushan T.L., Trotta P.P., Bugg C.E. Science 252:698-702(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
[15]	"Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor." Walter M.R., Windsor W.T., Nagabhushan T.L., Lundell D.J., Lunn C.A., Zauodny P.J., Narula S.K. Nature 376:230-235(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[16]	"Design, characterization, and structure of a biologically active single-chain mutant of human IFN-gamma." Landar A., Curry B., Parker M.H., DiGiacomo R., Indelicato S.R., Nagabhushan T.L., Rizzi G., Walter M.R. J. Mol. Biol. 299:169-179(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[17]	"Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex." Thiel D.J., le Du M.-H., Walter R.L., D'Arcy A., Chene C., Fountoulakis M., Garotta G., Winkler F.K., Ealick S.E. Structure 8:927-936(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF COMPLEX WITH RECEPTOR.
[18]	"1H, 13C, and 15N NMR backbone assignments and secondary structure of human interferon-gamma." Grzesiek S., Doebeli H., Gentz R., Garotta G., Labhardt A.M., Bax A. Biochemistry 31:8180-8190(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[19]	"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." Dufour C., Capasso M., Svahn J., Marrone A., Haupt R., Bacigalupo A., Giordani L., Longoni D., Pillon M., Pistorio A., Di Michele P., Iori A.P., Pongiglione C., Lanciotti M., Iolascon A. Br. J. Haematol. 126:682-685(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ASSOCIATION WITH APLASTIC ANEMIA.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Interferon gamma entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X13274 mRNA. Translation: CAA31639.1.
J00219 Genomic DNA. Translation: AAB59534.1.
X01992 mRNA. Translation: CAA26022.1.
V00543 mRNA. Translation: CAA23804.1.
AY255837 mRNA. Translation: AAP20098.1.
AF375790 Genomic DNA. Translation: AAK53058.1.
AB451324 mRNA. Translation: BAG70138.1.
AB451453 mRNA. Translation: BAG70267.1.
CH471054 Genomic DNA. Translation: EAW97180.1.
BC070256 mRNA. Translation: AAH70256.1.

IPI

IPI00307209.

PIR

IVHUG. A93284.

RefSeq

NP_000610.2. NM_000619.2.

UniGene

Hs.856.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EKU	X-ray	2.90	A/B	26-161	[»]
1FG9	X-ray	2.90	A/B	24-156	[»]
1FYH	X-ray	2.04	A/D	24-156	[»]
1HIG	X-ray	3.50	A/B/C/D	24-161	[»]
3BES	X-ray	2.20	L	24-161	[»]

ProteinModelPortal

P01579.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-483N.

IntAct

P01579. 2 interactions.

STRING

9606.ENSP00000229135.

PTM databases

GlycoSuiteDB

P01579.

PhosphoSite

P01579.

Polymorphism databases

DMDM

124479.

Proteomic databases

PaxDb

P01579.

PRIDE

P01579.

Protocols and materials databases

DNASU

3458.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000229135; ENSP00000229135; ENSG00000111537.

GeneID

3458.

KEGG

hsa:3458.

UCSC

uc001stw.1. human.

Organism-specific databases

CTD

3458.

GeneCards

GC12M068548.

HGNC

HGNC:5438. IFNG.

HPA

CAB010344.

MIM

147570. gene.
609135. phenotype.

neXtProt

NX_P01579.

Orphanet

88. Idiopathic aplastic anemia.

PharmGKB

PA29674.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG45353.

HOGENOM

HOG000254784.

HOVERGEN

HBG056912.

InParanoid

P01579.

KO

K04687.

OMA

KEYFNAS.

OrthoDB

EOG4MCX1G.

PhylomeDB

P01579.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
ifngpathway. IFN-gamma pathway.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
il2_1pathway. IL2-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.
pdgfrapathway. PDGFR-alpha signaling pathway.
telomerasepathway. Regulation of Telomerase.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01579.

Bgee

P01579.

CleanEx

HS_IFNG.

Genevestigator

P01579.

GermOnline

ENSG00000111537. Homo sapiens.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR002069. Interferon_gamma.
[Graphical view]

PANTHER

PTHR11419. PTHR11419. 1 hit.

Pfam

PF00714. IFN-gamma. 1 hit.
[Graphical view]

PIRSF

PIRSF001936. IFN-gamma. 1 hit.

ProDom

PD002435. Interferon_gamma. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB01296. Glucosamine.
DB00033. Interferon gamma-1b.
DB00641. Simvastatin.

EvolutionaryTrace

P01579.

GenomeRNAi

3458.

NextBio

13624.

PMAP-CutDB

P01579.

SOURCE

Search...

Entry information

Entry name

IFNG_HUMAN

Accession

Primary (citable) accession number: P01579
Secondary accession number(s): B5BU88, Q53ZV4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	April 1, 1988
Last modified:	May 1, 2013
This is version 155 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.