Reviewed, UniProtKB/Swiss-Prot P01579 (IFNG_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	In Caucasians, genetic variation in IFNG is associated with the risk of aplastic anemia (AA) [MIM:609135]. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis.
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
Gene Ontology (GO)
Biological process	cell cycle arrest Inferred from direct assay. Source: UniProtKB cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro negative regulation of smooth muscle cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of calcidiol 1-monooxygenase activity Inferred from direct assay. Source: UniProtKB positive regulation of interleukin-12 production Inferred from direct assay. Source: UniProtKB positive regulation of killing of cells of another organism Inferred from direct assay. Source: UniProtKB positive regulation of membrane protein ectodomain proteolysis Inferred from direct assay. Source: UniProtKB positive regulation of nitric oxide biosynthetic process Inferred from direct assay. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation of STAT protein Inferred from direct assay. Source: MGI positive regulation of smooth muscle cell apoptosis Inferred from direct assay. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from direct assay. Source: MGI positive regulation of vitamin D biosynthetic process Inferred from direct assay. Source: UniProtKB protein import into nucleus, translocation Inferred from direct assay. Source: UniProtKB regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW regulation of insulin secretion Inferred from direct assay. Source: UniProtKB response to virus Inferred from direct assay. Source: MGI tyrosine phosphorylation of Stat1 protein Inferred from direct assay. Source: UniProtKB
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW interferon-gamma receptor binding Traceable author statement. 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.8 Ref.9

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.8

Glycosylation

120

1

N-linked (GlcNAc...); in dimeric form Ref.8

Natural variations

Natural variant

29

1

K → Q

VAR_004017

Natural variant

160

1

R → Q

VAR_004018

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

166

Helix Strand Turn

Details...

Helix

2 – 18

17

Helix

25 – 38

14

Helix

53 – 58

6

Helix

62 – 81

20

Turn

82 – 85

4

Turn

87 – 89

3

Helix

90 – 104

15

Helix

109 – 119

11

Helix

126 – 140

15

Sequences

	Sequence		Length	Mass (Da)
	P01579-1 [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: 6180322] [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: 6173769] [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: 2860101] [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: 6329718] [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: 6176945] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood.
[8]	"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: 6427223] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-157, GLYCOSYLATION AT ASN-48 AND ASN-120.
[9]	"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: 3109913] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-161, PROTEOLYTIC PROCESSING OF THE C-TERMINUS.
[10]	"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: 2504704] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATES.
[11]	"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: 1902591] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS).
[12]	"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: 7617032] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[13]	"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: 10860730] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[14]	"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: 10986460] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF COMPLEX WITH RECEPTOR.
[15]	"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: 1525157] [Abstract] Cited for: STRUCTURE BY NMR.
[16]	"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: 15327519] [Abstract] Cited for: ASSOCIATION WITH APLASTIC ANEMIA.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Interferon gamma entry

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X13274 mRNA. Translation: CAA31639.1.
J00219 Genomic DNA. Translation: AAB59534.1.
X01992 mRNA. Translation: CAA26022.1.
V00543 mRNA. Translation: CAA23804.1.
AF375790 Genomic DNA. Translation: AAK53058.1.
BC070256 mRNA. Translation: AAH70256.1.

IPI

IPI00307209.

PIR

IVHUG. A93284.

RefSeq

NP_000610.2.

UniGene

Hs.856

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:483N.

PTM databases

GlycoSuiteDB

P01579.

PhosphoSite

P01579.

Proteomic databases

PRIDE

P01579.

Genome annotation databases

Ensembl

ENSG00000111537. Homo sapiens. [Contig view]

GeneID

3458.

KEGG

hsa:3458.

UCSC

uc001stw.1. human.

Organism-specific databases

GeneCards

GC12M066834.

H-InvDB

HIX0036727.

HGNC

HGNC:5438. IFNG.

HPA

CAB010344.

MIM

147570. gene.
609135. phenotype.

Orphanet

88. Aplastic anemia.

PharmGKB

PA29674.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P01579.

HOVERGEN

P01579.

OMA

P01579. NWKEESD.

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.

Gene expression databases

ArrayExpress

P01579.

Bgee

P01579.

CleanEx

HS_IFNG.

GermOnline

ENSG00000111537. Homo sapiens.

Family and domain databases

InterPro

IPR012351. 4_helix_cytokine_core.
IPR002069. Interferon_gamma.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

PANTHER

PTHR11419. IFN-gamma. 1 hit.

Pfam

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

PIRSF

PIRSF001936. IFN-gamma. 1 hit.

ProDom

PD002435. IFN-gamma. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Other Resources

DrugBank

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

NextBio

13624.

PMAP-CutDB

P01579.

SOURCE

Search...

Entry information

Entry name

IFNG_HUMAN

Accession

Primary (citable) accession number: P01579

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	April 1, 1988
Last modified:	July 7, 2009
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)