Reviewed, UniProtKB/Swiss-Prot P38484 (INGR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Interferon-gamma receptor beta chain
Alternative name(s):
    Interferon-gamma receptor accessory factor 1
      Short name=AF-1
    Interferon-gamma transducer 1

Gene names

Name:	IFNGR2
Synonyms:	IFNGT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	337 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	Part of the receptor for interferon gamma. Required for signal transduction. This accessory factor is an integral part of the IFN-gamma signal transduction pathway and is likely to interact with GAF, JAK1, and/or JAK2.
Subcellular location	Membrane; Single-pass type I membrane protein.
Involvement in disease	Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance.
Sequence similarities	Belongs to the type II cytokine receptor family. Contains 2 fibronectin type-III domains.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc response to virus Ref.1 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.4 Traceable author statement. Source: ProtInc
Molecular function	interferon-gamma receptor activity 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 – 27	27	Potential
	Chain	28 – 337	310	Interferon-gamma receptor beta chain		PRO_0000011011
Regions
	Topological domain	28 – 247	220	Extracellular Potential
	Transmembrane	248 – 268	21	Potential
	Topological domain	269 – 337	69	Cytoplasmic Potential
	Domain	31 – 129	99	Fibronectin type-III 1
	Domain	139 – 229	91	Fibronectin type-III 2
Amino acid modifications
	Modified residue	198	1	Phosphoserine
	Glycosylation	56	1	N-linked (GlcNAc...) Potential
	Glycosylation	85	1	N-linked (GlcNAc...) Potential
	Glycosylation	110	1	N-linked (GlcNAc...) Potential
	Glycosylation	137	1	N-linked (GlcNAc...) Potential
	Glycosylation	219	1	N-linked (GlcNAc...) Potential
	Glycosylation	231	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	58	1	T → R: dbSNP rs4986958.		VAR_020003
	Natural variant	64	1	Q → R: dbSNP rs9808753.		VAR_002718
	Natural variant	147	1	E → K: dbSNP rs17878639.		VAR_021383
	Natural variant	168	1	T → N in MSMD; does not affect receptor trafficking to the cell surface; loss of function due to gain of N-glycosylation.		VAR_023281
	Natural variant	182	1	K → E: dbSNP rs17878711.		VAR_021384
	Natural variant	222 – 230	9	Missing in MSMD; affects receptor trafficking to the cell surface.		VAR_023282
Experimental info
	Mutagenesis	168	1	T → A or Q: Does not affect function

Sequences

	Sequence		Length	Mass (Da)
	P38484-1 [UniParc]. Last modified March 6, 2007. Version 2. Checksum: 18C68BAF7D91B8AA	FASTA	337	37,806
	10 20 30 40 50 60 MRPTLLWSLL LLLGVFAAAA AAPPDPLSQL PAPQHPKIRL YNAEQVLSWE PVALSNSTRP 70 80 90 100 110 120 VVYQVQFKYT DSKWFTADIM SIGVNCTQIT ATECDFTAAS PSAGFPMDFN VTLRLRAELG 130 140 150 160 170 180 ALHSAWVTMP WFQHYRNVTV GPPENIEVTP GEGSLIIRFS SPFDIADTST AFFCYYVHYW 190 200 210 220 230 240 EKGGIQQVKG PFRSNSISLD NLKPSRVYCL QVQAQLLWNK SNIFRVGHLS NISCYETMAD 250 260 270 280 290 300 ASTELQQVIL ISVGTFSLLS VLAGACFFLV LKYRGLIKYW FHTPPSIPLQ IEEYLKDPTQ 310 320 330 PILEALDKDS SPKDDVWDSV SIISFPEKEQ EDVLQTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and sequence of an accessory factor required for activation of the human interferon gamma receptor." Soh J., Donnelly R.J., Kotenko S., Mariano T.M., Cook J.R., Wang N., Emanuel S.L., Schwartz B., Miki T., Pestka S. Cell 76:793-802(1994) [PubMed: 8124716] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-64. Tissue: Lung fibroblast.
[2]	SeattleSNPs program for genomic applications Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-58; LYS-147 AND GLU-182.
[3]	"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], VARIANT ARG-64. Tissue: Skin.
[4]	"The structure of the gene for the second chain of the human interferon gamma receptor." Rhee S., Ebensperger C., Dembic Z., Pestka S. J. Biol. Chem. 271:28947-28952(1996) [PubMed: 8910544] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
[5]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-198, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations." Vogt G., Chapgier A., Yang K., Chuzhanova N., Feinberg J., Fieschi C., Boisson-Dupuis S., Alcais A., Filipe-Santos O., Bustamante J., de Beaucoudrey L., Al-Mohsen I., Al-Hajjar S., Al-Ghonaium A., Adimi P., Mirsaeidi M., Khalilzadeh S., Rosenzweig S. , de la Calle-Martin O., Bauer T.R., Puck J.M., Ochs H.D., Furthner D., Engelhorn C., Belohradsky B., Mansouri D., Holland S.M., Schreiber R.D., Abel L., Cooper D.N., Soudais C., Casanova J.-L. Nat. Genet. 37:692-700(2005) [PubMed: 15924140] [Abstract] Cited for: VARIANTS MSMD ASN-168 AND 222-ASN--SER-230 DEL, MUTAGENESIS OF THR-168, CHARACTERIZATION OF VARIANTS MSMD ASN-168 AND 222-ASN--SER-230 DEL.
+	Additional computationally mapped references.

Web resources

IFNGR2base

IFNGR2 mutation db

GeneReviews

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U05875 mRNA. Translation: AAA16955.1. U05877 mRNA. Translation: AAA16956.1. AY644470 Genomic DNA. Translation: AAT45458.1. BC003624 mRNA. Translation: AAH03624.1. U68755 Genomic DNA. Translation: AAC52066.1.
PIR	I38500.
RefSeq	NP_005525.2.
UniGene	Hs.634632
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P38484.
Genome annotation databases
Ensembl	ENSG00000159128. Homo sapiens. [Contig view]
GeneID	3460.
KEGG	hsa:3460.
Organism-specific databases
H-InvDB	HIX0016076.
HGNC	HGNC:5440. IFNGR2.
HPA	HPA001535.
MIM	147569. gene. 209950. phenotype.
Orphanet	748. Mendelian susceptibility to atypical mycobacteria.
PharmGKB	PA29676.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P38484.
Gene expression databases
ArrayExpress	P38484.
CleanEx	HS_IFNGR2.
GermOnline	ENSG00000159128. Homo sapiens.
Family and domain databases
InterPro	IPR008957. Fibronectin_typ-III-like_fold. IPR003961. FN_III. [Graphical view]
Gene3D	G3DSA:2.60.40.30. FN_III-like. 1 hit.
Pfam	PF00041. fn3. 1 hit. [Graphical view]
SMART	SM00060. FN3. 1 hit. [Graphical view]
PROSITE	PS50853. FN3. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00033. Interferon gamma-1b.
NextBio	13632.
SOURCE	Search...

Entry information

Entry name

INGR2_HUMAN

Accession

Primary (citable) accession number: P38484
Secondary accession number(s): Q9BTL5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	March 6, 2007
Last modified:	November 25, 2008
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)