P38484 (INGR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon gamma receptor 2
Short name=IFN-gamma receptor 2
Short name=IFN-gamma-R2

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) [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	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	Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
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 Transmembrane helix
Molecular function	Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome response to virus Traceable author statement Ref.1. Source: ProtInc
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 16780588. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.4. Source: ProtInc
Molecular_function	interferon-gamma receptor activity Traceable author statement PubMed 9616207. 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 2		PRO_0000011011
Regions
	Topological domain	28 – 247	220	Extracellular Potential
	Transmembrane	248 – 268	21	Helical; 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
	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. Ref.2 Corresponds to variant rs4986958 [ dbSNP | Ensembl ].		VAR_020003
	Natural variant	64	1	Q → R. Ref.1 Ref.3 Corresponds to variant rs9808753 [ dbSNP | Ensembl ].		VAR_002718
	Natural variant	147	1	E → K. Ref.2 Corresponds to variant rs17878639 [ dbSNP | Ensembl ].		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. Ref.5		VAR_023281
	Natural variant	182	1	K → E. Ref.2 Corresponds to variant rs17878711 [ dbSNP | Ensembl ].		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. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P38484 [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-64. Tissue: Lung fibroblast.
[2]	SeattleSNPs variation discovery resource 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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
[5]	"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] [Europe PMC] [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
EMBL GenBank DDBJ	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.
IPI	IPI00221193.
PIR	I38500.
RefSeq	NP_005525.2. NM_005534.3.
UniGene	Hs.634632.
3D structure databases
ProteinModelPortal	P38484.
ModBase	Search...
Protein-protein interaction databases
IntAct	P38484. 2 interactions.
STRING	9606.ENSP00000290219.
Polymorphism databases
DMDM	145559548.
Proteomic databases
PaxDb	P38484.
PRIDE	P38484.
Protocols and materials databases
DNASU	3460.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290219; ENSP00000290219; ENSG00000159128. ENST00000576463; ENSP00000458487; ENSG00000262795.
GeneID	3460.
KEGG	hsa:3460.
UCSC	uc002yrp.4. human.
Organism-specific databases
CTD	3460.
GeneCards	GC21P034757.
HGNC	HGNC:5440. IFNGR2.
HPA	HPA001535.
MIM	147569. gene. 209950. phenotype.
neXtProt	NX_P38484.
Orphanet	748. Mendelian susceptibility to mycobacterial diseases.
PharmGKB	PA29676.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG42506.
HOGENOM	HOG000013157.
HOVERGEN	HBG052129.
KO	K05133.
OrthoDB	EOG4X97HJ.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P38484.
Bgee	P38484.
CleanEx	HS_IFNGR2.
Genevestigator	P38484.
GermOnline	ENSG00000159128. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR003961. Fibronectin_type3. IPR013783. Ig-like_fold. IPR015373. Interferon_alpha/beta_rcpt_bsu. [Graphical view]
Pfam	PF09294. Interfer-bind. 1 hit. [Graphical view]
SMART	SM00060. FN3. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits.
PROSITE	PS50853. FN3. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1890.
ChiTaRS	IFNGR2. human.
DrugBank	DB00033. Interferon gamma-1b.
GenomeRNAi	3460.
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:	May 1, 2013
This is version 127 of the entry and version 2 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.