Reviewed, UniProtKB/Swiss-Prot P48551 (INAR2_HUMAN)

Names and origin

Protein names

Recommended name:
    Interferon-alpha/beta receptor beta chain
Alternative name(s):
    Interferon alpha/beta receptor 2
      Short name=IFN-alpha-REC
    Type I interferon receptor
      Short name=IFN-R

Gene names

Name:	IFNAR2
Synonyms:	IFNABR, IFNARB

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	515 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	Receptor for interferons alpha and beta. Isoform 1 and isoform 3 are directly involved in signal transduction due to their interaction with the TYR kinase, JAK1. Isoform 1 also interacts with the transcriptional factors, STAT1 and STAT2. Both forms are potent inhibitors of type I IFN activity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Post-translational modification	Upon binding, it is phosphorylated on tyrosine residues.
Involvement in disease	Defects in IFNAR2 are associated with susceptibility to hepatitis B virus infection (HBV infection) [MIM:610424]. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma can be attributed to chronic HBV infection. HBV infection may result in subclinical or asymptomatic infection, acute self-limited hepatitis, or fulminant hepatitis requiring liver transplantation.
Sequence similarities	Belongs to the type II cytokine receptor family.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	JAK-STAT cascade Ref.1 Traceable author statement. Source: ProtInc cell surface receptor linked signal transduction Traceable author statement. Source: ProtInc response to virus Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular region Ref.1 Traceable author statement. Source: ProtInc integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	type I interferon receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CREBBP	Q92793	3	EBI-958408,EBI-81215
EP300	Q09472	1	EBI-958408,EBI-447295
GNB2L1	P63244	4	EBI-958408,EBI-296739
IRF9	Q00978	4	EBI-958408,EBI-626526
STAT2	P52630	2	EBI-958408,EBI-1546963

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P48551-1)

Also known as: IFNAR2-2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P48551-2)

Also known as: IFNAR2-1;

The sequence of this isoform differs from the canonical sequence as follows:
     281-331: NFHNFLAWPF...SDSDTEAAPR → RQGLAKGWNA...YKRASLCPSD
     332-515: Missing.

Isoform 3 (identifier: P48551-3)

Also known as: IFNAR2-3; P40;

The sequence of this isoform differs from the canonical sequence as follows:
     238-239: SA → FS
     240-515: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Chain

27 – 515

489

Interferon-alpha/beta receptor beta chain

PRO_0000011006

Regions

Topological domain

27 – 243

217

Extracellular Potential

Transmembrane

244 – 264

21

Potential

Topological domain

265 – 515

251

Cytoplasmic Potential

Amino acid modifications

Glycosylation

58

1

N-linked (GlcNAc...) Potential

Glycosylation

87

1

N-linked (GlcNAc...)

Glycosylation

116

1

N-linked (GlcNAc...) Potential

Glycosylation

188

1

N-linked (GlcNAc...) Potential

Glycosylation

192

1

N-linked (GlcNAc...)

Disulfide bond

39 ↔ 122

Disulfide bond

85 ↔ 93

Disulfide bond

207 ↔ 227

Natural variations

Alternative sequence

238 – 239

2

SA → FS in isoform 3.

VSP_001736

Alternative sequence

240 – 515

276

Missing in isoform 3.

VSP_001737

Alternative sequence

281 – 331

51

NFHNF…EAAPR → RQGLAKGWNAVAIHRCSHNA LQSETPELKQSSCLSFPSSW DYKRASLCPSD in isoform 2.

VSP_001738

Alternative sequence

332 – 515

184

Missing in isoform 2.

VSP_001739

Natural variant

8

1

F → S Associated with susceptibility to HVB infection; lower cell surface levels; lower induction of MHC class 1 expression by INF-alpha. dbSNP rs4986956.

VAR_020521

Natural variant

10

1

F → V: dbSNP rs7279064.

VAR_020522

Natural variant

196

1

I → V: dbSNP rs17860223.

VAR_020523

Experimental info

Sequence conflict

151

1

M → V in AAC50202. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

515

Helix Strand Turn

Details...

Beta strand

43 – 46

4

Beta strand

49 – 52

4

Beta strand

59 – 61

3

Beta strand

66 – 72

7

Beta strand

75 – 81

7

Helix

83 – 85

3

Beta strand

86 – 89

4

Beta strand

93 – 98

6

Beta strand

106 – 114

9

Beta strand

122 – 126

5

Helix

128 – 131

4

Beta strand

136 – 143

8

Beta strand

148 – 153

6

Helix

159 – 161

3

Beta strand

167 – 174

8

Beta strand

189 – 195

7

Beta strand

206 – 215

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (IFNAR2-2) [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 4D7730D93AA739F4	FASTA	515	57,759
	10 20 30 40 50 60 MLLSQNAFIF RSLNLVLMVY ISLVFGISYD SPDYTDESCT FKISLRNFRS ILSWELKNHS 70 80 90 100 110 120 IVPTHYTLLY TIMSKPEDLK VVKNCANTTR SFCDLTDEWR STHEAYVTVL EGFSGNTTLF 130 140 150 160 170 180 SCSHNFWLAI DMSFEPPEFE IVGFTNHINV MVKFPSIVEE ELQFDLSLVI EEQSEGIVKK 190 200 210 220 230 240 HKPEIKGNMS GNFTYIIDKL IPNTNYCVSV YLEHSDEQAV IKSPLKCTLL PPGQESESAE 250 260 270 280 290 300 SAKIGGIITV FLIALVLTST IVTLKWIGYI CLRNSLPKVL NFHNFLAWPF PNLPPLEAMD 310 320 330 340 350 360 MVEVIYINRK KKVWDYNYDD ESDSDTEAAP RTSGGGYTMH GLTVRPLGQA SATSTESQLI 370 380 390 400 410 420 DPESEEEPDL PEVDVELPTM PKDSPQQLEL LSGPCERRKS PLQDPFPEED YSSTEGSGGR 430 440 450 460 470 480 ITFNVDLNSV FLRVLDDEDS DDLEAPLMLS SHLEEMVDPE DPDNVQSNHL LASGEGTQPT 490 500 510 FPSPSSEGLW SEDAPSDQSD TSESDVDLGD GYIMR
	Isoform 2 (IFNAR2-1) [UniParc]. Checksum: 6F6A2FD6E7A7449B		331	37,393
	10 20 30 40 50 60 MLLSQNAFIF RSLNLVLMVY ISLVFGISYD SPDYTDESCT FKISLRNFRS ILSWELKNHS 70 80 90 100 110 120 IVPTHYTLLY TIMSKPEDLK VVKNCANTTR SFCDLTDEWR STHEAYVTVL EGFSGNTTLF 130 140 150 160 170 180 SCSHNFWLAI DMSFEPPEFE IVGFTNHINV MVKFPSIVEE ELQFDLSLVI EEQSEGIVKK 190 200 210 220 230 240 HKPEIKGNMS GNFTYIIDKL IPNTNYCVSV YLEHSDEQAV IKSPLKCTLL PPGQESESAE 250 260 270 280 290 300 SAKIGGIITV FLIALVLTST IVTLKWIGYI CLRNSLPKVL RQGLAKGWNA VAIHRCSHNA 310 320 330 LQSETPELKQ SSCLSFPSSW DYKRASLCPS D
	Isoform 3 (IFNAR2-3) (P40) [UniParc]. Checksum: 705E887E728A4FB6		239	27,384
	10 20 30 40 50 60 MLLSQNAFIF RSLNLVLMVY ISLVFGISYD SPDYTDESCT FKISLRNFRS ILSWELKNHS 70 80 90 100 110 120 IVPTHYTLLY TIMSKPEDLK VVKNCANTTR SFCDLTDEWR STHEAYVTVL EGFSGNTTLF 130 140 150 160 170 180 SCSHNFWLAI DMSFEPPEFE IVGFTNHINV MVKFPSIVEE ELQFDLSLVI EEQSEGIVKK 190 200 210 220 230 HKPEIKGNMS GNFTYIIDKL IPNTNYCVSV YLEHSDEQAV IKSPLKCTLL PPGQESEFS

References

[1]	"Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster." Lutfalla G., Holland S.J., Cinato E., Monneron D., Reboul J., Rogers N.C., Smith J.M., Stark G.R., Gardiner K., Mogensen K.E., Kerr I.M., Uze G. EMBO J. 14:5100-5108(1995) [PubMed: 7588638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3).
[2]	"The human interferon alpha/beta receptor: characterization and molecular cloning." Novick D., Cohen B., Rubinstein M. Cell 77:391-400(1994) [PubMed: 8181059] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE, VARIANT VAL-10. Tissue: Monocyte.
[3]	"Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling." Domanski P., Witte M., Kellum M., Rubinstein M., Hackett R., Pitha P., Colamonici O.R. J. Biol. Chem. 270:21606-21611(1995) [PubMed: 7665574] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[4]	Cohen B., Kim S.H., Novick D., Rubinstein M. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-10. Tissue: Blood.
[5]	SeattleSNPs program for genomic applications Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-8; VAL-10 AND VAL-196.
[6]	"Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor." Novick D., Cohen B., Tal N., Rubinstein M. J. Leukoc. Biol. 57:712-718(1995) [PubMed: 7759950] [Abstract] Cited for: DISCUSSION OF VARIOUS FORMS, PARTIAL PROTEIN SEQUENCE.
[7]	"The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding." Chill J.H., Quadt S.R., Levy R., Schreiber G., Anglister J. Structure 11:791-802(2003) [PubMed: 12842042] [Abstract] Cited for: STRUCTURE BY NMR OF 28-237, DISULFIDE BONDS.
[8]	"Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence." Frodsham A.J., Zhang L., Dumpis U., Taib N.A.M., Best S., Durham A., Hennig B.J.W., Hellier S., Knapp S., Wright M., Chiaramonte M., Bell J.I., Graves M., Whittle H.C., Thomas H.C., Thursz M.R., Hill A.V.S. Proc. Natl. Acad. Sci. U.S.A. 103:9148-9153(2006) [PubMed: 16757563] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION, VARIANTS SER-8 AND VAL-10, CHARACTERIZATION OF VARIANT SER-8.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

L42243 , L42238, L42239, L42240, L42323, L42241, L42242 Genomic DNA. Translation: AAB46417.1.
L42243 , L42238, L42239, L42240, L42323, L42241 Genomic DNA. Translation: AAB46418.1.
L42243 , L42238, L42239, L42240, L42323, L42241, L42242 Genomic DNA. Translation: AAB46419.1.
L41944 mRNA. Translation: AAB46415.1.
L41943 mRNA. Translation: AAB46414.1.
L41942 mRNA. Translation: AAB46413.1.
X77722 mRNA. Translation: CAA54785.1.
U29584 mRNA. Translation: AAC50202.1.
X89772 mRNA. Translation: CAA61914.1.
AY740397 Genomic DNA. Translation: AAU21038.1.

PIR

I39073.
S59501.

RefSeq

NP_000865.2.
NP_997468.1.

UniGene

Hs.701988

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N6U	NMR	-	A	28-237	[»]
1N6V	NMR	-	A	28-237	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:945N.

IntAct

P48551.

PTM databases

PhosphoSite

P48551.

Genome annotation databases

Ensembl

ENSG00000159110. Homo sapiens. [Contig view]

GeneID

3455.

KEGG

hsa:3455.

Organism-specific databases

H-InvDB

HIX0016073.

HGNC

HGNC:5433. IFNAR2.

MIM

602376. gene.
610424. phenotype.

PharmGKB

PA29671.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P48551.

HOVERGEN

P48551.

Gene expression databases

ArrayExpress

P48551.

CleanEx

HS_IFNAR2.

GermOnline

ENSG00000159110. Homo sapiens.

Family and domain databases

InterPro

IPR008957. Fibronectin_typ-III-like_fold.
IPR015373. Interfer-bind.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 2 hits.

Pfam

PF09294. Interfer-bind. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00034. Interferon Alfa-2a, Recombinant.
DB00105. Interferon Alfa-2b, Recombinant.
DB00011. Interferon alfa-n1.
DB00018. Interferon alfa-n3.
DB00069. Interferon alfacon-1.
DB00068. Interferon beta-1b.
DB00008. Peginterferon alfa-2a.
DB00022. Peginterferon alfa-2b.

NextBio

13610.

SOURCE

Search...

Entry information

Entry name

INAR2_HUMAN

Accession

Primary (citable) accession number: P48551

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	November 4, 2008
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)