P01563 (IFNA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interferon alpha-2
Short name=IFN-alpha-2

Alternative name(s):
Interferon alpha-A
Short name=LeIF A

Gene names

Name:

IFNA2

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	188 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 macrophages, IFN-alpha have antiviral activities.
Subunit structure	Interacts with IFNAR2. Ref.16 Ref.17
Subcellular location	Secreted.
Polymorphism	Three forms exist; alpha-2a (shown here), alpha-2b and alpha-2c.
Pharmaceutical use	Available under the names Roferon-A (Roche) or Intron-A (Schering-Plough). Used as an anticancer drug for its antiproliferative activity.
Sequence similarities	Belongs to the alpha/beta interferon family.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome cell-cell signaling Traceable author statement PubMed 10477584. Source: ProtInc defense response to virus Inferred from direct assay PubMed 22783022. Source: BHF-UCL induction of apoptosis Traceable author statement PubMed 10477584. Source: ProtInc inflammatory response Traceable author statement PubMed 10477584. Source: ProtInc negative regulation of T cell differentiation Inferred from direct assay PubMed 20554961. Source: UniProtKB negative regulation of T-helper 2 cell cytokine production Inferred from direct assay PubMed 20554961. Source: UniProtKB negative regulation of interleukin-13 secretion Inferred from direct assay PubMed 20554961. Source: UniProtKB negative regulation of interleukin-5 secretion Inferred from direct assay PubMed 20554961. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 20554961. Source: UniProtKB negative regulation of viral entry into host cell Inferred from direct assay PubMed 22783022. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay PubMed 22783022. Source: BHF-UCL regulation of type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome type I interferon-mediated signaling pathway Traceable author statement. Source: Reactome
Cellular_component	extracellular region Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	interferon-alpha/beta receptor binding Traceable author statement Ref.6. 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 – 188

165

Interferon alpha-2

PRO_0000016360

Amino acid modifications

Glycosylation

129

1

O-linked (GalNAc...) Ref.11

CAR_000049

Disulfide bond

24 ↔ 121

Ref.10 Ref.16 Ref.17

Disulfide bond

52 ↔ 161

Ref.10 Ref.16 Ref.17

Natural variations

Natural variant

6

1

A → D.
Corresponds to variant rs35971916 [ dbSNP | Ensembl ].

VAR_055972

Natural variant

46

1

K → R in alpha-2B and alpha-2C.
Corresponds to variant rs1061959 [ dbSNP | Ensembl ].

VAR_004012

Natural variant

57

1

H → R in alpha-2C.

VAR_013001

Natural variant

177

1

S → L in a breast cancer sample; somatic mutation. Ref.18

VAR_036329

Secondary structure

1

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188

Helix Strand Turn

Details...

Beta strand

26 – 28

3

Helix

32 – 44

13

Helix

50 – 55

6

Helix

63 – 65

3

Beta strand

67 – 69

3

Beta strand

71 – 75

5

Helix

76 – 89

14

Helix

93 – 98

6

Helix

101 – 120

20

Beta strand

126 – 129

4

Helix

138 – 155

18

Turn

156 – 158

3

Helix

160 – 177

18

Turn

179 – 182

4

Sequences

	Sequence		Length	Mass (Da)
	P01563 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 101DD21D394CBF97	FASTA	188	21,550
	10 20 30 40 50 60 MALTFALLVA LLVLSCKSSC SVGCDLPQTH SLGSRRTLML LAQMRKISLF SCLKDRHDFG 70 80 90 100 110 120 FPQEEFGNQF QKAETIPVLH EMIQQIFNLF STKDSSAAWD ETLLDKFYTE LYQQLNDLEA 130 140 150 160 170 180 CVIQGVGVTE TPLMKEDSIL AVRKYFQRIT LYLKEKKYSP CAWEVVRAEI MRSFSLSTNL QESLRSKE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human leukocyte interferon produced by E. coli is biologically active." Goeddel D.V., Yelverton E., Ullrich A., Heyneker H.L., Miozzari G., Holmes W., Seeburg P.H., Dull T.J., May L., Stebbing N., Crea R., Maeda S., McCandliss R., Sloma A., Tabor J.M., Gross M., Familletti P.C., Pestka S. Nature 287:411-416(1980) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"The structure of eight distinct cloned human leukocyte interferon cDNAs." Goeddel D.V., Leung D.W., Dull T.J., Gross M., Lawn R.M., McCandliss R., Seeburg P.H., Ullrich A., Yelverton E., Gray P.W. Nature 290:20-26(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"DNA sequence of a major human leukocyte interferon gene." Lawn R.M., Gross M., Houck C.M., Franke A.E., Gray P.V., Goeddel D.V. Proc. Natl. Acad. Sci. U.S.A. 78:5435-5439(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"Cloning of human leukocyte interferon cDNA and a strategy for its production in E. coli." Oliver G., Balbas P., Valle F., Soberon X., Bolivar F. Rev. Latinoam. Microbiol. 27:141-150(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Bone marrow tumor.
[5]	"A defective retroviral vector encoding human interferon alpha 2 can transduce human leukemic cell lines." Austruy E., Bagnis C., Carbuccia N., Maroc C., Birg F., Dubreuil P., Mannoni P., Chabannon C. Cancer Gene Ther. 5:247-256(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[6]	"At least three human type alpha interferons: structure of alpha 2." Streuli M., Nagata S., Weissmann C. Science 209:1343-1347(1980) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 7-188.
[7]	"Formation of genes coding for hybrid proteins by recombination between related, cloned genes in E. coli." Weber H., Weissmann C. Nucleic Acids Res. 11:5661-5669(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 24-188.
[8]	"A family of structural genes for human lymphoblastoid (leukocyte-type) interferon." Allen G., Fantes K.H. Nature 287:408-411(1980) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-112 AND 136-188.
[9]	"Identification of nine interferon-alpha subtypes produced by Sendai virus-induced human peripheral blood leucocytes." Nyman T.A., Toeloe H., Parkkinen J., Kalkkinen N. Biochem. J. 329:295-302(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-58.
[10]	"Assignment of the disulphide bonds of leukocyte interferon." Wetzel R. Nature 289:606-607(1981) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[11]	"Natural human interferon-alpha 2 is O-glycosylated." Adolf G.R., Kalsner I., Ahorn H., Maurer-Fogy I., Cantell K. Biochem. J. 276:511-518(1991) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-129, VARIANTS ALPHA-2B AND ALPHA-2C.
[12]	"Interferon-alpha 2 variants in the human genome." Lee N., Ni D., Brissette R., Chou M., Hussain M., Gill D.S., Liao M.-J., Testa D. J. Interferon Cytokine Res. 15:341-349(1995) [PubMed] [Europe PMC] [Abstract] Cited for: POLYMORPHISM.
[13]	"A homology model of human interferon alpha-2." Murgolo N.J., Windsor W.T., Hruza A., Reichert P., Tsarbopoulos A., Baldwin S., Huang E., Pramanik B., Ealick S., Trotta P.P. Proteins 17:62-74(1993) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[14]	"Zinc mediated dimer of human interferon-alpha 2b revealed by X-ray crystallography." Radhakrishnan R., Walter L.J., Hruza A., Reichert P., Trotta P.P., Nagabhushan T.L., Walter M.R. Structure 4:1453-1463(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[15]	"The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution." Klaus W., Gsell B., Labhardt A.M., Wipf B., Senn H. J. Mol. Biol. 274:661-675(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[16]	"Determination of the human type I interferon receptor binding site on human interferon-alpha2 by cross saturation and an NMR-based model of the complex." Quadt-Akabayov S.R., Chill J.H., Levy R., Kessler N., Anglister J. Protein Sci. 15:2656-2668(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 24-188 IN COMPLEX WITH IFNAR2, SUBUNIT, DISULFIDE BONDS.
[17]	"Intermolecular interactions in a 44 kDa interferon-receptor complex detected by asymmetric reverse-protonation and two-dimensional NOESY." Nudelman I., Akabayov S.R., Schnur E., Biron Z., Levy R., Xu Y., Yang D., Anglister J. Biochemistry 49:5117-5133(2010) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 24-188 IN COMPLEX WITH IFNAR2, SUBUNIT, DISULFIDE BONDS.
[18]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-177.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J00207 Genomic DNA. Translation: AAB59402.1.
V00544 mRNA. Translation: CAA23805.1.
V00548 mRNA. Translation: CAA23809.1.
V00549 mRNA. Translation: CAA23810.1.
Y11834 Genomic DNA. Translation: CAA72532.1.
M54886 mRNA. Translation: AAA59181.1.
M29883 Genomic DNA. Translation: AAA52715.1.

IPI

IPI00307184.

PIR

IVHUA2. A93234.
I78570.

RefSeq

NP_000596.2. NM_000605.3.

UniGene

Hs.211575.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ITF	NMR	-	A	24-188	[»]
1RH2	X-ray	2.90	A/B/C/D/E/F	24-188	[»]
2HIE	model	-	A	24-188	[»]
2HYM	NMR	-	B	24-188	[»]
2KZ1	NMR	-	A	24-188	[»]
2LAG	NMR	-	A	24-188	[»]
2LMS	NMR	-	A	24-188	[»]
3S9D	X-ray	2.00	A/C	24-188	[»]
3SE3	X-ray	4.00	B	24-188	[»]

ProteinModelPortal

P01563.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3784N.
DIP-481N.

IntAct

P01563. 1 interaction.

STRING

9606.ENSP00000369554.

Protein family/group databases

Allergome

9876. Hom s IFN alpha.

PTM databases

GlycoSuiteDB

P01563.

PhosphoSite

P01563.

Polymorphism databases

DMDM

124449.

Proteomic databases

PaxDb

P01563.

PRIDE

P01563.

Protocols and materials databases

DNASU

3440.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000380206; ENSP00000369554; ENSG00000188379.

GeneID

3440.

KEGG

hsa:3440.

Organism-specific databases

CTD

3440.

GeneCards

GC09M021374.

H-InvDB

HIX0034810.

HGNC

HGNC:5423. IFNA2.

HPA

HPA047557.

MIM

147562. gene.

neXtProt

NX_P01563.

PharmGKB

PA29662.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG246451.

HOGENOM

HOG000230500.

HOVERGEN

HBG052086.

InParanoid

P01563.

KO

K05414.

OrthoDB

EOG4KH2W5.

Enzyme and pathway databases

Pathway_Interaction_DB

cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.

Reactome

REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P01563.

CleanEx

HS_IFNA2.

Genevestigator

P01563.

GermOnline

ENSG00000188379. 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.
IPR015589. Interferon_alpha.
IPR000471. Interferon_alpha/beta/delta.
[Graphical view]

PANTHER

PTHR11691. PTHR11691. 1 hit.
PTHR11691:SF9. PTHR11691:SF9. 1 hit.

Pfam

PF00143. Interferon. 1 hit.
[Graphical view]

PRINTS

PR00266. INTERFERONAB.

SMART

SM00076. IFabd. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00252. INTERFERON_A_B_D. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00034. Interferon Alfa-2a, Recombinant.
DB00105. Interferon Alfa-2b, Recombinant.
DB00011. Interferon alfa-n1.
DB00008. Peginterferon alfa-2a.
DB00022. Peginterferon alfa-2b.

EvolutionaryTrace

P01563.

GenomeRNAi

3440.

NextBio

13556.

SOURCE

Search...

Entry information

Entry name

IFNA2_HUMAN

Accession

Primary (citable) accession number: P01563
Secondary accession number(s): P01564, Q14606, Q96KI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 137 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.