P60568 (IL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-2
Short name=IL-2

Alternative name(s):
T-cell growth factor
Short name=TCGF
INN=Aldesleukin

Gene names

Name:

IL2

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	153 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 T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.
Subcellular location	Secreted.
Involvement in disease	A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.
Pharmaceutical use	Available under the name Proleukin (Chiron). Used in patients with renal cell carcinoma or metastatic melanoma.
Sequence similarities	Belongs to the IL-2 family.
Sequence caution	The sequence AAA59140.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Secreted
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Pharmaceutical Reference proteome
Gene Ontology (GO)
Biological_process	T cell differentiation Traceable author statement PubMed 8476561. Source: UniProtKB cell adhesion Traceable author statement PubMed 10929056. Source: UniProtKB cell-cell signaling Traceable author statement PubMed 8476561. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara immune response Traceable author statement PubMed 2342538. Source: UniProtKB natural killer cell activation Traceable author statement PubMed 8476561. Source: UniProtKB negative regulation of B cell apoptotic process Inferred from direct assay PubMed 9184696. Source: MGI negative regulation of heart contraction Inferred from electronic annotation. Source: Compara negative regulation of inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of lymphocyte proliferation Inferred from electronic annotation. Source: Compara negative regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of B cell proliferation Inferred from direct assay PubMed 9184696. Source: MGI positive regulation of activated T cell proliferation Inferred from direct assay PubMed 10072077PubMed 1830926. Source: MGI positive regulation of cell growth Traceable author statement PubMed 8476561. Source: UniProtKB positive regulation of dendritic spine development Inferred from electronic annotation. Source: Compara positive regulation of immunoglobulin secretion Inferred from electronic annotation. Source: Compara positive regulation of inflammatory response Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of interferon-gamma production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-17 production Inferred from direct assay PubMed 16482511. Source: BHF-UCL positive regulation of isotype switching to IgG isotypes Inferred from electronic annotation. Source: Compara positive regulation of regulatory T cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of tissue remodeling Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from direct assay PubMed 19088061. Source: BHF-UCL protein kinase C-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara regulation of T cell homeostatic proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Traceable author statement Ref.6. Source: UniProtKB
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: Compara cytokine activity Inferred from direct assay PubMed 10072077PubMed 1830926. Source: MGI glycosphingolipid binding Inferred from electronic annotation. Source: Compara growth factor activity Traceable author statement PubMed 8476561. Source: UniProtKB interleukin-2 receptor binding Traceable author statement PubMed 3925347. Source: UniProtKB kinase activator activity Traceable author statement PubMed 8476561. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Ref.14

Chain

21 – 153

133

Interleukin-2

PRO_0000015484

Amino acid modifications

Glycosylation

23

1

O-linked (GalNAc...) Ref.14 Ref.15

CAR_000051

Disulfide bond

78 ↔ 125

Ref.14 Ref.22

Natural variations

Natural variant

21

1

Missing in FT-IL2-A and FT-IL2-B.

VAR_003967

Natural variant

22

1

Missing in FT-IL2-B.

VAR_003968

Secondary structure

1

.

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153

Helix Strand Turn

Details...

Helix

26 – 48

23

Beta strand

49 – 52

4

Helix

53 – 59

7

Helix

60 – 62

3

Beta strand

64 – 68

5

Helix

73 – 76

4

Helix

77 – 80

4

Helix

83 – 92

10

Helix

95 – 97

3

Beta strand

98 – 100

3

Helix

102 – 117

16

Beta strand

119 – 121

3

Beta strand

127 – 132

6

Helix

134 – 150

17

Sequences

	Sequence		Length	Mass (Da)
	P60568 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 59E2F40F25860F84	FASTA	153	17,628
	10 20 30 40 50 60 MYRMQLLSCI ALSLALVTNS APTSSSTKKT QLQLEHLLLD LQMILNGINN YKNPKLTRML 70 80 90 100 110 120 TFKFYMPKKA TELKHLQCLE EELKPLEEVL NLAQSKNFHL RPRDLISNIN VIVLELKGSE 130 140 150 TTFMCEYADE TATIVEFLNR WITFCQSIIS TLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of interleukin 2 mRNAs from human tonsils." Maeda S., Nishino N., Obaru K., Mita S., Nomiyama H., Shimada K., Fujimoto K., Teranishi T., Hirano T., Onoue K. Biochem. Biophys. Res. Commun. 115:1040-1047(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Structure and expression of a cloned cDNA for human interleukin-2." Taniguchi T., Matsui H., Fujita T., Takaoka C., Kashima N., Yoshimoto R., Hamuro J. Nature 302:305-310(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Molecular cloning of human interleukin 2 cDNA and its expression in E. coli." Devos R., Plaetinck G., Cheroutre H., Simons G., Degrave W., Tavernier J., Remaut E., Fiers W. Nucleic Acids Res. 11:4307-4323(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structure of the human interleukin 2 gene." Fujita T., Takaoka C., Matsui H., Taniguchi T. Proc. Natl. Acad. Sci. U.S.A. 80:7437-7441(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"DNA sequence of the 5' flanking region of the human interleukin 2 gene: homologies with adult T-cell leukemia virus." Holbrook N.J., Lieber M., Crabtree G.R. Nucleic Acids Res. 12:5005-5013(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"T-cell growth factor: complete nucleotide sequence and organization of the gene in normal and malignant cells." Holbrook N.J., Smith K.A., Fornace A.J. Jr., Comeau C.M., Wiskocil R.L., Crabtree G.R. Proc. Natl. Acad. Sci. U.S.A. 81:1634-1638(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Interleukin-2 transcripts in human and rodent brains: possible expression by astrocytes." Eizenberg O., Faber-Elman A., Lotan M., Schwartz M. J. Neurochem. 64:1928-1936(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]	"Sequence of interleukin-2 isolated from human placental poly A+ RNA: possible role in maintenance of fetal allograft." Chernicky C.L., Tan H., Burfeind P., Ilan J., Ilan J. Mol. Reprod. Dev. 43:180-186(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[9]	SeattleSNPs variation discovery resource Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[10]	"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]. Tissue: Blood.
[11]	"Organization of the DNA regions flanking the human interleukin 2 gene." Nishino N., Obaru K., Maeda S., Shimada K., Onoue K. Biomed. Res. 6:197-205(1985) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-68.
[12]	"Promoter region of interleukin-2 gene undergoes chromatin structure changes and confers inducibility on chloramphenicol acetyltransferase gene during activation of T cells." Siebenlist U., Durand D.B., Bressler P., Holbrook N.J., Norris C.A., Kamoun M., Kant J.A., Crabtree G.R. Mol. Cell. Biol. 6:3042-3049(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-69.
[13]	"Structure-activity relationships of recombinant human interleukin 2." Weir M.P., Chaplin M.A., Wallace D.M., Dykes C.W., Hobden A.N. Biochemistry 27:6883-6892(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 21-153.
[14]	"Amino acid sequence and post-translational modification of human interleukin 2." Robb R.J., Kutny R.M., Panico M., Morris H.R., Chowdhry V. Proc. Natl. Acad. Sci. U.S.A. 81:6486-6490(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-153, DISULFIDE BOND, GLYCOSYLATION AT THR-23.
[15]	"Expression of human interleukin-2 in recombinant baby hamster kidney, Ltk-, and Chinese hamster ovary cells. Structure of O-linked carbohydrate chains and their location within the polypeptide." Conradt H.S., Nimtz M., Dittmar K.E.J., Lindenmaier W., Hoppe J., Hauser H. J. Biol. Chem. 264:17368-17373(1989) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-23.
[16]	"Three-dimensional structure of interleukin-2." Brandhuber B.J., Boone T., Kenney W.C., McKay D.B. Science 238:1707-1709(1987) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[17]	"Unraveling the structure of IL-2." Bazan J.F. Science 257:410-412(1992) [PubMed] [Europe PMC] [Abstract] Cited for: COMPARISON OF X-RAY STRUCTURES.
[18]	McKay D.B. Science 257:412-413(1992) Cited for: RESPONSE TO PUBMED:1631562.
[19]	"Secondary structure of human interleukin 2 from 3D heteronuclear NMR experiments." Mott H.R., Driscoll P.C., Boyd J., Cooke R.M., Weir M.P., Campbell I.D. Biochemistry 31:7741-7744(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[20]	"The interleukin-2 and interleukin-4 receptors studied by molecular modelling." Bamborough P., Hedgecock C.J., Richards W.G. Structure 2:839-851(1994) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[21]	"Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors." Wang X., Rickert M., Garcia K.C. Science 310:1159-1163(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 21-153 IN COMPLEX WITH IL2RA; IL2RB AND IL2RC.
[22]	"Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor." Stauber D.J., Debler E.W., Horton P.A., Smith K.A., Wilson I.A. Proc. Natl. Acad. Sci. U.S.A. 103:2788-2793(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 21-153 IN COMPLEX WITH IL2RA; IL2RB AND IL2RC, DISULFIDE BOND.
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine source book: IL-2

Wikipedia

Interleukin-2 entry

SeattleSNPs

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X00695 Genomic DNA. Translation: CAA25292.1.
V00564 mRNA. Translation: CAA23827.1.
X01586 mRNA. Translation: CAA25742.1.
J00264 Genomic DNA. Translation: AAD48509.1.
K02056 Genomic DNA. Translation: AAA98792.1.
S77834 mRNA. Translation: AAD14263.2.
S82692 mRNA. Translation: AAB46883.1.
AF359939 Genomic DNA. Translation: AAK26665.1.
BC066255 mRNA. Translation: AAH66255.1.
BC066257 mRNA. Translation: AAH66257.1.
BC070338 mRNA. Translation: AAH70338.1.
M33199 Genomic DNA. Translation: AAA59139.1.
M13879 Genomic DNA. Translation: AAA59141.1.
M22005 Genomic DNA. Translation: AAA59140.1. Different initiation.

IPI

IPI00003099.

PIR

ICHU2. A01849.

RefSeq

NP_000577.2. NM_000586.3.

UniGene

Hs.89679.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ILM	model	-	2	26-153	[»]
1ILN	model	-	2	26-153	[»]
1IRL	NMR	-	A	21-153	[»]
1M47	X-ray	1.99	A	21-153	[»]
1M48	X-ray	1.95	A/B	21-153	[»]
1M49	X-ray	2.00	A/B	21-153	[»]
1M4A	X-ray	2.18	A	21-153	[»]
1M4B	X-ray	2.15	A	21-153	[»]
1M4C	X-ray	2.40	A/B	21-153	[»]
1NBP	X-ray	2.20	A	21-153	[»]
1PW6	X-ray	2.60	A/B	21-153	[»]
1PY2	X-ray	2.80	A/B/C/D	21-152	[»]
1QVN	X-ray	2.70	A/B/C/D	21-152	[»]
1Z92	X-ray	2.80	A	21-153	[»]
2B5I	X-ray	2.30	A	21-153	[»]
2ERJ	X-ray	3.00	D/H	21-153	[»]
3INK	X-ray	2.50	C/D	21-153	[»]
3QAZ	X-ray	3.80	A/D/G/J/M/P/S/V/Y/b/e/h	21-153	[»]
3QB1	X-ray	3.10	A/B/C/D/E/F/G/H	21-153	[»]

ProteinModelPortal

P60568.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-475N.

MINT

MINT-1522299.

STRING

9606.ENSP00000226730.

PTM databases

GlycoSuiteDB

P60568.

PhosphoSite

P60568.

Polymorphism databases

DMDM

45593462.

Proteomic databases

PaxDb

P60568.

PRIDE

P60568.

Protocols and materials databases

DNASU

3558.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000226730; ENSP00000226730; ENSG00000109471.

GeneID

3558.

KEGG

hsa:3558.

UCSC

uc003ier.3. human.

Organism-specific databases

CTD

3558.

GeneCards

GC04M123372.

HGNC

HGNC:6001. IL2.

HPA

CAB010310.

MIM

147680. gene.

neXtProt

NX_P60568.

PharmGKB

PA195.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG41211.

HOVERGEN

HBG007496.

InParanoid

P60568.

KO

K05429.

OMA

KWITFCQ.

OrthoDB

EOG46Q6V2.

PhylomeDB

P60568.

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.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.
telomerasepathway. Regulation of Telomerase.

Reactome

REACT_6900. Immune System.

SignaLink

P60568.

Gene expression databases

ArrayExpress

P60568.

Bgee

P60568.

CleanEx

HS_IL2.

Genevestigator

P60568.

GermOnline

ENSG00000109471. 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.
IPR000779. Interleukin-2.
[Graphical view]

PANTHER

PTHR11443. PTHR11443. 1 hit.

Pfam

PF00715. IL2. 1 hit.
[Graphical view]

PRINTS

PR00265. INTERLEUKIN2.

ProDom

PD003649. Interleukin-2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00189. IL2. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00424. INTERLEUKIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5880.

ChiTaRS

IL2. human.

EvolutionaryTrace

P60568.

GenomeRNAi

3558.

NextBio

13896.

SOURCE

Search...

Entry information

Entry name

IL2_HUMAN

Accession

Primary (citable) accession number: P60568
Secondary accession number(s): P01585

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 29, 2013
This is version 115 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.