P05112 (IL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-4
Short name=IL-4

Alternative name(s):
B-cell stimulatory factor 1
Short name=BSF-1
Binetrakin
Lymphocyte stimulatory factor 1
Pitrakinra

Gene names

Name:

IL4

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	Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes.
Subcellular location	Secreted.
Involvement in disease	Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.19
Sequence similarities	Belongs to the IL-4/IL-13 family.

Ontologies

Keywords
Biological process	B-cell activation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell costimulation Inferred from electronic annotation. Source: Compara B cell differentiation Traceable author statement PubMed 11418631. Source: UniProtKB T-helper 1 cell lineage commitment Inferred from electronic annotation. Source: Compara T-helper 2 cell cytokine production Inferred from direct assay PubMed 20554961. Source: UniProtKB T-helper 2 cell differentiation Inferred from electronic annotation. Source: Compara cellular defense response Traceable author statement PubMed 10725748. Source: ProtInc cellular response to mercury ion Inferred from electronic annotation. Source: Compara chemotaxis Traceable author statement PubMed 10725748. Source: ProtInc cholesterol metabolic process Inferred from sequence or structural similarity PubMed 11971948. Source: UniProtKB connective tissue growth factor biosynthetic process Traceable author statement PubMed 11967989. Source: UniProtKB dendritic cell differentiation Inferred from direct assay PubMed 21149635. Source: DFLAT female pregnancy Inferred from electronic annotation. Source: Compara innate immune response in mucosa Inferred from electronic annotation. Source: Compara negative regulation of T-helper 17 cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of acute inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of chronic inflammatory response Inferred from electronic annotation. Source: Compara negative regulation of macrophage activation Inferred from electronic annotation. Source: Compara negative regulation of nitric oxide biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of osteoclast differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 18579517. Source: UniProtKB positive regulation of B cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of MHC class II biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of T cell differentiation Inferred from direct assay PubMed 20554961. Source: UniProtKB positive regulation of T cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of activated T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of chemokine biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of interleukin-10 production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-13 production Inferred from direct assay PubMed 19346497. Source: UniProtKB positive regulation of isotype switching to IgE isotypes Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of isotype switching to IgG isotypes Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from electronic annotation. Source: Compara regulation of phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of proton transport Inferred from electronic annotation. Source: Compara response to cytokine stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular space Traceable author statement PubMed 11418631. Source: UniProtKB
Molecular_function	growth factor activity Non-traceable author statement PubMed 11418631. Source: UniProtKB interleukin-4 receptor binding Traceable author statement PubMed 11418631. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL13RA1	P78552	3	EBI-367025,EBI-1391535
IL4R	P24394	5	EBI-367025,EBI-367009

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P05112-1)

Also known as: Long;

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: P05112-2)

Also known as: Short; IL-4delta2;

The sequence of this isoform differs from the canonical sequence as follows:
     46-61: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Chain

25 – 153

129

Interleukin-4

PRO_0000015532

Amino acid modifications

Glycosylation

62

1

N-linked (GlcNAc...) Ref.7

Disulfide bond

27 ↔ 151

Ref.7 Ref.16

Disulfide bond

48 ↔ 89

Ref.7 Ref.16

Disulfide bond

70 ↔ 123

Ref.7 Ref.16

Natural variations

Alternative sequence

46 – 61

16

Missing in isoform 2.

VSP_002672

Natural variant

27

1

C → R.
Corresponds to variant rs4986964 [ dbSNP | Ensembl ].

VAR_020392

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

153

Helix Strand Turn

Details...

Turn

26 – 29

4

Helix

30 – 41

12

Helix

48 – 50

3

Beta strand

51 – 54

4

Helix

56 – 58

3

Turn

60 – 62

3

Helix

65 – 83

19

Turn

87 – 89

3

Helix

94 – 118

25

Beta strand

130 – 132

3

Helix

133 – 151

19

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified August 13, 1987. Version 1. Checksum: 8725BF64B34D45F7	FASTA	153	17,492
	10 20 30 40 50 60 MGLTSQLLPP LFFLLACAGN FVHGHKCDIT LQEIIKTLNS LTEQKTLCTE LTVTDIFAAS 70 80 90 100 110 120 KNTTEKETFC RAATVLRQFY SHHEKDTRCL GATAQQFHRH KQLIRFLKRL DRNLWGLAGL 130 140 150 NSCPVKEANQ STLENFLERL KTIMREKYSK CSS
	Isoform 2 (Short) (IL-4delta2) [UniParc]. Checksum: 3B621F60D0F0D261	FASTA	137	15,797
	10 20 30 40 50 60 MGLTSQLLPP LFFLLACAGN FVHGHKCDIT LQEIIKTLNS LTEQKNTTEK ETFCRAATVL 70 80 90 100 110 120 RQFYSHHEKD TRCLGATAQQ FHRHKQLIRF LKRLDRNLWG LAGLNSCPVK EANQSTLENF 130 LERLKTIMRE KYSKCSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities." Yokota T., Otsuka T., Mosmann T., Banchereau J., Defrance T., Blanchard D., de Vries J.E., Lee F., Arai K. Proc. Natl. Acad. Sci. U.S.A. 83:5894-5898(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression." Arai N., Nomura D., Villaret D., Malefijt R.D., Seiki M., Yoshida M., Minoshima S., Fukuyama R., Maekawa M., Kudoh J., Shimizu N., Yokota K., Abe E., Yokota T., Takebe Y., Arai K. J. Immunol. 142:274-282(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"An alternatively spliced interleukin 4 form in lymphoid cells." Klein S.C., Golverdingen J., Bouwens A.G.M., Tilanus M.G.J. Immunogenetics 41:57-57(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Blood.
[6]	"The 5' region of the human interleukin 4 gene: structure and potential regulatory elements." Eder A., Krafft-Czepa H., Krammer P.H. Nucleic Acids Res. 16:772-772(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
[7]	"Disulfide assignments in recombinant mouse and human interleukin 4." Carr C., Aykent S., Kimack N.M., Levine A.D. Biochemistry 30:1515-1523(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-62, DISULFIDE BONDS.
[8]	"Crystal structure of recombinant human interleukin-4." Walter M.R., Cook W.J., Zhao B.G., Cameron R.P. Jr., Ealick S.E., Walter R.L. Jr., Reichert P., Nagabhushan T.L., Trotta P.P., Bugg C.E. J. Biol. Chem. 267:20371-20376(1992) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS).
[9]	"Crystal structure of human recombinant interleukin-4 at 2.25-A resolution." Wlodaver A., Pavlovsky A., Gustchina A. FEBS Lett. 309:59-64(1992) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
[10]	"Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface." Hage T., Sebald W., Reinemer P. Cell 97:271-281(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 25-153 IN COMPLEX WITH IL4RALPHA.
[11]	"Secondary structure and topology of human interleukin 4 in solution." Redfield C., Smith L.J., Boyd J., Lawrence G.M.P., Edwards R.G., Smith R.A.G., Dobson C.M. Biochemistry 30:11029-11035(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[12]	"Human interleukin 4. The solution structure of a four-helix bundle protein." Smith L.J., Redfield C., Boyd J., Lawrence G.M.P., Edwards R.G., Smith R.A.G., Dobson C.M. J. Mol. Biol. 224:899-904(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[13]	"1H, 15N, 13C, and 13CO assignments of human interleukin-4 using three-dimensional double- and triple-resonance heteronuclear magnetic resonance spectroscopy." Powers R., Garret D.S., March C.J., Frieden E.A., Gronenborn A.M., Clore G.M. Biochemistry 31:4334-4346(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[14]	"Determination of the secondary structure and folding topology of human interleukin-4 using three-dimensional heteronuclear magnetic resonance spectroscopy." Garret D.S., Powers R., March C.J., Frieden E.A., Clore G.M., Gronenborn A.M. Biochemistry 31:4347-4353(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[15]	"Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy." Powers R., Garret D.S., March C.J., Frieden E.A., Gronenborn A.M., Clore G.M. Science 256:1673-1677(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR.
[16]	"Experimental and theoretical studies of the three-dimensional structure of human interleukin-4." Curtis B.M., Presnell S.R., Srinivasan S., Sassenfeld H., Klinke R., Jeffery E., Cosman D., March C.J., Cohen F.E. Proteins 11:111-119(1991) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS, 3D-STRUCTURE MODELING.
[17]	"Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy." Mueller T., Dieckmann T., Sebald W., Oschkinat H. J. Mol. Biol. 237:423-436(1994) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS, STRUCTURE BY NMR.
[18]	"Comparison of four independently determined structures of human recombinant interleukin-4." Smith L.J., Redfield C., Smith R.A.G., Dobson C.M., Clore G.M., Gronenborn A.M., Walter M.R., Naganbushan T.L., Wlodawer A. Nat. Struct. Biol. 1:301-310(1994) [PubMed] [Europe PMC] [Abstract] Cited for: COMPARISON OF STRUCTURES.
[19]	"Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis." Zee R.Y.L., Cook N.R., Cheng S., Reynolds R., Erlich H.A., Lindpaintner K., Ridker P.M. Hum. Mol. Genet. 13:389-396(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M13982 mRNA. Translation: AAA59149.1.
M23442 Genomic DNA. Translation: AAA59150.1.
X81851 mRNA. Translation: CAA57444.1.
AF395008 Genomic DNA. Translation: AAK71324.1.
BC067514 mRNA. Translation: AAH67514.1.
BC070123 mRNA. Translation: AAH70123.1.
X06750 Genomic DNA. Translation: CAA29925.1.

IPI

IPI00007081.
IPI00217945.

PIR

A25946. A30546.

RefSeq

NP_000580.1. NM_000589.3.
NP_758858.1. NM_172348.2.

UniGene

Hs.73917.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BBN	NMR	-	A	25-153	[»]
1BCN	NMR	-	A	25-153	[»]
1CYL	NMR	-	A	25-153	[»]
1HIJ	X-ray	3.00	A	25-153	[»]
1HIK	X-ray	2.60	A	25-153	[»]
1HZI	X-ray	2.05	A	25-153	[»]
1IAR	X-ray	2.30	A	25-153	[»]
1ILL	model	-	4	25-153	[»]
1ITE	model	-	A	25-153	[»]
1ITI	NMR	-	A	25-153	[»]
1ITL	NMR	-	A	25-153	[»]
1ITM	NMR	-	A	25-153	[»]
1RCB	X-ray	2.25	A	25-153	[»]
2B8U	X-ray	1.80	A	25-153	[»]
2B8X	X-ray	1.70	A	25-153	[»]
2B8Y	X-ray	1.80	A	25-153	[»]
2B8Z	X-ray	2.50	A	25-153	[»]
2B90	X-ray	2.10	A	25-153	[»]
2B91	X-ray	2.00	A	25-153	[»]
2CYK	NMR	-	A	25-153	[»]
2D48	X-ray	1.65	A	25-153	[»]
2INT	X-ray	2.35	A	25-153	[»]
3BPL	X-ray	2.93	A	25-153	[»]
3BPN	X-ray	3.02	A	25-153	[»]
3QB7	X-ray	3.24	A/B	25-140	[»]

ProteinModelPortal

P05112.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3222N.

IntAct

P05112. 3 interactions.

MINT

MINT-90320.

STRING

9606.ENSP00000231449.

Polymorphism databases

DMDM

124337.

Proteomic databases

PaxDb

P05112.

PRIDE

P05112.

Protocols and materials databases

DNASU

3565.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000231449; ENSP00000231449; ENSG00000113520.
ENST00000350025; ENSP00000325190; ENSG00000113520.

GeneID

3565.

KEGG

hsa:3565.

UCSC

uc003kxk.1. human.

Organism-specific databases

CTD

3565.

GeneCards

GC05P132009.

H-InvDB

HIX0164435.

HGNC

HGNC:6014. IL4.

MIM

147780. gene.
601367. phenotype.

neXtProt

NX_P05112.

PharmGKB

PA197.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG266404.

HOGENOM

HOG000254781.

HOVERGEN

HBG000290.

InParanoid

P05112.

KO

K05430.

OMA

MKEKYSK.

OrthoDB

EOG469QWD.

PhylomeDB

P05112.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
il12_2pathway. IL12-mediated signaling events.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il4_2pathway. IL4-mediated signaling events.

SignaLink

P05112.

Gene expression databases

ArrayExpress

P05112.

Bgee

P05112.

CleanEx

HS_IL4.

Genevestigator

P05112.

GermOnline

ENSG00000113520. 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.
IPR002354. Interleukin-4.
IPR018096. Interleukin-4/-13_CS.
IPR001325. Interleukin-4/13.
[Graphical view]

PANTHER

PTHR11456. PTHR11456. 1 hit.

Pfam

PF00727. IL4. 1 hit.
[Graphical view]

PIRSF

PIRSF001941. Interleukin_4. 1 hit.

PRINTS

PR00431. INTERLEUKIN4.

SMART

SM00190. IL4_13. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00838. INTERLEUKIN_4_13. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P05112.

GenomeRNAi

3565.

NextBio

13920.

SOURCE

Search...

Entry information

Entry name

IL4_HUMAN

Accession

Primary (citable) accession number: P05112
Secondary accession number(s): Q14630

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	May 29, 2013
This is version 164 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.