P40933 (IL15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-15
Short name=IL-15

Gene names

Name:

IL15

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	162 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	Cytokine that stimulates the proliferation of T-lymphocytes. Stimulation by IL-15 requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma but not IL-2R alpha.
Subcellular location	Isoform IL15-S48AA: Secreted. Isoform IL15-S21AA: Cytoplasm. Nucleus. Note: IL15-S21AA is not secreted, but rather is stored intracellularly, appearing in the nucleus and cytoplasmic components.
Tissue specificity	Most abundant in placenta and skeletal muscle. It is also detected in the heart, lung, liver and kidney. IL15-S21AA is preferentially expressed in tissues such as testis and thymus.
Sequence similarities	Belongs to the IL-15/IL-21 family.
Sequence caution	The sequence CAA71044.1 differs from that shown. Reason: Man-made cDNA construct with a sequence coding for signal peptide increasing the secretion of the protein (substitution with a signal peptide derived from the mouse IgV kappa chain).

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NK T cell proliferation Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara cell maturation Inferred from electronic annotation. Source: Compara cell-cell signaling Traceable author statement PubMed 7759105. Source: ProtInc cellular response to vitamin D Inferred from electronic annotation. Source: Compara extrathymic T cell selection Inferred from electronic annotation. Source: Compara hyaluronan metabolic process Inferred from electronic annotation. Source: Compara immune response Traceable author statement Ref.1. Source: ProtInc inflammatory response Inferred from electronic annotation. Source: Compara lymph node development Inferred from electronic annotation. Source: Compara natural killer cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of smooth muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Traceable author statement PubMed 10851076. Source: ProtInc positive regulation of immune response Inferred from electronic annotation. Source: Compara positive regulation of inflammatory response Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of interleukin-17 production Inferred from direct assay PubMed 16482511. Source: BHF-UCL positive regulation of natural killer cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of natural killer cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of tissue remodeling Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara regulation of T cell differentiation Inferred from electronic annotation. Source: Compara regulation of defense response to virus by host Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement Ref.1. Source: ProtInc skeletal muscle atrophy Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Traceable author statement PubMed 10851076. Source: ProtInc endosome Traceable author statement PubMed 10851076. Source: ProtInc extracellular space Traceable author statement PubMed 10851076. Source: ProtInc integral to plasma membrane Traceable author statement PubMed 10851076. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL15RA	Q13261	3	EBI-980274,EBI-980354

Alternative products

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

Isoform IL15-S48AA (identifier: P40933-1)

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 IL15-S21AA (identifier: P40933-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MRISKPHLRSISIQCYLCLLLNSHFLTEAGIHVFILG → MVLGTIDLCS

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Potential

Propeptide

30 – 48

19

Potential

PRO_0000015393

Chain

49 – 162

114

Interleukin-15

PRO_0000015394

Amino acid modifications

Glycosylation

127

1

N-linked (GlcNAc...) Potential

Disulfide bond

83 ↔ 133

By similarity

Disulfide bond

90 ↔ 136

By similarity

Natural variations

Alternative sequence

1 – 37

37

MRISK…VFILG → MVLGTIDLCS in isoform IL15-S21AA.

VSP_002660

Experimental info

Sequence conflict

141

1

E → K in AAB97518. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

162

Helix Strand Turn

Details...

Helix

49 – 64

16

Beta strand

73 – 75

3

Helix

81 – 83

3

Helix

84 – 102

19

Helix

105 – 119

15

Helix

136 – 138

3

Beta strand

139 – 142

4

Helix

144 – 158

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform IL15-S48AA [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 0CE0520C1D8379E2	FASTA	162	18,086
	10 20 30 40 50 60 MRISKPHLRS ISIQCYLCLL LNSHFLTEAG IHVFILGCFS AGLPKTEANW VNVISDLKKI 70 80 90 100 110 120 EDLIQSMHID ATLYTESDVH PSCKVTAMKC FLLELQVISL ESGDASIHDT VENLIILANN 130 140 150 160 SLSSNGNVTE SGCKECEELE EKNIKEFLQS FVHIVQMFIN TS
	Isoform IL15-S21AA [UniParc]. Checksum: EB44F422096B143E	FASTA	135	14,912
	10 20 30 40 50 60 MVLGTIDLCS CFSAGLPKTE ANWVNVISDL KKIEDLIQSM HIDATLYTES DVHPSCKVTA 70 80 90 100 110 120 MKCFLLELQV ISLESGDASI HDTVENLIIL ANNSLSSNGN VTESGCKECE ELEEKNIKEF 130 LQSFVHIVQM FINTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor." Grabstein K.H., Eisenman J., Shanebeck K., Rauch C., Srinivasan S., Fung V., Beers C., Richardson J., Schoenborn M.A., Ahdieh M., Johnson L., Alderson M.R., Watson J.D., Anderson D.M., Giri J.G. Science 264:965-968(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S48AA). Tissue: Bone marrow.
[2]	"Genomic sequence and chromosomal location of the human interleukin-15 gene (IL15)." Krause H., Jandrig B., Wernicke C., Bulfone-Paus S., Pohl T., Diamantstein T. Cytokine 8:667-674(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Identification of a novel interleukin-15 (IL-15) transcript isoform generated by alternative splicing in human small cell lung cancer cell lines." Meazza R., Verdiani S., Biassoni R., Coppolecchia M., Gaggero A., Orengo A.M., Colombo M.P., Azzarone B., Ferrini S. Oncogene 12:2187-2192(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S21AA). Tissue: Lung cancer.
[4]	"Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides." Tagaya Y., Kurys G., Thies T.A., Losi J.M., Azimi N., Hanover J.A., Bamford R.N., Waldmann T.A. Proc. Natl. Acad. Sci. U.S.A. 94:14444-14449(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S21AA). Tissue: Testis.
[5]	"Expression of two IL-15 mRNA isoforms in human tumors does not correlate with secretion: role of different signal peptides." Meazza R., Ferrini S. Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 IL15-S48AA). Tissue: Colon.
[8]	"IL15 expression in human keratinocytes." Sorel M.A., Jacques Y. Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 49-162. Tissue: Epidermis.
+	Additional computationally mapped references.

Web resources

R&D Systems' cytokine source book: IL-15

Wikipedia

Interleukin-15 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U14407 mRNA. Translation: AAA21551.1.
X91233 Genomic DNA. Translation: CAA62616.1.
X94223 mRNA. Translation: CAA63914.1.
X94222 mRNA. Translation: CAA63913.1.
AF031167 mRNA. Translation: AAB97518.1.
Y09908 mRNA. Translation: CAA71044.1. Sequence problems.
CH471056 Genomic DNA. Translation: EAX05085.1.
CH471056 Genomic DNA. Translation: EAX05087.1.
BC018149 mRNA. Translation: AAH18149.1.
BC100963 mRNA. Translation: AAI00964.1.
Z38000 mRNA. Translation: CAA86100.1.

IPI

IPI00031509.
IPI00220638.

RefSeq

NP_000576.1. NM_000585.4.
NP_751915.1. NM_172175.2.

UniGene

Hs.168132.
Hs.602618.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XQB	X-ray	2.60	A	49-162	[»]
2Z3Q	X-ray	1.85	A/C	49-162	[»]
2Z3R	X-ray	2.00	A/C/E/G/I/K/M/O	49-162	[»]
4GS7	X-ray	2.35	A	49-162	[»]

ProteinModelPortal

P40933.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3046N.

IntAct

P40933. 1 interaction.

STRING

9606.ENSP00000296545.

PTM databases

PhosphoSite

P40933.

Polymorphism databases

DMDM

729830.

Proteomic databases

PRIDE

P40933.

Protocols and materials databases

DNASU

3600.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296545; ENSP00000296545; ENSG00000164136.
ENST00000320650; ENSP00000323505; ENSG00000164136.
ENST00000394159; ENSP00000377714; ENSG00000164136.
ENST00000477265; ENSP00000436914; ENSG00000164136.
ENST00000514653; ENSP00000422271; ENSG00000164136.
ENST00000529613; ENSP00000435462; ENSG00000164136.

GeneID

3600.

KEGG

hsa:3600.

UCSC

uc003iis.3. human.

Organism-specific databases

CTD

3600.

GeneCards

GC04P142557.

HGNC

HGNC:5977. IL15.

HPA

CAB004457.

MIM

600554. gene.

neXtProt

NX_P40933.

PharmGKB

PA29790.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG44071.

HOVERGEN

HBG006142.

InParanoid

P40933.

KO

K05433.

OMA

RSTSIQC.

OrthoDB

EOG40CHJ8.

PhylomeDB

P40933.

Gene expression databases

ArrayExpress

P40933.

Bgee

P40933.

CleanEx

HS_IL15.

Genevestigator

P40933.

GermOnline

ENSG00000164136. Homo sapiens.

Family and domain databases

InterPro

IPR020439. Interleukin-15.
IPR020466. Interleukin-15_mammal.
IPR003443. Interleukin_15-like.
[Graphical view]

Pfam

PF02372. IL15. 1 hit.
[Graphical view]

PRINTS

PR01947. INTLKN15MAML.
PR01930. INTRLEUKIN15.

ProtoNet

Search...

Other

EvolutionaryTrace

P40933.

GenomeRNAi

3600.

NextBio

14065.

SOURCE

Search...

Entry information

Entry name

IL15_HUMAN

Accession

Primary (citable) accession number: P40933
Secondary accession number(s): D3DNZ2 , O00440, O43512, Q495Z8, Q93058, Q9UBA3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 119 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.