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Interleukin-15 (IL-15)

 IL15_HUMAN              Reviewed;         162 AA.
P40933; D3DNZ2; O00440; O43512; Q495Z8; Q6FGX7; Q93058; Q9UBA3;
01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
01-FEB-1995, sequence version 1.
27-SEP-2017, entry version 158.
RecName: Full=Interleukin-15;
Short=IL-15;
Flags: Precursor;
Name=IL15;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S48AA).
TISSUE=Bone marrow;
PubMed=8178155; DOI=10.1126/science.8178155;
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.;
"Cloning of a T cell growth factor that interacts with the beta chain
of the interleukin-2 receptor.";
Science 264:965-968(1994).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=8932977; DOI=10.1006/cyto.1996.0089;
Krause H., Jandrig B., Wernicke C., Bulfone-Paus S., Pohl T.,
Diamantstein T.;
"Genomic sequence and chromosomal location of the human interleukin-15
gene (IL15).";
Cytokine 8:667-674(1996).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S21AA).
TISSUE=Lung cancer;
PubMed=8668345;
Meazza R., Verdiani S., Biassoni R., Coppolecchia M., Gaggero A.,
Orengo A.M., Colombo M.P., Azzarone B., Ferrini S.;
"Identification of a novel interleukin-15 (IL-15) transcript isoform
generated by alternative splicing in human small cell lung cancer cell
lines.";
Oncogene 12:2187-2192(1996).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S21AA).
TISSUE=Testis;
PubMed=9405632; DOI=10.1073/pnas.94.26.14444;
Tagaya Y., Kurys G., Thies T.A., Losi J.M., Azimi N., Hanover J.A.,
Bamford R.N., Waldmann T.A.;
"Generation of secretable and nonsecretable interleukin 15 isoforms
through alternate usage of signal peptides.";
Proc. Natl. Acad. Sci. U.S.A. 94:14444-14449(1997).
[5]
NUCLEOTIDE SEQUENCE [MRNA].
Meazza R., Ferrini S.;
"Expression of two IL-15 mRNA isoforms in human tumors does not
correlate with secretion: role of different signal peptides.";
Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IL15-S21AA).
Li C.;
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IL15-S21AA).
TISSUE=Cerebellum, and Heart;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IL15-S21AA).
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry
vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[9]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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.
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS IL15-S48AA AND
IL15-S21AA).
TISSUE=Colon;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[11]
NUCLEOTIDE SEQUENCE [MRNA] OF 49-162.
TISSUE=Epidermis;
Sorel M.A., Jacques Y.;
"IL15 expression in human keratinocytes.";
Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
[12]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 49-162 IN COMPLEX WITH
ANTIBODY, AND DISULFIDE BONDS.
PubMed=21167836; DOI=10.1016/j.jmb.2010.12.017;
Lowe D.C., Gerhardt S., Ward A., Hargreaves D., Anderson M.,
Ferraro F., Pauptit R.A., Pattison D.V., Buchanan C., Popovic B.,
Finch D.K., Wilkinson T., Sleeman M., Vaughan T.J., Mallinder P.R.;
"Engineering a high-affinity anti-IL-15 antibody: crystal structure
reveals an alpha-helix in VH CDR3 as key component of paratope.";
J. Mol. Biol. 406:160-175(2011).
-!- 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.
-!- INTERACTION:
Q13261:IL15RA; NbExp=5; IntAct=EBI-980274, EBI-980354;
P14784:IL2RB; NbExp=3; IntAct=EBI-980274, EBI-2866779;
-!- SUBCELLULAR LOCATION: Isoform IL15-S48AA: Secreted.
-!- SUBCELLULAR LOCATION: Isoform IL15-S21AA: Cytoplasm. Nucleus.
Note=IL15-S21AA is not secreted, but rather is stored
intracellularly, appearing in the nucleus and cytoplasmic
components.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=IL15-S48AA;
IsoId=P40933-1; Sequence=Displayed;
Name=IL15-S21AA;
IsoId=P40933-2; Sequence=VSP_002660;
-!- 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.
-!- SIMILARITY: Belongs to the IL-15/IL-21 family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=CAA71044.1; Type=Miscellaneous discrepancy; Note=Man-made cDNA with a signal peptide sequence to increase protein secretion (substitution with a signal peptide derived from the mouse IgV kappa chain).; Evidence={ECO:0000305};
-!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-15 entry;
URL="https://en.wikipedia.org/wiki/Interleukin_15";
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EMBL; U14407; AAA21551.1; -; mRNA.
EMBL; X91233; CAA62616.1; -; Genomic_DNA.
EMBL; X94223; CAA63914.1; -; mRNA.
EMBL; X94222; CAA63913.1; -; mRNA.
EMBL; AF031167; AAB97518.1; -; mRNA.
EMBL; Y09908; CAA71044.1; ALT_SEQ; mRNA.
EMBL; AY720442; AAU21241.1; -; mRNA.
EMBL; AK122993; BAG53839.1; -; mRNA.
EMBL; AK290619; BAF83308.1; -; mRNA.
EMBL; CR541980; CAG46777.1; -; mRNA.
EMBL; CR542007; CAG46804.1; -; mRNA.
EMBL; CH471056; EAX05083.1; -; Genomic_DNA.
EMBL; CH471056; EAX05084.1; -; Genomic_DNA.
EMBL; CH471056; EAX05085.1; -; Genomic_DNA.
EMBL; CH471056; EAX05086.1; -; Genomic_DNA.
EMBL; CH471056; EAX05087.1; -; Genomic_DNA.
EMBL; BC018149; AAH18149.1; -; mRNA.
EMBL; BC100961; AAI00962.1; -; mRNA.
EMBL; BC100962; AAI00963.1; -; mRNA.
EMBL; BC100963; AAI00964.1; -; mRNA.
EMBL; Z38000; CAA86100.1; -; mRNA.
CCDS; CCDS3755.1; -. [P40933-1]
CCDS; CCDS3756.1; -. [P40933-2]
RefSeq; NP_000576.1; NM_000585.4. [P40933-1]
RefSeq; NP_751915.1; NM_172175.2. [P40933-2]
UniGene; Hs.168132; -.
UniGene; Hs.602618; -.
UniGene; Hs.735901; -.
PDB; 2XQB; X-ray; 2.60 A; A=49-162.
PDB; 2Z3Q; X-ray; 1.85 A; A/C=49-162.
PDB; 2Z3R; X-ray; 2.00 A; A/C/E/G/I/K/M/O=49-162.
PDB; 4GS7; X-ray; 2.35 A; A=49-162.
PDBsum; 2XQB; -.
PDBsum; 2Z3Q; -.
PDBsum; 2Z3R; -.
PDBsum; 4GS7; -.
ProteinModelPortal; P40933; -.
SMR; P40933; -.
BioGrid; 109813; 10.
DIP; DIP-3046N; -.
IntAct; P40933; 5.
STRING; 9606.ENSP00000296545; -.
ChEMBL; CHEMBL3712954; -.
iPTMnet; P40933; -.
PhosphoSitePlus; P40933; -.
BioMuta; IL15; -.
PaxDb; P40933; -.
PeptideAtlas; P40933; -.
PRIDE; P40933; -.
DNASU; 3600; -.
Ensembl; ENST00000296545; ENSP00000296545; ENSG00000164136. [P40933-1]
Ensembl; ENST00000320650; ENSP00000323505; ENSG00000164136. [P40933-1]
Ensembl; ENST00000394159; ENSP00000377714; ENSG00000164136. [P40933-2]
Ensembl; ENST00000477265; ENSP00000436914; ENSG00000164136. [P40933-2]
Ensembl; ENST00000514653; ENSP00000422271; ENSG00000164136. [P40933-2]
Ensembl; ENST00000529613; ENSP00000435462; ENSG00000164136. [P40933-1]
GeneID; 3600; -.
KEGG; hsa:3600; -.
UCSC; uc003iis.4; human. [P40933-1]
CTD; 3600; -.
DisGeNET; 3600; -.
EuPathDB; HostDB:ENSG00000164136.16; -.
GeneCards; IL15; -.
HGNC; HGNC:5977; IL15.
HPA; CAB004457; -.
HPA; HPA037738; -.
MIM; 600554; gene.
neXtProt; NX_P40933; -.
OpenTargets; ENSG00000164136; -.
PharmGKB; PA29790; -.
eggNOG; ENOG410IZ5D; Eukaryota.
eggNOG; ENOG41119SX; LUCA.
GeneTree; ENSGT00390000016264; -.
HOGENOM; HOG000113029; -.
HOVERGEN; HBG006142; -.
InParanoid; P40933; -.
KO; K05433; -.
OMA; TSIQCYL; -.
OrthoDB; EOG091G0VGG; -.
PhylomeDB; P40933; -.
TreeFam; TF336199; -.
Reactome; R-HSA-8983432; Interleukin-15 signaling.
SignaLink; P40933; -.
SIGNOR; P40933; -.
ChiTaRS; IL15; human.
EvolutionaryTrace; P40933; -.
GeneWiki; Interleukin_15; -.
GenomeRNAi; 3600; -.
PRO; PR:P40933; -.
Proteomes; UP000005640; Chromosome 4.
Bgee; ENSG00000164136; -.
CleanEx; HS_IL15; -.
Genevisible; P40933; HS.
GO; GO:0009986; C:cell surface; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0005768; C:endosome; TAS:ProtInc.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; TAS:ProtInc.
GO; GO:0005794; C:Golgi apparatus; TAS:ProtInc.
GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
GO; GO:0016020; C:membrane; TAS:ProtInc.
GO; GO:0016607; C:nuclear speck; IDA:HPA.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
GO; GO:0005126; F:cytokine receptor binding; IEA:InterPro.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0048469; P:cell maturation; IEA:Ensembl.
GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl.
GO; GO:0045062; P:extrathymic T cell selection; IEA:Ensembl.
GO; GO:0030212; P:hyaluronan metabolic process; IEA:Ensembl.
GO; GO:0006955; P:immune response; TAS:ProtInc.
GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IDA:CAFA.
GO; GO:0048535; P:lymph node development; IEA:Ensembl.
GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl.
GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
GO; GO:0001866; P:NK T cell proliferation; IEA:Ensembl.
GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
GO; GO:0050778; P:positive regulation of immune response; IEA:Ensembl.
GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL.
GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL.
GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IEA:Ensembl.
GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IEA:Ensembl.
GO; GO:1904100; P:positive regulation of protein O-linked glycosylation; IEA:Ensembl.
GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl.
GO; GO:0034105; P:positive regulation of tissue remodeling; IC:BHF-UCL.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
GO; GO:0050691; P:regulation of defense response to virus by host; IEA:Ensembl.
GO; GO:0045580; P:regulation of T cell differentiation; IEA:Ensembl.
GO; GO:0007165; P:signal transduction; TAS:ProtInc.
GO; GO:0014732; P:skeletal muscle atrophy; IEA:Ensembl.
GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:CACAO.
InterPro; IPR009079; 4_helix_cytokine-like_core.
InterPro; IPR020439; IL-15.
InterPro; IPR003443; IL-15/IL-21_fam.
InterPro; IPR020466; IL-15_mml.
Pfam; PF02372; IL15; 1.
PRINTS; PR01947; INTLKN15MAML.
PRINTS; PR01930; INTRLEUKIN15.
SUPFAM; SSF47266; SSF47266; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome; Cytokine;
Cytoplasm; Disulfide bond; Glycoprotein; Nucleus; Reference proteome;
Secreted; Signal.
SIGNAL 1 29 {ECO:0000255}.
PROPEP 30 48 {ECO:0000255}.
/FTId=PRO_0000015393.
CHAIN 49 162 Interleukin-15.
/FTId=PRO_0000015394.
CARBOHYD 127 127 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 83 133 {ECO:0000269|PubMed:21167836}.
DISULFID 90 136 {ECO:0000269|PubMed:21167836}.
VAR_SEQ 1 37 MRISKPHLRSISIQCYLCLLLNSHFLTEAGIHVFILG ->
MVLGTIDLCS (in isoform IL15-S21AA).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:8668345,
ECO:0000303|PubMed:9405632,
ECO:0000303|Ref.6, ECO:0000303|Ref.8}.
/FTId=VSP_002660.
CONFLICT 141 141 E -> K (in Ref. 4; AAB97518).
{ECO:0000305}.
HELIX 49 64 {ECO:0000244|PDB:2Z3Q}.
STRAND 73 75 {ECO:0000244|PDB:2Z3Q}.
HELIX 81 83 {ECO:0000244|PDB:2Z3Q}.
HELIX 84 102 {ECO:0000244|PDB:2Z3Q}.
HELIX 105 119 {ECO:0000244|PDB:2Z3Q}.
HELIX 136 138 {ECO:0000244|PDB:2Z3Q}.
STRAND 139 142 {ECO:0000244|PDB:2Z3Q}.
HELIX 144 158 {ECO:0000244|PDB:2Z3Q}.
SEQUENCE 162 AA; 18086 MW; 0CE0520C1D8379E2 CRC64;
MRISKPHLRS ISIQCYLCLL LNSHFLTEAG IHVFILGCFS AGLPKTEANW VNVISDLKKI
EDLIQSMHID ATLYTESDVH PSCKVTAMKC FLLELQVISL ESGDASIHDT VENLIILANN
SLSSNGNVTE SGCKECEELE EKNIKEFLQS FVHIVQMFIN TS


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E0065h ELISA CD121 antigen-like family member A,Homo sapiens,Human,IL1R,IL1R1,IL-1R-1,IL1RA,IL-1R-alpha,IL1RT1,IL-1RT1,IL-1RT-1,Interleukin-1 receptor alpha,Interleukin-1 receptor type 1,Interleukin-1 recept 96T
E0066h ELISA CD121 antigen-like family member B,CDw121b,Homo sapiens,Human,IL1R2,IL-1R-2,IL1RB,IL-1R-beta,IL-1RT2,IL-1RT-2,Interleukin-1 receptor beta,Interleukin-1 receptor type 2,Interleukin-1 receptor typ 96T
10-663-45193 Interleukin-12 Human - Interleukin 12A.; Interleukin 12. P35 N_A 0.1 mg
10-663-45193 Interleukin-12 Human - Interleukin 12A.; Interleukin 12. P35 N_A 0.002 mg
10-663-45193 Interleukin-12 Human - Interleukin 12A.; Interleukin 12. P35 N_A 0.01 mg
U0066h CLIA CD121 antigen-like family member B,CDw121b,Homo sapiens,Human,IL1R2,IL-1R-2,IL1RB,IL-1R-beta,IL-1RT2,IL-1RT-2,Interleukin-1 receptor beta,Interleukin-1 receptor type 2,Interleukin-1 receptor type 96T


 

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