Reviewed, UniProtKB/Swiss-Prot Q13261 (I15RA_HUMAN)

Names and origin

Protein names

Recommended name:
    Interleukin-15 receptor subunit alpha
      Short name=IL-15R-alpha
      Short name=IL-15RA
Cleaved into the following chain:
    1- Recommended name:
            Soluble interleukin-15 receptor subunit alpha
                Short name=sIL-15R-alpha
                Short name=sIL-15RA

Gene names

Name:

IL15RA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	267 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	Receptor for interleukin-15. Expression of different isoforms may alter or interfere with signal transduction. Isoform 6, isoform 7, isoform 8 and isoform 9 do not bind IL15. Signal transduction involves STAT3, STAT5, STAT6, JAK2 By similarity and SYK.
Subunit structure	The interleukin-15 receptor IL15R is a heterotrimer of IL15RA, IL2RB and IL2RG. IL15RA also self-associates By similarity. Interacts with SYK.
Subcellular location	Membrane; Single-pass type I membrane protein. Nucleus membrane; Single-pass type I membrane protein. Note= Mainly found associated with the nuclear membrane. Isoform 6: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Membrane; Single-pass type I membrane protein. Note= Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane. Isoform 7: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Membrane; Single-pass type I membrane protein. Note= Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane. Isoform 8: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Membrane; Single-pass type I membrane protein. Note= Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane. Isoform 9: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Cytoplasmic vesicle membrane; Single-pass type I membrane protein. Membrane; Single-pass type I membrane protein. Note= Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane. Soluble interleukin-15 receptor subunit alpha: Secreted › extracellular space.
Tissue specificity	Isoform 1, isoform 3, isoform 4, isoform 5, isoform 6, isoform 7, isoform 8 and isoform 9 are widely expressed. Expressed in fetal brain with higher expression in the hippocampus and cerebellum than in cortex and thalamus. Higher levels of soluble sIL-15RA form in comparison with membrane-bound forms is present in all brain structures.
Post-translational modification	A soluble form (sIL-15RA) arises from proteolytic shedding of the membrane-anchored receptor. The cleavage involves ADAM17/TACE By similarity. It also binds IL-15 and thus interferes with IL-15 binding to the membrane receptor. Phosphorylated by activated SYK. N-glycosylated and O-glycosylated.
Sequence similarities	Contains 1 Sushi (CCP/SCR) domain.

Ontologies

Keywords
Cellular component	Cytoplasmic vesicle Endoplasmic reticulum Golgi apparatus Membrane Nucleus Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Sushi Transmembrane
Molecular function	Receptor
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	interleukin receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL15	P40933	1	EBI-980354,EBI-980274

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13261-1)

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 2 (identifier: Q13261-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Isoform 3 (identifier: Q13261-3)

Also known as: delta3E1E7Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     95-128: RDPALVHQRPAPPSTVTTAGVTPQPESLSPSGKE → K

Isoform 4 (identifier: Q13261-4)

Also known as: E1E7'Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     232-267: QTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL → ASVCSCHPRSAGHTCSVGSV

Isoform 5 (identifier: Q13261-5)

Also known as: delta3E1E7'Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     95-128: RDPALVHQRPAPPSTVTTAGVTPQPESLSPSGKE → K
     232-267: QTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL → ASVCSCHPRSAGHTCSVGSV

Isoform 6 (identifier: Q13261-6)

Also known as: delta2E1E7Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     31-95: Missing.

Notes: Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane.

Isoform 7 (identifier: Q13261-7)

Also known as: delta2E1E7'Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     31-95: Missing.
     232-267: QTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL → ASVCSCHPRSAGHTCSVGSV

Notes: Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane.

Isoform 8 (identifier: Q13261-8)

Also known as: delta2deltaE1E73Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     30-127: Missing.

Notes: Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane.

Isoform 9 (identifier: Q13261-9)

Also known as: delta2delta3E1E7'Il-15RA;

The sequence of this isoform differs from the canonical sequence as follows:
     30-127: Missing.
     232-267: QTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL → ASVCSCHPRSAGHTCSVGSV

Notes: Isoform 6, isoform 7, isoform 8 and isoform 9 are associated with endoplasmic reticulum, Golgi and cytoplasmic vesicles, but not with the nuclear membrane.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 267

237

Interleukin-15 receptor subunit alpha

PRO_0000011044

Chain

31 – ?

Soluble interleukin-15 receptor subunit alpha

PRO_0000333855

Regions

Topological domain

31 – 205

175

Extracellular Potential

Transmembrane

206 – 228

23

Potential

Topological domain

229 – 267

39

Cytoplasmic Potential

Domain

31 – 95

65

Sushi

Amino acid modifications

Glycosylation

137

1

N-linked (GlcNAc...) Potential

Disulfide bond

33 ↔ 75

Disulfide bond

59 ↔ 93

Natural variations

Alternative sequence

1 – 36

36

Missing in isoform 2.

VSP_012622

Alternative sequence

30 – 127

98

Missing in isoform 8 and isoform 9.

VSP_012623

Alternative sequence

31 – 95

65

Missing in isoform 6 and isoform 7.

VSP_012624

Alternative sequence

95 – 128

34

RDPAL…PSGKE → K in isoform 3 and isoform 5.

VSP_012625

Alternative sequence

232 – 267

36

QTPPL…CSHHL → ASVCSCHPRSAGHTCSVGSV in isoform 4, isoform 5, isoform 7 and isoform 9.

VSP_012626

Natural variant

182

1

N → T: dbSNP rs2228059.

VAR_020967

Experimental info

Mutagenesis

227

1

Y → F: Abrogates association with SYK and phosphorylation upon IL-15 stimulation

Sequence conflict

200

1

G → D in AAH74726. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

267

Helix Strand Turn

Details...

Beta strand

42 – 44

3

Beta strand

54 – 59

6

Beta strand

63 – 65

3

Beta strand

72 – 77

6

Turn

79 – 81

3

Beta strand

84 – 86

3

Beta strand

93 – 95

3

Helix

97 – 102

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A9CFC885189E96BE	FASTA	267	28,233
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRG ITCPPPMSVE HADIWVKSYS LYSRERYICN 70 80 90 100 110 120 SGFKRKAGTS SLTECVLNKA TNVAHWTTPS LKCIRDPALV HQRPAPPSTV TTAGVTPQPE 130 140 150 160 170 180 SLSPSGKEPA ASSPSSNNTA ATTAAIVPGS QLMPSKSPST GTTEISSHES SHGTPSQTTA 190 200 210 220 230 240 KNWELTASAS HQPPGVYPQG HSDTTVAIST STVLLCGLSA VSLLACYLKS RQTPPLASVE 250 260 MEAMEALPVT WGTSSRDEDL ENCSHHL
	Isoform 2 [UniParc]. Checksum: 85A770AB71977219		231	24,388
	10 20 30 40 50 60 MSVEHADIWV KSYSLYSRER YICNSGFKRK AGTSSLTECV LNKATNVAHW TTPSLKCIRD 70 80 90 100 110 120 PALVHQRPAP PSTVTTAGVT PQPESLSPSG KEPAASSPSS NNTAATTAAI VPGSQLMPSK 130 140 150 160 170 180 SPSTGTTEIS SHESSHGTPS QTTAKNWELT ASASHQPPGV YPQGHSDTTV AISTSTVLLC 190 200 210 220 230 GLSAVSLLAC YLKSRQTPPL ASVEMEAMEA LPVTWGTSSR DEDLENCSHH L
	Isoform 3 (delta3E1E7Il-15RA) [UniParc]. Checksum: 9ACAD3E117A8C9AF		234	24,870
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRG ITCPPPMSVE HADIWVKSYS LYSRERYICN 70 80 90 100 110 120 SGFKRKAGTS SLTECVLNKA TNVAHWTTPS LKCIKPAASS PSSNNTAATT AAIVPGSQLM 130 140 150 160 170 180 PSKSPSTGTT EISSHESSHG TPSQTTAKNW ELTASASHQP PGVYPQGHSD TTVAISTSTV 190 200 210 220 230 LLCGLSAVSL LACYLKSRQT PPLASVEMEA MEALPVTWGT SSRDEDLENC SHHL
	Isoform 4 (E1E7'Il-15RA) [UniParc]. Checksum: 7933D9E843EDC69E		251	26,196
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRG ITCPPPMSVE HADIWVKSYS LYSRERYICN 70 80 90 100 110 120 SGFKRKAGTS SLTECVLNKA TNVAHWTTPS LKCIRDPALV HQRPAPPSTV TTAGVTPQPE 130 140 150 160 170 180 SLSPSGKEPA ASSPSSNNTA ATTAAIVPGS QLMPSKSPST GTTEISSHES SHGTPSQTTA 190 200 210 220 230 240 KNWELTASAS HQPPGVYPQG HSDTTVAIST STVLLCGLSA VSLLACYLKS RASVCSCHPR 250 SAGHTCSVGS V
	Isoform 5 (delta3E1E7'Il-15RA) [UniParc]. Checksum: F64A227CB6AA3FC5		218	22,833
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRG ITCPPPMSVE HADIWVKSYS LYSRERYICN 70 80 90 100 110 120 SGFKRKAGTS SLTECVLNKA TNVAHWTTPS LKCIKPAASS PSSNNTAATT AAIVPGSQLM 130 140 150 160 170 180 PSKSPSTGTT EISSHESSHG TPSQTTAKNW ELTASASHQP PGVYPQGHSD TTVAISTSTV 190 200 210 LLCGLSAVSL LACYLKSRAS VCSCHPRSAG HTCSVGSV
	Isoform 6 (delta2E1E7Il-15RA) [UniParc]. Checksum: D4F5DD2EA004C6D2		202	20,904
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRG DPALVHQRPA PPSTVTTAGV TPQPESLSPS 70 80 90 100 110 120 GKEPAASSPS SNNTAATTAA IVPGSQLMPS KSPSTGTTEI SSHESSHGTP SQTTAKNWEL 130 140 150 160 170 180 TASASHQPPG VYPQGHSDTT VAISTSTVLL CGLSAVSLLA CYLKSRQTPP LASVEMEAME 190 200 ALPVTWGTSS RDEDLENCSH HL
	Isoform 7 (delta2E1E7'Il-15RA) [UniParc]. Checksum: F5B6202C329FB0C8		186	18,866
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRG DPALVHQRPA PPSTVTTAGV TPQPESLSPS 70 80 90 100 110 120 GKEPAASSPS SNNTAATTAA IVPGSQLMPS KSPSTGTTEI SSHESSHGTP SQTTAKNWEL 130 140 150 160 170 180 TASASHQPPG VYPQGHSDTT VAISTSTVLL CGLSAVSLLA CYLKSRASVC SCHPRSAGHT CSVGSV
	Isoform 8 (delta2deltaE1E73Il-15RA) [UniParc]. Checksum: 238A6ECC5B7675A1		169	17,641
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRE PAASSPSSNN TAATTAAIVP GSQLMPSKSP 70 80 90 100 110 120 STGTTEISSH ESSHGTPSQT TAKNWELTAS ASHQPPGVYP QGHSDTTVAI STSTVLLCGL 130 140 150 160 SAVSLLACYL KSRQTPPLAS VEMEAMEALP VTWGTSSRDE DLENCSHHL
	Isoform 9 (delta2delta3E1E7'Il-15RA) [UniParc]. Checksum: 1224FD25881D2C79		153	15,604
	10 20 30 40 50 60 MAPRRARGCR TLGLPALLLL LLLRPPATRE PAASSPSSNN TAATTAAIVP GSQLMPSKSP 70 80 90 100 110 120 STGTTEISSH ESSHGTPSQT TAKNWELTAS ASHQPPGVYP QGHSDTTVAI STSTVLLCGL 130 140 150 SAVSLLACYL KSRASVCSCH PRSAGHTCSV GSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes." Anderson D.M., Kumaki S., Ahdieh M., Bertles J., Tometsko M., Loomis A., Giri J., Copeland N.G., Gilbert D.J., Jenkins N.A., Valentine V., Shapiro D.N., Morris S.W., Park L.S., Cosman D. J. Biol. Chem. 270:29862-29869(1995) [PubMed: 8530383] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), FUNCTION, TISSUE SPECIFICITY, VARIANT THR-182. Tissue: Bone marrow stroma.
[2]	"Large-scale concatenation cDNA sequencing." Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Genome Res. 7:353-358(1997) [PubMed: 9110174] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[4]	SeattleSNPs program for genomic applications Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-182.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[7]	"Natural splicing of exon 2 of human interleukin-15 receptor alpha-chain mRNA results in a shortened form with a distinct pattern of expression." Dubois S., Magrangeas F., Lehours P., Raher S., Bernard J., Boisteau O., Leroy S., Minvielle S., Godard A., Jacques Y. J. Biol. Chem. 274:26978-26984(1999) [PubMed: 10480910] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 1; 3; 4; 5; 6; 7; 8 AND 9), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, GLYCOSYLATION.
[8]	"The IL-15R alpha chain signals through association with Syk in human B cells." Bulanova E., Budagian V., Pohl T., Krause H., Durkop H., Paus R., Bulfone-Paus S. J. Immunol. 167:6292-6302(2001) [PubMed: 11714793] [Abstract] Cited for: FUNCTION, INTERACTION WITH SYK, PHOSPHORYLATION BY SYK, MUTAGENESIS OF TYR-227.
[9]	"Expression of IL-15 and IL-15 receptor isoforms in select structures of human fetal brain." Kurowska M., Rudnicka W., Maslinska D., Maslinski W. Ann. N. Y. Acad. Sci. 966:441-445(2002) [PubMed: 12114302] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Identification of an interleukin-15alpha receptor-binding site on human interleukin-15." Bernard J., Harb C., Mortier E., Quemener A., Meloen R.H., Vermot-Desroches C., Wijdeness J., van Dijken P., Grotzinger J., Slootstra J.W., Plet A., Jacques Y. J. Biol. Chem. 279:24313-24322(2004) [PubMed: 15039446] [Abstract] Cited for: LIGAND-BINDING.
[11]	"Natural, proteolytic release of a soluble form of human IL-15 receptor alpha-chain that behaves as a specific, high affinity IL-15 antagonist." Mortier E., Bernard J., Plet A., Jacques Y. J. Immunol. 173:1681-1688(2004) [PubMed: 15265897] [Abstract] Cited for: PROTEOLYTIC PROCESSING, LIGAND-BINDING.
[12]	"The structure of the interleukin-15 alpha receptor and its implications for ligand binding." Lorenzen I., Dingley A.J., Jacques Y., Grotzinger J. J. Biol. Chem. 281:6642-6647(2006) [PubMed: 16377614] [Abstract] Cited for: STRUCTURE BY NMR OF 31-96, DISULFIDE BONDS.
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