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Q9HBE5 (IL21R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-21 receptor

Short name=IL-21 receptor
Short name=IL-21R
Alternative name(s):
Novel interleukin receptor
CD_antigen=CD360
Gene names
Name:IL21R
Synonyms:NILR
ORF Names:UNQ3121/PRO10273
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length538 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is a receptor for interleukin-21.

Subunit structure

Heterodimer with the common gamma subunit. Associates with JAK1.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Selectively expressed in lymphoid tissues. Most highly expressed in thymus and spleen.

Domain

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. Ref.10

The box 1 motif is required for JAK interaction and/or activation. Ref.10

Post-translational modification

C-mannosylated at Trp-214 in the WSXWS motif, the sugar chain makes extensive hydrogen bonds with Asn-73 sugar, and bridges the two fibronectin domains transforming the V-shaped receptor into an A-frame.

Involvement in disease

IL21R immunodeficiency (IL21RID) [MIM:615207]: An autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B-cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Chromosomal aberrations involving IL21R is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;16)(q27;p11), with BCL6.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 4 subfamily.

Contains 2 fibronectin type-III domains.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.8
Chain20 – 538519Interleukin-21 receptor
PRO_0000010881

Regions

Topological domain20 – 232213Extracellular Potential
Transmembrane233 – 25321Helical; Potential
Topological domain254 – 538285Cytoplasmic Potential
Domain21 – 11898Fibronectin type-III 1
Domain119 – 228110Fibronectin type-III 2
Motif214 – 2185WSXWS motif
Motif266 – 2749Box 1 motif

Amino acid modifications

Glycosylation731N-linked (GlcNAc...) Ref.10
Glycosylation971N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1351N-linked (GlcNAc...) Potential
Glycosylation2141C-linked (Man) Ref.10
Disulfide bond20 ↔ 109 Ref.10
Disulfide bond25 ↔ 35 Ref.10
Disulfide bond65 ↔ 81 Ref.10

Natural variations

Natural variant81 – 822Missing in IL21RID; loss of function mutation.
VAR_069898
Natural variant1911R → C. Ref.4
Corresponds to variant rs3093370 [ dbSNP | Ensembl ].
VAR_014360
Natural variant2011R → L in IL21RID; loss of function mutation; the mutation results in defective trafficking of the protein, with misfolding, impaired processing and abnormal subcellular distribution rather than proper expression at the plasma membrane. Ref.11
VAR_069899
Natural variant3181S → R. Ref.4
Corresponds to variant rs3093385 [ dbSNP | Ensembl ].
VAR_014361
Natural variant4841G → S. Ref.4
Corresponds to variant rs3093386 [ dbSNP | Ensembl ].
VAR_014362

Experimental info

Sequence conflict3861G → R in AAG23419. Ref.2

Secondary structure

.................................... 538
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9HBE5 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 414079CCB974850A

FASTA53859,130
        10         20         30         40         50         60 
MPRGWAAPLL LLLLQGGWGC PDLVCYTDYL QTVICILEMW NLHPSTLTLT WQDQYEELKD 

        70         80         90        100        110        120 
EATSCSLHRS AHNATHATYT CHMDVFHFMA DDIFSVNITD QSGNYSQECG SFLLAESIKP 

       130        140        150        160        170        180 
APPFNVTVTF SGQYNISWRS DYEDPAFYML KGKLQYELQY RNRGDPWAVS PRRKLISVDS 

       190        200        210        220        230        240 
RSVSLLPLEF RKDSSYELQV RAGPMPGSSY QGTWSEWSDP VIFQTQSEEL KEGWNPHLLL 

       250        260        270        280        290        300 
LLLLVIVFIP AFWSLKTHPL WRLWKKIWAV PSPERFFMPL YKGCSGDFKK WVGAPFTGSS 

       310        320        330        340        350        360 
LELGPWSPEV PSTLEVYSCH PPRSPAKRLQ LTELQEPAEL VESDGVPKPS FWPTAQNSGG 

       370        380        390        400        410        420 
SAYSEERDRP YGLVSIDTVT VLDAEGPCTW PCSCEDDGYP ALDLDAGLEP SPGLEDPLLD 

       430        440        450        460        470        480 
AGTTVLSCGC VSAGSPGLGG PLGSLLDRLK PPLADGEDWA GGLPWGGRSP GGVSESEAGS 

       490        500        510        520        530 
PLAGLDMDTF DSGFVGSDCS SPVECDFTSP GDEGPPRSYL RQWVVIPPPL SSPGPQAS 

« Hide

References

« Hide 'large scale' references
[1]"Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function."
Parrish-Novak J., Dillon S.R., Nelson A., Hammond A., Sprecher C., Gross J.A., Johnston J., Madden K., Xu W., West J., Schrader S., Burkhead S., Heipel M., Brandt C., Kuijper J.L., Kramer J., Conklin D., Presnell S.R. expand/collapse author list , Berry J., Shiota F., Bort S., Hambly K., Mudri S., Clegg C., Moore M., Grant F.J., Lofton-Day C., Gilbert T., Raymond F., Ching A., Yao L., Smith D., Webster P., Whitmore T., Maurer M., Kaushansky K., Holly R.D., Foster D.
Nature 408:57-63(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain."
Ozaki K., Kikly K., Michalovich D., Young P.R., Leonard W.J.
Proc. Natl. Acad. Sci. U.S.A. 97:11439-11444(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]SeattleSNPs variation discovery resource
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-191; ARG-318 AND SER-484.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thymus.
[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. expand/collapse author list , 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].
Tissue: B-cell and Lymph.
[8]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-34.
[9]"The gene for interleukin-21 receptor is the partner of BCL6 in t(3;16)(q27;p11), which is recurrently observed in diffuse large B-cell lymphoma."
Ueda C., Akasaka T., Kurata M., Maesako Y., Nishikori M., Ichinohasama R., Imada K., Uchiyama T., Ohno H.
Oncogene 21:368-376(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, CHROMOSOMAL TRANSLOCATION WITH BCL6.
[10]"Crystal structure of interleukin-21 receptor (IL-21R) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R."
Hamming O.J., Kang L., Svensson A., Karlsen J.L., Rahbek-Nielsen H., Paludan S.R., Hjorth S.A., Bondensgaard K., Hartmann R.
J. Biol. Chem. 287:9454-9460(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 20-232 IN COMPLEX WITH IL21, DOMAIN WSXWS MOTIF, GLYCOSYLATION AT ASN-73 AND TRP-214, DOMAINS FIBRONECTIN, DISULFIDE BONDS.
[11]"Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome."
Kotlarz D., Zietara N., Uzel G., Weidemann T., Braun C.J., Diestelhorst J., Krawitz P.M., Robinson P.N., Hecht J., Puchalka J., Gertz E.M., Schaeffer A.A., Lawrence M.G., Kardava L., Pfeifer D., Baumann U., Pfister E.D., Hanson E.P. expand/collapse author list , Schambach A., Jacobs R., Kreipe H., Moir S., Milner J.D., Schwille P., Mundlos S., Klein C.
J. Exp. Med. 210:433-443(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IL21RID 81-CYS-HIS-82 DEL AND LEU-201, CHARACTERIZATION VARIANT IL21RID LEU-201.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF254067 mRNA. Translation: AAG29346.1.
AF269133 mRNA. Translation: AAG23419.1.
AY358826 mRNA. Translation: AAQ89185.1.
AY064474 Genomic DNA. Translation: AAL39168.1.
AK292663 mRNA. Translation: BAF85352.1.
CH471145 Genomic DNA. Translation: EAW55746.1.
CH471145 Genomic DNA. Translation: EAW55747.1.
CH471145 Genomic DNA. Translation: EAW55748.1.
BC004348 mRNA. Translation: AAH04348.1.
BC007946 mRNA. Translation: AAH07946.2.
RefSeqNP_068570.1. NM_021798.3.
NP_851564.1. NM_181078.2.
NP_851565.4. NM_181079.4.
UniGeneHs.210546.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3TGXX-ray2.80A/C/E/G/I/K/M/O20-232[»]
ProteinModelPortalQ9HBE5.
SMRQ9HBE5. Positions 20-228.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119095. 4 interactions.
STRING9606.ENSP00000338010.

Polymorphism databases

DMDM20454997.

Proteomic databases

PaxDbQ9HBE5.
PRIDEQ9HBE5.

Protocols and materials databases

DNASU50615.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000337929; ENSP00000338010; ENSG00000103522.
ENST00000395754; ENSP00000379103; ENSG00000103522.
ENST00000395755; ENSP00000379104; ENSG00000103522.
ENST00000564089; ENSP00000456707; ENSG00000103522.
GeneID50615.
KEGGhsa:50615.
UCSCuc002doq.2. human.

Organism-specific databases

CTD50615.
GeneCardsGC16P027413.
H-InvDBHIX0012914.
HGNCHGNC:6006. IL21R.
HPAHPA042296.
MIM605383. gene.
615207. phenotype.
neXtProtNX_Q9HBE5.
Orphanet357329. Cryptosporidiosis - chronic cholangitis - liver disease.
PharmGKBPA29821.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40447.
HOGENOMHOG000013192.
HOVERGENHBG052105.
InParanoidQ9HBE5.
KOK05075.
OMARDRPYGL.
OrthoDBEOG767398.
PhylomeDBQ9HBE5.
TreeFamTF337874.

Enzyme and pathway databases

SignaLinkQ9HBE5.

Gene expression databases

BgeeQ9HBE5.
CleanExHS_IL21R.
GenevestigatorQ9HBE5.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR003961. Fibronectin_type3.
IPR003531. Hempt_rcpt_S_F1_CS.
IPR013783. Ig-like_fold.
[Graphical view]
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 1 hit.
PS01355. HEMATOPO_REC_S_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiInterleukin-21_receptor.
GenomeRNAi50615.
NextBio53120.
PROQ9HBE5.
SOURCESearch...

Entry information

Entry nameIL21R_HUMAN
AccessionPrimary (citable) accession number: Q9HBE5
Secondary accession number(s): A8K9E8 expand/collapse secondary AC list , D3DWF7, Q96HZ1, Q9HB91
Entry history
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries