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Q9HBE4 (IL21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-21

Short name=IL-21
Alternative name(s):
Za11
Gene names
Name:IL21
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length155 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG1 and IgG3 in B-cells By similarity. May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation. Ref.1 Ref.6

Subcellular location

Secreted Ref.1.

Tissue specificity

Expressed in activated CD4-positive T-cells but not in CD8-positive T-cells, B-cells, or monocytes. Ref.1

Sequence similarities

Belongs to the IL-15/IL-21 family.

Sequence caution

The sequence AAG29348.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH66258.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH66259.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH66260.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH66261.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH66262.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH69124.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAU88182.1 differs from that shown. Reason: Erroneous initiation.

The sequence ABG36529.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell maturation

Inferred from direct assay PubMed 14635054. Source: UniProtKB

immune response

Inferred from electronic annotation. Source: InterPro

positive regulation of B cell proliferation

Inferred from direct assay Ref.2. Source: MGI

positive regulation of T cell proliferation

Inferred from direct assay PubMed 15207081. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay Ref.2. Source: MGI

positive regulation of inflammatory response

Inferred by curator PubMed 16482511. Source: BHF-UCL

positive regulation of interferon-gamma biosynthetic process

Non-traceable author statement PubMed 15765404. Source: UniProtKB

positive regulation of interleukin-10 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-17 production

Inferred from direct assay PubMed 16482511. Source: BHF-UCL

positive regulation of natural killer cell cytokine production

Inferred from electronic annotation. Source: Ensembl

positive regulation of natural killer cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of natural killer cell mediated cytotoxicity

Inferred from electronic annotation. Source: Ensembl

positive regulation of tissue remodeling

Inferred by curator PubMed 16482511. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat1 protein

Inferred from direct assay Ref.2. Source: MGI

positive regulation of tyrosine phosphorylation of Stat3 protein

Inferred from direct assay Ref.2. Source: MGI

signal transduction

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentextracellular space

Non-traceable author statement Ref.1. Source: UniProtKB

   Molecular_functioncytokine receptor binding

Traceable author statement PubMed 15546387. Source: UniProtKB

interleukin-2 receptor binding

Inferred from physical interaction PubMed 12504082. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HBE4-1)

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: Q9HBE4-2)

Also known as: IL-21iso;

The sequence of this isoform differs from the canonical sequence as follows:
     140-155: MIHQHLSSRTHGSEDS → VSTLSFI

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 155133Interleukin-21
PRO_0000015505

Amino acid modifications

Glycosylation901N-linked (GlcNAc...) Potential
Disulfide bond64 ↔ 115 Ref.8 Ref.9
Disulfide bond71 ↔ 118 Ref.8 Ref.9

Natural variations

Alternative sequence140 – 15516MIHQH…GSEDS → VSTLSFI in isoform 2.
VSP_030129

Secondary structure

................... 155
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 23, 2004. Version 2.
Checksum: E994A3D19029B914

FASTA15517,923
        10         20         30         40         50         60 
MERIVICLMV IFLGTLVHKS SSQGQDRHMI RMRQLIDIVD QLKNYVNDLV PEFLPAPEDV 

        70         80         90        100        110        120 
ETNCEWSAFS CFQKAQLKSA NTGNNERIIN VSIKKLKRKP PSTNAGRRQK HRLTCPSCDS 

       130        140        150 
YEKKPPKEFL ERFKSLLQKM IHQHLSSRTH GSEDS 

« Hide

Isoform 2 (IL-21iso) [UniParc].

Checksum: CCC4D7F9602AD06A
Show »

FASTA14616,867

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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"Cloning and characterization of an isoform of interleukin-21."
Rahman M., Nara H., Onoda T., Araki A., Li J., Hoshino T., Asao H.
FEBS Lett. 581:4001-4009(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]SeattleSNPs variation discovery resource
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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).
[6]"IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells."
Strengell M., Julkunen I., Matikainen S.
J. Leukoc. Biol. 76:416-422(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responses."
Sivakumar P.V., Foster D.C., Clegg C.H.
Immunology 112:177-182(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"The existence of multiple conformers of interleukin-21 directs engineering of a superpotent analogue."
Bondensgaard K., Breinholt J., Madsen D., Omkvist D.H., Kang L., Worsaae A., Becker P., Schioedt C.B., Hjorth S.A.
J. Biol. Chem. 282:23326-23336(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 23-155, DISULFIDE BONDS.
[9]"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 23-155 IN COMPLEX WITH IL21R, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF254069 mRNA. Translation: AAG29348.1. Different initiation.
DQ645417 mRNA. Translation: ABG36529.1. Different initiation.
AY763518 Genomic DNA. Translation: AAU88182.1. Different initiation.
AC053545 Genomic DNA. No translation available.
BC066258 mRNA. Translation: AAH66258.1. Different initiation.
BC066259 mRNA. Translation: AAH66259.1. Different initiation.
BC066260 mRNA. Translation: AAH66260.1. Different initiation.
BC066261 mRNA. Translation: AAH66261.1. Different initiation.
BC066262 mRNA. Translation: AAH66262.1. Different initiation.
BC069124 mRNA. Translation: AAH69124.1. Different initiation.
RefSeqNP_001193935.1. NM_001207006.2.
NP_068575.1. NM_021803.3.
UniGeneHs.567559.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OQPNMR-A23-155[»]
3TGXX-ray2.80B/D/F/H/J/L/N/P23-155[»]
ProteinModelPortalQ9HBE4.
SMRQ9HBE4. Positions 23-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121857. 2 interactions.
IntActQ9HBE4. 1 interaction.
MINTMINT-8201759.
STRING9606.ENSP00000264497.

Polymorphism databases

DMDM55976599.

Proteomic databases

PaxDbQ9HBE4.
PRIDEQ9HBE4.

Protocols and materials databases

DNASU59067.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264497; ENSP00000264497; ENSG00000138684.
GeneID59067.
KEGGhsa:59067.
UCSCuc003ies.3. human. [Q9HBE4-1]
uc010int.4. human. [Q9HBE4-2]

Organism-specific databases

CTD59067.
GeneCardsGC04M123534.
H-InvDBHIX0031753.
HGNCHGNC:6005. IL21.
MIM605384. gene.
neXtProtNX_Q9HBE4.
PharmGKBPA29820.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40525.
HOGENOMHOG000113039.
HOVERGENHBG052106.
InParanoidQ9HBE4.
KOK05434.
OrthoDBEOG7M98JN.
PhylomeDBQ9HBE4.
TreeFamTF336380.

Enzyme and pathway databases

SignaLinkQ9HBE4.

Gene expression databases

BgeeQ9HBE4.
CleanExHS_IL21.
GenevestigatorQ9HBE4.

Family and domain databases

InterProIPR009079. 4_helix_cytokine-like_core.
IPR003443. IL-15/IL-21_fam.
IPR028151. IL-21.
[Graphical view]
PANTHERPTHR14356:SF0. PTHR14356:SF0. 1 hit.
PfamPF02372. IL15. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9HBE4.
GeneWikiInterleukin_21.
GenomeRNAi59067.
NextBio65134.
PROQ9HBE4.
SOURCESearch...

Entry information

Entry nameIL21_HUMAN
AccessionPrimary (citable) accession number: Q9HBE4
Secondary accession number(s): A5J0L4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: November 23, 2004
Last modified: April 16, 2014
This is version 101 of the entry and version 2 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 chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM