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Protein

Interleukin-21

Gene

IL21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • cytokine receptor binding Source: UniProtKB
  • interleukin-2 receptor binding Source: UniProtKB

GO - Biological processi

  • cell maturation Source: UniProtKB
  • immune response Source: InterPro
  • interleukin-21-mediated signaling pathway Source: Reactome
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cytokine production Source: CACAO
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
  • positive regulation of interleukin-17 production Source: BHF-UCL
  • positive regulation of natural killer cell mediated cytotoxicity Source: CACAO
  • positive regulation of T cell proliferation Source: UniProtKB
  • positive regulation of tissue remodeling Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: MGI
  • signal transduction Source: UniProtKB
  • tyrosine phosphorylation of STAT protein Source: CACAO

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-HSA-9020958 Interleukin-21 signaling
SignaLinkiQ9HBE4
SIGNORiQ9HBE4

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-21
Short name:
IL-21
Alternative name(s):
Za11
Gene namesi
Name:IL21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000138684.7
HGNCiHGNC:6005 IL21
MIMi605384 gene
neXtProtiNX_Q9HBE4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency, common variable, 11 (CVID11)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.
See also OMIM:615767
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07129249L → P in CVID11; interferes with binding to IL21R. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi59067
MalaCardsiIL21
MIMi615767 phenotype
Orphaneti238569 Autosomal recessive early-onset inflammatory bowel disease
PharmGKBiPA29820

Polymorphism and mutation databases

BioMutaiIL21
DMDMi55976599

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001550523 – 155Interleukin-21Add BLAST133

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi64 ↔ 115
Disulfide bondi71 ↔ 118
Glycosylationi90N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9HBE4
PeptideAtlasiQ9HBE4
PRIDEiQ9HBE4

PTM databases

iPTMnetiQ9HBE4
PhosphoSitePlusiQ9HBE4

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000138684
CleanExiHS_IL21
GenevisibleiQ9HBE4 HS

Interactioni

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • cytokine receptor binding Source: UniProtKB
  • interleukin-2 receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121857, 4 interactors
IntActiQ9HBE4, 2 interactors
MINTiQ9HBE4
STRINGi9606.ENSP00000264497

Structurei

Secondary structure

1155
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi25 – 42Combined sources18
Helixi43 – 48Combined sources6
Helixi62 – 64Combined sources3
Helixi65 – 74Combined sources10
Helixi85 – 96Combined sources12
Beta strandi101 – 105Combined sources5
Beta strandi107 – 109Combined sources3
Beta strandi113 – 115Combined sources3
Turni118 – 120Combined sources3
Helixi126 – 142Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OQPNMR-A23-155[»]
3TGXX-ray2.80B/D/F/H/J/L/N/P23-155[»]
ProteinModelPortaliQ9HBE4
SMRiQ9HBE4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HBE4

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IWTD Eukaryota
ENOG411198G LUCA
HOGENOMiHOG000113039
HOVERGENiHBG052106
InParanoidiQ9HBE4
KOiK05434
OrthoDBiEOG091G0OEJ
PhylomeDBiQ9HBE4
TreeFamiTF336380

Family and domain databases

Gene3Di1.20.1250.70, 1 hit
InterProiView protein in InterPro
IPR009079 4_helix_cytokine-like_core
IPR003443 IL-15/IL-21_fam
IPR038327 IL-15/IL-21_sf
IPR028151 IL-21
PANTHERiPTHR14356 PTHR14356, 1 hit
PfamiView protein in Pfam
PF02372 IL15, 1 hit
SUPFAMiSSF47266 SSF47266, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9HBE4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MERIVICLMV IFLGTLVHKS SSQGQDRHMI RMRQLIDIVD QLKNYVNDLV
60 70 80 90 100
PEFLPAPEDV ETNCEWSAFS CFQKAQLKSA NTGNNERIIN VSIKKLKRKP
110 120 130 140 150
PSTNAGRRQK HRLTCPSCDS YEKKPPKEFL ERFKSLLQKM IHQHLSSRTH

GSEDS
Length:155
Mass (Da):17,923
Last modified:November 23, 2004 - v2
Checksum:iE994A3D19029B914
GO
Isoform 2 (identifier: Q9HBE4-2) [UniParc]FASTAAdd to basket
Also known as: IL-21iso

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

Show »
Length:146
Mass (Da):16,867
Checksum:iCCC4D7F9602AD06A
GO

Sequence cautioni

The sequence AAG29348 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH66258 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH66259 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH66260 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH66261 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH66262 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH69124 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAU88182 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence ABG36529 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07129249L → P in CVID11; interferes with binding to IL21R. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030129140 – 155MIHQH…GSEDS → VSTLSFI in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_001193935.1, NM_001207006.2
NP_068575.1, NM_021803.3
UniGeneiHs.567559

Genome annotation databases

EnsembliENST00000264497; ENSP00000264497; ENSG00000138684
ENST00000611104; ENSP00000477555; ENSG00000138684
GeneIDi59067
KEGGihsa:59067
UCSCiuc003ies.4 human [Q9HBE4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiIL21_HUMAN
AccessioniPrimary (citable) accession number: Q9HBE4
Secondary accession number(s): A5J0L4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: November 23, 2004
Last modified: March 28, 2018
This is version 130 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health