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Protein

Interleukin-21

Gene

IL21

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 receptor binding Source: UniProtKB
  • interleukin-2 receptor binding Source: UniProtKB

GO - Biological processi

  • cell maturation Source: UniProtKB
  • immune response Source: InterPro
  • 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 Stat1 protein Source: MGI
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: MGI
  • signal transduction Source: UniProtKB
  • tyrosine phosphorylation of Stat3 protein Source: CACAO
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138684-MONOMER.
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

HGNCiHGNC:6005. IL21.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • intracellular Source: GOC
Complete GO annotation...

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...)Sequence 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 receptor binding Source: UniProtKB
  • interleukin-2 receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121857. 4 interactors.
IntActiQ9HBE4. 2 interactors.
MINTiMINT-8201759.
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

InterProiIPR009079. 4_helix_cytokine-like_core.
IPR003443. IL-15/IL-21_fam.
IPR028151. IL-21.
[Graphical view]
PANTHERiPTHR14356. PTHR14356. 1 hit.
PfamiPF02372. IL15. 1 hit.
[Graphical view]
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

Cross-referencesi

Web resourcesi

SeattleSNPs

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.

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...

Protein-protein interaction databases

BioGridi121857. 4 interactors.
IntActiQ9HBE4. 2 interactors.
MINTiMINT-8201759.
STRINGi9606.ENSP00000264497.

PTM databases

iPTMnetiQ9HBE4.
PhosphoSitePlusiQ9HBE4.

Polymorphism and mutation databases

BioMutaiIL21.
DMDMi55976599.

Proteomic databases

PaxDbiQ9HBE4.
PeptideAtlasiQ9HBE4.
PRIDEiQ9HBE4.

Protocols and materials databases

DNASUi59067.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi59067.
DisGeNETi59067.
GeneCardsiIL21.
H-InvDBHIX0031753.
HGNCiHGNC:6005. IL21.
MalaCardsiIL21.
MIMi605384. gene.
615767. phenotype.
neXtProtiNX_Q9HBE4.
Orphaneti238569. Autosomal recessive early-onset inflammatory bowel disease.
PharmGKBiPA29820.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWTD. Eukaryota.
ENOG411198G. LUCA.
HOGENOMiHOG000113039.
HOVERGENiHBG052106.
InParanoidiQ9HBE4.
KOiK05434.
OrthoDBiEOG091G0OEJ.
PhylomeDBiQ9HBE4.
TreeFamiTF336380.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138684-MONOMER.
SignaLinkiQ9HBE4.
SIGNORiQ9HBE4.

Miscellaneous databases

EvolutionaryTraceiQ9HBE4.
GeneWikiiInterleukin_21.
GenomeRNAii59067.
PROiQ9HBE4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138684.
CleanExiHS_IL21.
GenevisibleiQ9HBE4. HS.

Family and domain databases

InterProiIPR009079. 4_helix_cytokine-like_core.
IPR003443. IL-15/IL-21_fam.
IPR028151. IL-21.
[Graphical view]
PANTHERiPTHR14356. PTHR14356. 1 hit.
PfamiPF02372. IL15. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiIL21_HUMAN
AccessioniPrimary (citable) accession number: Q9HBE4
Secondary accession number(s): A5J0L4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: November 23, 2004
Last modified: November 2, 2016
This is version 122 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.