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Q9HBE4

- IL21_HUMAN

UniProt

Q9HBE4 - IL21_HUMAN

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Protein

Interleukin-21

Gene

IL21

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. cytokine receptor binding Source: UniProtKB
  2. interleukin-2 receptor binding Source: UniProtKB

GO - Biological processi

  1. cell maturation Source: UniProtKB
  2. immune response Source: InterPro
  3. positive regulation of B cell proliferation Source: MGI
  4. positive regulation of cell proliferation Source: MGI
  5. positive regulation of inflammatory response Source: BHF-UCL
  6. positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
  7. positive regulation of interleukin-10 production Source: Ensembl
  8. positive regulation of interleukin-17 production Source: BHF-UCL
  9. positive regulation of natural killer cell cytokine production Source: Ensembl
  10. positive regulation of natural killer cell differentiation Source: Ensembl
  11. positive regulation of natural killer cell mediated cytotoxicity Source: Ensembl
  12. positive regulation of T cell proliferation Source: UniProtKB
  13. positive regulation of tissue remodeling Source: BHF-UCL
  14. positive regulation of tyrosine phosphorylation of Stat1 protein Source: MGI
  15. positive regulation of tyrosine phosphorylation of Stat3 protein Source: MGI
  16. signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

SignaLinkiQ9HBE4.

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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:6005. IL21.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency, common variable, 11 (CVID11) [MIM:615767]: A 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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti49 – 491L → P in CVID11; interferes with binding to IL21R. 1 Publication
VAR_071292

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Chaini23 – 155133Interleukin-21PRO_0000015505Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi64 ↔ 115
Disulfide bondi71 ↔ 118
Glycosylationi90 – 901N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9HBE4.
PRIDEiQ9HBE4.

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

BgeeiQ9HBE4.
CleanExiHS_IL21.
GenevestigatoriQ9HBE4.

Interactioni

Protein-protein interaction databases

BioGridi121857. 2 interactions.
IntActiQ9HBE4. 2 interactions.
MINTiMINT-8201759.
STRINGi9606.ENSP00000264497.

Structurei

Secondary structure

1
155
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi25 – 4218Combined sources
Helixi43 – 486Combined sources
Helixi62 – 643Combined sources
Helixi65 – 7410Combined sources
Helixi85 – 9612Combined sources
Beta strandi101 – 1055Combined sources
Beta strandi107 – 1093Combined sources
Beta strandi113 – 1153Combined sources
Turni118 – 1203Combined sources
Helixi126 – 14217Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2OQPNMR-A23-155[»]
3TGXX-ray2.80B/D/F/H/J/L/N/P23-155[»]
ProteinModelPortaliQ9HBE4.
SMRiQ9HBE4. Positions 23-155.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9HBE4.

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG40525.
GeneTreeiENSGT00390000010494.
HOGENOMiHOG000113039.
HOVERGENiHBG052106.
InParanoidiQ9HBE4.
KOiK05434.
OrthoDBiEOG7M98JN.
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. Align

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 AAG29348.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAH66258.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAH66259.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAH66260.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAH66261.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAH66262.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAH69124.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence AAU88182.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated
The sequence ABG36529.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortenedCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti49 – 491L → P in CVID11; interferes with binding to IL21R. 1 Publication
VAR_071292

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei140 – 15516MIHQH…GSEDS → VSTLSFI in isoform 2. 1 PublicationVSP_030129Add
BLAST

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.3. human. [Q9HBE4-1]
uc010int.4. human. [Q9HBE4-2]

Polymorphism databases

DMDMi55976599.

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.
RefSeqi NP_001193935.1. NM_001207006.2.
NP_068575.1. NM_021803.3.
UniGenei Hs.567559.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2OQP NMR - A 23-155 [» ]
3TGX X-ray 2.80 B/D/F/H/J/L/N/P 23-155 [» ]
ProteinModelPortali Q9HBE4.
SMRi Q9HBE4. Positions 23-155.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121857. 2 interactions.
IntActi Q9HBE4. 2 interactions.
MINTi MINT-8201759.
STRINGi 9606.ENSP00000264497.

Polymorphism databases

DMDMi 55976599.

Proteomic databases

PaxDbi Q9HBE4.
PRIDEi Q9HBE4.

Protocols and materials databases

DNASUi 59067.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264497 ; ENSP00000264497 ; ENSG00000138684 .
ENST00000611104 ; ENSP00000477555 ; ENSG00000138684 .
GeneIDi 59067.
KEGGi hsa:59067.
UCSCi uc003ies.3. human. [Q9HBE4-1 ]
uc010int.4. human. [Q9HBE4-2 ]

Organism-specific databases

CTDi 59067.
GeneCardsi GC04M123534.
H-InvDB HIX0031753.
HGNCi HGNC:6005. IL21.
MIMi 605384. gene.
615767. phenotype.
neXtProti NX_Q9HBE4.
Orphaneti 238569. Autosomal recessive early-onset inflammatory bowel disease.
PharmGKBi PA29820.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG40525.
GeneTreei ENSGT00390000010494.
HOGENOMi HOG000113039.
HOVERGENi HBG052106.
InParanoidi Q9HBE4.
KOi K05434.
OrthoDBi EOG7M98JN.
PhylomeDBi Q9HBE4.
TreeFami TF336380.

Enzyme and pathway databases

SignaLinki Q9HBE4.

Miscellaneous databases

EvolutionaryTracei Q9HBE4.
GeneWikii Interleukin_21.
GenomeRNAii 59067.
NextBioi 65134.
PROi Q9HBE4.
SOURCEi Search...

Gene expression databases

Bgeei Q9HBE4.
CleanExi HS_IL21.
Genevestigatori Q9HBE4.

Family and domain databases

InterProi IPR009079. 4_helix_cytokine-like_core.
IPR003443. IL-15/IL-21_fam.
IPR028151. IL-21.
[Graphical view ]
PANTHERi PTHR14356. PTHR14356. 1 hit.
Pfami PF02372. IL15. 1 hit.
[Graphical view ]
SUPFAMi SSF47266. SSF47266. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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.
  10. Cited for: VARIANT CVID11 PRO-49, CHARACTERIZATION OF VARIANT CVID11 PRO-49.

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 26, 2014
This is version 106 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

External Data

Dasty 3