Q9HBE4 (IL21_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-21
Short name=IL-21

Alternative name(s):
Za11

Gene names

Name:

IL21

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	155 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell 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 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: Compara 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: Compara positive regulation of natural killer cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of natural killer cell mediated cytotoxicity Inferred from electronic annotation. Source: Compara 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_component	extracellular space Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	cytokine receptor binding Traceable author statement PubMed 15546387. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 155

133

Interleukin-21

PRO_0000015505

Amino acid modifications

Glycosylation

90

1

N-linked (GlcNAc...) Potential

Disulfide bond

64 ↔ 115

Ref.8 Ref.9

Disulfide bond

71 ↔ 118

Ref.8 Ref.9

Natural variations

Alternative sequence

140 – 155

16

MIHQH…GSEDS → VSTLSFI in isoform 2.

VSP_030129

Secondary structure

1

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155

Helix Strand Turn

Details...

Helix

25 – 42

18

Helix

43 – 48

6

Helix

62 – 64

3

Helix

65 – 74

10

Helix

85 – 96

12

Beta strand

101 – 105

5

Beta strand

107 – 109

3

Beta strand

113 – 115

3

Turn

118 – 120

3

Helix

126 – 142

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 23, 2004. Version 2. Checksum: E994A3D19029B914	FASTA	155	17,923
	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
	Isoform 2 (IL-21iso) [UniParc]. Checksum: CCC4D7F9602AD06A	FASTA	146	16,867
	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 YEKKPPKEFL ERFKSLLQKV STLSFI

References

	« Hide 'large scale' referencesShow '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. , 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. , 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

SeattleSNPs

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.

IPI

IPI00029151.
IPI00877605.

RefSeq

NP_001193935.1. NM_001207006.2.
NP_068575.1. NM_021803.3.

UniGene

Hs.567559.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q9HBE4.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000264497.

Polymorphism databases

DMDM

55976599.

Proteomic databases

PaxDb

Q9HBE4.

PRIDE

Q9HBE4.

Protocols and materials databases

DNASU

59067.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264497; ENSP00000264497; ENSG00000138684.

GeneID

59067.

KEGG

hsa:59067.

UCSC

uc003ies.2. human.
uc010int.3. human.

Organism-specific databases

CTD

59067.

GeneCards

GC04M123534.

H-InvDB

HIX0031753.

HGNC

HGNC:6005. IL21.

MIM

605384. gene.

neXtProt

NX_Q9HBE4.

PharmGKB

PA29820.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40525.

HOGENOM

HOG000113039.

HOVERGEN

HBG052106.

InParanoid

Q9HBE4.

KO

K05434.

OrthoDB

EOG4DJJXM.

Gene expression databases

Bgee

Q9HBE4.

CleanEx

HS_IL21.

Genevestigator

Q9HBE4.

GermOnline

ENSG00000138684. Homo sapiens.

Family and domain databases

InterPro

IPR003443. Interleukin_15-like.
[Graphical view]

Pfam

PF02372. IL15. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9HBE4.

GenomeRNAi

59067.

NextBio

65134.

SOURCE

Search...

Entry information

Entry name

IL21_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.