Interleukin-23 subunit alpha precursor

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Reviewed, UniProtKB/Swiss-Prot Q9NPF7 (IL23A_HUMAN)

Last modified June 16, 2009. Version 55. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Interleukin-23 subunit alpha
      Short name=IL-23 subunit alpha
Alternative name(s):
    Interleukin-23 subunit p19
      Short name=IL-23p19

Gene names

Name:	IL23A
Synonyms:	SGRF
ORF Names:	UNQ2498/PRO5798

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	189 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Associates with IL12B to form the IL-23 interleukin, an heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to an heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. Ref.1 Ref.5 Ref.11
Subunit structure	Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-23. Ref.14
Subcellular location	Secreted. Note: Secreted upon association with IL12B. Ref.1
Tissue specificity	Secreted by activated dendritic and phagocytic cells and keratinocytes. Also expressed by dermal Langerhans cells (at protein level). Ref.1 Ref.11
Developmental stage	Expressed by newborns dendritic cells. Ref.10
Induction	Up-regulated by a wide array of pathogens and pathogen-products together with self-signals for danger or injury. Up-regulated in psoriatic dermal tissues, in dendritic cells of multiple sclerosis patients and in tumors. Ref.11 Ref.6 Ref.7 Ref.8 Ref.9 Ref.12 Ref.13
Sequence similarities	Belongs to the IL-6 superfamily.

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Ontologies

Keywords
Biological process	Antiviral defense Immune response Inflammatory response Innate immunity Tissue remodeling
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	3D-structure
Gene Ontology (GO)
Biological process	inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW response to virus Inferred from electronic annotation. Source: UniProtKB-KW tissue remodeling Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

Potential

Chain

20 – 189

170

Interleukin-23 subunit alpha

PRO_0000259488

Experimental info

Sequence conflict

122

G → A in AAG37232. Ref.1

Sequence conflict

147

I → M in AAH66267. Ref.4

Sequence conflict

168

S → N in AAH66267. Ref.4

Sequence conflict

173

V → A in AAH66269. Ref.4

Sequence conflict

189

P → L in AAH66269. Ref.4

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9NPF7-1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 51B5C0F188EC1B9F
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FASTA

189

20,730

        10         20         30         40         50         60 
MLGSRAVMLL LLLPWTAQGR AVPGGSSPAW TQCQQLSQKL CTLAWSAHPL VGHMDLREEG 

        70         80         90        100        110        120 
DEETTNDVPH IQCGDGCDPQ GLRDNSQFCL QRIHQGLIFY EKLLGSDIFT GEPSLLPDSP 

       130        140        150        160        170        180 
VGQLHASLLG LSQLLQPEGH HWETQQIPSL SPSQPWQRLL LRFKILRSLQ AFVAVAARVF 


AHGAATLSP

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12." Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F., Yu N., Wang J., Singh K.P., Zonin F., Vaisberg E., Churakova T., Liu M.-R., Gorman D., Wagner J., Zurawski S., Liu Y.-J. Kastelein R.A. Immunity 13:715-725(2000) [PubMed: 11114383] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH IL12B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"SGRF; a novel member of the IL-6/G-CSF family." Hirata Y., Kosuge Y. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Spleen.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R." Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., Rennick D.M. , Kastelein R.A., de Waal Malefyt R., Moore K.W. J. Immunol. 168:5699-5708(2002) [PubMed: 12023369] [Abstract] Cited for: FUNCTION, INTERACTION WITH IL12RB1 AND IL23R.
[6]	"Regulation of virus-induced IL-12 and IL-23 expression in human macrophages." Pirhonen J., Matikainen S., Julkunen I. J. Immunol. 169:5673-5678(2002) [PubMed: 12421946] [Abstract] Cited for: INDUCTION.
[7]	"Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development." Smits H.H., van Beelen A.J., Hessle C., Westland R., de Jong E., Soeteman E., Wold A., Wierenga E.A., Kapsenberg M.L. Eur. J. Immunol. 34:1371-1380(2004) [PubMed: 15114670] [Abstract] Cited for: INDUCTION.
[8]	"Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway." Schnurr M., Toy T., Shin A., Wagner M., Cebon J., Maraskovsky E. Blood 105:1582-1589(2005) [PubMed: 15486065] [Abstract] Cited for: INDUCTION.
[9]	"Bordetella pertussis-infected human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization and interleukin-23 expression." Fedele G., Stefanelli P., Spensieri F., Fazio C., Mastrantonio P., Ausiello C.M. Infect. Immun. 73:1590-1597(2005) [PubMed: 15731058] [Abstract] Cited for: INDUCTION.
[10]	"Preferential production of the IL-12(p40)/IL-23(p19) heterodimer by dendritic cells from human newborns." Vanden Eijnden S., Goriely S., De Wit D., Goldman M., Willems F. Eur. J. Immunol. 36:21-26(2006) [PubMed: 16342235] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[11]	"In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin." Piskin G., Sylva-Steenland R.M.R., Bos J.D., Teunissen M.B.M. J. Immunol. 176:1908-1915(2006) [PubMed: 16424222] [Abstract] Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[12]	"IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production." Vaknin-Dembinsky A., Balashov K., Weiner H.L. J. Immunol. 176:7768-7774(2006) [PubMed: 16751425] [Abstract] Cited for: INDUCTION.
[13]	"IL-23 promotes tumour incidence and growth." Langowski J.L., Zhang X., Wu L., Mattson J.D., Chen T., Smith K., Basham B., McClanahan T.K., Kastelein R.A., Oft M. Nature 442:461-465(2006) [PubMed: 16688182] [Abstract] Cited for: INDUCTION.
[14]	"The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12." Lupardus P.J., Garcia K.C. J. Mol. Biol. 382:931-941(2008) [PubMed: 18680750] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 20-189 IN COMPLEX WITH IL12B, SUBUNIT.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

AF301620 mRNA. Translation: AAG37232.1.
AB030000 mRNA. Translation: BAA93686.1.
AB030001 Genomic DNA. Translation: BAA93687.1.
AY359083 mRNA. Translation: AAQ89442.1.
BC066267 mRNA. Translation: AAH66267.1.
BC066268 mRNA. Translation: AAH66268.1.
BC066269 mRNA. Translation: AAH66269.1.
BC067511 mRNA. Translation: AAH67511.1.
BC067512 mRNA. Translation: AAH67512.1.
BC067513 mRNA. Translation: AAH67513.1.

IPI

IPI00300835.

RefSeq

NP_057668.1.

UniGene

Hs.621461
Hs.98309

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3D85	X-ray	1.90	C	20-189	[»]
3D87	X-ray	2.90	A/C	20-189	[»]
3DUH	X-ray	2.30	C/D	20-189	[»]

ModBase

Search...

Proteomic databases

PRIDE

Q9NPF7.

Genome annotation databases

Ensembl

ENSG00000110944. Homo sapiens. [Contig view]

GeneID

51561.

KEGG

hsa:51561.

Organism-specific databases

GeneCards

GC12P055021.

HGNC

HGNC:15488. IL23A.

HPA

HPA001554.

MIM

605580. gene.

PharmGKB

PA29824.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9NPF7.

OMA

Q9NPF7. RIHQGLV.

Enzyme and pathway databases

Pathway_Interaction_DB

il23pathway. IL23-mediated signaling events.

Gene expression databases

Bgee

Q9NPF7.

CleanEx

HS_IL23A.

GermOnline

ENSG00000110944. Homo sapiens.

Family and domain databases

InterPro

IPR012351. 4_helix_cytokine_core.
IPR010831. IL23A.
IPR003573. IL6_MGF_GCSF.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

PANTHER

PTHR15947. IL23A. 1 hit.

Pfam

PF00489. IL6. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

55362.

SOURCE

Search...

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Entry information

Entry name

IL23A_HUMAN

Accession

Primary (citable) accession number: Q9NPF7
Secondary accession number(s): Q6NZ80, Q6NZ82, Q9H2A5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	October 1, 2000
Last modified:	June 16, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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