Q9NPF7 (IL23A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-23 subunit alpha
Short name=IL-23 subunit alpha
Short name=IL-23-A

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) [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	189 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	Associates with IL12B to form the IL-23 interleukin, a 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 a 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.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13
Sequence similarities	Belongs to the IL-6 superfamily.

Ontologies

Keywords
Biological process	Antiviral defense Immunity Inflammatory response Innate immunity Tissue remodeling
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell proliferation Inferred from electronic annotation. Source: Compara defense response to Gram-negative bacterium Inferred from direct assay Ref.7PubMed 20027291. Source: BHF-UCL defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of interleukin-10 production Inferred from mutant phenotype Ref.12. Source: BHF-UCL positive regulation of NF-kappaB import into nucleus Traceable author statement PubMed 20428758. Source: BHF-UCL positive regulation of NK T cell activation Inferred from direct assay PubMed 19088061. Source: BHF-UCL positive regulation of NK T cell proliferation Inferred from direct assay PubMed 19088061. Source: BHF-UCL positive regulation of T cell mediated cytotoxicity Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of T-helper 1 type immune response Inferred from direct assay Ref.7. Source: BHF-UCL positive regulation of T-helper 17 cell lineage commitment Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of T-helper 17 type immune response Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of activated T cell proliferation Inferred from direct assay Ref.1. Source: BHF-UCL positive regulation of activation of JAK2 kinase activity Inferred from direct assay Ref.5. Source: BHF-UCL positive regulation of defense response to virus by host Inferred from direct assay Ref.6. Source: BHF-UCL positive regulation of granulocyte macrophage colony-stimulating factor production Inferred from direct assay PubMed 20027291. Source: BHF-UCL positive regulation of inflammatory response Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of interferon-gamma production Inferred from direct assay Ref.1PubMed 17888176PubMed 20027291. Source: BHF-UCL positive regulation of interleukin-10 production Inferred from direct assay PubMed 15265908. Source: BHF-UCL positive regulation of interleukin-12 production Inferred from direct assay PubMed 20027291. Source: BHF-UCL positive regulation of interleukin-17 production Inferred from direct assay PubMed 16482511Ref.12PubMed 17888176. Source: BHF-UCL positive regulation of memory T cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of natural killer cell proliferation Inferred from direct assay PubMed 19088061. Source: BHF-UCL positive regulation of neutrophil chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of osteoclast differentiation Inferred from direct assay PubMed 17888176. Source: BHF-UCL positive regulation of tissue remodeling Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of tumor necrosis factor production Inferred from mutant phenotype Ref.12. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat3 protein Inferred from direct assay Ref.5PubMed 19088061. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat4 protein Inferred from direct assay Ref.1Ref.5PubMed 19088061. Source: BHF-UCL positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from direct assay Ref.5. Source: BHF-UCL regulation of tyrosine phosphorylation of Stat1 protein Inferred from direct assay Ref.5. Source: BHF-UCL tissue remodeling Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	interleukin-23 complex Inferred from direct assay Ref.1. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Potential

Chain

20 – 189

170

Interleukin-23 subunit alpha

PRO_0000259488

Experimental info

Sequence conflict

122

1

G → A in AAG37232. Ref.1

Sequence conflict

147

1

I → M in AAH66267. Ref.4

Sequence conflict

168

1

S → N in AAH66267. Ref.4

Sequence conflict

173

1

V → A in AAH66269. Ref.4

Sequence conflict

189

1

P → L in AAH66269. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

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.

.

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.

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.

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.

189

Helix Strand Turn

Details...

Helix

30 – 45

16

Turn

49 – 51

3

Helix

73 – 75

3

Helix

79 – 84

6

Helix

87 – 104

18

Helix

107 – 110

4

Beta strand

111 – 113

3

Helix

121 – 135

15

Beta strand

136 – 138

3

Helix

155 – 157

3

Helix

158 – 186

29

Sequences

	Sequence		Length	Mass (Da)
	Q9NPF7 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 51B5C0F188EC1B9F	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

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. , Abrams J.S., Moore K.W., Rennick D.M., de Waal-Malefyt R., Hannum C., Bazan J.F., Kastelein R.A. Immunity 13:715-725(2000) [PubMed] [Europe PMC] [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. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 20-189 IN COMPLEX WITH IL12B, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_016584.2.

UniGene

Hs.382212.
Hs.98309.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]
3QWR	X-ray	3.25	B	20-189	[»]

ProteinModelPortal

Q9NPF7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NPF7. 1 interaction.

STRING

9606.ENSP00000228534.

Polymorphism databases

DMDM

74761641.

Proteomic databases

PaxDb

Q9NPF7.

PRIDE

Q9NPF7.

Protocols and materials databases

DNASU

51561.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000228534; ENSP00000228534; ENSG00000110944.

GeneID

51561.

KEGG

hsa:51561.

UCSC

uc001sla.3. human.

Organism-specific databases

CTD

51561.

GeneCards

GC12P056732.

HGNC

HGNC:15488. IL23A.

HPA

HPA001554.

MIM

605580. gene.

neXtProt

NX_Q9NPF7.

PharmGKB

PA29824.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42887.

HOGENOM

HOG000048728.

HOVERGEN

HBG081786.

InParanoid

Q9NPF7.

KO

K05426.

OMA

IHQGLVF.

OrthoDB

EOG43BMQ2.

Enzyme and pathway databases

Pathway_Interaction_DB

il23pathway. IL23-mediated signaling events.

Gene expression databases

Bgee

Q9NPF7.

CleanEx

HS_IL23A.

Genevestigator

Q9NPF7.

GermOnline

ENSG00000110944. Homo sapiens.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR010831. IL23A.
IPR003573. IL6_MGF_GCSF.
[Graphical view]

PANTHER

PTHR15947. PTHR15947. 1 hit.

Pfam

PF00489. IL6. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NPF7.

GenomeRNAi

51561.

NextBio

55362.

SOURCE

Search...

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:	May 1, 2013
This is version 95 of the entry and version 1 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.