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P29459 (IL12A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-12 subunit alpha

Short name=IL-12A
Alternative name(s):
Cytotoxic lymphocyte maturation factor 35 kDa subunit
Short name=CLMF p35
IL-12 subunit p35
NK cell stimulatory factor chain 1
Short name=NKSF1
Gene names
Name:IL12A
Synonyms:NKSF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length219 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated Killer cells, and stimulate the production of IFN-gamma by resting PBMC.

Subunit structure

Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12. Ref.8

Subcellular location

Secreted.

Induction

Down-regulated in response to enterovirus 71 (EV71) infection. Ref.7

Sequence similarities

Belongs to the IL-6 superfamily.

Sequence caution

The sequence AAA59937.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   Molecular functionCytokine
Growth factor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell cycle arrest

Inferred from direct assay PubMed 16942485. Source: BHF-UCL

cell migration

Inferred from direct assay PubMed 7903063. Source: UniProtKB

defense response to Gram-positive bacterium

Inferred from expression pattern PubMed 1357073. Source: UniProtKB

defense response to protozoan

Inferred from electronic annotation. Source: Ensembl

extrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 16942485. Source: BHF-UCL

immune response

Traceable author statement PubMed 9789052. Source: UniProtKB

negative regulation of interleukin-17 production

Inferred from direct assay PubMed 16482511. Source: BHF-UCL

negative regulation of smooth muscle cell proliferation

Inferred from direct assay PubMed 16942485. Source: BHF-UCL

positive regulation of NK T cell activation

Inferred from direct assay PubMed 19088061. Source: BHF-UCL

positive regulation of T cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell mediated cytotoxicity

Inferred from direct assay Ref.2Ref.5. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell adhesion

Inferred from direct assay PubMed 7903063. Source: UniProtKB

positive regulation of interferon-gamma production

Inferred from direct assay Ref.2. Source: UniProtKB

positive regulation of lymphocyte proliferation

Inferred from direct assay Ref.2Ref.5. Source: UniProtKB

positive regulation of natural killer cell activation

Inferred from direct assay Ref.2. Source: UniProtKB

positive regulation of natural killer cell mediated cytotoxicity

Inferred from direct assay Ref.5. Source: UniProtKB

positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target

Inferred from direct assay PubMed 7903063. Source: UniProtKB

positive regulation of smooth muscle cell apoptotic process

Inferred from direct assay PubMed 16942485. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat4 protein

Inferred from direct assay PubMed 12372421. Source: UniProtKB

response to UV-B

Inferred from direct assay PubMed 8992506. Source: UniProtKB

response to lipopolysaccharide

Inferred from direct assay PubMed 7605994PubMed 8557999. Source: UniProtKB

response to virus

Inferred from expression pattern Ref.7. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from direct assay PubMed 16456693. Source: UniProtKB

interleukin-12 complex

Inferred from direct assay Ref.5. Source: UniProtKB

   Molecular_functioninterleukin-12 receptor binding

Non-traceable author statement Ref.2. Source: UniProtKB

interleukin-27 binding

Inferred from physical interaction PubMed 9342359. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction Ref.2. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IL12BP294602EBI-1029636,EBI-1029614

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.5
Chain23 – 219197Interleukin-12 subunit alpha
PRO_0000015604

Amino acid modifications

Glycosylation931N-linked (GlcNAc...) Potential
Glycosylation1071N-linked (GlcNAc...) Potential
Disulfide bond64 ↔ 196 Ref.8
Disulfide bond85 ↔ 123 Ref.8
Disulfide bond96Interchain (with C-199 in IL12B) Ref.8

Experimental info

Sequence conflict2131M → T in AAA35694. Ref.2

Secondary structure

.................... 219
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P29459 [UniParc].

Last modified January 23, 2002. Version 2.
Checksum: 7C658AB7716112B2

FASTA21924,874
        10         20         30         40         50         60 
MCPARSLLLV ATLVLLDHLS LARNLPVATP DPGMFPCLHH SQNLLRAVSN MLQKARQTLE 

        70         80         90        100        110        120 
FYPCTSEEID HEDITKDKTS TVEACLPLEL TKNESCLNSR ETSFITNGSC LASRKTSFMM 

       130        140        150        160        170        180 
ALCLSSIYED LKMYQVEFKT MNAKLLMDPK RQIFLDQNML AVIDELMQAL NFNSETVPQK 

       190        200        210 
SSLEEPDFYK TKIKLCILLH AFRIRAVTID RVMSYLNAS 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells."
Wolf S.F., Temple P.A., Kobayashi M., Young D., Dicig M., Lowe L., Dzialo R., Fitz L., Ferenz C., Hewick R.M., Kelleher K., Herrmann S.H., Clark S.C., Azzoni L., Chan S.H., Trinchieri G., Perussia B.
J. Immunol. 146:3074-3081(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor."
Gubler U., Chua A.O., Schoenhaut D.S., Dwyer C.M., McComas W., Motyka R., Nabavi N., Wolitzky A.G., Quinn P.M., Familletti P.C., Gately M.K.
Proc. Natl. Acad. Sci. U.S.A. 88:4143-4147(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]SeattleSNPs variation discovery resource
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells."
Stern A.S., Podlaski F.J., Hulmes J.D., Pan Y.C.E., Quinn P.M., Wolitzky A.G., Familletti P.C., Stremlo D.L., Truitt T., Chizzonite R., Gately M.K.
Proc. Natl. Acad. Sci. U.S.A. 87:6808-6812(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 23-48.
[6]"Sequence similarity between NKSF and the IL-6/G-CSF family."
Merberg D.M., Wolf S.F., Clark S.C.
Immunol. Today 13:77-78(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SIMILARITY TO IL-6.
[7]"Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection."
Leong W.F., Chow V.T.
Cell. Microbiol. 8:565-580(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12."
Yoon C., Johnston S.C., Tang J., Stahl M., Tobin J.F., Somers W.S.
EMBO J. 19:3530-3541(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-219, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-12 entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M65291 mRNA. Translation: AAA59937.1. Different initiation.
M65271 mRNA. Translation: AAA35694.1.
AF404773 Genomic DNA. Translation: AAK84425.1.
AC010370 Genomic DNA. No translation available.
RefSeqNP_000873.2. NM_000882.3.
UniGeneHs.673.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1F45X-ray2.80B23-219[»]
3HMXX-ray3.00B23-219[»]
ProteinModelPortalP29459.
SMRP29459. Positions 34-219.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109806. 1 interaction.
DIPDIP-3772N.
IntActP29459. 2 interactions.
STRING9606.ENSP00000303231.

Chemistry

ChEMBLCHEMBL2364153.

Polymorphism databases

DMDM20141534.

Proteomic databases

PaxDbP29459.
PRIDEP29459.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000305579; ENSP00000303231; ENSG00000168811.
GeneID3592.
KEGGhsa:3592.

Organism-specific databases

CTD3592.
GeneCardsGC03P159706.
HGNCHGNC:5969. IL12A.
HPAHPA001886.
MIM161560. gene.
neXtProtNX_P29459.
Orphanet186. Primary biliary cirrhosis.
PharmGKBPA29784.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47298.
HOVERGENHBG063691.
InParanoidP29459.
KOK05406.
OrthoDBEOG7VDXQX.
PhylomeDBP29459.
TreeFamTF330814.

Enzyme and pathway databases

SignaLinkP29459.

Gene expression databases

ArrayExpressP29459.
BgeeP29459.
CleanExHS_IL12A.
GenevestigatorP29459.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR004281. IL-12_alpha.
[Graphical view]
PANTHERPTHR10523. PTHR10523. 1 hit.
PfamPF03039. IL12. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP29459.
GeneWikiIL12A.
GenomeRNAi3592.
NextBio14035.
PROP29459.
SOURCESearch...

Entry information

Entry nameIL12A_HUMAN
AccessionPrimary (citable) accession number: P29459
Secondary accession number(s): Q96QZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2002
Last modified: April 16, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM