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P29459

- IL12A_HUMAN

UniProt

P29459 - IL12A_HUMAN

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Protein
Interleukin-12 subunit alpha
Gene
IL12A, NKSF1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. interleukin-12 beta subunit binding Source: AgBase
  2. interleukin-12 receptor binding Source: UniProtKB
  3. interleukin-27 binding Source: UniProtKB
  4. protein binding Source: IntAct
  5. protein heterodimerization activity Source: UniProtKB

GO - Biological processi

  1. cell cycle arrest Source: BHF-UCL
  2. cell migration Source: UniProtKB
  3. defense response to Gram-positive bacterium Source: UniProtKB
  4. defense response to protozoan Source: Ensembl
  5. extrinsic apoptotic signaling pathway Source: BHF-UCL
  6. immune response Source: UniProtKB
  7. negative regulation of interleukin-17 production Source: BHF-UCL
  8. negative regulation of smooth muscle cell proliferation Source: BHF-UCL
  9. positive regulation of NK T cell activation Source: BHF-UCL
  10. positive regulation of T cell differentiation Source: Ensembl
  11. positive regulation of T cell mediated cytotoxicity Source: UniProtKB
  12. positive regulation of T cell proliferation Source: Ensembl
  13. positive regulation of cell adhesion Source: UniProtKB
  14. positive regulation of interferon-gamma production Source: UniProtKB
  15. positive regulation of lymphocyte proliferation Source: UniProtKB
  16. positive regulation of mononuclear cell proliferation Source: AgBase
  17. positive regulation of natural killer cell activation Source: UniProtKB
  18. positive regulation of natural killer cell mediated cytotoxicity Source: UniProtKB
  19. positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target Source: UniProtKB
  20. positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
  21. positive regulation of tyrosine phosphorylation of Stat4 protein Source: UniProtKB
  22. response to UV-B Source: UniProtKB
  23. response to lipopolysaccharide Source: UniProtKB
  24. response to virus Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Enzyme and pathway databases

SignaLinkiP29459.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IL12A
Synonyms:NKSF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:5969. IL12A.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. extracellular space Source: UniProtKB
  3. interleukin-12 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti186. Primary biliary cirrhosis.
PharmGKBiPA29784.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 Publication
Add
BLAST
Chaini23 – 219197Interleukin-12 subunit alpha
PRO_0000015604Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi64 ↔ 1961 Publication
Disulfide bondi85 ↔ 1231 Publication
Glycosylationi93 – 931N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi96 – 96Interchain (with C-199 in IL12B)1 Publication
Glycosylationi107 – 1071N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP29459.
PRIDEiP29459.

Expressioni

Inductioni

Down-regulated in response to enterovirus 71 (EV71) infection.1 Publication

Gene expression databases

ArrayExpressiP29459.
BgeeiP29459.
CleanExiHS_IL12A.
GenevestigatoriP29459.

Organism-specific databases

HPAiHPA001886.

Interactioni

Subunit structurei

Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
IL12BP294602EBI-1029636,EBI-1029614

Protein-protein interaction databases

BioGridi109806. 1 interaction.
DIPiDIP-3772N.
IntActiP29459. 2 interactions.
STRINGi9606.ENSP00000303231.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 5816
Helixi59 – 613
Turni74 – 785
Helixi81 – 844
Helixi88 – 925
Beta strandi107 – 1093
Turni114 – 1163
Helixi118 – 14528
Helixi155 – 16915
Helixi190 – 21728

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1F45X-ray2.80B23-219[»]
3HMXX-ray3.00B23-219[»]
ProteinModelPortaliP29459.
SMRiP29459. Positions 34-219.

Miscellaneous databases

EvolutionaryTraceiP29459.

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-6 superfamily.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG47298.
HOVERGENiHBG063691.
InParanoidiP29459.
KOiK05406.
OrthoDBiEOG7VDXQX.
PhylomeDBiP29459.
TreeFamiTF330814.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR004281. IL-12_alpha.
[Graphical view]
PANTHERiPTHR10523. PTHR10523. 1 hit.
PfamiPF03039. IL12. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P29459-1 [UniParc]FASTAAdd to Basket

« Hide

MCPARSLLLV ATLVLLDHLS LARNLPVATP DPGMFPCLHH SQNLLRAVSN    50
MLQKARQTLE FYPCTSEEID HEDITKDKTS TVEACLPLEL TKNESCLNSR 100
ETSFITNGSC LASRKTSFMM ALCLSSIYED LKMYQVEFKT MNAKLLMDPK 150
RQIFLDQNML AVIDELMQAL NFNSETVPQK SSLEEPDFYK TKIKLCILLH 200
AFRIRAVTID RVMSYLNAS 219
Length:219
Mass (Da):24,874
Last modified:January 23, 2002 - v2
Checksum:i7C658AB7716112B2
GO

Sequence cautioni

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti213 – 2131M → T in AAA35694. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M65291 mRNA. Translation: AAA59937.1. Different initiation.
M65271 mRNA. Translation: AAA35694.1.
AF404773 Genomic DNA. Translation: AAK84425.1.
AC010370 Genomic DNA. No translation available.
RefSeqiNP_000873.2. NM_000882.3.
UniGeneiHs.673.

Genome annotation databases

EnsembliENST00000305579; ENSP00000303231; ENSG00000168811.
GeneIDi3592.
KEGGihsa:3592.

Polymorphism databases

DMDMi20141534.

Cross-referencesi

Web resourcesi

Wikipedia

Interleukin-12 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M65291 mRNA. Translation: AAA59937.1 . Different initiation.
M65271 mRNA. Translation: AAA35694.1 .
AF404773 Genomic DNA. Translation: AAK84425.1 .
AC010370 Genomic DNA. No translation available.
RefSeqi NP_000873.2. NM_000882.3.
UniGenei Hs.673.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1F45 X-ray 2.80 B 23-219 [» ]
3HMX X-ray 3.00 B 23-219 [» ]
ProteinModelPortali P29459.
SMRi P29459. Positions 34-219.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109806. 1 interaction.
DIPi DIP-3772N.
IntActi P29459. 2 interactions.
STRINGi 9606.ENSP00000303231.

Chemistry

ChEMBLi CHEMBL2364153.

Polymorphism databases

DMDMi 20141534.

Proteomic databases

PaxDbi P29459.
PRIDEi P29459.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000305579 ; ENSP00000303231 ; ENSG00000168811 .
GeneIDi 3592.
KEGGi hsa:3592.

Organism-specific databases

CTDi 3592.
GeneCardsi GC03P159706.
HGNCi HGNC:5969. IL12A.
HPAi HPA001886.
MIMi 161560. gene.
neXtProti NX_P29459.
Orphaneti 186. Primary biliary cirrhosis.
PharmGKBi PA29784.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG47298.
HOVERGENi HBG063691.
InParanoidi P29459.
KOi K05406.
OrthoDBi EOG7VDXQX.
PhylomeDBi P29459.
TreeFami TF330814.

Enzyme and pathway databases

SignaLinki P29459.

Miscellaneous databases

EvolutionaryTracei P29459.
GeneWikii IL12A.
GenomeRNAii 3592.
NextBioi 14035.
PROi P29459.
SOURCEi Search...

Gene expression databases

ArrayExpressi P29459.
Bgeei P29459.
CleanExi HS_IL12A.
Genevestigatori P29459.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR004281. IL-12_alpha.
[Graphical view ]
PANTHERi PTHR10523. PTHR10523. 1 hit.
Pfami PF03039. IL12. 1 hit.
[Graphical view ]
SUPFAMi SSF47266. SSF47266. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiIL12A_HUMAN
AccessioniPrimary (citable) accession number: P29459
Secondary accession number(s): Q96QZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2002
Last modified: July 9, 2014
This is version 138 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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