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Protein

Interleukin-12 subunit alpha

Gene

IL12A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 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 cell adhesion Source: UniProtKB
  10. positive regulation of interferon-gamma production Source: UniProtKB
  11. positive regulation of lymphocyte proliferation Source: UniProtKB
  12. positive regulation of mononuclear cell proliferation Source: AgBase
  13. positive regulation of natural killer cell activation Source: UniProtKB
  14. positive regulation of natural killer cell mediated cytotoxicity Source: UniProtKB
  15. positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target Source: UniProtKB
  16. positive regulation of NK T cell activation Source: BHF-UCL
  17. positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
  18. positive regulation of T cell differentiation Source: Ensembl
  19. positive regulation of T cell mediated cytotoxicity Source: UniProtKB
  20. positive regulation of T cell proliferation Source: GO_Central
  21. positive regulation of tyrosine phosphorylation of Stat4 protein Source: UniProtKB
  22. response to lipopolysaccharide Source: UniProtKB
  23. response to UV-B 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 Componenti: 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.

Polymorphism and mutation databases

BioMutaiIL12A.
DMDMi20141534.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 22221 PublicationAdd
BLAST
Chaini23 – 219197Interleukin-12 subunit alphaPRO_0000015604Add
BLAST

Amino acid modifications

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

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

BgeeiP29459.
CleanExiHS_IL12A.
ExpressionAtlasiP29459. baseline and differential.
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. 8 interactions.
DIPiDIP-3772N.
IntActiP29459. 2 interactions.
STRINGi9606.ENSP00000303231.

Structurei

Secondary structure

1
219
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 5816Combined sources
Helixi59 – 613Combined sources
Turni74 – 785Combined sources
Helixi81 – 844Combined sources
Helixi88 – 925Combined sources
Beta strandi107 – 1093Combined sources
Turni114 – 1163Combined sources
Helixi118 – 14528Combined sources
Helixi155 – 16915Combined sources
Helixi190 – 21728Combined sources

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP29459.

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-6 superfamily.Curated

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

        10         20         30         40         50
MCPARSLLLV ATLVLLDHLS LARNLPVATP DPGMFPCLHH SQNLLRAVSN
60 70 80 90 100
MLQKARQTLE FYPCTSEEID HEDITKDKTS TVEACLPLEL TKNESCLNSR
110 120 130 140 150
ETSFITNGSC LASRKTSFMM ALCLSSIYED LKMYQVEFKT MNAKLLMDPK
160 170 180 190 200
RQIFLDQNML AVIDELMQAL NFNSETVPQK SSLEEPDFYK TKIKLCILLH
210
AFRIRAVTID RVMSYLNAS
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. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti213 – 2131M → T in AAA35694 (PubMed:1674604).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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 and mutation databases

BioMutaiIL12A.

Cross-referencesi

Web resourcesi

Wikipedia

Interleukin-12 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi109806. 8 interactions.
DIPiDIP-3772N.
IntActiP29459. 2 interactions.
STRINGi9606.ENSP00000303231.

Chemistry

ChEMBLiCHEMBL2364153.

Polymorphism and mutation databases

BioMutaiIL12A.
DMDMi20141534.

Proteomic databases

PaxDbiP29459.
PRIDEiP29459.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3592.
GeneCardsiGC03P159706.
HGNCiHGNC:5969. IL12A.
HPAiHPA001886.
MIMi161560. gene.
neXtProtiNX_P29459.
Orphaneti186. Primary biliary cirrhosis.
PharmGKBiPA29784.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

SignaLinkiP29459.

Miscellaneous databases

EvolutionaryTraceiP29459.
GeneWikiiIL12A.
GenomeRNAii3592.
NextBioi14035.
PROiP29459.
SOURCEiSearch...

Gene expression databases

BgeeiP29459.
CleanExiHS_IL12A.
ExpressionAtlasiP29459. baseline and differential.
GenevestigatoriP29459.

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.
ProtoNetiSearch...

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: April 29, 2015
This is version 144 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.