ID   IL12A_HUMAN             Reviewed;         219 AA.
AC   P29459; Q96QZ1;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2002, sequence version 2.
DT   16-DEC-2008, entry version 86.
DE   RecName: Full=Interleukin-12 subunit alpha;
DE            Short=IL-12A;
DE   AltName: Full=IL-12 subunit p35;
DE   AltName: Full=Cytotoxic lymphocyte maturation factor 35 kDa subunit;
DE            Short=CLMF p35;
DE   AltName: Full=NK cell stimulatory factor chain 1;
DE            Short=NKSF1;
DE   Flags: Precursor;
GN   Name=IL12A; Synonyms=NKSF1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=91201875; PubMed=1673147;
RA   Wolf S.F., Temple P.A., Kobayashi M., Young D., Dicig M., Lowe L.,
RA   Dzialo R., Fitz L., Ferenz C., Hewick R.M., Kelleher K.,
RA   Herrmann S.H., Clark S.C., Azzoni L., Chan S.H., Trinchieri G.,
RA   Perussia B.;
RT   "Cloning of cDNA for natural killer cell stimulatory factor, a
RT   heterodimeric cytokine with multiple biologic effects on T and natural
RT   killer cells.";
RL   J. Immunol. 146:3074-3081(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=91239523; PubMed=1674604;
RA   Gubler U., Chua A.O., Schoenhaut D.S., Dwyer C.M., McComas W.,
RA   Motyka R., Nabavi N., Wolitzky A.G., Quinn P.M., Familletti P.C.,
RA   Gately M.K.;
RT   "Coexpression of two distinct genes is required to generate secreted
RT   bioactive cytotoxic lymphocyte maturation factor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:4143-4147(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG   SeattleSNPs program for genomic applications;
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA   Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA   Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA   Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA   Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA   Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA   Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA   Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA   Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA   Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA   Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA   Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA   Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA   Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA   Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA   Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [5]
RP   PROTEIN SEQUENCE OF 23-48.
RX   MEDLINE=90370873; PubMed=2204066;
RA   Stern A.S., Podlaski F.J., Hulmes J.D., Pan Y.C.E., Quinn P.M.,
RA   Wolitzky A.G., Familletti P.C., Stremlo D.L., Truitt T.,
RA   Chizzonite R., Gately M.K.;
RT   "Purification to homogeneity and partial characterization of cytotoxic
RT   lymphocyte maturation factor from human B-lymphoblastoid cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:6808-6812(1990).
RN   [6]
RP   SIMILARITY TO IL-6.
RX   MEDLINE=92247293; PubMed=1374259; DOI=10.1016/0167-5699(92)90140-3;
RA   Merberg D.M., Wolf S.F., Clark S.C.;
RT   "Sequence similarity between NKSF and the IL-6/G-CSF family.";
RL   Immunol. Today 13:77-78(1992).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-219, AND DISULFIDE BONDS.
RX   PubMed=10899108; DOI=10.1093/emboj/19.14.3530;
RA   Yoon C., Johnston S.C., Tang J., Stahl M., Tobin J.F., Somers W.S.;
RT   "Charged residues dominate a unique interlocking topography in the
RT   heterodimeric cytokine interleukin-12.";
RL   EMBO J. 19:3530-3541(2000).
CC   -!- FUNCTION: Cytokine that can act as a growth factor for activated T
CC       and NK cells, enhance the lytic activity of NK/lymphokine-
CC       activated Killer cells, and stimulate the production of IFN-gamma
CC       by resting PBMC.
CC   -!- SUBUNIT: Heterodimer with IL12B; disulfide-linked. The heterodimer
CC       is known as interleukin IL-12.
CC   -!- INTERACTION:
CC       P29460:IL12B; NbExp=1; IntAct=EBI-1029636, EBI-1029614;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the IL-6 superfamily.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-12 entry;
CC       URL="http://en.wikipedia.org/wiki/Interleukin_12";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/il12a/";
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DR   EMBL; M65291; AAA59937.1; ALT_INIT; mRNA.
DR   EMBL; M65271; AAA35694.1; -; mRNA.
DR   EMBL; AF404773; AAK84425.1; -; Genomic_DNA.
DR   EMBL; AC010370; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_000873.2; -.
DR   UniGene; Hs.673; -.
DR   PDB; 1F45; X-ray; 2.80 A; B=23-219.
DR   PDBsum; 1F45; -.
DR   DIP; DIP:3772N; -.
DR   IntAct; P29459; 1.
DR   PhosphoSite; P29459; -.
DR   PRIDE; P29459; -.
DR   Ensembl; ENSG00000168811; Homo sapiens.
DR   GeneID; 3592; -.
DR   KEGG; hsa:3592; -.
DR   GeneCards; GC03P161189; -.
DR   H-InvDB; HIX0030715; -.
DR   HGNC; HGNC:5969; IL12A.
DR   HPA; HPA001886; -.
DR   MIM; 161560; gene.
DR   PharmGKB; PA29784; -.
DR   HOVERGEN; P29459; -.
DR   NextBio; 14035; -.
DR   ArrayExpress; P29459; -.
DR   CleanEx; HS_IL12A; -.
DR   GO; GO:0043514; C:interleukin-12 complex; IDA:UniProtKB.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0005143; F:interleukin-12 receptor binding; NAS:UniProtKB.
DR   GO; GO:0045513; F:interleukin-27 binding; IPI:UniProtKB.
DR   GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR   GO; GO:0007050; P:cell cycle arrest; IDA:UniProtKB.
DR   GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; IEP:UniProtKB.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell p...; IDA:UniProtKB.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; IDA:UniProtKB.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma pro...; IDA:UniProtKB.
DR   GO; GO:0002860; P:positive regulation of natural killer cell ...; IDA:UniProtKB.
DR   GO; GO:0032816; P:positive regulation of natural killer cell ...; IDA:UniProtKB.
DR   GO; GO:0034393; P:positive regulation of smooth muscle cell a...; IDA:UniProtKB.
DR   GO; GO:0001916; P:positive regulation of T cell mediated cyto...; IDA:UniProtKB.
DR   GO; GO:0042520; P:positive regulation of tyrosine phosphoryla...; IDA:UniProtKB.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB.
DR   GO; GO:0010224; P:response to UV-B; IDA:UniProtKB.
DR   InterPro; IPR012351; 4_helix_cytokine_core.
DR   InterPro; IPR004281; IL12.
DR   Gene3D; G3DSA:1.20.1250.10; 4_helix_cytokine_core; 1.
DR   PANTHER; PTHR10523; IL12; 1.
DR   Pfam; PF03039; IL12; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytokine; Direct protein sequencing; Glycoprotein;
KW   Growth factor; Secreted; Signal.
FT   SIGNAL        1     22
FT   CHAIN        23    219       Interleukin-12 subunit alpha.
FT                                /FTId=PRO_0000015604.
FT   CARBOHYD     93     93       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    107    107       N-linked (GlcNAc...) (Potential).
FT   DISULFID     64    196
FT   DISULFID     85    123
FT   DISULFID     96     96       Interchain (with C-199 in IL12B).
FT   CONFLICT    213    213       M -> T (in Ref. 2; AAA35694).
FT   HELIX        43     58
FT   HELIX        59     61
FT   HELIX        81     84
FT   HELIX        88     92
FT   HELIX       118    145
FT   HELIX       155    169
FT   HELIX       190    217
SQ   SEQUENCE   219 AA;  24874 MW;  7C658AB7716112B2 CRC64;
     MCPARSLLLV ATLVLLDHLS LARNLPVATP DPGMFPCLHH SQNLLRAVSN MLQKARQTLE
     FYPCTSEEID HEDITKDKTS TVEACLPLEL TKNESCLNSR ETSFITNGSC LASRKTSFMM
     ALCLSSIYED LKMYQVEFKT MNAKLLMDPK RQIFLDQNML AVIDELMQAL NFNSETVPQK
     SSLEEPDFYK TKIKLCILLH AFRIRAVTID RVMSYLNAS
//