Reviewed, UniProtKB/Swiss-Prot P29459 (IL12A_HUMAN)

Names and origin

Protein names

Recommended name:
    Interleukin-12 subunit alpha
      Short name=IL-12A
Alternative name(s):
    IL-12 subunit p35
    Cytotoxic lymphocyte maturation factor 35 kDa subunit
      Short name=CLMF p35
    NK cell stimulatory factor chain 1
      Short name=NKSF1

Gene names

Name:	IL12A
Synonyms:	NKSF1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	219 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	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.7
Subcellular location	Secreted.
Sequence similarities	Belongs to the IL-6 superfamily.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell cycle arrest Inferred from direct assay. Source: UniProtKB cell migration Inferred from direct assay. Source: UniProtKB defense response to Gram-positive bacterium Inferred from expression pattern. Source: UniProtKB immune response Traceable author statement. Source: UniProtKB negative regulation of smooth muscle cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of T cell mediated cytotoxicity Ref.2 Ref.5 Inferred from direct assay. Source: UniProtKB positive regulation of cell adhesion Inferred from direct assay. Source: UniProtKB positive regulation of interferon-gamma production Ref.2 Inferred from direct assay. Source: UniProtKB positive regulation of natural killer cell activation Ref.2 Inferred from direct assay. Source: UniProtKB positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target Inferred from direct assay. Source: UniProtKB positive regulation of smooth muscle cell apoptosis Inferred from direct assay. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat4 protein Inferred from direct assay. Source: UniProtKB response to UV-B Inferred from direct assay. Source: UniProtKB response to lipopolysaccharide Inferred from direct assay. Source: UniProtKB
Cellular component	interleukin-12 complex Ref.2 Ref.5 Inferred from direct assay. Source: UniProtKB
Molecular function	cytokine activity Ref.1 Ref.2 Inferred from electronic annotation. Source: UniProtKB-KW interleukin-12 receptor binding Ref.2 Non-traceable author statement. Source: UniProtKB interleukin-27 binding Inferred from physical interaction. Source: UniProtKB protein heterodimerization activity Ref.2 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL12B	P29460	1	EBI-1029636,EBI-1029614

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.5

Chain

23 – 219

197

Interleukin-12 subunit alpha

PRO_0000015604

Amino acid modifications

Glycosylation

93

1

N-linked (GlcNAc...) Potential

Glycosylation

107

1

N-linked (GlcNAc...) Potential

Disulfide bond

64 ↔ 196

Ref.7

Disulfide bond

85 ↔ 123

Ref.7

Disulfide bond

96

Interchain (with C-199 in IL12B) Ref.7

Experimental info

Sequence conflict

213

1

M → T in AAA35694. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

219

Helix Strand Turn

Details...

Helix

43 – 58

16

Helix

59 – 61

3

Helix

81 – 84

4

Helix

88 – 92

5

Helix

118 – 145

28

Helix

155 – 169

15

Helix

190 – 217

28

Sequences

	Sequence		Length	Mass (Da)
	P29459-1 [UniParc]. Last modified January 23, 2002. Version 2. Checksum: 7C658AB7716112B2	FASTA	219	24,874
	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

References

	« Hide 'large scale' referencesShow '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: 1673147] [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: 1674604] [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: 16641997] [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: 2204066] [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: 1374259] [Abstract] Cited for: SIMILARITY TO IL-6.
[7]	"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: 10899108] [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

EMBLGenBankDDBJ

M65291 mRNA. Translation: AAA59937.1. Different initiation.
M65271 mRNA. Translation: AAA35694.1.
AF404773 Genomic DNA. Translation: AAK84425.1.
AC010370 Genomic DNA. No translation available.

IPI

IPI00182737.

RefSeq

NP_000873.2.

UniGene

Hs.673

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F45	X-ray	2.80	B	23-219	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:3772N.

IntAct

P29459. 1 interaction.

Proteomic databases

PRIDE

P29459.

Genome annotation databases

Ensembl

ENSG00000168811. Homo sapiens. [Contig view]

GeneID

3592.

KEGG

hsa:3592.

Organism-specific databases

GeneCards

GC03P161189.

H-InvDB

HIX0030715.

HGNC

HGNC:5969. IL12A.

HPA

HPA001886.

MIM

161560. gene.

PharmGKB

PA29784.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P29459.

Enzyme and pathway databases

Pathway_Interaction_DB

il12_2pathway. IL12-mediated signaling events.
il27pathway. IL27-mediated signaling events.

Gene expression databases

ArrayExpress

P29459.

Bgee

P29459.

CleanEx

HS_IL12A.

Family and domain databases

InterPro

IPR012351. 4_helix_cytokine_core.
IPR004281. IL12.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

PANTHER

PTHR10523. IL12. 1 hit.

Pfam

PF03039. IL12. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

14035.

SOURCE

Search...

Entry information

Entry name

IL12A_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)