P29459 (IL12A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	IL12A
Synonyms:	NKSF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.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 component	Secreted
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell 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: Compara 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 mediated cytotoxicity Inferred from direct assay Ref.2Ref.5. Source: UniProtKB positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara 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 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_component	cytoplasm Inferred from electronic annotation. Source: Compara interleukin-12 complex Inferred from direct assay Ref.5. Source: UniProtKB
Molecular_function	interleukin-12 receptor binding Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IL12B	P29460	2	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.8

Disulfide bond

85 ↔ 123

Ref.8

Disulfide bond

96

Interchain (with C-199 in IL12B) Ref.8

Experimental info

Sequence conflict

213

1

M → T in AAA35694. Ref.2

Secondary structure

1

.

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219

Helix Strand Turn

Details...

Helix

43 – 58

16

Helix

59 – 61

3

Turn

74 – 78

5

Helix

81 – 84

4

Helix

88 – 92

5

Beta strand

107 – 109

3

Turn

114 – 116

3

Helix

118 – 145

28

Helix

155 – 169

15

Helix

190 – 217

28

Sequences

	Sequence		Length	Mass (Da)
	P29459 [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] [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, 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.

IPI

IPI00182737.

RefSeq

NP_000873.2. NM_000882.3.

UniGene

Hs.673.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F45	X-ray	2.80	B	23-219	[»]
3HMX	X-ray	3.00	B	23-219	[»]

ProteinModelPortal

P29459.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3772N.

IntAct

P29459. 2 interactions.

STRING

9606.ENSP00000303231.

Polymorphism databases

DMDM

20141534.

Proteomic databases

PaxDb

P29459.

PRIDE

P29459.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000305579; ENSP00000303231; ENSG00000168811.

GeneID

3592.

KEGG

hsa:3592.

Organism-specific databases

CTD

3592.

GeneCards

GC03P159706.

HGNC

HGNC:5969. IL12A.

HPA

HPA001886.

MIM

161560. gene.

neXtProt

NX_P29459.

Orphanet

186. Primary biliary cirrhosis.

PharmGKB

PA29784.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47298.

HOVERGEN

HBG063691.

InParanoid

P29459.

KO

K05406.

OrthoDB

EOG46HGBM.

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.

Genevestigator

P29459.

Family and domain databases

Gene3D

1.20.1250.10. 1 hit.

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR004281. IL12.
[Graphical view]

PANTHER

PTHR10523. PTHR10523. 1 hit.

Pfam

PF03039. IL12. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P29459.

GenomeRNAi

3592.

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:	May 1, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.