Summary: Cytokine interleukin-12p40 C-terminus
Cytokine interleukin-12p40 C-terminus Provide feedback
IL12p40_C is the largely beta stranded C-terminal, D3, domain of interleukin-12p40 or interleukin-12B. This interleukin is produced on stimulation by macrophage-engulfed micro-organisms and other stimuli, when it dimerises with interleukin-12p35 to form a heterodimer which then binds to receptors on natural killer cells to activate them to destroy the micro-organisms . This domain contains two disulfide bridges, one of which serves to bind p40 to p35 and the other to hold the beta strands within the domain together. The cupped shape of the p35 binding interface matches the elbow-like bend between D2 and D3 in p40 . The domain is often associated with family fn3, PF00041.
Yoon C, Johnston SC, Tang J, Stahl M, Tobin JF, Somers WS; , EMBO J. 2000;19:3530-3541.: Charged residues dominate a unique interlocking topography in the heterodimeric cytokine interleukin-12. PUBMED:10899108 EPMC:10899108
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR019482
This entry represents the central domain (domain 2) of the beta subunit (also known as subunit p40) interleukin-12 (IL-12). This domain is largely beta-stranded with a fibronectin III-like structure. IL-12 is produced on stimulation by macrophage-engulfed micro-organisms and other stimuli, when it dimerises with IL-12 subunit alpha (subunit p35) to form a heterodimer which then binds to receptors on natural killer cells to activate them to destroy the micro-organisms [PUBMED:10899108]. This domain contains two disulphide bridges, one of which serves to bind the beta subunit to the alpha subunit, and the other to hold the beta strands within the domain together. The cupped shape of the alpha subunit binding interface matches the elbow-like bend between domains 2 and 3 in the beta subunit [PUBMED:15661020]. Domain 3 also has a fibronectin iii-like structure.
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We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Gene3D, pdb_1f42|
|Author:||Finn RD, Coggill PC|
|Number in seed:||21|
|Number in full:||132|
|Average length of the domain:||87.30 aa|
|Average identity of full alignment:||42 %|
|Average coverage of the sequence by the domain:||29.28 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||4|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IL12p40_C domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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