Mitogen-activated protein kinase kinase kinase 12/13 (IPR017419)

Short name: MAP3K12_MAP3K13

Overlapping homologous superfamilies


Family relationships


This entry represents mitogen-activated protein kinase kinase kinase, types 12/13 (MAP3K12 and MAP3K13), which form part of the mixed lineage kinase (MLK) family.

MAP3K12 (also known as leucine-zipper protein kinase (ZPK), dual leucine zipper-bearing kinase (DLK) or MAPK-upstream kinase (MUK)) is a MAPKKK class protein kinase that induces JNK/SAPK activation. MAP3K12 is known to interact with MUK-binding inhibitory protein (MBIP). MBIP contains two tandem leucine-zipper-like motifs; MBIP interacts with one of the two leucine-zipper-like motifs of MAP3K12 and inhibits the activity of MAP3K12 to induce JNK/SAPK activation [PMID: 10801814, PMID: 14697235]. MAP3K12 is autophosphorylated on Ser/Thr in cytosol under basal conditions, and dephosphorylated when membrane-associated.

MAP3K13 (also known as leucine zipper-bearing kinase LZK) activates the c-Jun-NH2 terminal kinase (JNK) pathway through activation of the MAP kinase kinase MAP2K7 [PMID: 12492477]. MAP3K13 acts synergistically with peroxiredoxin-3 (PRDX3) to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B [PMID: 12492477].

GO terms

Biological Process

GO:0000186 activation of MAPKK activity
GO:0046777 protein autophosphorylation

Molecular Function

GO:0005524 ATP binding
GO:0004709 MAP kinase kinase kinase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.