MLK1-3, SH3 domain (IPR035779)

Short name: MLK1-3_SH3

Overlapping homologous superfamilies

Domain relationships

  • SH3 domain (IPR001452)
    • MLK1-3, SH3 domain (IPR035779)


MLKs 1, 2, and 3 are Serine/Threonine Kinases (STKs), catalyzing the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals [PMID: 20067472, PMID: 27259981].

MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation [PMID: 17408454, PMID: 11416147]. Little is known about the specific function of MLK1, also called MAP3K9. It is capable of activating the c-Jun N-terminal kinase pathway [PMID: 15610029]. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans [PMID: 18414056]. MLK2, also called MAP3K10, is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease [PMID: 19332348]. MLK3, also called MAP3K11, is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells [PMID: 20514022]. It also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and thus impacts inflammation and immunity [PMID: 19782705]. MLKs contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac.

This entry represents the SH3 domains of MLKs.

Contributing signatures

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