MAP3K1

[13][14] MAP3K1 contains a protein kinase domain, PHD finger (which has a RING finger domain-like structure) that serves as an E3 ubiquitin ligase, and scaffold protein regions that mediate protein–protein interactions.

[20] MAP3K1 was analysed genetically by targeted mutagenesis using transgenic mice (C57BL/6 and C57BL/6 × 129 backgrounds), embryonic stem cells, and the DT40 cell line to identify genetic traits.

[34] Later analysis of syngenic mice that harbour mutations in TRAF2, UBE2N, Map3k1 and Map3k7 identified critical regulators of cytokine-induced MAPK signal transduction in B cells.

[39][40] Genetic analysis has demonstrated that the E3 Ub ligase  and the kinase domains of MAP3K1 are required for MAPK activation.

[43] MAP3K1 has been associated with several diseases in non-syngeneic human populations,[44] including: breast cancer,[45] adenocarcinoma of the prostate,[46] sarcomatoid hepatocellular carcinoma,[47] acute respiratory distress syndrome,[48] Langerhans cell histiocytosis,[49] and 46,XY disorders of sex development.

MAP3K1 signal transduction . A . Cytokine receptor prior to ligation by cytokine. B . Recruitment of TRAFs 2, 3 and 6 to the cytokine receptor. C . Ubiquitination of TRAFs. Recruitment of MAP3K1 and MAP3K7 signaling modules to TRAFs and scaffolding. D . Degradation of canonical Ubiquitin-TRAF3 by the proteasome, release of non-canonical Ubiquitin-TRAF2 and -MAP3Ks into the cytoplasm, and activation of MAP2K signaling.