KMT2A (myeloid/lymphoid or mixed lineage leukemia)

11q23.3

A major transcript of 14982 bp produces a 3969 amino acids protein from 36 of the 37 exons. Contains from N-term to C-term a binding site for MEN1, 3 AT hooks (binds to the minor grove of DNA); 2 speckled nuclear localisation signals; 2 repression domains RD1 and RD2: RD1 or CXXC: cystein methyl transferase, binds CpG rich DNA, has a transcriptional repression activity; RD2 recruits histone desacetylases HDAC1 and HDAC2; 3 plant homeodomains (cystein rich zinc finger domains, with homodimerization properties), 1 bromodomain (may bind acetylated histones), and 1 plant homeodomain; these domains may be involved in protein-protein interaction; a FYRN and a FRYC domain; a transactivation domain which binds CBP; may acetylates H3 and H4 in the HOX area; a SET domain: methyltransferase; methylates H3, including histones in the HOX area for allowing chromatin to be open to transcription. MLL is cleaved by taspase 1 into 2 proteins before entering the nucleus: a p300/320 N-term protein called MLL-N, and a p180 C-term protein, called MLL-C. The FYRN and a FRYC domains of native MLL associate MLL-N and MLL-C in a stable complex; they form a multiprotein complex with transcription factor TFIID. General transcription factor; maintains HOX genes expression in undifferentiated cells. Major regulator of hematopoiesis and embryonic development; role in cell cycle regulation.

ARHGEF12 (Rho guanine nucleotide exchange factor (GEF) 12)

11q23.3

Better known as LARG, ARHGEF12 contains a PDZ (postsynaptic density protein, Drosophila disc large tumor suppressor, and zonula occludens-1 protein) domain, which localize ARHGEF12 to the membrane, a regulator of G protein signalling-like domain (RGSL or RH), which binds to activated heterotrimeric G protein alpha12/13 subunits, a Dbl homology (DH) domain, responsible for exchange activity, and a pleckstrin homology (PH) domain, involved in the regulation of the process. Regulatory protein involved in the GDP/GTP exchange reaction of the Rho proteins; activates a Rho-GTPase-dependent signaling pathway; activated by FYN.