MLTK, ZAK, HCCS4, Mitogen-activated protein kinase kinase kinase MLT, Human cervical cancer suppressor gene 4 protein, HCCS-4, Leucine zipper- and sterile alpha motif-containing kinase, MLK-like mitogen-activated protein triple kinase, Mixe
This gene is a member of the MAPKKK family of signal transduction molecules and encodes a protein with an N-terminal kinase catalytic domain, followed by a leucine zipper motif and a sterile-alpha motif (SAM). This magnesium-binding protein forms homodimers and is located in the cytoplasm. The protein mediates gamma radiation signaling leading to cell cycle arrest and activity of this protein plays a role in cell cycle checkpoint regulation in cells. The protein also has pro-apoptotic activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008],catalytic activity:ATP + a protein = ADP + a phosphoprotein.,cofactor:Magnesium.,enzyme regulation:Activated by phosphorylation by PKN1 and autophosphorylation on Thr-161 and Ser-165.,function:Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2. Isoform 1, but not isoform 2, causes cell shrinkage and disruption of actin stress fibers. Isoform 1 may have role in neoplastic cell transformation and cancer development. Isoform 1, but not isoform 2, phosphorylates histone H3 at Ser-28.,similarity:Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.,similarity:Contains 1 protein kinase domain.,similarity:Contains 1 SAM (sterile alpha motif) domain.,subcellular location:Translocates to the nucleus upon ultraviolet B irradiation.,subunit:Homodimer. Interacts with PKN1 and ZNF33A.,tissue specificity:Ubiquitously expressed. Isoform 2 is the predominant form in all tissues examined, except for liver, in which isoform 1 is more highly expressed.,
