MAP3K12
Description
The MAP3K12 (mitogen-activated protein kinase kinase kinase 12) is a protein-coding gene located on chromosome 12.
MAP3K12 is an enzyme involved in cell signaling. It's a member of the serine/threonine protein kinase family and contains a leucine-zipper domain. Primarily expressed in neuronal cells, its phosphorylation state is regulated by membrane depolarization via calcineurin. It forms heterodimers with transcription factors like CREB and MYC, suggesting a role in neuronal differentiation. MAP3K12 interacts with proteins like MAPK8IP1, MAP2K7, and MAPK8IP2. It's essential for neuronal development, affecting neuronal migration and axon growth. Deficiencies in MAP3K12 lead to abnormalities in neuronal migration and axon formation, impacting brain regions like the cingulum and internal capsule. Additionally, inhibiting MAP3K12 or JNK disrupts neocortex formation.
MAP3K12 is part of a non-canonical MAPK signaling pathway. It can be activated by APOE and enhances AP-1-mediated transcription of APP through a MAP kinase signal transduction pathway involving MAP2K7, MAPK1/ERK2, and MAPK3/ERK1. It may also activate the JNK/SAPK pathway.
MAP3K12 is also known as DLK, HP09298, MEKK12, MUK, ZPK, ZPKP1.
Associated Diseases
- schizencephaly
- mirror movements 1
- autosomal recessive primary microcephaly
- lissencephaly due to TUBA1A mutation
- sub-cortical nodular heterotopia
- microlissencephaly
- Chudley-McCullough syndrome
- complex cortical dysplasia with other brain malformations 7
- lissencephaly type 1 due to doublecortin gene mutation
