MAP3K20

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.

Full Name

Mitogen-Activated Protein Kinase Kinase Kinase 20

Function

Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phosphorylation of CHEK2 (PubMed:10924358, PubMed:11836244, PubMed:15342622, PubMed:21224381).
Involved in limb development (PubMed:26755636).
Isoform 1
Phosphorylates histone H3 at 'Ser-28' (PubMed:15684425).
May have role in neoplastic cell transformation and cancer development (PubMed:15172994).
Causes cell shrinkage and disruption of actin stress fibers (PubMed:11042189).

Biological Process

Cell cycleIEA:UniProtKB-KW
Cell death1 PublicationNAS:UniProtKB
Cell differentiation1 PublicationNAS:UniProtKB
Cellular response to gamma radiationManual Assertion Based On ExperimentIDA:UniProtKB
Cytoskeleton organizationIEA:Ensembl
DNA damage checkpoint signalingManual Assertion Based On ExperimentIMP:UniProtKB
Embryonic digit morphogenesisManual Assertion Based On ExperimentIMP:UniProtKB
JNK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Limb developmentManual Assertion Based On ExperimentIMP:UniProtKB
p38MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of mitotic DNA damage checkpointManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Stress-activated MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cytoplasm
Nucleus
Translocates to the nucleus upon ultraviolet B irradiation.

Involvement in disease

Split-foot malformation with mesoaxial polydactyly (SFMMP):
An autosomal recessive disorder characterized by a split-foot defect, mesoaxial polydactyly, nail abnormalities of the hands, and sensorineural hearing loss.
Myopathy, centronuclear, 6, with fiber-type disproportion (CNM6):
A form of centronuclear myopathy, a congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers. CNM6 is an autosomal recessive, slowly progressive form with onset in infancy or early childhood.