mitogen activated protein kinase kinse kinase kinase 4 (MAP4K4, MAPK/ERK kinase kinase kinase 4, MEK kinase kinase 4, MEKKK 4, HPK1/GCK-like kinase, HGK, Nck interacting kinase)

Function: - serine/threonine kinase - may play a role in the response to environmental stress & cytokines such as TNF-alpha - appears to act upstream of the JUN N-terminal pathway - interacts with the SH3 domain of the adapter proteins Nck (putative) - binds, via its CNH regulatory domain, to the N-terminal region of SPG3A - phosphorylated upon DNA damage, probably by ATM or ATR ATP + a protein ADP + a phosphoprotein Cofactor: Mg⁺² Structure: - belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily - contains 1 CNH domain contains 1 protein kinase domain Alternative splicing: named isoforms=5 Expression: - ubiquitous, expressed in all tissue types examined - isoform 5 appears to be more abundant in brain - isoform 4 is predominant in the liver, skeletal muscle & placenta

Properties

SIZE: entity length = 1239 aa MW = 142 kD STATE: active state MOTIF: kinase domain SITE: 25-289 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 31-39 ATP-binding site NAME: ATP-binding site SITE: 54-54 aspartate residue {D153} Thr phosphorylation site {T181} Ser phosphorylation site {S602} Ser phosphorylation site {S629} Ser phosphorylation site {S631} Ser phosphorylation site {S639} Ser phosphorylation site {S692} Ser phosphorylation site {S696} Ser phosphorylation site {S801} Ser phosphorylation site {S805} CNH {844-1143} MOTIF: Ser phosphorylation site {S900}

References

UniProt :accession O95819

Databases & Figures

OMIM 604666 UniProt O95819 PFAM correlations Entrez Gene 9448 ENZYME 2.7.11.1 MAP kinase pathways