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mitogen-activated protein kinase kinase kinase MLT; human cervical cancer suppressor gene 4 protein; HCCS-4; leucine zipper- & sterile alpha motif-containing kinase; MLK-like mitogen-activated protein triple kinase; mixed lineage kinase-related kinase; MLK-related kinase; MRK; sterile alpha motif- & leucine zipper-containing kinase AZK (MLTK, ZAK, HCCS4)
Function:
- stress-activated serine/threonine protein kinase
- regulates the JNK & p38 pathways
- promotes apoptotis
- regulation of S & G2 cell cycle checkpoint via phosphorylation of CHEK2
- isoform 1, but not isoform 2, causes cell shrinkage & disruption of actin stress fibers
- isoform 1, but not isoform 2, phosphorylates histone H3 at Ser-28
- activated by phosphorylation by PKN1
- phosphorylated on Ser-339, Ser-429, Ser-434 & Ser-454
- autophosphorylation on Thr-161 & Ser-165
- interacts with PKN1 & ZNF33A
Cofactor: Mg+2
Structure:
- homodimer
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
- contains 1 protein kinase domain
- contains 1 SAM (sterile alpha motif) domain
Compartment:
- cytoplasm, nucleus
- translocates to the nucleus upon ultraviolet B irradiation
Alternative splicing: named isoforms=3
Expression:
- ubiquitously expressed
- isoform 2 is the predominant form in most tissues
- isoform 1 is predominant in liver
Pathology:
- isoform 1 may have role in neoplastic transformation
General
oligomerizing protein
serine/threonine kinase
Properties
SIZE: entity length = 800 aa
MW = 91 kD
COMPARTMENT: cytoplasm
cell nucleus
STATE: active state
MOTIF: Ser phosphorylation site {S2}
Ser phosphorylation site {S3}
kinase domain
SITE: 16-277
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 22-30
ATP-binding site
NAME: ATP-binding site
SITE: 45-45
aspartate residue {D133}
Ser phosphorylation site {S155}
Thr phosphorylation site {T161}
Ser phosphorylation site {S165}
Ser phosphorylation site {S264}
Ser phosphorylation site {S268}
Ser phosphorylation site {S275}
leucine zipper
SITE: 287-308
FOR-BINDING-VIA: leucine zipper
MOTIF: Ser phosphorylation site {S302}
Ser phosphorylation site {S326}
Thr phosphorylation site {T328}
sterile alpha motif
NAME: sterile alpha motif
SITE: 339-410
Ser phosphorylation site {S557}
Ser phosphorylation site {S565}
Ser phosphorylation site {S568}
Ser phosphorylation site {S584}
Thr phosphorylation site {T586}
Ser phosphorylation site {S591}
Ser phosphorylation site {S593}
Ser phosphorylation site {S599}
Thr phosphorylation site {T628}
Ser phosphorylation site {S633}
Ser phosphorylation site {S635}
Ser phosphorylation site {S636}
Ser phosphorylation site {S637}
Thr phosphorylation site {T639}
Ser phosphorylation site {S648}
Ser phosphorylation site {S660}
Thr phosphorylation site {T666}
Ser phosphorylation site {S667}
Ser phosphorylation site {S668}
Ser phosphorylation site {S687}
Ser phosphorylation site {S690}
Ser phosphorylation site {S691}
Ser phosphorylation site {S718}
Ser phosphorylation site {S727}
Ser phosphorylation site {S733}
Ser phosphorylation site {S754}
Ser phosphorylation site {S781}
Database Correlations
OMIM 609479
UniProt Q9NYL2
PFAM correlations
Entrez Gene 51776
Kegg hsa:51776
ENZYME 2.7.11.25
References
UniProt :accession Q9NYL2