UniProt functional annotation for Q9JLS3



	UniProt functional annotation for Q9JLS3

UniProt code: Q9JLS3.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress- activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. May affect microtubule organization and stability. May play a role in the osmotic stress-MAPK8 pathway. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14/p38 MAPK activation. {ECO:0000269|PubMed:10497253, ECO:0000269|PubMed:17988630}.

Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;

Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;

Activity regulation: Moderately inhibited by staurosporine, a broad- range protein kinase inhibitor. {ECO:0000269|PubMed:16761096}.

Subunit: Self-associates. Interacts with MAP2K3 and MAP2K6. Interacts with tubulins. Interacts with MAP3K7 and interfers with MAP3K7-binding to CHUK and thus prevents NF-kappa-B activation (By similarity). Isoform 2 interacts with PCDH8; this complex may also include CDH2. {ECO:0000250, ECO:0000269|PubMed:10497253, ECO:0000269|PubMed:16761096, ECO:0000269|PubMed:17988630}.

Subcellular location: Cytoplasmic vesicle membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Found to be perinuclear and localized to vesicular compartment. {ECO:0000250}.

Subcellular location: [Isoform 2]: Cell projection, dendrite. Note=In dendrites, colocalizes with PCDH8.

Ptm: Autophosphorylated. Phosphorylated by ATM (By similarity). {ECO:0000250}.

Ptm: [Isoform 2]: Phosphorylated on Ser-1038 by MAPK14. This phosphorylation is required PCDH8 for endocytosis. {ECO:0000269|PubMed:15458637}.

Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress- activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. May affect microtubule organization and stability. May play a role in the osmotic stress-MAPK8 pathway. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14/p38 MAPK activation. {ECO:0000269\|PubMed:10497253, ECO:0000269\|PubMed:17988630}.


Catalytic activity:		Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
Catalytic activity:		Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Activity regulation:		Moderately inhibited by staurosporine, a broad- range protein kinase inhibitor. {ECO:0000269\|PubMed:16761096}.
Subunit:		Self-associates. Interacts with MAP2K3 and MAP2K6. Interacts with tubulins. Interacts with MAP3K7 and interfers with MAP3K7-binding to CHUK and thus prevents NF-kappa-B activation (By similarity). Isoform 2 interacts with PCDH8; this complex may also include CDH2. {ECO:0000250, ECO:0000269\|PubMed:10497253, ECO:0000269\|PubMed:16761096, ECO:0000269\|PubMed:17988630}.
Subcellular location:		Cytoplasmic vesicle membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Found to be perinuclear and localized to vesicular compartment. {ECO:0000250}.
Subcellular location:		[Isoform 2]: Cell projection, dendrite. Note=In dendrites, colocalizes with PCDH8.
Ptm:		Autophosphorylated. Phosphorylated by ATM (By similarity). {ECO:0000250}.
Ptm:		[Isoform 2]: Phosphorylated on Ser-1038 by MAPK14. This phosphorylation is required PCDH8 for endocytosis. {ECO:0000269\|PubMed:15458637}.
Similarity:		Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. {ECO:0000305}.