UniProt functional annotation for O08679



	UniProt functional annotation for O08679

UniProt code: O08679.

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 cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule- dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000250|UniProtKB:Q7KZI7, ECO:0000269|PubMed:14517247, ECO:0000269|PubMed:14741102, ECO:0000269|PubMed:15466480, ECO:0000269|PubMed:16717194, ECO:0000269|PubMed:18509032}.

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; Evidence={ECO:0000250|UniProtKB:Q7KZI7};

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; Evidence={ECO:0000250|UniProtKB:Q7KZI7};

Catalytic activity: Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl- [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA- COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;

Catalytic activity: Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L- threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703, Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.26;

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q7KZI7};

Activity regulation: Inhibited by hymenialdisine (By similarity). Activated by phosphorylation on Thr-208 by STK11/LKB1 and TAOK1. Inhibited by phosphorylation at Ser-212 or Thr-539. Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5. {ECO:0000250, ECO:0000269|PubMed:14517247}.

Subunit: Homodimer (PubMed:16472737). Interacts (when phosphorylated at Thr-539) with YWHAZ (By similarity). Interacts with MTCL1; the interaction is direct and increases MARK2 microtubule-binding ability (By similarity). Interacts with PAK5; leading to inhibit the protein kinase activity (PubMed:16014608). Interacts with MAPT/TAU (By similarity). Interacts with YWHAB, YWHAG and YWHAQ (By similarity). {ECO:0000250|UniProtKB:Q7KZI7, ECO:0000269|PubMed:16014608, ECO:0000269|PubMed:16472737}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:14741102}; Peripheral membrane protein {ECO:0000269|PubMed:14741102}. Lateral cell membrane {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm {ECO:0000250|UniProtKB:Q7KZI7}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q7KZI7}. Note=Phosphorylation at Thr-539 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm. {ECO:0000250}.

Domain: The KA1 domain mediates binding to phospholipids and targeting to membranes. {ECO:0000250}.

Domain: The UBA domain does not seem to bind ubiquitin and ubiquitin- like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain (By similarity). {ECO:0000250}.

Ptm: Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-539 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm. {ECO:0000269|PubMed:14517247, ECO:0000269|PubMed:16257959, ECO:0000269|PubMed:16717194, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18424437}.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 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 cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule- dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000250\|UniProtKB:Q7KZI7, ECO:0000269\|PubMed:14517247, ECO:0000269\|PubMed:14741102, ECO:0000269\|PubMed:15466480, ECO:0000269\|PubMed:16717194, ECO:0000269\|PubMed:18509032}.


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; Evidence={ECO:0000250\|UniProtKB:Q7KZI7};
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; Evidence={ECO:0000250\|UniProtKB:Q7KZI7};
Catalytic activity:		Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl- [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA- COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
Catalytic activity:		Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L- threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703, Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.26;
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250\|UniProtKB:Q7KZI7};
Activity regulation:		Inhibited by hymenialdisine (By similarity). Activated by phosphorylation on Thr-208 by STK11/LKB1 and TAOK1. Inhibited by phosphorylation at Ser-212 or Thr-539. Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5. {ECO:0000250, ECO:0000269\|PubMed:14517247}.
Subunit:		Homodimer (PubMed:16472737). Interacts (when phosphorylated at Thr-539) with YWHAZ (By similarity). Interacts with MTCL1; the interaction is direct and increases MARK2 microtubule-binding ability (By similarity). Interacts with PAK5; leading to inhibit the protein kinase activity (PubMed:16014608). Interacts with MAPT/TAU (By similarity). Interacts with YWHAB, YWHAG and YWHAQ (By similarity). {ECO:0000250\|UniProtKB:Q7KZI7, ECO:0000269\|PubMed:16014608, ECO:0000269\|PubMed:16472737}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:14741102}; Peripheral membrane protein {ECO:0000269\|PubMed:14741102}. Lateral cell membrane {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cytoplasm {ECO:0000250\|UniProtKB:Q7KZI7}. Cell projection, dendrite {ECO:0000250\|UniProtKB:Q7KZI7}. Note=Phosphorylation at Thr-539 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm. {ECO:0000250}.
Domain:		The KA1 domain mediates binding to phospholipids and targeting to membranes. {ECO:0000250}.
Domain:		The UBA domain does not seem to bind ubiquitin and ubiquitin- like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain (By similarity). {ECO:0000250}.
Ptm:		Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-539 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm. {ECO:0000269\|PubMed:14517247, ECO:0000269\|PubMed:16257959, ECO:0000269\|PubMed:16717194, ECO:0000269\|PubMed:17442826, ECO:0000269\|PubMed:18424437}.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. {ECO:0000305}.