UniProt functional annotation for Q28021



	UniProt functional annotation for Q28021

UniProt code: Q28021.

Organism: Bos taurus (Bovine).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.

Function: Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1- p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10209029, ECO:0000269|PubMed:10818093, ECO:0000269|PubMed:10873572, ECO:0000269|PubMed:8641286, ECO:0000269|PubMed:8702756, ECO:0000269|PubMed:9456324, ECO:0000269|PubMed:9565595}.

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; Evidence={ECO:0000250};

Activity regulation: Activated by RHOA binding. Inhibited by Y-27632.

Subunit: Homodimer (PubMed:12954645). Interacts with IRS1 (By similarity). Interacts with RAF1 (By similarity). Interacts with RHOA (activated by GTP) (PubMed:12954645). Interacts with RHOB and RHOC (By similarity). Interacts with PPP1R12A (By similarity). Interacts with EP300 (By similarity). Interacts with CHORDC1 (By similarity). Interacts with BRCA2 (By similarity). Interacts with NPM1; this interaction enhances ROCK2 activity (By similarity). Interacts with SORL1 (By similarity). Interacts with PJVK (By similarity). {ECO:0000250|UniProtKB:O75116, ECO:0000250|UniProtKB:P70336, ECO:0000250|UniProtKB:Q62868, ECO:0000269|PubMed:12954645}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:8641286}. Cell membrane {ECO:0000269|PubMed:8641286}; Peripheral membrane protein {ECO:0000269|PubMed:8641286}. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Note=Cytoplasmic, and associated with actin microfilaments and the plasma membrane.

Tissue specificity: Highly expressed in whole brain and in cerebellum, and at lower levels in heart and lung. Detected at low levels in skeletal muscle, spleen, liver, kidney and pancreas. {ECO:0000269|PubMed:8641286}.

Domain: An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization. {ECO:0000250}.

Ptm: Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity (By similarity). {ECO:0000250}.

Ptm: Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing (By similarity). {ECO:0000250}.

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

Annotations taken from UniProtKB at the EBI.


Organism:		Bos taurus (Bovine).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.



Function:		Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1- p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269\|PubMed:10209029, ECO:0000269\|PubMed:10818093, ECO:0000269\|PubMed:10873572, ECO:0000269\|PubMed:8641286, ECO:0000269\|PubMed:8702756, ECO:0000269\|PubMed:9456324, ECO:0000269\|PubMed:9565595}.


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; Evidence={ECO:0000250};
Activity regulation:		Activated by RHOA binding. Inhibited by Y-27632.
Subunit:		Homodimer (PubMed:12954645). Interacts with IRS1 (By similarity). Interacts with RAF1 (By similarity). Interacts with RHOA (activated by GTP) (PubMed:12954645). Interacts with RHOB and RHOC (By similarity). Interacts with PPP1R12A (By similarity). Interacts with EP300 (By similarity). Interacts with CHORDC1 (By similarity). Interacts with BRCA2 (By similarity). Interacts with NPM1; this interaction enhances ROCK2 activity (By similarity). Interacts with SORL1 (By similarity). Interacts with PJVK (By similarity). {ECO:0000250\|UniProtKB:O75116, ECO:0000250\|UniProtKB:P70336, ECO:0000250\|UniProtKB:Q62868, ECO:0000269\|PubMed:12954645}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:8641286}. Cell membrane {ECO:0000269\|PubMed:8641286}; Peripheral membrane protein {ECO:0000269\|PubMed:8641286}. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Note=Cytoplasmic, and associated with actin microfilaments and the plasma membrane.
Tissue specificity:		Highly expressed in whole brain and in cerebellum, and at lower levels in heart and lung. Detected at low levels in skeletal muscle, spleen, liver, kidney and pancreas. {ECO:0000269\|PubMed:8641286}.
Domain:		An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization. {ECO:0000250}.
Ptm:		Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity (By similarity). {ECO:0000250}.
Ptm:		Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing (By similarity). {ECO:0000250}.
Similarity:		Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. {ECO:0000305}.