UniProt functional annotation for Q8VDP3



	UniProt functional annotation for Q8VDP3

UniProt code: Q8VDP3.

Organism: Mus musculus (Mouse).

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

Function: Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (By similarity). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels. May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000250|UniProtKB:Q8TDZ2, ECO:0000269|PubMed:21730291, ECO:0000269|PubMed:23911929, ECO:0000269|PubMed:25007825, ECO:0000269|PubMed:26935886}.

Catalytic activity: Reaction=H(+) + L-methionyl-[F-actin] + NADPH + O2 = H2O + L-methionyl- (R)-S-oxide-[F-actin] + NADP(+); Xref=Rhea:RHEA:51308, Rhea:RHEA- COMP:12953, Rhea:RHEA-COMP:12956, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16044, ChEBI:CHEBI:45764, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.225; Evidence={ECO:0000269|PubMed:23911929, ECO:0000269|PubMed:26935886};

Cofactor: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:16275925};

Biophysicochemical properties: Kinetic parameters: KM=9.3 uM for actin (for a monooxygenase domain construct) {ECO:0000269|PubMed:26935886}; KM=28.8 uM for NADPH (for a monooxygenase domain construct) {ECO:0000269|PubMed:26935886};

Subunit: Associates with the SH3 domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B is of low affinity compared to other Rab proteins; at least in case of RAB8A and RAB10 can bind 2 molecules of the Rab proteins simultaneously (By similarity). Interacts with STK38 and STK38L. {ECO:0000250, ECO:0000250|UniProtKB:Q8TDZ2, ECO:0000269|PubMed:16275925, ECO:0000269|PubMed:18094055, ECO:0000269|PubMed:21730291}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q8TDZ2}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q8TDZ2}.

Tissue specificity: Expressed in the postnatal and adult hippocampus; found in dentate gyrus, the polymorphic layer, cornu ammonis (CA) 1-3 and in mossy fibers of the striatum lucidum. In adult hippocampus strongly expressed in CA3 pyramidial neurons. {ECO:0000269|PubMed:25007825}.

Domain: The C-terminal coiled coil part contains the plexin-interacting region.

Domain: The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms). {ECO:0000250|UniProtKB:Q8TDZ2}.

Similarity: Belongs to the Mical family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (By similarity). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels. May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000250\|UniProtKB:Q8TDZ2, ECO:0000269\|PubMed:21730291, ECO:0000269\|PubMed:23911929, ECO:0000269\|PubMed:25007825, ECO:0000269\|PubMed:26935886}.


Catalytic activity:		Reaction=H(+) + L-methionyl-[F-actin] + NADPH + O2 = H2O + L-methionyl- (R)-S-oxide-[F-actin] + NADP(+); Xref=Rhea:RHEA:51308, Rhea:RHEA- COMP:12953, Rhea:RHEA-COMP:12956, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16044, ChEBI:CHEBI:45764, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.225; Evidence={ECO:0000269\|PubMed:23911929, ECO:0000269\|PubMed:26935886};
Cofactor:		Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269\|PubMed:16275925};
Biophysicochemical properties:		Kinetic parameters: KM=9.3 uM for actin (for a monooxygenase domain construct) {ECO:0000269\|PubMed:26935886}; KM=28.8 uM for NADPH (for a monooxygenase domain construct) {ECO:0000269\|PubMed:26935886};
Subunit:		Associates with the SH3 domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B is of low affinity compared to other Rab proteins; at least in case of RAB8A and RAB10 can bind 2 molecules of the Rab proteins simultaneously (By similarity). Interacts with STK38 and STK38L. {ECO:0000250, ECO:0000250\|UniProtKB:Q8TDZ2, ECO:0000269\|PubMed:16275925, ECO:0000269\|PubMed:18094055, ECO:0000269\|PubMed:21730291}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q8TDZ2}. Cytoplasm, cytoskeleton {ECO:0000250\|UniProtKB:Q8TDZ2}.
Tissue specificity:		Expressed in the postnatal and adult hippocampus; found in dentate gyrus, the polymorphic layer, cornu ammonis (CA) 1-3 and in mossy fibers of the striatum lucidum. In adult hippocampus strongly expressed in CA3 pyramidial neurons. {ECO:0000269\|PubMed:25007825}.
Domain:		The C-terminal coiled coil part contains the plexin-interacting region.
Domain:		The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms). {ECO:0000250\|UniProtKB:Q8TDZ2}.
Similarity:		Belongs to the Mical family. {ECO:0000305}.