UniProt functional annotation for Q8TDZ2



	UniProt functional annotation for Q8TDZ2

UniProt code: Q8TDZ2.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (By similarity). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023). 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 (By similarity). May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000250|UniProtKB:Q8VDP3, ECO:0000269|PubMed:18305261, ECO:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023, ECO:0000269|PubMed:28230050, ECO:0000305, ECO:0000305|PubMed:27552051}.

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:0000250|UniProtKB:Q8VDP3};

Cofactor: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:21864500};

Biophysicochemical properties: Kinetic parameters: KM=4.7 uM for F-actin (at saturing NADPH concentration) {ECO:0000269|PubMed:21864500}; KM=375 uM for NADPH (for the NADPH oxidase reaction) {ECO:0000269|PubMed:26845023}; Note=kcat is 0.28 sec(-1) for NADPH for the NADPH oxidase reaction. {ECO:0000269|PubMed:26845023};

Subunit: Interacts with STK38 and STK38L (By similarity). 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; ternary complex formation of RAB8A, RAB13 and MICAL1 is possible. Associates with the SH3 domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B. {ECO:0000250, ECO:0000269|PubMed:11827972, ECO:0000269|PubMed:12110185, ECO:0000269|PubMed:12788069, ECO:0000269|PubMed:15694364, ECO:0000269|PubMed:27552051}.

Subcellular location: Cytoplasm. Cytoplasm, cytoskeleton. Midbody {ECO:0000269|PubMed:28230050}. Note=Accumulates transiently at the abscission site before abscission occurs. {ECO:0000269|PubMed:28230050}.

Tissue specificity: Expressed in the thymus, lung, spleen, kidney, testis and hematopoietic cells. {ECO:0000269|PubMed:11827972}.

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:0000269|PubMed:27552051}.

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

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

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (By similarity). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023). 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 (By similarity). May act as Rab effector protein and play a role in vesicle trafficking. {ECO:0000250\|UniProtKB:Q8VDP3, ECO:0000269\|PubMed:18305261, ECO:0000269\|PubMed:21864500, ECO:0000269\|PubMed:26845023, ECO:0000269\|PubMed:28230050, ECO:0000305, ECO:0000305\|PubMed:27552051}.


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:0000250\|UniProtKB:Q8VDP3};
Cofactor:		Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269\|PubMed:21864500};
Biophysicochemical properties:		Kinetic parameters: KM=4.7 uM for F-actin (at saturing NADPH concentration) {ECO:0000269\|PubMed:21864500}; KM=375 uM for NADPH (for the NADPH oxidase reaction) {ECO:0000269\|PubMed:26845023}; Note=kcat is 0.28 sec(-1) for NADPH for the NADPH oxidase reaction. {ECO:0000269\|PubMed:26845023};
Subunit:		Interacts with STK38 and STK38L (By similarity). 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; ternary complex formation of RAB8A, RAB13 and MICAL1 is possible. Associates with the SH3 domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B. {ECO:0000250, ECO:0000269\|PubMed:11827972, ECO:0000269\|PubMed:12110185, ECO:0000269\|PubMed:12788069, ECO:0000269\|PubMed:15694364, ECO:0000269\|PubMed:27552051}.
Subcellular location:		Cytoplasm. Cytoplasm, cytoskeleton. Midbody {ECO:0000269\|PubMed:28230050}. Note=Accumulates transiently at the abscission site before abscission occurs. {ECO:0000269\|PubMed:28230050}.
Tissue specificity:		Expressed in the thymus, lung, spleen, kidney, testis and hematopoietic cells. {ECO:0000269\|PubMed:11827972}.
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:0000269\|PubMed:27552051}.
Domain:		The C-terminal coiled coil part contains the plexin-interacting region.
Similarity:		Belongs to the Mical family. {ECO:0000305}.