UniProt functional annotation for O08808



	UniProt functional annotation for O08808

UniProt code: O08808.

Organism: Mus musculus (Mouse).

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

Function: Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (PubMed:10678165, PubMed:15044801, PubMed:18572016, PubMed:23558171). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (PubMed:10678165, PubMed:15044801, PubMed:18572016). Required for cytokinesis, and transcriptional activation of the serum response factor (PubMed:10678165, PubMed:15044801, PubMed:18572016). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (PubMed:10678165, PubMed:15044801, PubMed:18572016). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (PubMed:15311282). Has neurite outgrowth promoting activity (PubMed:10678165, PubMed:15044801, PubMed:18572016). Acts in a Rho-dependent manner to recruit PFY1 to the membrane (PubMed:9214622). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (By similarity). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (By similarity). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Required in the control of cell shape (By similarity). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF- MRTFA activity (PubMed:23558171). {ECO:0000250|UniProtKB:O60610, ECO:0000269|PubMed:10678165, ECO:0000269|PubMed:15044801, ECO:0000269|PubMed:15311282, ECO:0000269|PubMed:18572016, ECO:0000269|PubMed:23558171, ECO:0000269|PubMed:9214622}.

Subunit: Homodimer (PubMed:14992721, PubMed:15864301). Interacts with the GTP-bound form of RHOA (PubMed:9214622). Interacts with RHOC, PFY1, MAPRE1, BAIAP2 and APC (PubMed:10814512, PubMed:15311282, PubMed:15864301). Interacts with SCAI (PubMed:19350017). Interacts with DCAF7, via FH2 domain (By similarity). Interacts with NCDN (PubMed:18572016). Interacts with OSBPL10, OSBPL2, VIM, TUBB and DYN1 (By similarity). {ECO:0000250|UniProtKB:O60610, ECO:0000269|PubMed:10814512, ECO:0000269|PubMed:14992721, ECO:0000269|PubMed:15311282, ECO:0000269|PubMed:15864301, ECO:0000269|PubMed:18572016, ECO:0000269|PubMed:19350017, ECO:0000269|PubMed:9214622}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:9214622}. Cell projection, ruffle membrane {ECO:0000269|PubMed:9214622}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:9214622}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:O60610}. Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:O60610}. Cytoplasm {ECO:0000269|PubMed:23558171}. Nucleus {ECO:0000269|PubMed:23558171}. Note=Membrane ruffles, especially at the tip of ruffles, of motile cells. {ECO:0000269|PubMed:9214622}.

Tissue specificity: Widely expressed. In the organ of Corti, it is expressed at the outer and inner hair cell layers. Expression at the inner hair cell layer is restricted to inner pillar cells. Detected in cochlear spiral ganglion neurons (PubMed:27808407). {ECO:0000269|PubMed:27808407}.

Developmental stage: Expressed in the ventricular and subventricular zone progenitor cells of the dorsal and ventral forebrain and the brainstem, at 12.5 dpc, 14.5 dpc, and 17.5 dpc. At later embryonic age, it is observed in neurons of the cortex and hippocampus. During postnatal development, expression is detected in the cerebral cortex, basal ganglia, hippocampus, thalamus, and external granular layer of the cerebellum. {ECO:0000269|PubMed:24781755}.

Domain: The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments. {ECO:0000269|PubMed:16292343}.

Ptm: Phosphorylation at Thr-751 is stimulated by cAMP and regulates stability, complex formation and mitochondrial movement (By similarity). {ECO:0000250|UniProtKB:O60610}.

Disruption phenotype: Knockout mice show normal organization of the cerebral cortex with no significant differences in cortical white matter or callosal thickness (PubMed:24781755). Histological analysis of coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement (PubMed:24781755). {ECO:0000269|PubMed:24781755}.

Similarity: Belongs to the formin homology family. Diaphanous subfamily. {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:		Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (PubMed:10678165, PubMed:15044801, PubMed:18572016, PubMed:23558171). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (PubMed:10678165, PubMed:15044801, PubMed:18572016). Required for cytokinesis, and transcriptional activation of the serum response factor (PubMed:10678165, PubMed:15044801, PubMed:18572016). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (PubMed:10678165, PubMed:15044801, PubMed:18572016). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (PubMed:15311282). Has neurite outgrowth promoting activity (PubMed:10678165, PubMed:15044801, PubMed:18572016). Acts in a Rho-dependent manner to recruit PFY1 to the membrane (PubMed:9214622). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (By similarity). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (By similarity). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Required in the control of cell shape (By similarity). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF- MRTFA activity (PubMed:23558171). {ECO:0000250\|UniProtKB:O60610, ECO:0000269\|PubMed:10678165, ECO:0000269\|PubMed:15044801, ECO:0000269\|PubMed:15311282, ECO:0000269\|PubMed:18572016, ECO:0000269\|PubMed:23558171, ECO:0000269\|PubMed:9214622}.


Subunit:		Homodimer (PubMed:14992721, PubMed:15864301). Interacts with the GTP-bound form of RHOA (PubMed:9214622). Interacts with RHOC, PFY1, MAPRE1, BAIAP2 and APC (PubMed:10814512, PubMed:15311282, PubMed:15864301). Interacts with SCAI (PubMed:19350017). Interacts with DCAF7, via FH2 domain (By similarity). Interacts with NCDN (PubMed:18572016). Interacts with OSBPL10, OSBPL2, VIM, TUBB and DYN1 (By similarity). {ECO:0000250\|UniProtKB:O60610, ECO:0000269\|PubMed:10814512, ECO:0000269\|PubMed:14992721, ECO:0000269\|PubMed:15311282, ECO:0000269\|PubMed:15864301, ECO:0000269\|PubMed:18572016, ECO:0000269\|PubMed:19350017, ECO:0000269\|PubMed:9214622}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:9214622}. Cell projection, ruffle membrane {ECO:0000269\|PubMed:9214622}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:9214622}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250\|UniProtKB:O60610}. Cytoplasm, cytoskeleton, spindle {ECO:0000250\|UniProtKB:O60610}. Cytoplasm {ECO:0000269\|PubMed:23558171}. Nucleus {ECO:0000269\|PubMed:23558171}. Note=Membrane ruffles, especially at the tip of ruffles, of motile cells. {ECO:0000269\|PubMed:9214622}.
Tissue specificity:		Widely expressed. In the organ of Corti, it is expressed at the outer and inner hair cell layers. Expression at the inner hair cell layer is restricted to inner pillar cells. Detected in cochlear spiral ganglion neurons (PubMed:27808407). {ECO:0000269\|PubMed:27808407}.
Developmental stage:		Expressed in the ventricular and subventricular zone progenitor cells of the dorsal and ventral forebrain and the brainstem, at 12.5 dpc, 14.5 dpc, and 17.5 dpc. At later embryonic age, it is observed in neurons of the cortex and hippocampus. During postnatal development, expression is detected in the cerebral cortex, basal ganglia, hippocampus, thalamus, and external granular layer of the cerebellum. {ECO:0000269\|PubMed:24781755}.
Domain:		The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments. {ECO:0000269\|PubMed:16292343}.
Ptm:		Phosphorylation at Thr-751 is stimulated by cAMP and regulates stability, complex formation and mitochondrial movement (By similarity). {ECO:0000250\|UniProtKB:O60610}.
Disruption phenotype:		Knockout mice show normal organization of the cerebral cortex with no significant differences in cortical white matter or callosal thickness (PubMed:24781755). Histological analysis of coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement (PubMed:24781755). {ECO:0000269\|PubMed:24781755}.
Similarity:		Belongs to the formin homology family. Diaphanous subfamily. {ECO:0000305}.