UniProt functional annotation for Q08509



	UniProt functional annotation for Q08509

UniProt code: Q08509.

Organism: Mus musculus (Mouse).

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

Function: Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin- based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes. {ECO:0000269|PubMed:10499589, ECO:0000269|PubMed:11524436, ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19564905, ECO:0000269|PubMed:20532239, ECO:0000269|PubMed:21236676, ECO:0000269|PubMed:21835647, ECO:0000269|PubMed:8404850}.

Subunit: Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with BAIAP2. Interacts with SHB and LANCL1. Interacts with EGFR; mediates EPS8 phosphorylation. Interacts with MYO15A and WHRN. {ECO:0000269|PubMed:10499589, ECO:0000269|PubMed:11524436, ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19528316, ECO:0000269|PubMed:21236676, ECO:0000269|PubMed:7537362, ECO:0000269|PubMed:8404850}.

Subcellular location: Cytoplasm, cell cortex. Cell projection, ruffle membrane. Cell projection, growth cone {ECO:0000250}. Cell projection, stereocilium {ECO:0000269|PubMed:23918390, ECO:0000269|PubMed:24741995}. Cell junction, synapse, synaptosome {ECO:0000250}. Note=Localizes at the tips of the stereocilia of the inner and outer hair cells (PubMed:24741995, PubMed:23918390). Localizes to the midzone of dividing cells. {ECO:0000269|PubMed:23918390, ECO:0000269|PubMed:24741995}.

Tissue specificity: Expressed in neuronal cell body and neurites, and prominently enriched in the axonal growth cone (PubMed:19564905). Expressed at the tips of cochlear hair cells stereocilia (PubMed:23918390). {ECO:0000269|PubMed:19564905, ECO:0000269|PubMed:23918390}.

Domain: The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity (PubMed:11524436). It mediates both barbed-end actin capping and actin bundling activities (PubMed:20532239). The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (PubMed:20532239). {ECO:0000269|PubMed:11524436, ECO:0000269|PubMed:20532239}.

Domain: The SH3 domain mediates interaction with SHB. {ECO:0000250}.

Ptm: Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during G2 phase, leading to its transient degradation and subsequent cell shape changes required to allow mitotic progression. Reappears at the midzone of dividing cells. {ECO:0000269|PubMed:23314863}.

Ptm: Phosphorylation at Ser-624 and Thr-628 by MAPK following BDNF treatment promotes removal from actin and filopodia formation. Phosphorylated by several receptor tyrosine kinases. {ECO:0000269|PubMed:19564905, ECO:0000269|PubMed:8404850}.

Disruption phenotype: No visible phenotype. Defects in PDGF-induced membrane ruffling due to defects in Ras to Rac signals. Dendritic cells are impaired in directional and chemotactic migration and are delayed in reaching the draining lymph node in vivo after inflammatory challenge. Mice show short stereocilia. {ECO:0000269|PubMed:10499589, ECO:0000269|PubMed:21236676, ECO:0000269|PubMed:21835647}.

Similarity: Belongs to the EPS8 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:		Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin- based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes. {ECO:0000269\|PubMed:10499589, ECO:0000269\|PubMed:11524436, ECO:0000269\|PubMed:15558031, ECO:0000269\|PubMed:17115031, ECO:0000269\|PubMed:19564905, ECO:0000269\|PubMed:20532239, ECO:0000269\|PubMed:21236676, ECO:0000269\|PubMed:21835647, ECO:0000269\|PubMed:8404850}.


Subunit:		Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with BAIAP2. Interacts with SHB and LANCL1. Interacts with EGFR; mediates EPS8 phosphorylation. Interacts with MYO15A and WHRN. {ECO:0000269\|PubMed:10499589, ECO:0000269\|PubMed:11524436, ECO:0000269\|PubMed:15558031, ECO:0000269\|PubMed:17115031, ECO:0000269\|PubMed:19528316, ECO:0000269\|PubMed:21236676, ECO:0000269\|PubMed:7537362, ECO:0000269\|PubMed:8404850}.
Subcellular location:		Cytoplasm, cell cortex. Cell projection, ruffle membrane. Cell projection, growth cone {ECO:0000250}. Cell projection, stereocilium {ECO:0000269\|PubMed:23918390, ECO:0000269\|PubMed:24741995}. Cell junction, synapse, synaptosome {ECO:0000250}. Note=Localizes at the tips of the stereocilia of the inner and outer hair cells (PubMed:24741995, PubMed:23918390). Localizes to the midzone of dividing cells. {ECO:0000269\|PubMed:23918390, ECO:0000269\|PubMed:24741995}.
Tissue specificity:		Expressed in neuronal cell body and neurites, and prominently enriched in the axonal growth cone (PubMed:19564905). Expressed at the tips of cochlear hair cells stereocilia (PubMed:23918390). {ECO:0000269\|PubMed:19564905, ECO:0000269\|PubMed:23918390}.
Domain:		The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity (PubMed:11524436). It mediates both barbed-end actin capping and actin bundling activities (PubMed:20532239). The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (PubMed:20532239). {ECO:0000269\|PubMed:11524436, ECO:0000269\|PubMed:20532239}.
Domain:		The SH3 domain mediates interaction with SHB. {ECO:0000250}.
Ptm:		Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during G2 phase, leading to its transient degradation and subsequent cell shape changes required to allow mitotic progression. Reappears at the midzone of dividing cells. {ECO:0000269\|PubMed:23314863}.
Ptm:		Phosphorylation at Ser-624 and Thr-628 by MAPK following BDNF treatment promotes removal from actin and filopodia formation. Phosphorylated by several receptor tyrosine kinases. {ECO:0000269\|PubMed:19564905, ECO:0000269\|PubMed:8404850}.
Disruption phenotype:		No visible phenotype. Defects in PDGF-induced membrane ruffling due to defects in Ras to Rac signals. Dendritic cells are impaired in directional and chemotactic migration and are delayed in reaching the draining lymph node in vivo after inflammatory challenge. Mice show short stereocilia. {ECO:0000269\|PubMed:10499589, ECO:0000269\|PubMed:21236676, ECO:0000269\|PubMed:21835647}.
Similarity:		Belongs to the EPS8 family. {ECO:0000305}.