UniProt functional annotation for Q92558



	UniProt functional annotation for Q92558

UniProt code: Q92558.

Organism: Homo sapiens (Human).

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

Function: Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation (PubMed:29961568). The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). Also involved in the regulation of mitochondrial dynamics (PubMed:29961568). {ECO:0000250|UniProtKB:Q8R5H6, ECO:0000269|PubMed:29961568, ECO:0000269|PubMed:9889097}.

Subunit: Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Interacts with SHANK3; the interaction mediates the association of SHANK3 with the WAVE1 complex. Interacts with ABI1 (via N-terminus). Interacts with SORBS2; this interaction greatly enhances phosphorylation by ABL1 and dephosphorylation by PTPN12 and might mediate partial to focal adhesion sites. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:21107423}.

Subcellular location: Cytoplasm, cytoskeleton {ECO:0000269|PubMed:9889097}. Cell junction, synapse {ECO:0000250|UniProtKB:Q5BJU7}. Cell junction, focal adhesion {ECO:0000269|PubMed:18559503}. Note=Dot-like pattern in the cytoplasm. Concentrated in Rac-regulated membrane-ruffling areas (PubMed:9889097). Partial translocation to focal adhesion sites might be mediated by interaction with SORBS2 (PubMed:18559503). In neurons, colocalizes with activated NTRK2 after BDNF addition in endocytic sites through the association with TMEM108 (By similarity). {ECO:0000250|UniProtKB:Q8R5H6, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:9889097}.

Tissue specificity: Highly expressed in brain. Lowly expressed in testis, ovary, colon, kidney, pancreas, thymus, small intestine and peripheral blood.

Domain: Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain. {ECO:0000269|PubMed:9889097}.

Ptm: Phosphorylated on tyrosine residues by ABL1 and dephosphorylated by PTPN12. {ECO:0000269|PubMed:18559503}.

Disease: Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) [MIM:618707]: A disorder characterized by neurodevelopmental abnormalities, including moderate to profound intellectual disability, with autistic features, seizures, severe impairments in speech, and gross motor delay. {ECO:0000269|PubMed:29961568}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the SCAR/WAVE family. {ECO:0000305}.

Sequence caution: Sequence=BAA13399.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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:		Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation (PubMed:29961568). The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). Also involved in the regulation of mitochondrial dynamics (PubMed:29961568). {ECO:0000250\|UniProtKB:Q8R5H6, ECO:0000269\|PubMed:29961568, ECO:0000269\|PubMed:9889097}.


Subunit:		Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Interacts with SHANK3; the interaction mediates the association of SHANK3 with the WAVE1 complex. Interacts with ABI1 (via N-terminus). Interacts with SORBS2; this interaction greatly enhances phosphorylation by ABL1 and dephosphorylation by PTPN12 and might mediate partial to focal adhesion sites. {ECO:0000269\|PubMed:11130076, ECO:0000269\|PubMed:18559503, ECO:0000269\|PubMed:21107423}.
Subcellular location:		Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:9889097}. Cell junction, synapse {ECO:0000250\|UniProtKB:Q5BJU7}. Cell junction, focal adhesion {ECO:0000269\|PubMed:18559503}. Note=Dot-like pattern in the cytoplasm. Concentrated in Rac-regulated membrane-ruffling areas (PubMed:9889097). Partial translocation to focal adhesion sites might be mediated by interaction with SORBS2 (PubMed:18559503). In neurons, colocalizes with activated NTRK2 after BDNF addition in endocytic sites through the association with TMEM108 (By similarity). {ECO:0000250\|UniProtKB:Q8R5H6, ECO:0000269\|PubMed:18559503, ECO:0000269\|PubMed:9889097}.
Tissue specificity:		Highly expressed in brain. Lowly expressed in testis, ovary, colon, kidney, pancreas, thymus, small intestine and peripheral blood.
Domain:		Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain. {ECO:0000269\|PubMed:9889097}.
Ptm:		Phosphorylated on tyrosine residues by ABL1 and dephosphorylated by PTPN12. {ECO:0000269\|PubMed:18559503}.
Disease:		Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) [MIM:618707]: A disorder characterized by neurodevelopmental abnormalities, including moderate to profound intellectual disability, with autistic features, seizures, severe impairments in speech, and gross motor delay. {ECO:0000269\|PubMed:29961568}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the SCAR/WAVE family. {ECO:0000305}.
Sequence caution:		Sequence=BAA13399.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};