UniProt functional annotation for P97924

UniProt code: P97924.

Organism: Rattus norvegicus (Rat).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.
 
Function: Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. Isoforms 1 and 7 are necessary for neuronal development and axonal outgrowth. Isoform 6 is required for dendritic spine formation. {ECO:0000269|PubMed:10692441, ECO:0000269|PubMed:11606631, ECO:0000269|PubMed:15950621}.
 
Catalytic activity: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
Catalytic activity: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
Subunit: Interacts with the C-terminal of peptidylglycine alpha- amidating monooxygenase (PAM) and with the huntingtin-associated protein 1 (HAP1). Interacts with FASLG (By similarity). {ECO:0000250}.
Subcellular location: Cytoplasm. Cytoplasm, cytoskeleton. Note=Isoform 6 is largely associated with synaptosomal membranes and to punctate structures in cortical neurons. Isoforms 1 and 7 are expressed in neuronal cell bodies, isoform 7 is also found in neuronal processes.
Tissue specificity: Highly expressed in the brain and nervous system. Isoform 6 is highly enriched in the postsynaptic density fraction of the cerebral cortex. {ECO:0000269|PubMed:10692441, ECO:0000269|PubMed:10777487}.
Developmental stage: Isoforms 1 and 7 are prevelant 2 dpp, isoform 6 is not detectable until 2 weeks after birth. {ECO:0000269|PubMed:11606631}.
Domain: The two GEF domains catalyze nucleotide exchange for RAC1 and RhoA which are bound by DH1 and DH2 respectively. The two GEF domains appear to play differing roles in neuronal development and axonal outgrowth. SH3 1 binds to the first GEF domain inhibiting GEF activity only when in the presence of a PXXP peptide, suggesting that the SH3 domain/peptide interaction mediates binding to GEF1. CRK1 SH3 domain binds to and inhibits GEF1 activity. {ECO:0000269|PubMed:11606631, ECO:0000269|PubMed:16644733}.
Ptm: Autophosphorylated. {ECO:0000250}.
Miscellaneous: Called DUO because the encoded protein is closely related to but shorter than TRIO.
Miscellaneous: [Isoform 1]: Produced by alternative splicing.
Miscellaneous: [Isoform 2]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous: [Isoform 3]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous: [Isoform 4]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous: [Isoform 5]: Produced by alternative initiation at Met- 624 of isoform 6. {ECO:0000305}.
Miscellaneous: [Isoform 6]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous: [Isoform 7]: Produced by alternative splicing. {ECO:0000305}.
Miscellaneous: [Isoform 8]: Produced by alternative splicing. {ECO:0000305}.
Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.