RAP1GDS1
Function
Acts as a GEF (guanine nucleotide exchange factor) for the Rho family of small GTP-binding proteins (G proteins) that stimulates the dissociation of GDP to enable subsequent binding of GTP (PubMed:11948427, PubMed:1549351, PubMed:20709748, PubMed:28630045, PubMed:30190425). Additionally, appears to chaperone the processing and/or trafficking of small GTPases containing a C-terminal polybasic region independently of GEF activity (PubMed:20709748, PubMed:21242305). Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1 and KRAS (PubMed:11948427, PubMed:1549351, PubMed:20709748, PubMed:24415755). Regulates mitochondrial dynamics by controlling RHOT function to promote mitochondrial fission during high calcium conditions (PubMed:27716788). Able to promote the Ca(2+) release from the endoplasmic reticulum via both inositol trisphosphate (Ins3P) and ryanodine sensitive receptors leading to a enhanced mitochondrial Ca(2+) uptake (PubMed:24349085).
Isoform 1
Acts as a GEF (guanine nucleotide exchange factor) for unprenylated RHOA (PubMed:24415755, PubMed:28630045, PubMed:30190425). Chaperones the entry and passage of small GTPases through the prenylation pathway (PubMed:20709748). Recognizes the last amino acid in the GTPase C-terminal CAAX motif with a preference for 'Leu' over 'Met', indicating involvement in the geranylgeranylation pathway (PubMed:24415755).
Isoform 2
Acts as a GEF (guanine nucleotide exchange factor) for prenylated RHOA (PubMed:21242305, PubMed:28630045, PubMed:30190425). Acts as a GEF for RHOC (PubMed:21242305). Chaperones the downstream trafficking and/or processing of small newly prenylated GTPases (PubMed:20709748). Escorts RAC1 to the nucleus (PubMed:12551911).
Involvement in disease
Alfadhel syndrome
AFDL
An autosomal recessive neurodevelopmental disorder characterized by global developmental delay and regression, intellectual disability, hypotonia, delayed motor development, stereotypy, behavioral abnormalities, and dysmorphic features.
None
The disease is caused by variants affecting the gene represented in this entry.
A chromosomal aberration involving RAP1GDS1 has been found in M0 type acute myeloid leukemia. Translocation (t4;11)(q23;p15) with NUP98.
A chromosomal aberration involving RAP1GDS1 has been found in T-cell acute lymphocytic leukemia. Translocation t(4;11)(q23;p15) with NUP98.
Post-translational modifications
Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers.
Cellular localization
- Cytoplasm
- Cytosol
- Endoplasmic reticulum
- Mitochondrion
- Nucleus
- Nuclear import is dependent on complexing with a GTPase containing a C-terminal polybasic region.
Alternative names
SMGGDS, RAP1GDS1, Rap1 GTPase-GDP dissociation stimulator 1, Exchange factor smgGDS, SMG GDS protein, SMG P21 stimulatory GDP/GTP exchange protein