Human Gene SRGAP2 (ENST00000573034.8) from GENCODE V44
Description: Homo sapiens SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2), transcript variant 1, mRNA. (from RefSeq NM_015326) RefSeq Summary (NM_015326): This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. The encoded protein stimulates GTPase activity of Rac1, and plays a role in cortical neuron development. This locus has several paralogs on human chromosome 1 resulting from segmental duplication. While this locus itself is conserved among various species, the paralogs are found only in the genus Homo, and not in the genomes of non-human great apes. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Jul 2014]. Gencode Transcript: ENST00000573034.8 Gencode Gene: ENSG00000266028.8 Transcript (Including UTRs) Position: hg38 chr1:206,203,541-206,464,436 Size: 260,896 Total Exon Count: 23 Strand: + Coding Region Position: hg38 chr1:206,205,971-206,461,420 Size: 255,450 Coding Exon Count: 22
ID:SRGP2_HUMAN DESCRIPTION: RecName: Full=SLIT-ROBO Rho GTPase-activating protein 2; Short=srGAP2; AltName: Full=Formin-binding protein 2; AltName: Full=Rho GTPase-activating protein 34; FUNCTION: RAC1 GTPase activating protein (GAP) that binds and deforms membranes, and regulates actin dynamics to regulate cell migration and differentiation. Plays an important role in different aspects of neuronal morphogenesis and migration mainly during development of the cerebral cortex. This includes the biogenesis of neurites, where it is required for both axons and dendrites outgrowth, and the maturation of the dendritic spines. Also stimulates the branching of the leading process and negatively regulates neuron radial migration in the cerebral cortex. Its interaction and inhibition by SRGAP2C reduces the rate of spine maturation, alters dendritic spine morphology and density and indirectly increases neuronal migration. It may have implications for cognition, learning and memory. In non-neuronal cells, it may also play a role in cell migration by regulating the formation of lamellipodia and filopodia. SUBUNIT: Homodimer (Probable). Forms heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain. Interacts (via SH3 domain) with GPHN (By similarity). Interacts with SRGAP2C; formation of the heterodimer alters SRGAP2 function. Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1 and actin dynamics. Interacts (via SH3 domain) with FMNL3. Interacts with RAC1; specifically stimulates RAC1 GTPase activity. Probably interacts with ROBO1 and ROBO2. Interacts with FASLG. Interacts with PRMT5. INTERACTION: O95466:FMNL1; NbExp=3; IntAct=EBI-1051034, EBI-720020; O14744:PRMT5; NbExp=4; IntAct=EBI-1051034, EBI-351098; SUBCELLULAR LOCATION: Cell membrane. Cell projection, dendritic spine. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density (By similarity). Cell junction, synapse, postsynaptic cell membrane (By similarity). Cell projection, lamellipodium. Cytoplasmic vesicle, phagosome (By similarity). Nucleus (By similarity). Cytoplasm (By similarity). Note=Recruited to actin-rich phagosomes during phagocytosis (By similarity). Translocates from nucleus to cytoplasm during development (By similarity). DOMAIN: The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions. PTM: Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions. DISEASE: Note=A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13). MISCELLANEOUS: There are 3 duplications of SRGAP2 in the human genome as a result of segmental gene duplications. SRGAP2C is the only one to be fixed at a diploid state in the human genome. Moreover, SRGAP2C is functional, interacts with and inhibits SRGAP2 and is human-specific. The appearance of SRGAP2C in the human genome is estimated to 2,4 million years ago, which corresponds to the beginning of neocortex expansion in human evolution and it may have played an important role in this process through its interaction with SRGAP2 function. SIMILARITY: Contains 1 FCH domain. SIMILARITY: Contains 1 Rho-GAP domain. SIMILARITY: Contains 1 SH3 domain. SEQUENCE CAUTION: Sequence=BAA32301.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O75044
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0003363 lamellipodium assembly involved in ameboidal cell migration GO:0007165 signal transduction GO:0007399 nervous system development GO:0021816 extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration GO:0034446 substrate adhesion-dependent cell spreading GO:0043547 positive regulation of GTPase activity GO:0046847 filopodium assembly GO:0048812 neuron projection morphogenesis GO:0051014 actin filament severing GO:0051056 regulation of small GTPase mediated signal transduction GO:0060996 dendritic spine development GO:2001223 negative regulation of neuron migration GO:0008283 cell proliferation GO:0060548 negative regulation of cell death