ARHGAP11B
Identifiers
Aliases	ARHGAP11B, B'-T, FAM7B1, Rho GTPase activating protein 11B, GAP (1-8), ArhGAP11B and human encephalisation
External IDs	OMIM: 616310 GeneCards: ARHGAP11B
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q13.2 Start 30,624,494 bp[1] End 30,649,529 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bone marrow bone marrow cells ganglionic eminence stromal cell of endometrium lymph node monocyte appendix rectum thymus Achilles tendon n/a More reference expression data BioGPS n/a
Gene ontology Molecular function GTPase activator activity Cellular component cytosol Biological process regulation of small GTPase mediated signal transduction signal transduction cerebral cortex development positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 89839 n/a Ensembl ENSG00000274734 ENSG00000286139 ENSG00000285077 n/a UniProt Q3KRB8 n/a RefSeq (mRNA) NM_001039841 n/a RefSeq (protein) NP_001034930 n/a Location (UCSC) Chr 15: 30.62 – 30.65 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

ARHGAP11B is a human-specific gene that amplifies basal progenitors, controls neural progenitor proliferation, and contributes to neocortex folding. It is capable of causing neocortex folding in mice. This likely reflects a role for ARHGAP11B in development and evolutionary expansion of the human neocortex, a conclusion consistent with the finding that the gene duplication that created ARHGAP11B occurred on the human lineage after the divergence from the chimpanzee lineage but before the divergence from Neanderthals.^[3]

Structure

ARHGAP11B encodes 267 amino acids. A truncated copy of ARHGAP11A, which is found throughout the animal kingdom and encodes a Rho GTPase-activating-protein (RhoGAP domain), ARHGAP11B comprises most of the GAP domain (until lysine-220), followed by a novel C-terminal sequence that lacks the 756 C-terminal amino acids of ARHGAP11A.

Activity

In contrast to full-length ARHGAP11A and ARHGAP11A 1-250, ARHGAP11B, like ARHGAP11A1-220, did not exhibit RhoGAP activity in a RhoA/Rho-kinase–based cell transfection assay. This indicates that the C-terminal 47 amino-acids of ARHGAP11B (after lysine-220) constitute not only a unique sequence, resulting from a frameshifting deletion, but also are functionally distinct from their counterpart in ARHGAP11A. In this assay, co-expression of ARHGAP11B along with ARHGAP11A did not inhibit the latter's RhoGAP activity.^[3]

Function

ARHGAP11B is involved in neocortex folding; however, its precise function remains unknown. Several genes involved in intellectual disability encode proteins with RhoGAP domains or other proteins in the Rho signalling pathway.^[4] It has been reported^[5] that it is located in mitochondria, where it binds to the adenine nucleotide translocator. It does not affect the adenine nucleotide exchange activity of the translocator, but it does lead to delayed opening of the mitochondrial permeability transition pore, thus allowing for greater sequestration of calcium. Furthermore, the presence of ARHGAP11B in the mitochondria boosts glutaminolysis, most likely due to the ability of mitochondria to sequester calcium, thereby activating mitochondrial matrix dehydrogenases in the citric acid cycle, particularly the oxoglutarate dehydrogenase complex.

Human evolution

Changes in ARHGAP11B are one of several key genetic factors of recent brain evolution and difference of modern humans to (other) apes and Neanderthals.^[6] A 2016 study suggests, one mutation, a "single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex".^[7]

References

Further reading