RHGBB_HUMAN
ID RHGBB_HUMAN Reviewed; 267 AA.
AC Q3KRB8;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Inactive Rho GTPase-activating protein 11B {ECO:0000305};
DE AltName: Full=Rho-type GTPase-activating protein 11B {ECO:0000305};
DE Flags: Precursor;
GN Name=ARHGAP11B {ECO:0000303|PubMed:25721503, ECO:0000312|HGNC:HGNC:15782};
GN Synonyms=FAM7B1 {ECO:0000312|HGNC:HGNC:15782};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=25721503; DOI=10.1126/science.aaa1975;
RA Florio M., Albert M., Taverna E., Namba T., Brandl H., Lewitus E.,
RA Haffner C., Sykes A., Wong F.K., Peters J., Guhr E., Klemroth S.,
RA Pruefer K., Kelso J., Naumann R., Nuesslein I., Dahl A., Lachmann R.,
RA Paeaebo S., Huttner W.B.;
RT "Human-specific gene ARHGAP11B promotes basal progenitor amplification and
RT neocortex expansion.";
RL Science 347:1465-1470(2015).
RN [4]
RP FUNCTION.
RX PubMed=27957544; DOI=10.1126/sciadv.1601941;
RA Florio M., Namba T., Paeaebo S., Hiller M., Huttner W.B.;
RT "A single splice site mutation in human-specific ARHGAP11B causes basal
RT progenitor amplification.";
RL Sci. Adv. 2:e1601941-e1601941(2016).
RN [5]
RP MISCELLANEOUS.
RX PubMed=28580430; DOI=10.1038/s41559-016-0069;
RA Dennis M.Y., Harshman L., Nelson B.J., Penn O., Cantsilieris S.,
RA Huddleston J., Antonacci F., Penewit K., Denman L., Raja A., Baker C.,
RA Mark K., Malig M., Janke N., Espinoza C., Stessman H.A.F., Nuttle X.,
RA Hoekzema K., Lindsay-Graves T.A., Wilson R.K., Eichler E.E.;
RT "The evolution and population diversity of human-specific segmental
RT duplications.";
RL Nat. Ecol. Evol. 1:69-69(2017).
RN [6]
RP FUNCTION.
RX PubMed=30484771; DOI=10.7554/elife.41241;
RA Kalebic N., Gilardi C., Albert M., Namba T., Long K.R., Kostic M.,
RA Langen B., Huttner W.B.;
RT "Human-specific ARHGAP11B induces hallmarks of neocortical expansion in
RT developing ferret neocortex.";
RL Elife 7:0-0(2018).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SLC25A4 AND SLC25A5.
RX PubMed=31883789; DOI=10.1016/j.neuron.2019.11.027;
RA Namba T., Doczi J., Pinson A., Xing L., Kalebic N., Wilsch-Braeuninger M.,
RA Long K.R., Vaid S., Lauer J., Bogdanova A., Borgonovo B., Shevchenko A.,
RA Keller P., Drechsel D., Kurzchalia T., Wimberger P., Chinopoulos C.,
RA Huttner W.B.;
RT "Human-specific ARHGAP11B acts in mitochondria to expand neocortical
RT progenitors by glutaminolysis.";
RL Neuron 105:867-881(2020).
RN [8]
RP FUNCTION.
RX PubMed=32554627; DOI=10.1126/science.abb2401;
RA Heide M., Haffner C., Murayama A., Kurotaki Y., Shinohara H., Okano H.,
RA Sasaki E., Huttner W.B.;
RT "Human-specific ARHGAP11B increases size and folding of primate neocortex
RT in the fetal marmoset.";
RL Science 369:546-550(2020).
RN [9]
RP FUNCTION.
RX PubMed=33938018; DOI=10.15252/embj.2020107093;
RA Xing L., Kubik-Zahorodna A., Namba T., Pinson A., Florio M., Prochazka J.,
RA Sarov M., Sedlacek R., Huttner W.B.;
RT "Expression of human-specific ARHGAP11B in mice leads to neocortex
RT expansion and increased memory flexibility.";
RL EMBO J. 40:e107093-e107093(2021).
CC -!- FUNCTION: Hominin-specific protein that promotes development and
CC evolutionary expansion of the brain neocortex (PubMed:25721503,
CC PubMed:27957544, PubMed:30484771, PubMed:32554627, PubMed:33938018).
CC Able to promote amplification of basal progenitors in the
CC subventricular zone, producing more neurons during fetal
CC corticogenesis, thereby playing a key role in neocortex expansion
CC (PubMed:25721503). Promotes the proliferation of basal progenitors by
CC inhibiting the mitochondrial permeability transition pore (mPTP):
CC delays the opening of the mPTP via interaction with ADP:ATP
CC translocase, thereby increasing mitochondrial Ca(2+) concentration and
CC inducing glutamine catabolism, which is required for basal progenitor
CC proliferation (PubMed:31883789). Does not possess GTPase activator
CC activity: the absence of GTPase activator activity is required to
CC promote amplification of basal progenitors during neocortex development
CC (PubMed:25721503, PubMed:27957544). {ECO:0000269|PubMed:25721503,
CC ECO:0000269|PubMed:27957544, ECO:0000269|PubMed:30484771,
CC ECO:0000269|PubMed:31883789, ECO:0000269|PubMed:32554627,
CC ECO:0000269|PubMed:33938018}.
CC -!- SUBUNIT: Interacts with ADP:ATP translocase components SLC25A4/ANT1 and
CC SLC25A5/ANT2. {ECO:0000269|PubMed:31883789}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:31883789}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed in radial glia cells of
CC cortical neural stem and progenitor cells (NPCs) during neocortex
CC development. Preferentially expressed in apical and basal radial glia
CC (PubMed:25721503). Not detected in cortical neurons and cortical plate
CC (PubMed:25721503). {ECO:0000269|PubMed:25721503}.
CC -!- MISCELLANEOUS: When expressed in embryonic mouse neocortex, promotes
CC basal progenitor generation and self-renewal, and can increase cortical
CC plate area and induce gyrification (PubMed:25721503, PubMed:33938018).
CC Mice exhibit increased neocortical size and upper-layer neuron numbers
CC persisting into adulthood (PubMed:33938018). Moreover, mice display
CC altered neurobehaviour, characterized by an increased memory
CC flexibility and a reduced anxiety level (PubMed:33938018). When
CC expressed in the developing neocortex of the gyrencephalic ferret,
CC strongly increases proliferative basal radial glia, a progenitor cell
CC type thought to be instrumental for neocortical expansion, resulting in
CC extension of the neurogenic period and an increase in upper-layer
CC neurons (PubMed:30484771). As consequence, the postnatal ferret
CC neocortex displays increased neuron density in the upper cortical
CC layers and expands in both the radial and tangential dimensions
CC (PubMed:30484771). Expression in fetal neocortex of the common marmoset
CC increases the numbers of upper-layer neurons, promoting enlargement of
CC the neocortex and inducing its folding (PubMed:32554627).
CC {ECO:0000269|PubMed:25721503, ECO:0000269|PubMed:30484771,
CC ECO:0000269|PubMed:32554627, ECO:0000269|PubMed:33938018}.
CC -!- MISCELLANEOUS: ARHGAP11B arose from partial duplication of ARHGAP11A on
CC the human lineage after separation from the chimpanzee lineage, but
CC before the divergence from Neandertals. {ECO:0000269|PubMed:25721503,
CC ECO:0000269|PubMed:28580430}.
CC -!- CAUTION: Although it contains a Rho-GAP domains, does not have GTPase
CC activator activity (PubMed:25721503, PubMed:27957544). The absence of
CC GTPase activator activity is required to promote amplification of basal
CC progenitors (PubMed:27957544). Restoring this activity abolishes
CC ability to promote amplification of basal progenitors during neocortex
CC development (PubMed:27957544). {ECO:0000269|PubMed:25721503,
CC ECO:0000269|PubMed:27957544}.
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DR EMBL; AC243687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105788; AAI05789.1; -; mRNA.
DR CCDS; CCDS32185.1; -.
DR RefSeq; NP_001034930.1; NM_001039841.1.
DR AlphaFoldDB; Q3KRB8; -.
DR SMR; Q3KRB8; -.
DR BioGRID; 124615; 29.
DR IntAct; Q3KRB8; 16.
DR STRING; 9606.ENSP00000481934; -.
DR iPTMnet; Q3KRB8; -.
DR PhosphoSitePlus; Q3KRB8; -.
DR BioMuta; ARHGAP11B; -.
DR DMDM; 121942629; -.
DR jPOST; Q3KRB8; -.
DR MassIVE; Q3KRB8; -.
DR MaxQB; Q3KRB8; -.
DR PaxDb; Q3KRB8; -.
DR PeptideAtlas; Q3KRB8; -.
DR PRIDE; Q3KRB8; -.
DR Antibodypedia; 82252; 9 antibodies from 3 providers.
DR DNASU; 89839; -.
DR Ensembl; ENST00000428041.4; ENSP00000392760.2; ENSG00000285077.3.
DR Ensembl; ENST00000693711.1; ENSP00000508838.1; ENSG00000285077.3.
DR GeneID; 89839; -.
DR KEGG; hsa:89839; -.
DR UCSC; uc001zet.2; human.
DR CTD; 89839; -.
DR DisGeNET; 89839; -.
DR GeneCards; ARHGAP11B; -.
DR HGNC; HGNC:15782; ARHGAP11B.
DR HPA; ENSG00000285077; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 616310; gene.
DR neXtProt; NX_Q3KRB8; -.
DR PharmGKB; PA134987257; -.
DR VEuPathDB; HostDB:ENSG00000284906; -.
DR eggNOG; KOG2710; Eukaryota.
DR GeneTree; ENSGT00940000155312; -.
DR HOGENOM; CLU_048582_0_0_1; -.
DR InParanoid; Q3KRB8; -.
DR OMA; NINIRCH; -.
DR OrthoDB; 1169366at2759; -.
DR PhylomeDB; Q3KRB8; -.
DR TreeFam; TF342052; -.
DR PathwayCommons; Q3KRB8; -.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR SignaLink; Q3KRB8; -.
DR SIGNOR; Q3KRB8; -.
DR BioGRID-ORCS; 89839; 121 hits in 995 CRISPR screens.
DR ChiTaRS; ARHGAP11B; human.
DR GenomeRNAi; 89839; -.
DR Pharos; Q3KRB8; Tbio.
DR PRO; PR:Q3KRB8; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q3KRB8; protein.
DR Bgee; ENSG00000285077; Expressed in bone marrow and 98 other tissues.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; TAS:Reactome.
DR GO; GO:0021987; P:cerebral cortex development; IDA:UniProtKB.
DR GO; GO:0006543; P:glutamine catabolic process; IDA:UniProtKB.
DR GO; GO:0035795; P:negative regulation of mitochondrial membrane permeability; IDA:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.555.10; -; 1.
DR InterPro; IPR042869; ARHGAP11A/B.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR PANTHER; PTHR15670; PTHR15670; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Mitochondrion; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..267
FT /note="Inactive Rho GTPase-activating protein 11B"
FT /id="PRO_0000317291"
FT DOMAIN 49..250
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
SQ SEQUENCE 267 AA; 30251 MW; 6817B9B13951F4BA CRC64;
MWDQRLVKLA LLQHLRAFYG IKVKGVRGQC DRRRHETAAT EIGGKIFGVP FNALPHSAVP
EYGHIPSFLV DACTSLEEHI HTEGLFRKSG SVIRLKALKN KVDHGEGCLS SAPPCDIAGL
LKQFFRELPE PILPADLHEA LLKAQQLGTE EKNKAILLLS CLLADHTVHV LRYFFNFLRN
VSLRSSENKM DSSNLAVIFA PNLLQTSEGH EKMSSNAEKK GVYQTLSWKR YQPCWVLMVS
VLLHHWKALK KVNMKLLVNI REREDNV
