RIC8_CAEEL
ID RIC8_CAEEL Reviewed; 566 AA.
AC Q9GSX9; Q86DD4;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Synembryn;
DE AltName: Full=Resistance to inhibitors of cholinesterase protein 8;
GN Name=ric-8; ORFNames=Y69A2AR.2;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=10985349; DOI=10.1016/s0896-6273(00)00037-4;
RA Miller K.G., Emerson M.D., McManus J.R., Rand J.B.;
RT "RIC-8 (Synembryn): a novel conserved protein that is required for Gq alpha
RT signaling in the C. elegans nervous system.";
RL Neuron 27:289-299(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING,
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP LEU-267 AND ALA-275.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION.
RX PubMed=11102364; DOI=10.1093/genetics/156.4.1649;
RA Miller K.G., Rand J.B.;
RT "A role for RIC-8 (Synembryn) and GOA-1 (G(o)alpha) in regulating a subset
RT of centrosome movements during early embryogenesis in Caenorhabditis
RT elegans.";
RL Genetics 156:1649-1660(2000).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GOA-1.
RX PubMed=15479638; DOI=10.1016/j.cell.2004.09.025;
RA Hess H.A., Roeper J.-C., Grill S.W., Koelle M.R.;
RT "RGS-7 completes a receptor-independent heterotrimeric G protein cycle to
RT asymmetrically regulate mitotic spindle positioning in C. elegans.";
RL Cell 119:209-218(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GOA-1.
RX PubMed=15479639; DOI=10.1016/j.cell.2004.09.026;
RA Afshar K., Willard F.S., Colombo K., Johnston C.A., McCudden C.R.,
RA Siderovski D.P., Goenczy P.;
RT "RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric
RT division of C. elegans embryos.";
RL Cell 119:219-230(2004).
RN [6]
RP FUNCTION, AND INTERACTION WITH GOA-1.
RX PubMed=15498497; DOI=10.1016/j.cub.2004.09.059;
RA Couwenbergs C., Spilker A.C., Gotta M.;
RT "Control of embryonic spindle positioning and Galpha activity by C. elegans
RT RIC-8.";
RL Curr. Biol. 14:1871-1876(2004).
RN [7]
RP FUNCTION, AND INTERACTION WITH GPA-16.
RX PubMed=16162648; DOI=10.1242/dev.02039;
RA Afshar K., Willard F.S., Colombo K., Siderovski D.P., Goenczy P.;
RT "Cortical localization of the Galpha protein GPA-16 requires RIC-8 function
RT during C. elegans asymmetric cell division.";
RL Development 132:4449-4459(2005).
RN [8]
RP FUNCTION.
RX PubMed=15489510; DOI=10.1534/genetics.104.032334;
RA Schade M.A., Reynolds N.K., Dollins C.M., Miller K.G.;
RT "Mutations that rescue the paralysis of Caenorhabditis elegans ric-8
RT (synembryn) mutants activate the G alpha(s) pathway and define a third
RT major branch of the synaptic signaling network.";
RL Genetics 169:631-649(2005).
RN [9]
RP FUNCTION.
RX PubMed=15489511; DOI=10.1534/genetics.104.031286;
RA Reynolds N.K., Schade M.A., Miller K.G.;
RT "Convergent, RIC-8-dependent Galpha signaling pathways in the
RT Caenorhabditis elegans synaptic signaling network.";
RL Genetics 169:651-670(2005).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF), which can activate
CC some, but not all, G-alpha proteins independently of G-protein coupled
CC receptors. Acts by exchanging bound GDP for free GTP. Able to
CC facilitate synaptic transmission in the nervous system probably by
CC activating G(q)-alpha (egl-30). Also able to activate the G(s)-alpha in
CC synaptic signaling network. Plays a key role in asymmetric spindle
CC positioning, a step for asymmetric cell division that generates cell
CC diversity during development by activating G(i)-alpha protein goa-1 and
CC gpa-16 independently of G-protein coupled receptors. While it acts as a
CC GEF for goa-1, it has no GEF activity toward gpa-16. In addition to its
CC GEF activity, it is required for cortical subcellular localization of
CC G-alpha proteins such as gpa-16. Also required for the interaction of
CC goa-1 and gpr-1/2, suggesting that it may act by generating G-alpha
CC proteins free from G-beta-gamma subunits, enabling gpr-1/2 to mediate
CC asymmetric cell division. {ECO:0000269|PubMed:11102364,
CC ECO:0000269|PubMed:15479638, ECO:0000269|PubMed:15479639,
CC ECO:0000269|PubMed:15489510, ECO:0000269|PubMed:15489511,
CC ECO:0000269|PubMed:15498497, ECO:0000269|PubMed:16162648,
CC ECO:0000269|PubMed:9851916}.
CC -!- SUBUNIT: Interacts with GDP-bound G-alpha proteins goa-1 and gpa-16.
CC Does not interact with G-alpha proteins when they are in complex with
CC subunits beta and gamma. {ECO:0000269|PubMed:15479638,
CC ECO:0000269|PubMed:15479639, ECO:0000269|PubMed:15498497,
CC ECO:0000269|PubMed:16162648}.
CC -!- INTERACTION:
CC Q9GSX9-1; P51875: goa-1; NbExp=9; IntAct=EBI-1004494, EBI-316062;
CC Q9GSX9-1; Q9N2V6: gpa-16; NbExp=2; IntAct=EBI-1004494, EBI-1005005;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:15479638, ECO:0000269|PubMed:15479639,
CC ECO:0000269|PubMed:9851916}. Note=Localizes to the cell cortex.
CC Excluded from interphase nuclei and becomes localized around what
CC appeared to be kinetochore microtubules at the onset of mitosis,
CC becoming more diffuse during anaphase.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q9GSX9-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q9GSX9-2; Sequence=VSP_018516, VSP_018517;
CC -!- TISSUE SPECIFICITY: Present throughout the nervous system in juveniles
CC and adults (at protein level). {ECO:0000269|PubMed:9851916}.
CC -!- SIMILARITY: Belongs to the synembryn family. {ECO:0000305}.
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DR EMBL; AF288812; AAG10199.1; -; mRNA.
DR EMBL; FO081818; CCD74109.1; -; Genomic_DNA.
DR EMBL; FO081818; CCD74110.1; -; Genomic_DNA.
DR RefSeq; NP_001023561.1; NM_001028390.2. [Q9GSX9-1]
DR RefSeq; NP_001023562.1; NM_001028391.3.
DR AlphaFoldDB; Q9GSX9; -.
DR SMR; Q9GSX9; -.
DR BioGRID; 42196; 9.
DR DIP; DIP-26607N; -.
DR IntAct; Q9GSX9; 6.
DR STRING; 6239.Y69A2AR.2a; -.
DR iPTMnet; Q9GSX9; -.
DR EPD; Q9GSX9; -.
DR PaxDb; Q9GSX9; -.
DR PeptideAtlas; Q9GSX9; -.
DR EnsemblMetazoa; Y69A2AR.2a.1; Y69A2AR.2a.1; WBGene00004367. [Q9GSX9-1]
DR EnsemblMetazoa; Y69A2AR.2b.1; Y69A2AR.2b.1; WBGene00004367. [Q9GSX9-2]
DR GeneID; 177048; -.
DR KEGG; cel:CELE_Y69A2AR.2; -.
DR UCSC; Y69A2AR.2a; c. elegans. [Q9GSX9-1]
DR CTD; 177048; -.
DR WormBase; Y69A2AR.2a; CE27516; WBGene00004367; ric-8. [Q9GSX9-1]
DR WormBase; Y69A2AR.2b; CE33952; WBGene00004367; ric-8. [Q9GSX9-2]
DR eggNOG; KOG4464; Eukaryota.
DR HOGENOM; CLU_018602_1_0_1; -.
DR InParanoid; Q9GSX9; -.
DR OMA; EDNHQFR; -.
DR OrthoDB; 1110075at2759; -.
DR PhylomeDB; Q9GSX9; -.
DR PRO; PR:Q9GSX9; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00004367; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q9GSX9; baseline.
DR GO; GO:0005818; C:aster; IDA:WormBase.
DR GO; GO:0005938; C:cell cortex; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005828; C:kinetochore microtubule; IDA:WormBase.
DR GO; GO:0005819; C:spindle; IDA:WormBase.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IBA:GO_Central.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:WormBase.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0090038; P:negative regulation of protein kinase C signaling; IGI:WormBase.
DR GO; GO:0072697; P:protein localization to cell cortex; IMP:WormBase.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; IGI:WormBase.
DR GO; GO:0060259; P:regulation of feeding behavior; IMP:WormBase.
DR InterPro; IPR019318; Gua_nucleotide_exch_fac_Ric8.
DR InterPro; IPR008376; Synembryn.
DR PANTHER; PTHR12425; PTHR12425; 1.
DR Pfam; PF10165; Ric8; 1.
DR PRINTS; PR01802; SYNEMBRYN.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein;
KW Guanine-nucleotide releasing factor; Reference proteome.
FT CHAIN 1..566
FT /note="Synembryn"
FT /id="PRO_0000235904"
FT VAR_SEQ 109..157
FT /note="TLMEAQKCLINTLFHSQRMRDRFYANPKTGENLQFFLGEFEENRRKTSS ->
FT SKAILSLKILEFPAKNHNFSTNGGAKMSNQHFVSLTTNERSILCKPENW (in
FT isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_018516"
FT VAR_SEQ 158..566
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_018517"
FT MUTAGEN 267
FT /note="L->F: In md1712; exhibits partial embryonic
FT lethality that appears to result from defects in the
FT regulation of a subset of centrosome movements during early
FT embryogenesis."
FT /evidence="ECO:0000269|PubMed:9851916"
FT MUTAGEN 275
FT /note="A->E: In md303; exhibits partial embryonic lethality
FT that appears to result from defects in the regulation of a
FT subset of centrosome movements during early embryogenesis;
FT impairs interaction with goa-1."
FT /evidence="ECO:0000269|PubMed:9851916"
SQ SEQUENCE 566 AA; 63447 MW; 10C4E5423BB81FBF CRC64;
MSEELHSDLI ASIFGGKPAK IEEFFSKWNF ANAAVSKFDM ANSAKNELGD RICEVIENGE
LTHVLLETIK ILSREKDGLE GLLNDPLCDK ILAFAELSSN ENNSKTVHTL MEAQKCLINT
LFHSQRMRDR FYANPKTGEN LQFFLGEFEE NRRKTSSIDW IRLLNPVQAA EIWYFYHRIA
FIATALGREF QKNWANDPKT IDSLLLAVEI CTNRSENSTQ DINRATEALK TFFNVFCHFH
GDVKAIDHKN AAKTCQILRD AICSDVLTDD VVQSAIHCLS VPPLPMVLSV LCGKNSKNNG
GENEEEKFFV EELSNMQLTE AILMHLDKQL TKVVALLLND APNQQQNPML SAEASTLTDL
VGPYFQVLAR LCTDSKYVRR YCRIRVIPPL VSEEVQKRPE ENNTLRGRIA RIMMLPSSTK
DVAAEFLFII CKRSVNRMIK YLGFGHSAGH LANLGLLGQI NQPKHASDSE DSETEDYNQI
KDSVNPVTGA IYPSDHGSAL AGMSEEQKEY EAMKLVDAMN QMMETGIVKP GTIGDDGKIR
EVSHVLELLK NAPEPAPAEN SDSDEE
