GEFA_DICDI
ID GEFA_DICDI Reviewed; 605 AA.
AC Q54PQ4; Q23867; Q8IS22;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Ras guanine nucleotide exchange factor A;
DE Short=Aimless;
DE AltName: Full=RasGEF domain-containing protein A;
GN Name=gefA; Synonyms=aleA, rasGEFA; ORFNames=DDB_G0284329;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DISRUPTION PHENOTYPE, AND FUNCTION.
RC STRAIN=AX3;
RX PubMed=8793298; DOI=10.1016/s0960-9822(09)00453-9;
RA Insall R.H., Borleis J., Devreotes P.N.;
RT "The aimless RasGEF is required for processing of chemotactic signals
RT through G-protein-coupled receptors in Dictyostelium.";
RL Curr. Biol. 6:719-729(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=AX4;
RX PubMed=16086850; DOI=10.1186/gb-2005-6-8-r68;
RA Wilkins A., Szafranski K., Fraser D.J., Bakthavatsalam D., Mueller R.,
RA Fisher P.R., Gloeckner G., Eichinger L., Noegel A.A., Insall R.H.;
RT "The Dictyostelium genome encodes numerous RasGEFs with multiple biological
RT roles.";
RL Genome Biol. 6:R68.1-R68.12(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=10473630; DOI=10.1091/mbc.10.9.2829;
RA Lee S., Parent C.A., Insall R., Firtel R.A.;
RT "A novel Ras-interacting protein required for chemotaxis and cyclic
RT adenosine monophosphate signal relay in Dictyostelium.";
RL Mol. Biol. Cell 10:2829-2845(1999).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=11422293; DOI=10.1046/j.1440-169x.2001.00572.x;
RA Tsujioka M., Yokoyama M., Nishio K., Kuwayama H., Morio T., Katoh M.,
RA Urushihara H., Saito T., Ochiai H., Tanaka Y., Takeuchi I., Maeda M.;
RT "Spatial expression patterns of genes involved in cyclic AMP responses in
RT Dictyostelium discoideum development.";
RL Dev. Growth Differ. 43:275-283(2001).
RN [6]
RP FUNCTION.
RX PubMed=16234315; DOI=10.1093/bioinformatics/bti726;
RA Booth E.O., Van Driessche N., Zhuchenko O., Kuspa A., Shaulsky G.;
RT "Microarray phenotyping in Dictyostelium reveals a regulon of chemotaxis
RT genes.";
RL Bioinformatics 21:4371-4377(2005).
RN [7]
RP FUNCTION.
RX PubMed=17380187; DOI=10.1038/sj.embor.7400936;
RA Kae H., Kortholt A., Rehmann H., Insall R.H., Van Haastert P.J.,
RA Spiegelman G.B., Weeks G.;
RT "Cyclic AMP signalling in Dictyostelium: G-proteins activate separate Ras
RT pathways using specific RasGEFs.";
RL EMBO Rep. 8:477-482(2007).
RN [8]
RP IDENTIFICATION IN THE SCA1 COMPLEX, INTERACTION WITH GEFH, FUNCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=20493808; DOI=10.1016/j.devcel.2010.03.017;
RA Charest P.G., Shen Z., Lakoduk A., Sasaki A.T., Briggs S.P., Firtel R.A.;
RT "A Ras signaling complex controls the RasC-TORC2 pathway and directed cell
RT migration.";
RL Dev. Cell 18:737-749(2010).
CC -!- FUNCTION: Ras-bound GDP/GTP exchange factor required for normal
CC activation of adenylyl cyclase (PubMed:17380187). Component of the Sca1
CC complex, a regulator of cell motility, chemotaxis and signal relay
CC (PubMed:8793298, PubMed:16234315, PubMed:20493808). The Sca1 complex is
CC recruited to the plasma membrane in a chemoattractant- and F-actin-
CC dependent manner and is enriched at the leading edge of chemotaxing
CC cells where it regulates F-actin dynamics and signal relay by
CC controlling the activation of rasC and the downstream target of
CC rapamycin complex 2 (TORC2)-Akt/protein kinase B (PKB) pathway
CC (PubMed:20493808). {ECO:0000269|PubMed:16234315,
CC ECO:0000269|PubMed:17380187, ECO:0000269|PubMed:20493808,
CC ECO:0000269|PubMed:8793298}.
CC -!- SUBUNIT: Component of the Sca1 complex composed of at least gefA, gefH,
CC scaA, phr, and the protein phosphatase 2A subunits pppA and pho2B
CC (PubMed:20493808). Interacts directly with gefH (PubMed:20493808).
CC {ECO:0000269|PubMed:20493808}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20493808}.
CC Note=The Sca1 complex is recruited to the plasma membrane in a
CC chemoattractant- and F-actin-dependent manner and is enriched at the
CC leading edge of chemotaxing cells (PubMed:20493808). Membrane
CC localization of the Sca1 complex is regulated by scaA phosphorylation
CC by PKB and PKB-related PKBR1 (PubMed:20493808).
CC {ECO:0000269|PubMed:20493808}.
CC -!- DEVELOPMENTAL STAGE: Expressed during development; especially until 8
CC hours of development (PubMed:16086850). Expression is higher in the tip
CC regions of slugs and early culminants (PubMed:11422293).
CC {ECO:0000269|PubMed:11422293, ECO:0000269|PubMed:16086850}.
CC -!- DISRUPTION PHENOTYPE: Grows at a normal rate, but are severely impaired
CC in both chemotaxis and activation of adenylyl cyclase, both of which
CC are critical for the early stages of development (PubMed:8793298,
CC PubMed:10473630, PubMed:20493808). Unable to aggregate
CC (PubMed:8793298). {ECO:0000269|PubMed:10473630,
CC ECO:0000269|PubMed:20493808, ECO:0000269|PubMed:8793298}.
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DR EMBL; U53884; AAB09441.1; -; mRNA.
DR EMBL; AY160090; AAN46870.1; -; Genomic_DNA.
DR EMBL; AAFI02000064; EAL65212.1; -; Genomic_DNA.
DR RefSeq; XP_638600.1; XM_633508.1.
DR AlphaFoldDB; Q54PQ4; -.
DR SMR; Q54PQ4; -.
DR STRING; 44689.DDB0191187; -.
DR PaxDb; Q54PQ4; -.
DR PRIDE; Q54PQ4; -.
DR EnsemblProtists; EAL65212; EAL65212; DDB_G0284329.
DR GeneID; 8624571; -.
DR KEGG; ddi:DDB_G0284329; -.
DR dictyBase; DDB_G0284329; gefA.
DR eggNOG; KOG3417; Eukaryota.
DR HOGENOM; CLU_452309_0_0_1; -.
DR InParanoid; Q54PQ4; -.
DR OMA; ITAICEP; -.
DR PhylomeDB; Q54PQ4; -.
DR Reactome; R-DDI-1169092; Activation of RAS in B cells.
DR Reactome; R-DDI-171007; p38MAPK events.
DR Reactome; R-DDI-193648; NRAGE signals death through JNK.
DR Reactome; R-DDI-354192; Integrin signaling.
DR Reactome; R-DDI-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-DDI-392517; Rap1 signalling.
DR Reactome; R-DDI-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DDI-9013148; CDC42 GTPase cycle.
DR Reactome; R-DDI-9013149; RAC1 GTPase cycle.
DR PRO; PR:Q54PQ4; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IDA:dictyBase.
DR GO; GO:1905742; C:Ras guanyl-nucleotide exchange factor complex; IDA:dictyBase.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:dictyBase.
DR GO; GO:0030250; F:guanylate cyclase activator activity; IMP:dictyBase.
DR GO; GO:0030295; F:protein kinase activator activity; IDA:dictyBase.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:dictyBase.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IMP:dictyBase.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0000165; P:MAPK cascade; IMP:dictyBase.
DR GO; GO:1903665; P:negative regulation of asexual reproduction; IMP:dictyBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:dictyBase.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:dictyBase.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:dictyBase.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:dictyBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:dictyBase.
DR GO; GO:0051602; P:response to electrical stimulus; IMP:dictyBase.
DR GO; GO:0030587; P:sorocarp development; HMP:dictyBase.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR InterPro; IPR006594; LisH.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00667; LisH; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR PROSITE; PS50896; LISH; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Guanine-nucleotide releasing factor; Membrane;
KW Reference proteome.
FT CHAIN 1..605
FT /note="Ras guanine nucleotide exchange factor A"
FT /id="PRO_0000384459"
FT DOMAIN 67..99
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 198..320
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 353..597
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT CONFLICT 17
FT /note="K -> E (in Ref. 1; AAB09441 and 2; AAN46870)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="N -> D (in Ref. 1; AAB09441 and 2; AAN46870)"
FT /evidence="ECO:0000305"
FT CONFLICT 23..26
FT /note="NWKK -> EWRR (in Ref. 1; AAB09441 and 2; AAN46870)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="F -> L (in Ref. 2; AAN46870)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 605 AA; 70793 MW; B9ABCF37604278B3 CRC64;
MITPTSFEPV ELLYSKKKVN RTNWKKNVLK SNPEINNLCE RIYPINRAIQ FGKQFHPGKA
EVKQKLDKTA IIQLILQHLS TKGLKQTKQT LEKEARTTTP IVEGLNESRL VTYIRNALKD
TDRIYDLSME HTEYSKEERQ SKITEREELL FQMDLLEDED EDDGVNIWDE PTENIITEKV
HTTEYDINKS KENKDDQDDE VVKFASLNKL VEHLTHDSKH DLQFLKTFLM TYQSFCTPEK
LMSKLQQRYN CPSGHDEMAT RNIQIRVINV LKGWVDNYYS DFDDKLIAML RTFIDQIQIK
FPAPASAVNK SLTKMVEKLS PVNDSKHIFN EKTPEPMVPK NIFSNNLSIY DIDEEEIARQ
LTLIEFEIYR NIKPPELLNQ SWNKTKLKSR APNVLKMIDR FNSVSMWVAT MIIQTTKVKA
RARMMTRFIK IADHLKNLNN YNSLMAIIAG LNFSSVYRLK YTREELSAQT MRTYSDLEKI
MNSEGSFKTY RTRLQNVPPM LPYLGVHLTD LTFIDENPNN FVTDVGGKQV SLINFTKRTL
VFKIISLIQE TQVVPYNLQP VHQIQEFLLN IRSDLKAHTL DQYQQELYRE SLKREPKKAQ
RSDVL
