GEFH_DICDI
ID GEFH_DICDI Reviewed; 604 AA.
AC Q8IS16; Q550U8;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Ras guanine nucleotide exchange factor H;
DE AltName: Full=RasGEF domain-containing protein H;
GN Name=gefH; Synonyms=rasGEFH; ORFNames=DDB_G0276963;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
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 IDENTIFICATION IN THE SCA1 COMPLEX, INTERACTION WITH GEFA AND PHR,
RP FUNCTION, AND 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: Promotes the exchange of Ras-bound GDP by GTP
CC (PubMed:20493808). Component of the Sca1 complex, a regulator of cell
CC motility, chemotaxis and signal relay (PubMed:20493808). The Sca1
CC complex is recruited to the plasma membrane in a chemoattractant- and
CC F-actin-dependent manner and is enriched at the leading edge of
CC chemotaxing cells where it regulates F-actin dynamics and signal relay
CC by 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:20493808}.
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 gefA and phr
CC (PubMed:20493808). {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 from
CC early development (PubMed:16086850). {ECO:0000269|PubMed:16086850}.
CC -!- DISRUPTION PHENOTYPE: Display directionality defects during chemotaxis
CC as well as defects in random motility (PubMed:20493808).
CC {ECO:0000269|PubMed:20493808}.
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DR EMBL; AY160097; AAN46877.1; -; Genomic_DNA.
DR EMBL; AAFI02000019; EAL68983.1; -; Genomic_DNA.
DR RefSeq; XP_642834.1; XM_637742.1.
DR AlphaFoldDB; Q8IS16; -.
DR SMR; Q8IS16; -.
DR STRING; 44689.DDB0185196; -.
DR PaxDb; Q8IS16; -.
DR PRIDE; Q8IS16; -.
DR EnsemblProtists; EAL68983; EAL68983; DDB_G0276963.
DR GeneID; 8620698; -.
DR KEGG; ddi:DDB_G0276963; -.
DR dictyBase; DDB_G0276963; gefH.
DR eggNOG; KOG3417; Eukaryota.
DR HOGENOM; CLU_452309_0_0_1; -.
DR InParanoid; Q8IS16; -.
DR OMA; FNDFTKW; -.
DR PhylomeDB; Q8IS16; -.
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:Q8IS16; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005829; C:cytosol; IMP:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IMP:dictyBase.
DR GO; GO:1905742; C:Ras guanyl-nucleotide exchange factor complex; IDA:dictyBase.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IMP:dictyBase.
DR GO; GO:0030295; F:protein kinase activator activity; IDA: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:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:dictyBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
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; 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..604
FT /note="Ras guanine nucleotide exchange factor H"
FT /id="PRO_0000384466"
FT DOMAIN 115..147
FT /note="LisH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00126"
FT DOMAIN 221..335
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 365..591
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 1..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 604 AA; 69714 MW; 2510BE3CC4E10B7A CRC64;
MSNTNINVQS STPKKSLGSS QYSLAGSSSS NLNNINNNNN NNNNNNNNST GQENSIDDSG
SSSFVNFPAS EWLSKAMHKH PDILELRERT RPITQVKSYS RNKRSSKTEA SHSINDTMLL
KLIMQYFHEE NLTTSLKKIQ EETKVQFTPN EVDKDSLENL LRIGIKDTNW FGPLEDIEDA
DPEVETYHSY ISEDSLNENG LEGEGNLIED RYDESQISRN PDGTIKAATF NRLLLWLIGN
FNGPDVNEFK KIFFLTYPSF TTAEAILNKF TQIYQLFDNI ESAQVICFIR FWIEQHPTDF
NEKLLAILNN FIEHQVAASH AKQLRAVINL KIENYKEARK EIKDPPEPKV PKNIFSPTLT
FDDIDEEEIA RQLCCIDFAL YELIKPSEFL IKGWTKPQYR NKAVNLLNMM RRFNDFTKWI
AASILNEQNS KGRSKLLGRF LKISEHLRAN NNFHSLMAIY GGINNTHVFR TKAIRKDLSR
QQQETYAELE KLFASENSFR NYRIAYKDAK PPCIPFLGIH LRDLAFVDES NPDRINNLLN
LNKRRVIWRV IVNTMRYQPI PYYFLKVHQI SLFLTELKTE SEQPQLTLDL SSHDTVLPSS
PSSK
