GFLB_DICDI
ID GFLB_DICDI Reviewed; 1601 AA.
AC Q54L90;
DT 03-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 25-MAY-2022, entry version 121.
DE RecName: Full=Ras guanine nucleotide exchange factor glfB {ECO:0000303|PubMed:27237792};
DE AltName: Full=GEF-Like protein B {ECO:0000303|PubMed:27237792};
GN Name=gflB {ECO:0000303|PubMed:27237792}; Synonyms=RacGAP;
GN ORFNames=DDB0187142;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
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 [2]
RP INTERACTION WITH GALPHA2 AND RAPA, FUNCTION, DISRUPTION PHENOTYPE,
RP MUTAGENESIS OF THR-1180, DOMAIN, SUBCELLULAR LOCATION, AND PHOSPHORYLATION
RP AT SER-197 AND THR-201.
RX PubMed=27237792; DOI=10.1016/j.devcel.2016.05.001;
RA Liu Y., Lacal J., Veltman D.M., Fusetti F., van Haastert P.J., Firtel R.A.,
RA Kortholt A.;
RT "A Galpha-Stimulated RapGEF Is a Receptor-Proximal Regulator of
RT Dictyostelium Chemotaxis.";
RL Dev. Cell 37:458-472(2016).
RN [3]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH
RP F-ACTIN, AND DOMAIN.
RX PubMed=28778987; DOI=10.1242/jcs.194126;
RA Inaba H., Yoda K., Adachi H.;
RT "The F-actin-binding RapGEF GflB is required for efficient macropinocytosis
RT in Dictyostelium.";
RL J. Cell Sci. 130:3158-3172(2017).
RN [4]
RP FUNCTION.
RX PubMed=29626371; DOI=10.1111/1462-2920.14126;
RA Baumgardner K., Lin C., Firtel R.A., Lacal J.;
RT "Phosphodiesterase PdeD, dynacortin, and a Kelch repeat-containing protein
RT are direct GSK3 substrates in Dictyostelium that contribute to chemotaxis
RT towards cAMP.";
RL Environ. Microbiol. 20:1888-1903(2018).
CC -!- FUNCTION: GpaB-activated, rapA-specific guanine nucleotide exchange
CC factor, involved in the regulation of the balance between Ras and Rap
CC signaling at the leading edge of chemotaxing cells (PubMed:27237792,
CC PubMed:29626371). Spatially localized activation of Rap and Ras induces
CC F-actin polymerization at the leading edge of chemotaxing cells through
CC the Rac, PI3K, and TORC2 pathways (PubMed:27237792). Acts also as a key
CC regulator of actin-driven membrane protrusions during processes such as
CC phagocytosis and cytokinesis, possibly by modulating rapA signaling
CC pathways (PubMed:28778987). {ECO:0000269|PubMed:27237792,
CC ECO:0000269|PubMed:28778987, ECO:0000269|PubMed:29626371}.
CC -!- SUBUNIT: Interacts with gpaB and rapA (PubMed:27237792). Interacts
CC directly with F-actin (PubMed:28778987). {ECO:0000269|PubMed:27237792,
CC ECO:0000269|PubMed:28778987}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:27237792, ECO:0000269|PubMed:28778987}. Cytoplasm,
CC cytoskeleton {ECO:0000269|PubMed:28778987}. Cell projection, filopodium
CC {ECO:0000269|PubMed:28778987}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:28778987}. Note=During chemotaxis, localizes at the
CC leading edge of cells, whereas in response to cAMP stimulation, rapidly
CC and transiently translocates to the cortex (PubMed:27237792). Localizes
CC to F-actin-rich regions (PubMed:28778987). During macropinocytosis,
CC strongly localizes to crowns and remains there for a short time after
CC the cups were enclosed (PubMed:28778987). During phagocytosis of heat-
CC killed yeast, strongly localizes to phagocytic cups with F-actin
CC (PubMed:28778987). During cytokinesis, mainly colocalizes with F-actin
CC at filopodia or lamellipodia of daughter cells (PubMed:28778987).
CC {ECO:0000269|PubMed:27237792, ECO:0000269|PubMed:28778987}.
CC -!- DOMAIN: The N-terminus (residues 1262 to 1601) functions to regulate
CC both GflB-GEF activity and its localization at the leading edge of
CC cells by binding F-actin directly. {ECO:0000269|PubMed:27237792,
CC ECO:0000269|PubMed:28778987}.
CC -!- PTM: Simultaneously phosphorylated at Ser-197 and Thr-201 after cAMP
CC stimulation. {ECO:0000269|PubMed:27237792}.
CC -!- DISRUPTION PHENOTYPE: Leads to considerable chemotaxis defects,
CC including poorer directionality, more directional changes, and slower
CC speed (PubMed:27237792). Exhibits impaired crown formation and
CC particularly retraction, resulting in more crowns (macropinocytic cups)
CC per cell and longer crown lifetimes (PubMed:28778987). Leads to defects
CC in macropinocytosis, phagocytosis and cytokinesis (PubMed:28778987).
CC Leads to increased level of F-actin as well as to flatter and more
CC polarized cells during vegetative growth (PubMed:28778987).
CC {ECO:0000269|PubMed:27237792, ECO:0000269|PubMed:28778987}.
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DR EMBL; AAFI01000139; EAL64142.1; -; Genomic_DNA.
DR RefSeq; XP_637671.1; XM_632579.1.
DR AlphaFoldDB; Q54L90; -.
DR SMR; Q54L90; -.
DR STRING; 44689.DDB0231996; -.
DR iPTMnet; Q54L90; -.
DR PaxDb; Q54L90; -.
DR GeneID; 8625811; -.
DR KEGG; ddi:DDB_G0286773; -.
DR dictyBase; DDB_G0286773; gflB.
DR eggNOG; KOG3417; Eukaryota.
DR HOGENOM; CLU_244302_0_0_1; -.
DR InParanoid; Q54L90; -.
DR OMA; KLWVDYC; -.
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:Q54L90; -.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0031252; C:cell leading edge; IDA:dictyBase.
DR GO; GO:1904269; C:cell leading edge cell cortex; IDA:dictyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:dictyBase.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0070687; C:macropinocytic cup cytoskeleton; IDA:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0051015; F:actin filament binding; IDA:dictyBase.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:dictyBase.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:dictyBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:dictyBase.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:dictyBase.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0060097; P:cytoskeletal rearrangement involved in phagocytosis, engulfment; IMP:dictyBase.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:dictyBase.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IMP:dictyBase.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IMP:dictyBase.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:1905511; P:positive regulation of myosin II filament assembly; IMP:dictyBase.
DR GO; GO:0032486; P:Rap protein signal transduction; IDA:dictyBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0061118; P:regulation of positive chemotaxis to cAMP; IMP:dictyBase.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.10.840.10; -; 1.
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 InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Cell projection; Chemotaxis; Cytoplasm; Cytoskeleton;
KW Guanine-nucleotide releasing factor; Phosphoprotein.
FT CHAIN 1..1601
FT /note="Ras guanine nucleotide exchange factor glfB"
FT /id="PRO_0000447604"
FT DOMAIN 649..836
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 851..983
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 1021..1255
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 43..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 310..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 475..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1262..1601
FT /note="N-terminal F-actin-binding domain"
FT /evidence="ECO:0000303|PubMed:27237792"
FT REGION 1443..1474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..358
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 475..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 521..535
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..579
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 580..614
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1455..1474
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27237792"
FT MOD_RES 201
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:27237792"
FT MUTAGEN 1180
FT /note="T->E: Affects chemotaxis with reduced
FT directionality."
FT /evidence="ECO:0000269|PubMed:27237792"
SQ SEQUENCE 1601 AA; 177519 MW; 1F67D705F686BCA9 CRC64;
MTDLNSESFS ALNFWKSVEK KNISTNFQGT KVVAPSKKIN SFPLLAPPAP PPPPTEQEIN
IGSGNSTFIS SNNNNSNNNN NNNSNNNNNN NLNNSNNNNN NLNSNNNNNN NNNNNNNNGN
NNNNSNFLTR QDSSTQKEWD EQNVTEAFGF WKQKAVQLQK ETERYNARRN ARQTIDLTNI
LRKSTSSDLL IKPPVESPPL TPVGQDDEGE QQQQQQQQKQ SSPSTPSNDT DTETTAAAVT
TTTTTTTTTT TSTTTTTTET VLQANQLEIK YGGETIAVVD DSGTTPRDYR RSRSISCEII
PKINGVITTS PQRVTTTTTT TTPSTGGVVV ADEESDSSEE ESDSSEEESD EYTDEESETE
LQVVSNATPR RSDDFTPTIV ESPPLTSVNS NDNTSSGTVV APIDLNSSTG GNTGSQQPPQ
PSSQQQKPDQ ASENTAVAAS SISATTNVTS AASTTTVAPD SIINTKDVTV VSSTLTTTTS
ATSSTTSATT QSIPAPPSPS QQRAAQSIST SSVTPAAITK PTKDAKDKKD PAKKSIGATL
TRTVTKTFIR DSKENNKVPT GTSPPVSSST SISSSTGIKK DKVKLSKEEK DRIKKEKSAK
KKKEKDEKKQ QKTNKKALTK NNSSTDVKKG FVSPQQQQIL DSPYRIYGVR LTQLVLSNDG
DLPAILTQTI TVLSNSNKLD VNSVFVGAEN EPAVREIRKR SDLERIDFSI IGDPRVVAGL
LILFFAELPQ PLFNSKFFGD LVEINDITNP QVKLNDLKQL INSLSQLRRS LLQILVTFFT
SKYINGNSVT TRAIAIQSIA QSFGPQFFRG TSSSDSDIQV GIETLKLIID NYVFLFEKTN
EPDVKYKNID GKMIISEGSI DKLIDKATDQ YYPYNEKYFS LTFFITHLFF IQPHELADKL
ITLYRENLDT LETKKKWKKH RRSKKASFIN EAVKLWVDYC YKEMREDKEL SKKILKGFPH
LEAQLASRLS HRTTINDFLK LPKRVHSRTR SASFSDTLLS TGGIGSTSGG IGGGVNNCLL
SAMEIAEQCT LVDYDLFTNV RLSDWVRLVQ GSVDPQTAPS LSLALKRSTI WAQWAMGEIL
STEDKSQRVA IINLLVDVAI NCKDLANFNT AISIHTALTN HHIKRLQQTW DSVPKETLNK
ITQLEQSLQV WLKPDATNPF GVICQSINSA CVPNFSILRT ILSQIDQKIP TFSNDGSMVN
VEKLRTIFGI VVEIQRLQQQ RNYTMKPTKL FIQLQDINTV SMDELADLSL KCEPPVSKAK
KYNAPADIVD EDWRLKITKT FNKPLATTSV GIDLPRLASS FTFNTTGHKT TPEEKSAYGN
KIQDIFHVLV SLAQIESSEL ETDVREKFTT YIPMSTDPDS DFKRELLKFL DEVCHADNSK
LVRVLKCCNQ AIIAPVIIEI TLNIAKGVPF MDAGGWRILI SNINNSNNSV ILDKIDEINE
DSSNVEKEKL SSSQEQQEQQ EQKQQEQQQQ QQEPQPLFIR HYKKQRSRSA QSKDFFEFEW
FIQLNLDADC KNILSFDLKI SNLVFSTDTS PNIRDQLLES FKSYLVSQEC VQYINFNENK
QPVAAPVTPA TTIVTTKEES TTVTSSTTTV VQESVPSTNA E
