GAPA_DICDI
ID GAPA_DICDI Reviewed; 860 AA.
AC O00899; Q55DP3;
DT 03-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Ras GTPase-activating-like protein gapA;
DE AltName: Full=IQGAP-related protein gapA;
GN Name=gapA; ORFNames=DDB_G0269140;
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], FUNCTION, DISRUPTION PHENOTYPE, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=AX2;
RX PubMed=9151691; DOI=10.1083/jcb.137.4.891;
RA Adachi H., Takahashi Y., Hasebe T., Shirouzu M., Yokoyama S., Sutoh K.;
RT "Dictyostelium IQGAP-related protein specifically involved in the
RT completion of cytokinesis.";
RL J. Cell Biol. 137:891-898(1997).
RN [2]
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 [3]
RP FUNCTION, AND MUTAGENESIS OF ARG-442 AND LYS-474.
RX PubMed=11577743; DOI=10.1271/bbb.65.1912;
RA Sakurai M., Adachi H., Sutoh K.;
RT "Mutational analyses of Dictyostelium IQGAP-related protein GAPA: possible
RT interaction with small GTPases in cytokinesis.";
RL Biosci. Biotechnol. Biochem. 65:1912-1916(2001).
RN [4]
RP FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=11447112; DOI=10.1093/emboj/20.14.3705;
RA Faix J., Weber I., Mintert U., Koehler J., Lottspeich F., Marriott G.;
RT "Recruitment of cortexillin into the cleavage furrow is controlled by Rac1
RT and IQGAP-related proteins.";
RL EMBO J. 20:3705-3715(2001).
RN [5]
RP INDUCTION.
RX PubMed=12771188; DOI=10.1242/jcs.00501;
RA Araki T., Tsujioka M., Abe T., Fukuzawa M., Meima M., Schaap P., Morio T.,
RA Urushihara H., Katoh M., Maeda M., Tanaka Y., Takeuchi I., Williams J.G.;
RT "A STAT-regulated, stress-induced signalling pathway in Dictyostelium.";
RL J. Cell Sci. 116:2907-2915(2003).
RN [6]
RP IDENTIFICATION.
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 INDUCTION.
RX PubMed=17517120; DOI=10.1186/1471-2164-8-123;
RA Na J., Tunggal B., Eichinger L.;
RT "STATc is a key regulator of the transcriptional response to hyperosmotic
RT shock.";
RL BMC Genomics 8:123-123(2007).
CC -!- FUNCTION: Part of signaling pathway that is required for completion of
CC cytokinesis. gapA and rgaA control cortexillin localization to the
CC cleavage furrow and hence may be involved in cleavage of the midbody in
CC the final stage of cytokinesis by regulating the actin cytoskeleton.
CC Forms a complex by linking activated rac1A to ctxA in the absence of
CC rgaA. Assembly of this complex is necessary for the recruitment of
CC cortexillin to the midzone of the dividing cell.
CC {ECO:0000269|PubMed:11447112, ECO:0000269|PubMed:11577743,
CC ECO:0000269|PubMed:9151691}.
CC -!- SUBUNIT: Heterotetramer. Quaternary complex with activated rac1A, ctxA
CC and ctxB in the absence of rgaA. {ECO:0000269|PubMed:11447112}.
CC -!- DEVELOPMENTAL STAGE: Not required for development.
CC {ECO:0000269|PubMed:9151691}.
CC -!- INDUCTION: Rapidly up-regulated by hyperosmotic stress, which is
CC dependent on dstC. Strongly inducible by 8-bromo-cGMP and to a lesser
CC extent by 8-bromo-cAMP. Not induced by DIF (differentiation-inducing
CC factor- a chlorinated hexaphenone). {ECO:0000269|PubMed:12771188,
CC ECO:0000269|PubMed:17517120}.
CC -!- DISRUPTION PHENOTYPE: Cells initiate cleavage furrow formation but
CC rarely complete cytokinesis. They grow as giant and multinucleate cells
CC both on a substratum and in suspension culture with increased cell mass
CC but development remains unaffected. Mutants lacking both rgaA and gapA
CC are extremely large, flat and multinucleate, and exhibit cytokinesis
CC defects similar to that seen with simultaneous loss of ctxA and ctxB.
CC Starved null cells form normal fruiting bodies with viable spores at
CC the same time as wild-type cells and the increase in size of the plaque
CC on the bacterial lawn and the terminal phenotype also unaffected.
CC Earlier stages of cytokinesis characterized by accumulation of myosin
CC II at the furrow not affected. {ECO:0000269|PubMed:11447112,
CC ECO:0000269|PubMed:9151691}.
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DR EMBL; D88027; BAA20434.1; -; Genomic_DNA.
DR EMBL; AAFI02000005; EAL71920.1; -; Genomic_DNA.
DR RefSeq; XP_646088.1; XM_640996.1.
DR AlphaFoldDB; O00899; -.
DR SMR; O00899; -.
DR IntAct; O00899; 1.
DR STRING; 44689.DDB0191293; -.
DR PaxDb; O00899; -.
DR EnsemblProtists; EAL71920; EAL71920; DDB_G0269140.
DR GeneID; 8617038; -.
DR KEGG; ddi:DDB_G0269140; -.
DR dictyBase; DDB_G0269140; gapA.
DR eggNOG; KOG2128; Eukaryota.
DR HOGENOM; CLU_009455_0_0_1; -.
DR InParanoid; O00899; -.
DR OMA; CERFFTG; -.
DR PhylomeDB; O00899; -.
DR Reactome; R-DDI-5626467; RHO GTPases activate IQGAPs.
DR Reactome; R-DDI-6798695; Neutrophil degranulation.
DR Reactome; R-DDI-9013149; RAC1 GTPase cycle.
DR Reactome; R-DDI-9013406; RHOQ GTPase cycle.
DR PRO; PR:O00899; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0031254; C:cell trailing edge; IDA:dictyBase.
DR GO; GO:0032154; C:cleavage furrow; IDA:dictyBase.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0030175; C:filopodium; IDA:dictyBase.
DR GO; GO:0030027; C:lamellipodium; IDA:dictyBase.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:dictyBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IGI:dictyBase.
DR GO; GO:0050982; P:detection of mechanical stimulus; IMP:dictyBase.
DR GO; GO:0006972; P:hyperosmotic response; IEP:dictyBase.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:dictyBase.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:dictyBase.
DR GO; GO:1905345; P:protein localization to cleavage furrow; IMP:dictyBase.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:dictyBase.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0043520; P:regulation of myosin II filament assembly; IMP:dictyBase.
DR GO; GO:0006979; P:response to oxidative stress; IEP:dictyBase.
DR GO; GO:0019953; P:sexual reproduction; IEP:dictyBase.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0051225; P:spindle assembly; IMP:dictyBase.
DR Gene3D; 1.10.506.10; -; 1.
DR InterPro; IPR000593; RasGAP_C.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR Pfam; PF00616; RasGAP; 1.
DR Pfam; PF03836; RasGAP_C; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Coiled coil; Reference proteome.
FT CHAIN 1..860
FT /note="Ras GTPase-activating-like protein gapA"
FT /id="PRO_0000386631"
FT DOMAIN 253..481
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 146..185
FT /evidence="ECO:0000255"
FT COILED 663..732
FT /evidence="ECO:0000255"
FT COMPBIAS 1..17
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 442
FT /note="R->E: Unable to complement a gapA null mutant."
FT /evidence="ECO:0000269|PubMed:11577743"
FT MUTAGEN 442
FT /note="R->K: Able to complement a gapA null mutant."
FT /evidence="ECO:0000269|PubMed:11577743"
FT MUTAGEN 474
FT /note="K->E: Unable to complement a gapA null mutant."
FT /evidence="ECO:0000269|PubMed:11577743"
FT MUTAGEN 474
FT /note="K->R: Able to complement a gapA null mutant."
FT /evidence="ECO:0000269|PubMed:11577743"
SQ SEQUENCE 860 AA; 98825 MW; 9FA629B483DA53C4 CRC64;
MEGLEIEDED VILLDEDDDS SSSSTVNNSS SNIKNNGNTN NNIGNDDSNK VTLMTSLREK
GWGSGMLVDK EKNQYGTIKS YKDDKSSPWF EERQVIATLY KARVLLHEMI YTKMNQERLL
SGNLCVGEIQ SLLNTQKEDV ETDWIAEIQE LKRNMVAEIR RNHLLERDVN KLDKRIALLI
KHRSNIKDLL LEQNKGKKDK KKKGDDKAEY ITLDQKQLES YQNLFYLLQT EPHYLAKLVT
LIQADQMEDF LDTVFLTLFG DDFSPREEFL ILSLFRLAIG QEMSRIKSAG DLLAVESVVP
KMIITYTRRK QGHEFLKQII APILENNVVN APDLNLELNA VQVYQNMISE QEIQTGAKST
LNRGLAEDQI IQLKEVQSIL EPRVEKCIQI CERFFTGIIQ SLNRLPYGIR WICKQIQSIA
QKNFDSKPDE IAKVIGYFVY YRFINLAIVT PDAFEILDKE LSITSRKNLV NIAKVLQNLF
TLKTFQNQGS ERWMQPLNKW ILSKTSIVRQ YLEDLIQVTD PSEYLRVDKY NELTLKLNPV
VVISLGEISQ THRLLIANLA ALKMKEKEDP LELILKALPA PLEVVDENDR EIQLTLINRF
KENIEKEISI SASLLAETKE LVISVLRSIP IQQKQQQQQH DDEKRDDLIS ILQNAIKHGK
ETNNPQLSSN AEKIINNLKK MEAEGSIQSE NNQYEGFIKV IALEVINRQE IREQQRKERM
RLTIALRDLR KHQSYLNDQI QHYTSYLKDV LLHYGPKDKK KSTKPMKISF KELTKKGVIV
ESDIPKLSHG STSFYISSDA PGIFDIEARI GVASVGTLSL SLDDLLDKSS AGIPYLKLEN
IVLDVNMTLH LLNRHFLKNI
