GCA_DICDI
ID GCA_DICDI Reviewed; 1483 AA.
AC Q553Y7; Q869Y1; Q9XZS0;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Guanylyl cyclase, membrane {ECO:0000303|PubMed:11522784};
DE EC=4.6.1.2 {ECO:0000269|PubMed:11237875, ECO:0000269|PubMed:11522784, ECO:0000269|PubMed:11777934};
DE AltName: Full=DdGCA {ECO:0000303|PubMed:11237875};
DE Short=GCA {ECO:0000303|PubMed:11777934};
DE AltName: Full=Guanylate cyclase {ECO:0000303|PubMed:11237875};
GN Name=gca; ORFNames=DDB_G0275009;
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], FUNCTION, CATALYTIC ACTIVITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RC STRAIN=AX3;
RX PubMed=11237875; DOI=10.1042/0264-6021:3540697;
RA Roelofs J., Snippe H., Kleineidam R.G., Van Haastert P.J.;
RT "Guanylate cyclase in Dictyostelium discoideum with the topology of
RT mammalian adenylate cyclase.";
RL Biochem. J. 354:697-706(2001).
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 CHARACTERIZATION, AND SUBCELLULAR LOCATION.
RC STRAIN=NC-4;
RX PubMed=2564393; DOI=10.1016/s0021-9258(18)83745-0;
RA Janssens P.M.W., De Jong C.C.C., Vink A.A., Van Haastert P.J.M.;
RT "Regulatory properties of magnesium-dependent guanylate cyclase in
RT Dictyostelium discoideum membranes.";
RL J. Biol. Chem. 264:4329-4335(1989).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF GLU-440; SER-502 AND HIS-504.
RC STRAIN=AX3;
RX PubMed=11522784; DOI=10.1074/jbc.m105154200;
RA Roelofs J., Loovers H.M., Van Haastert P.J.M.;
RT "GTPgammaS regulation of a 12-transmembrane guanylyl cyclase is retained
RT after mutation to an adenylyl cyclase.";
RL J. Biol. Chem. 276:40740-40745(2001).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND COFACTOR.
RC STRAIN=AX3;
RX PubMed=11777934; DOI=10.1074/jbc.m111437200;
RA Roelofs J., Van Haastert P.J.M.;
RT "Characterization of two unusual guanylyl cyclases from dictyostelium.";
RL J. Biol. Chem. 277:9167-9174(2002).
CC -!- FUNCTION: Synthesizes cyclic GMP (cGMP) from GTP, after activation by
CC heterotrimeric or monomeric G proteins (PubMed:11237875,
CC PubMed:11522784, PubMed:11777934). Involved in chemotaxis
CC (PubMed:11777934). {ECO:0000269|PubMed:11237875,
CC ECO:0000269|PubMed:11522784, ECO:0000269|PubMed:11777934,
CC ECO:0000303|PubMed:11777934}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC Evidence={ECO:0000269|PubMed:11237875, ECO:0000269|PubMed:11522784,
CC ECO:0000269|PubMed:11777934};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13666;
CC Evidence={ECO:0000269|PubMed:11237875, ECO:0000269|PubMed:11522784,
CC ECO:0000269|PubMed:11777934};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11777934};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by guanosine 5'-3-O-(thio)triphosphate
CC (GTPgammaS) (PubMed:11522784, PubMed:11777934). Inhibited by calcium
CC (PubMed:11777934). {ECO:0000269|PubMed:11522784,
CC ECO:0000269|PubMed:11777934}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=250 uM for GTP {ECO:0000269|PubMed:11777934};
CC KM=340 uM for GTP {ECO:0000269|PubMed:11522784};
CC KM=200 uM for GTPgammaS {ECO:0000269|PubMed:11522784,
CC ECO:0000269|PubMed:11777934};
CC Vmax=75 pmol/min/mg enzyme toward GTP {ECO:0000269|PubMed:11522784};
CC Vmax=75 pmol/min/mg enzyme toward GTPgammaS
CC {ECO:0000269|PubMed:11522784};
CC Vmax=6.9 pmol/min/mg enzyme toward GTP {ECO:0000269|PubMed:11777934};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:2564393}; Multi-pass
CC membrane protein {ECO:0000305|PubMed:2564393}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in vegetative cells; expression
CC decreases approximately 3-fold during the aggregation stage, and then
CC increases again during the later stages of development (mound, finger
CC and slug). {ECO:0000269|PubMed:11237875}.
CC -!- INDUCTION: By cAMP and osmotic shock. {ECO:0000269|PubMed:11237875}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; AJ238883; CAB42641.1; -; mRNA.
DR EMBL; AAFI02000013; EAL69785.1; -; Genomic_DNA.
DR RefSeq; XP_643824.1; XM_638732.1.
DR AlphaFoldDB; Q553Y7; -.
DR SMR; Q553Y7; -.
DR STRING; 44689.DDB0191309; -.
DR PaxDb; Q553Y7; -.
DR EnsemblProtists; EAL69785; EAL69785; DDB_G0275009.
DR GeneID; 8619871; -.
DR KEGG; ddi:DDB_G0275009; -.
DR dictyBase; DDB_G0275009; gcA.
DR eggNOG; KOG1023; Eukaryota.
DR HOGENOM; CLU_249557_0_0_1; -.
DR InParanoid; Q553Y7; -.
DR OMA; FRVANMA; -.
DR PhylomeDB; Q553Y7; -.
DR Reactome; R-DDI-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR SABIO-RK; Q553Y7; -.
DR PRO; PR:Q553Y7; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0031252; C:cell leading edge; IDA:dictyBase.
DR GO; GO:0016021; C:integral component of membrane; TAS:dictyBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:dictyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0019934; P:cGMP-mediated signaling; TAS:dictyBase.
DR GO; GO:0006935; P:chemotaxis; IGI:dictyBase.
DR GO; GO:0120320; P:lateral pseudopodium retraction; IGI:dictyBase.
DR GO; GO:0031033; P:myosin filament organization; IGI:dictyBase.
DR GO; GO:0031037; P:myosin II filament disassembly; TAS:dictyBase.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IBA:GO_Central.
DR GO; GO:0050920; P:regulation of chemotaxis; IGI:dictyBase.
DR GO; GO:0051602; P:response to electrical stimulus; IGI:dictyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd07302; CHD; 2.
DR Gene3D; 3.30.70.1230; -; 2.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF00211; Guanylate_cyc; 2.
DR SMART; SM00044; CYCc; 2.
DR SUPFAM; SSF55073; SSF55073; 2.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 1: Evidence at protein level;
KW cGMP biosynthesis; Chemotaxis; GTP-binding; Lyase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1483
FT /note="Guanylyl cyclase, membrane"
FT /id="PRO_0000328216"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..218
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 242..262
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 907..927
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 982..1002
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1016..1036
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1040..1060
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1061..1081
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1094..1114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 395..517
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 1168..1296
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 323..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 672..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1348..1369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1393..1483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 351..376
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 672..813
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1415..1442
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1443..1483
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 1173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 1174
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 1217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 1217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT MUTAGEN 440
FT /note="E->K: Catalytic activity preferentially toward ATP
FT instead of GTP, still activated by GTPgammaS; when
FT associated with Q-502 and D-504."
FT /evidence="ECO:0000269|PubMed:11522784"
FT MUTAGEN 502
FT /note="S->Q: Catalytic activity preferentially toward ATP
FT instead of GTP, still activated by GTPgammaS; when
FT associated with K-440 and D-504."
FT /evidence="ECO:0000269|PubMed:11522784"
FT MUTAGEN 504
FT /note="H->D: Catalytic activity preferentially toward ATP
FT instead of GTP, still activated by GTPgammaS; when
FT associated with K-440 and Q-502."
FT /evidence="ECO:0000269|PubMed:11522784"
FT CONFLICT 707
FT /note="Q -> P (in Ref. 1; CAB42641)"
FT /evidence="ECO:0000305"
FT CONFLICT 765
FT /note="N -> NNNN (in Ref. 1; CAB42641)"
FT /evidence="ECO:0000305"
FT CONFLICT 868
FT /note="E -> P (in Ref. 1; CAB42641)"
FT /evidence="ECO:0000305"
FT CONFLICT 877
FT /note="L -> S (in Ref. 1; CAB42641)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1483 AA; 167362 MW; FC80F26D801AED90 CRC64;
MMFGNLPDVR KPKEGYKKYL EYFDLRFPRI QEEKHFQSYY YYTYLKQIRI SIIFLTSVLF
IGTMTAYISP LDISYLPYYD SKNIYYFNYV QPNVTTTSSS TTTTSSTTNS IDSTVENNNF
TEADGHLTNY YFPYLANKAR DTFILRMITI GLLLFYFIFT FTAKFKRLWK LFTTITLFLV
SCIVLIFESD IRTIPGRMVL LFIIIAISSG MTFLPSMLAS GGLCLFFFFY FMFYSQIAGK
QMVLLSLVLL ISWIILMIIS RFKEQLFRDK FRTLENLKIQ TIRSEKIINQ MLPTVVVQRL
RLQSSKDQSL ETTLENDKEL SIKKDEESNL TGKKQSKVVV SPPPPPTAAA PQQQDNEIST
PQNSRKIVDP QSPSSLMPGQ YSVTDLIVDS YDPVTVLFCE IVNFNALVEK MSSTQVINLL
NEVYNSFDRL TDVYGVTKVE HIGNVYMVVG GCPELCPDHA QRVAHMSLGM LSVIRRFGIV
QVRIGMHTGP VVGGIIGKKK LSWHLFGDTI NTSSRMASHS SIGRIQVSHP VQQLLRPYFL
FEDRGKIQVK GKGLMRTFYL VKTKQLDKRY TSIFSSLHRE KPYIPPVDIS EVSFENQNNT
IGKGDDIASG SATGPTHPNI PNSMLSAIPS RVSIEMNPLG GSGSIQKRER KGSIFANVMP
PKVLNFLQTG SLTSPQQQPL PQQSNSEETI SNSPRLSSTP QSTSTLQHSS STGALGSLIN
NNNNNNNNNN NNNNNNNNNN NNNNNNNNNN NNNNNNNNNN NNNNNLPVSL ISPISQNTTP
TGSLSLPVTE KKKQTVQFGS ISRSSSISKG TVGRSPSPAL FDGGIEMDDN GGGAGDDFNT
MEPNLDLGKG IHGSNVISTN NSKLNKLEKD LTKHYTLDKF KLSFISRGNL VEKEYRNEYI
LKNWNRILAS MLMIVALFGL SGLVDYFFLK LSSISSIVKV EPMPSSSSSS LSSSSSNSMT
SSEEKFITLH TIRSEENLIY DIITGVRYGF VFFCLIVIYV VSKFKTFSIR KWIQEVVMVF
FIVLAAVLIV LTSVPPLNKI PLDSVILSIE IMFITICYNF SGIKFWYSNI VCAFCIIFIE
ISKTWKQAYH SRDIYLSHNY YLITAVLINI ITSYFEELFN RLNWVHGRLL DKDQRETESL
VAEILPADIV KSMKSGRQLI VDEFKNVTIF LSDIVGFTEM AARMSPRQLV ETLNQIYSTF
DEIAQEFGVL KIATIGDAYF CVSGCPDKDQ TDHAFRVANM AIKMLESIKS IRTVDNIPIR
MRIGIHTGPV IAGVVGIKMI HYQLWGESVQ ITQQMESTSR ADMIHVSEDT FNILKSKYLF
EERPDGIIKK RKIKTYFLLR ALTENDPQPE VKTRSVSVSK SNFGGSLQYN QITPTLNLPV
SQLIIKDQNE IKNQNDHDND DENGNENGNE SSSSNINEEE EDDDNSNNNN NNEDDESSYE
DDQEMNQYLN NSENNKNNNN NSNQINEEDG NWAKNYDGSS ESS
