GCYDA_DROME
ID GCYDA_DROME Reviewed; 667 AA.
AC Q9VEU6; Q0KI63; Q4V501;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Soluble guanylate cyclase 89Da;
DE EC=4.6.1.2;
GN Name=Gyc89Da {ECO:0000312|FlyBase:FBgn0038435};
GN Synonyms=Gyc-89Da {ECO:0000312|FlyBase:FBgn0038435};
GN ORFNames=CG14885 {ECO:0000312|FlyBase:FBgn0038435};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000305}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAY55259.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH GYC88E.
RX PubMed=15485853; DOI=10.1074/jbc.c400461200;
RA Morton D.B.;
RT "Atypical soluble guanylyl cyclases in Drosophila can function as molecular
RT oxygen sensors.";
RL J. Biol. Chem. 279:50651-50653(2004).
RN [5] {ECO:0000305}
RP INTERACTION WITH GYC88E.
RX PubMed=15159437; DOI=10.1242/jeb.01025;
RA Langlais K.K., Stewart J.A., Morton D.B.;
RT "Preliminary characterization of two atypical soluble guanylyl cyclases in
RT the central and peripheral nervous system of Drosophila melanogaster.";
RL J. Exp. Biol. 207:2323-2338(2004).
CC -!- FUNCTION: Heterodimers with Gyc-89Da and Gyc-89Db are activated in
CC response to changing oxygen concentrations, alerting flies to hypoxic
CC environments. Under normal oxygen concentrations, oxygen binds to the
CC heme group and results in low levels of guanylyl cyclase activity. When
CC exposed to reduced oxygen concentrations, the oxygen dissociates from
CC the heme group resulting in activation of the enzyme.
CC {ECO:0000269|PubMed:15485853}.
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:0000303|PubMed:15159437};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC Note=Binds 1 or 2 heme groups per heterodimer. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Probably not activated by nitric oxide (NO).
CC Heterodimer also exhibits some stimulation, some compounds (SIN-1 and
CC two of the NONOates) that were ineffective at stimulating Gyc-88E alone
CC did stimulate the heterodimer. {ECO:0000303|PubMed:15159437}.
CC -!- SUBUNIT: Heterodimer; with Gyc88E, in the presence of magnesium or
CC manganese. {ECO:0000269|PubMed:15485853, ECO:0000303|PubMed:15159437}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- MISCELLANEOUS: There are two types of guanylate cyclases: soluble forms
CC and membrane-associated receptor forms. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY55271.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014297; ABI31174.1; -; Genomic_DNA.
DR EMBL; BT022818; AAY55234.1; -; mRNA.
DR EMBL; BT022843; AAY55259.1; -; mRNA.
DR EMBL; BT022855; AAY55271.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001036718.1; NM_001043253.1.
DR RefSeq; NP_001036719.1; NM_001043254.2.
DR AlphaFoldDB; Q9VEU6; -.
DR SMR; Q9VEU6; -.
DR BioGRID; 67046; 5.
DR IntAct; Q9VEU6; 1.
DR STRING; 7227.FBpp0110262; -.
DR PaxDb; Q9VEU6; -.
DR DNASU; 42001; -.
DR EnsemblMetazoa; FBtr0110962; FBpp0110262; FBgn0038435.
DR EnsemblMetazoa; FBtr0110963; FBpp0110263; FBgn0038435.
DR GeneID; 42001; -.
DR KEGG; dme:Dmel_CG14885; -.
DR CTD; 42001; -.
DR FlyBase; FBgn0038435; Gyc89Da.
DR VEuPathDB; VectorBase:FBgn0038435; -.
DR eggNOG; KOG4171; Eukaryota.
DR GeneTree; ENSGT00940000165461; -.
DR HOGENOM; CLU_011614_4_1_1; -.
DR InParanoid; Q9VEU6; -.
DR OMA; MHNPGAN; -.
DR OrthoDB; 531253at2759; -.
DR PhylomeDB; Q9VEU6; -.
DR BRENDA; 4.6.1.2; 1994.
DR BioGRID-ORCS; 42001; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 42001; -.
DR PRO; PR:Q9VEU6; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038435; Expressed in central nervous system and 4 other tissues.
DR ExpressionAtlas; Q9VEU6; baseline and differential.
DR Genevisible; Q9VEU6; DM.
DR GO; GO:0008074; C:guanylate cyclase complex, soluble; IDA:FlyBase.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019934; P:cGMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IMP:FlyBase.
DR GO; GO:0070482; P:response to oxygen levels; IBA:GO_Central.
DR GO; GO:0000302; P:response to reactive oxygen species; IDA:UniProtKB.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.450.260; -; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR Gene3D; 3.90.1520.10; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR038158; H-NOX_domain_sf.
DR InterPro; IPR011644; Heme_NO-bd.
DR InterPro; IPR011645; HNOB_dom_associated.
DR InterPro; IPR042463; HNOB_dom_associated_sf.
DR InterPro; IPR024096; NO_sig/Golgi_transp_ligand-bd.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07700; HNOB; 1.
DR Pfam; PF07701; HNOBA; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF111126; SSF111126; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
PE 1: Evidence at protein level;
KW cGMP biosynthesis; Coiled coil; Cytoplasm; GTP-binding; Heme; Iron; Lyase;
KW Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..667
FT /note="Soluble guanylate cyclase 89Da"
FT /id="PRO_0000074106"
FT DOMAIN 491..617
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 337..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 427..455
FT /evidence="ECO:0000255"
FT BINDING 104
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT /evidence="ECO:0000250|UniProtKB:P16068"
SQ SEQUENCE 667 AA; 76146 MW; C761213C3A591F80 CRC64;
MYGMLYESVQ HYVQEEYGVD IWRKVCHIID CKHNSFKTHQ IYPDKLMPDI AEALSACTGE
SFDFCMNFFG RCFVRFFSNF GYDKMIRSTG RYFCDFLQSI DNIHLIMRFT YPKMKSPSMQ
LTNMDDNGAV ILYRSSRTGM SKYLIGQMTE VAREFYGLEI KAYVIESQND ISGGTAGPIK
LTDGPLTVIV KYRLDFDNRE YMAKRVNTEA HPSQLKMPTV KLDVFLDLFP FTFVLNHDMK
ITHAGEKIVE TWIMHNPGAN PKSFIGTHVM DLFQCRRPKD TTIDWDTLIQ MRAVLFEFEL
IRTGHNRAAY DAVLNMDFEN YDEMDLNEAQ TMALAKAQEF SESHPVDDDE SAREDEIDPA
TGERRSSQGL RSILLKGQMF YIKDVDSLIF LCSPLIENLD ELHGIGLYLN DLNPHGLSRE
LVMAGWQHCS KLEIMFEKEE QRSDELEKSL ELADSWKRQG DELLYSMIPR PIAERMRLSE
EQVCQSFEEV SVIFLEVMNV YDEGLNSIQG AMQTVNTLNK VFSALDEEII SPFVYKVETV
GMVYMAVSGA PDVNPLHAEH ACDLALRVMK KFKAHDMGDV AIRVGINSGP VVAGVVGQKV
PRYCLFGDTV NTASRMESSS DPWKIQLSKY TGDKVRQVGY KVESRGTVQV KGKGDMETYW
LLEGPEG
