GCYDB_DROME
ID GCYDB_DROME Reviewed; 669 AA.
AC Q9VEU5;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Soluble guanylate cyclase 89Db {ECO:0000303|PubMed:15485853};
DE EC=4.6.1.2;
GN Name=Gyc89Db {ECO:0000312|FlyBase:FBgn0038436};
GN Synonyms=Gyc-89Db {ECO:0000303|PubMed:15485853};
GN ORFNames=CG14886 {ECO:0000312|FlyBase:FBgn0038436};
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] {ECO:0000312|EMBL:AAF55323.1}
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, ECO:0000312|EMBL:AAF55323.1}
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:0000305, ECO:0000312|EMBL:AAK92845.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK92845.1};
RC TISSUE=Head {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
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 ACTIVITY REGULATION, INTERACTION WITH GYC88E, AND TISSUE SPECIFICITY.
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 Gyc88E are activated in response to
CC changing oxygen concentrations, alerting flies to hypoxic environments.
CC Under normal oxygen concentrations, oxygen binds to the heme group and
CC results in low levels of guanylyl cyclase activity. When exposed to
CC reduced oxygen concentrations, the oxygen dissociates from the heme
CC 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 exhibits some stimulation, compounds (SIN-1 and two of the
CC NONOates) that were ineffective at stimulating Gyc-88E homodimer did
CC stimulate the heterodimer. {ECO:0000269|PubMed:15159437}.
CC -!- SUBUNIT: Heterodimer; with Gyc88E, in the presence of magnesium or
CC manganese. {ECO:0000269|PubMed:15159437, ECO:0000269|PubMed:15485853}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in embryos in a segmental pattern in the
CC ventral nerve cord (VNC) and in the brain, beginning at stage 13 and
CC continuing through to stage 17. Colocalized with Gyc-89Db in several
CC peripheral neurons that innervate trachea, basiconical sensilla and the
CC sensory cones in the posterior segments of the embryo. Expression in
CC wandering 3rd instar larvae is most prominent in a small cluster of
CC cells located in the anterior medial region of each brain lobe. In the
CC VNC, expression is found in scattered cells both laterally and at the
CC midline. {ECO:0000269|PubMed:15159437}.
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}.
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DR EMBL; AE014297; AAF55323.1; -; Genomic_DNA.
DR EMBL; AY051421; AAK92845.1; -; mRNA.
DR RefSeq; NP_650551.1; NM_142294.4.
DR AlphaFoldDB; Q9VEU5; -.
DR SMR; Q9VEU5; -.
DR BioGRID; 67047; 9.
DR IntAct; Q9VEU5; 1.
DR STRING; 7227.FBpp0082745; -.
DR PaxDb; Q9VEU5; -.
DR DNASU; 42002; -.
DR EnsemblMetazoa; FBtr0083294; FBpp0082745; FBgn0038436.
DR GeneID; 42002; -.
DR KEGG; dme:Dmel_CG14886; -.
DR CTD; 42002; -.
DR FlyBase; FBgn0038436; Gyc89Db.
DR VEuPathDB; VectorBase:FBgn0038436; -.
DR eggNOG; KOG4171; Eukaryota.
DR GeneTree; ENSGT00940000165461; -.
DR HOGENOM; CLU_011614_4_1_1; -.
DR InParanoid; Q9VEU5; -.
DR OMA; VQHYIQE; -.
DR OrthoDB; 531253at2759; -.
DR PhylomeDB; Q9VEU5; -.
DR BRENDA; 4.6.1.2; 1994.
DR BioGRID-ORCS; 42002; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 42002; -.
DR PRO; PR:Q9VEU5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038436; Expressed in embryonic brain and 5 other tissues.
DR Genevisible; Q9VEU5; 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:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0055093; P:response to hyperoxia; IMP:FlyBase.
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..669
FT /note="Soluble guanylate cyclase 89Db"
FT /id="PRO_0000074107"
FT DOMAIN 494..620
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT COILED 430..458
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 669 AA; 75882 MW; E2727DA85CBCC788 CRC64;
MYGMLYESVQ HYIQQEYGME TWRKVCQIVD CKHQSFKTHQ IYPDKLMPDF AAALSASTGE
SFDFCMNFFG RCFVRFFSNF GYDKMIRSTG RYFCDFLQSI DNIHVQMRFT YPKMKSPSMQ
LTNMDDDGAV ILYRSGRTGM SKYLIGQMTE VAKEFYGLDM TAYVLESQND ICGGTAGPIK
LTEGPLTVIV KYRLDFDNRD YMAKRVNVIA HPSQLKMPSV DLNVFLELFP FTIVLDHDMK
ITLAGEKIVE TWILHNPGVN PKTFIGSHIL ERFKCRRPKD TQIQWETILQ MRTVLFEFEL
IRTGHNRAAY DAALNFDFEN FDEASSLNEA QAMALASAKE FSAENAKEEA AAAATSKDEI
DPATGQRRHS VGLRSILLKG QMFYIKDVDS LIFLCSPLIE NLDELHGIGL YLNDLNPHGL
SRELVMAGWQ HCSKLEIMFE KEEQRSDELE KSLELADSWK RQGDELLYSM IPRPIAERMR
KSEEHVCQSF EEVSVIFIEV MNIYDSGSNN IQDAMQAVTT LNKVFSALDE EIISPFVYKV
ETVGMVYMAV SGAPDVNPLH AEHACDLALR VMKKVKAHAL PGVAIRVGIN SGPVVAGVVG
MKVPRYCLFG DTVNTASRME SSSDPWMIQL SNYTALKVQK VGYKVEARGF VKVKGKGEME
TYWLLEGPE
