GCY8E_DROME
ID GCY8E_DROME Reviewed; 1097 AA.
AC Q8INF0; A2RVE6; Q0KI72; Q6U839; Q6U840; Q9VFC5;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 4.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Soluble guanylate cyclase 88E;
DE EC=4.6.1.2;
GN Name=Gyc88E {ECO:0000312|FlyBase:FBgn0038295};
GN ORFNames=CG4154 {ECO:0000312|FlyBase:FBgn0038295};
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, AND ALTERNATIVE SPLICING.
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:ABM92811.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D).
RA Stapleton M., Carlson J., Frise E., Kapadia B., Park S., Wan K., Yu C.,
RA Celniker S.;
RL Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAQ84039.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-947 (ISOFORMS D AND F), ACTIVITY
RP REGULATION, INTERACTION WITH GYC-89DA AND GYC-89DB, DEVELOPMENTAL STAGE,
RP 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).
RN [5] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH GYC-89DA AND GYC-89DB.
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).
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 Homodimer is slightly stimulated by the NO donor sodium nitroprusside
CC (SNP) but not the NO donor DEA-NONOate or the NO-independent activator
CC YC-1. Heterodimer also exhibits some stimulation, some compounds (SIN-1
CC and two of the NONOates) that were ineffective at stimulating Gyc-88E
CC alone did stimulate the heterodimer. {ECO:0000269|PubMed:15159437}.
CC -!- SUBUNIT: Homodimer, and heterodimer; with Gyc-89Db and Gyc-89Da, in the
CC presence of magnesium or manganese. {ECO:0000269|PubMed:15159437,
CC ECO:0000269|PubMed:15485853}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=D {ECO:0000312|FlyBase:FBgn0038295}; Synonyms=Long
CC {ECO:0000303|PubMed:15159437}, E {ECO:0000312|FlyBase:FBgn0038295};
CC IsoId=Q8INF0-1; Sequence=Displayed;
CC Name=F; Synonyms=Short {ECO:0000303|PubMed:15159437};
CC IsoId=Q8INF0-2; Sequence=VSP_051918;
CC -!- TISSUE SPECIFICITY: Expressed in embryos in a segmental pattern in the
CC ventral nerve cord (VNC) and in the brain, beginning at stage 15 or 16
CC and continuing through to stage 1. 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 third 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 -!- DEVELOPMENTAL STAGE: Expressed in embryos, larvae and adults.
CC {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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ84038.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=AAQ84039.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=ABM92811.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014297; AAF55135.5; -; Genomic_DNA.
DR EMBL; AE014297; ABI31167.1; -; Genomic_DNA.
DR EMBL; AE014297; AFH06433.1; -; Genomic_DNA.
DR EMBL; BT029937; ABM92811.1; ALT_FRAME; mRNA.
DR EMBL; AY376404; AAQ84038.1; ALT_SEQ; mRNA.
DR EMBL; AY376405; AAQ84039.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001036711.1; NM_001043246.4. [Q8INF0-1]
DR RefSeq; NP_001247115.1; NM_001260186.2. [Q8INF0-1]
DR RefSeq; NP_731974.4; NM_169616.4. [Q8INF0-2]
DR AlphaFoldDB; Q8INF0; -.
DR SMR; Q8INF0; -.
DR BioGRID; 66890; 1.
DR IntAct; Q8INF0; 1.
DR STRING; 7227.FBpp0110261; -.
DR PaxDb; Q8INF0; -.
DR EnsemblMetazoa; FBtr0110961; FBpp0110261; FBgn0038295. [Q8INF0-1]
DR EnsemblMetazoa; FBtr0306245; FBpp0297355; FBgn0038295. [Q8INF0-1]
DR EnsemblMetazoa; FBtr0334926; FBpp0306946; FBgn0038295. [Q8INF0-2]
DR GeneID; 41825; -.
DR KEGG; dme:Dmel_CG4154; -.
DR UCSC; CG4154-RD; d. melanogaster.
DR CTD; 41825; -.
DR FlyBase; FBgn0038295; Gyc88E.
DR VEuPathDB; VectorBase:FBgn0038295; -.
DR eggNOG; KOG4171; Eukaryota.
DR GeneTree; ENSGT00940000165461; -.
DR InParanoid; Q8INF0; -.
DR OMA; VCPMRSK; -.
DR BioGRID-ORCS; 41825; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Gyc88E; fly.
DR GenomeRNAi; 41825; -.
DR PRO; PR:Q8INF0; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0038295; Expressed in brain and 6 other tissues.
DR ExpressionAtlas; Q8INF0; baseline and differential.
DR Genevisible; Q8INF0; DM.
DR GO; GO:0008074; C:guanylate cyclase complex, soluble; IDA:FlyBase.
DR GO; GO:0070025; F:carbon monoxide binding; IDA:FlyBase.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070026; F:nitric oxide binding; IDA:FlyBase.
DR GO; GO:0019825; F:oxygen binding; IDA:FlyBase.
DR GO; GO:0019826; F:oxygen sensor activity; IDA:FlyBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:FlyBase.
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: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 Alternative splicing; cGMP biosynthesis; Coiled coil; Cytoplasm;
KW GTP-binding; Heme; Iron; Lyase; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..1097
FT /note="Soluble guanylate cyclase 88E"
FT /id="PRO_0000074105"
FT DOMAIN 421..549
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 739..766
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 795..831
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 842..861
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 913..956
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1017..1048
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 354..392
FT /evidence="ECO:0000255"
FT COILED 960..987
FT /evidence="ECO:0000255"
FT COMPBIAS 845..861
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 913..939
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1019..1041
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
FT VAR_SEQ 869..876
FT /note="KKITFSNS -> N (in isoform F)"
FT /evidence="ECO:0000305"
FT /id="VSP_051918"
FT CONFLICT 876
FT /note="S -> SS (in Ref. 4; AAQ84038)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1097 AA; 121201 MW; FF93CF321C8AC1C0 CRC64;
MYGLLLENLS EYIKSVYGEE KWEDIRRQAG IDSPSFSVHQ VYPENLLQKL AKKAQQVLGV
SERDFMDQMG VYFVGFVGQY GYDRVLSVLG RHMRDFLNGL DNLHEYLKFS YPRMRAPSFI
CENETKQGLT LHYRSKRRGF VYYTMGQIRE VARYFYHKEM HIELVREEIL FDTVHVTFQL
TFDNRAFTLA SLAMTREEKH LPISAHVLFE IFPFCMVFGA DMVVRSIGNS LMVILPELLG
KKITAWFDLV RPLIAFKFQT ILNRTNNIFE LVTVDPVTER FDVQNEDLLQ HEDGSEPEKS
LRLKGQMVYM ENWRMIMFLG TPVMPDLTSL ITTGLYINDL SMHDFSRDLM LAGTQQSVEL
KLALDQEQQK SKKLEESMRL LDEEMRRTDE LLYQMIPKQV ADRLRRGENP IDTCEMFDSV
SILFSDIVTF TEICSRITPM EVVSMLNAMY SIFDKLTERN SVYKVETIGD AYMVVAGAPD
KDANHAERVC DMALDMVDAI TDLKDPSTGQ HLRIRVGVHS GAVVAGIVGL KMPRYCLFGD
TVNTASRMES TSIAMKVHIS ESTKVLIGPN YKIIERGEID VKGKGTMGTY WLEERENRLP
LQLTAALQVH PLSPVPPTPT PKTKAIMPPV SKPLTPMMPV SVSLAASMPT SNVPAVDVMA
SSSSISGLAL TAAAAAHMSL HHQAVVAEAL TGASVEVALP SVASGATGAA AGGGAPSDDR
NSRIYSPVTF KDVARRSVAN SPVRSCAQPD QERRRESRSN STGHVFMRTP SEIFGSLILD
TEEFLEDLQI SRSSLANNNN NQSPCGFSPT PPFRIGSAPP KPRPSNPDKF TPEELAAMDQ
LTPPSTAPAR ETASCSSASL DRDKATKLKK ITFSNSSSLD ATTPTALAAV VCPMRTKSPP
MAVAPVMHMV QASTSKGDGQ RPGSKDSVSS ISLHSPPPHR SNSAPARPHS MSKAARKAFL
AAKQTKAMEK LDKMIEEVQE VESQSVAKAA NMRLALYGHD GGGDLAAGGC PLFLPPPPQQ
QQQQQQSLMP SSISDSGLCS HGHSHAPSCH HMDPKMTNSQ SFQHSPRGGI THQCCSGFGH
GNGRHSHRMH SNACRIL
