ADCY2_DROME
ID ADCY2_DROME Reviewed; 1307 AA.
AC Q9VW60; O77247; Q8MRK9;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Adenylate cyclase type 2;
DE EC=4.6.1.1 {ECO:0000250|UniProtKB:P26769};
DE AltName: Full=ATP pyrophosphate-lyase 2;
DE AltName: Full=Adenylyl cyclase 76E;
GN Name=Ac76E {ECO:0000312|EMBL:AAF49089.3}; ORFNames=CG7978;
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:AAC62509.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Canton-S {ECO:0000312|EMBL:AAC62509.1};
RX PubMed=1739965; DOI=10.1016/0092-8674(92)90185-f;
RA Levin L.R., Han P.-L., Hwang P.M., Feinstein P.G., Davis R.L., Reed R.R.;
RT "The Drosophila learning and memory gene rutabaga encodes a
RT Ca2+/Calmodulin-responsive adenylyl cyclase.";
RL Cell 68:479-489(1992).
RN [2] {ECO:0000312|EMBL:AAF49089.3}
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 [3] {ECO:0000305, ECO:0000312|EMBL:AAF49089.3}
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 [4] {ECO:0000305, ECO:0000312|EMBL:AAM50201.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 434-1307.
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM50201.1};
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).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling. {ECO:0000250|UniProtKB:P26769}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000250|UniProtKB:P26769};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P26769};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P26769};
CC Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC (in vitro). {ECO:0000250|UniProtKB:P26769};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P26769}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:P26769}. Cell membrane
CC {ECO:0000250|UniProtKB:P26769}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P26769}.
CC -!- DOMAIN: The protein contains two modules with six transmembrane helices
CC each; both are required for catalytic activity. Isolated N-terminal or
CC C-terminal guanylate cyclase domains have no catalytic activity, but
CC when they are brought together, enzyme activity is restored. The active
CC site is at the interface of the two domains. Both contribute substrate-
CC binding residues, but the catalytic metal ions are bound exclusively
CC via the N-terminal guanylate cyclase domain.
CC {ECO:0000250|UniProtKB:P26769}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000250|UniProtKB:P26769, ECO:0000255|PROSITE-
CC ProRule:PRU00099}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM50201.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF093454; AAC62509.1; -; mRNA.
DR EMBL; AE014296; AAF49089.3; -; Genomic_DNA.
DR EMBL; AY119547; AAM50201.1; ALT_INIT; mRNA.
DR PIR; B42088; B42088.
DR PIR; T13158; T13158.
DR RefSeq; NP_524173.2; NM_079449.4.
DR AlphaFoldDB; Q9VW60; -.
DR SMR; Q9VW60; -.
DR IntAct; Q9VW60; 1.
DR STRING; 7227.FBpp0293288; -.
DR GlyGen; Q9VW60; 4 sites.
DR PaxDb; Q9VW60; -.
DR PRIDE; Q9VW60; -.
DR EnsemblMetazoa; FBtr0074897; FBpp0074666; FBgn0004852.
DR GeneID; 40180; -.
DR KEGG; dme:Dmel_CG7978; -.
DR CTD; 40180; -.
DR FlyBase; FBgn0004852; Ac76E.
DR VEuPathDB; VectorBase:FBgn0004852; -.
DR eggNOG; KOG3619; Eukaryota.
DR GeneTree; ENSGT00940000172626; -.
DR HOGENOM; CLU_001072_3_1_1; -.
DR InParanoid; Q9VW60; -.
DR PhylomeDB; Q9VW60; -.
DR Reactome; R-DME-163615; PKA activation.
DR Reactome; R-DME-170660; Adenylate cyclase activating pathway.
DR Reactome; R-DME-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-DME-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-DME-5610787; Hedgehog 'off' state.
DR BioGRID-ORCS; 40180; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40180; -.
DR PRO; PR:Q9VW60; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0004852; Expressed in antenna and 26 other tissues.
DR ExpressionAtlas; Q9VW60; baseline and differential.
DR Genevisible; Q9VW60; DM.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006171; P:cAMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0002165; P:instar larval or pupal development; IMP:FlyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:FlyBase.
DR GO; GO:0042594; P:response to starvation; IDA:FlyBase.
DR CDD; cd07302; CHD; 2.
DR Gene3D; 3.30.70.1230; -; 2.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR032628; AC_N.
DR InterPro; IPR030672; Adcy.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF16214; AC_N; 1.
DR Pfam; PF00211; Guanylate_cyc; 2.
DR PIRSF; PIRSF039050; Ade_cyc; 1.
DR SMART; SM00044; CYCc; 2.
DR SUPFAM; SSF55073; SSF55073; 2.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 2.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; cAMP biosynthesis; Cell membrane; Glycoprotein; Lyase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1307
FT /note="Adenylate cyclase type 2"
FT /id="PRO_0000195713"
FT TRANSMEM 85..105
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..828
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 829..849
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 851..871
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 900..920
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 963..983
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 987..1007
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1024..1044
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1045..1307
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 317..444
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 1110..1255
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 510..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 647..693
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..532
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 594..617
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 647..670
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 322..327
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 322
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P30803,
FT ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 322
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P30803,
FT ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 323
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 364..366
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P30803,
FT ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P30803,
FT ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 410
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1242..1244
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1249..1253
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1289
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 941
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 948
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1019
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 538
FT /note="V -> G (in Ref. 1; AAC62509)"
FT /evidence="ECO:0000305"
FT CONFLICT 679
FT /note="A -> VSS (in Ref. 1; AAC62509)"
FT /evidence="ECO:0000305"
FT CONFLICT 1037
FT /note="I -> T (in Ref. 1; AAC62509)"
FT /evidence="ECO:0000305"
FT CONFLICT 1183
FT /note="T -> TSRSFA (in Ref. 4; AAM50201)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1307 AA; 142817 MW; D7EE45CF93F80161 CRC64;
MVNHNAETAK TGNGTNATAN LIVKADGNAT QPKAMTSSAA RMNDALSASL ADLSEQENGT
TAEDIHLNDL YTRYRQRLRK SLFRSGLLTS LLACVVSIII GIVYGQHLVQ TMLLVLAALI
SGSILTALQF PAVLSSPAAA LAFAIVTTFS LGTIAAITGD ELAPLPMYAL FLCIHSMLPI
SWPVSVVLAL FMTAIHIVYR IGTSPDYAPN LPMLFGEIVM LASASVSGLY YRIMSDAAHN
RTVDGTRTGI EQRVKLECER EQQEQLLLSV IPAYIAAEVK RSIMLKMADA CQRAGGQAST
SATRFHELHV QRHTNVTILF ADIVNFTPLS SSLTASDLVK TLNDLFGRFD QIAQENQCLR
IKILGDCYYC VSGLPISRPQ HATNCVNMGL QMIDAIRHVR EATGINVDMR IGIHTGNVLC
GVLGLRKWQF DVWSDDVTLA NHMESGGVAG RVHITKQTLD FLGDKFEVEQ GEGGNRDAYL
ADHKVESYLI VPPKPAYTYS VPRVVECIEQ NDPSPTTEET KEIKETDQSH EATDVADVLL
PVTVAPPPAI VDEKMSPTSI NSQEAPLHAP LASAASMSIK ELSEEEDEAD EATAVTEPLM
HRDQDGKNDK EPKANGGHRG SGDSAASESV AKSAALSLPA DDLLSMSGSE SGISNSGAQA
QSSNPASVTP TAAAPAGGAA SNSLTVAEAP ERSRRKLSVQ GLMSFADRRR SSGAFIEGRK
LSIHSGESFR SHAGHVTRNR PSSKMTKYVE CWGADRPFAN IAESKLVKNI GLASIAMIES
NLLPPERKCF NFNFFGPPTE LKPFTMWYRN TPREAMYRAQ PDTHFRFDLI CAFVLFLSLA
VVQLIVIELN LALLGSLLAS FVSLALFLYL SNMSVPDVHA STTERNGPGQ VVASSRYLRL
AMFVVVNILI SSCAVFSVIN YTVPDGVSKE PSSNQTILES NFSSVFVNST LEDVQLWEID
YAIPIAPVFL YCCAISLAAI SAFLRSGFIL KLIAMLVAVI AQVTVLGYSD LFEMYNDANI
THGLPLEIKG FLLLLVIILV LHTLDRQGEY VARTDFLWKA KLKVEQEEVE TMRGINKILL
ENILPAHVAT HFLHLERSTE LYHESYSCVA VMFASIPNYK EFYDETDVNK QGLECLRLLN
EIICDFDKLL LKPKFSGIEK IKTIASTYMC ASGLRPGKED GATDEKRTEE HNVVILVEFA
IALMSILDSI NRESFQRFRL RIGLNHGPVI AGVIGAQKPQ YDIWSNTVNV ASRMDSCGVM
GRLQTTENTA KILMTAGYEC ECRGLTYVKG KGNLVTYFVK TPFDGKL
