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 07-OCT-2020, entry version 146. 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; Holometabola; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; Q9VW60; -. DR IntAct; Q9VW60; 1. DR STRING; 7227.FBpp0293288; -. 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 eggNOG; KOG3619; Eukaryota. DR GeneTree; ENSGT00940000172626; -. DR HOGENOM; CLU_001072_3_1_1; -. DR InParanoid; Q9VW60; -. DR KO; K08042; -. DR PhylomeDB; Q9VW60; -. 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-418597; G alpha (z) signalling events. DR Reactome; R-DME-5610787; Hedgehog 'off' state. DR BioGRID-ORCS; 40180; 0 hits in 5 CRISPR screens. DR GenomeRNAi; 40180; -. DR PRO; PR:Q9VW60; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; FBgn0004852; Expressed in antenna and 30 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:0040015; P:negative regulation of multicellular organism growth; IMP:FlyBase. DR GO; GO:0042594; P:response to starvation; IDA:FlyBase. 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 NP_BIND 322..327 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P30803" FT NP_BIND 364..366 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P30803" FT NP_BIND 1242..1244 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P26769" FT NP_BIND 1249..1253 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P26769" FT METAL 322 FT /note="Magnesium 1; catalytic" FT /evidence="ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099" FT METAL 322 FT /note="Magnesium 2; catalytic" FT /evidence="ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099" FT METAL 323 FT /note="Magnesium 2; via carbonyl oxygen; catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099" FT METAL 366 FT /note="Magnesium 1; catalytic" FT /evidence="ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099" FT METAL 366 FT /note="Magnesium 2; catalytic" FT /evidence="ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099" FT BINDING 410 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P30803" FT BINDING 1162 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P26769" FT BINDING 1289 FT /note="ATP" 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 //