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 17-FEB-2016, entry version 111. 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; OC Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; 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., RA 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., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA 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., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA 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., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic 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., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., 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 CC in response to G-protein signaling. CC {ECO:0000250|UniProtKB:P26769}. CC -!- CATALYTIC ACTIVITY: ATP = 3',5'-cyclic AMP + diphosphate. CC {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 CC manganese (in vitro). {ECO:0000250|UniProtKB:P26769}; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P26769}; CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P26769}. Cell CC membrane {ECO:0000250|UniProtKB:P26769}; Multi-pass membrane CC protein {ECO:0000250|UniProtKB:P26769}. CC -!- DOMAIN: The protein contains two modules with six transmembrane CC helices each; both are required for catalytic activity. Isolated CC N-terminal or C-terminal guanylate cyclase domains have no CC catalytic activity, but when they are brought together, enzyme CC activity is restored. The active site is at the interface of the CC two domains. Both contribute substrate-binding residues, but the CC catalytic metal ions are bound exclusively via the N-terminal CC guanylate cyclase domain. {ECO:0000250|UniProtKB:P26769}. CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl CC cyclase family. {ECO:0000250|UniProtKB:P26769, CC ECO:0000255|PROSITE-ProRule:PRU00099}. CC -!- SIMILARITY: Contains 2 guanylate cyclase domains. CC {ECO:0000255|PROSITE-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 UniGene; Dm.2181; -. DR ProteinModelPortal; Q9VW60; -. DR SMR; Q9VW60; 305-491, 1102-1301. DR IntAct; Q9VW60; 1. DR STRING; 7227.FBpp0293288; -. DR PaxDb; Q9VW60; -. DR EnsemblMetazoa; FBtr0074897; FBpp0074666; FBgn0004852. DR GeneID; 40180; -. DR CTD; 40180; -. DR FlyBase; FBgn0004852; Ac76E. DR eggNOG; KOG3619; Eukaryota. DR eggNOG; COG2114; LUCA. DR GeneTree; ENSGT00760000119042; -. DR InParanoid; Q9VW60; -. DR OrthoDB; EOG76X5ZC; -. DR PhylomeDB; Q9VW60; -. DR Reactome; R-DME-163359; Glucagon signaling in metabolic regulation. DR Reactome; R-DME-163615; PKA activation. DR Reactome; R-DME-164378; PKA activation in glucagon signalling. DR Reactome; R-DME-170660; Adenylate cyclase activating pathway. DR Reactome; R-DME-418555; G alpha (s) signalling events. DR Reactome; R-DME-418597; G alpha (z) signalling events. DR Reactome; R-DME-432040; Vasopressin regulates renal water homeostasis via Aquaporins. DR GenomeRNAi; 40180; -. DR NextBio; 817433; -. DR PRO; PR:Q9VW60; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; Q9VW60; -. DR ExpressionAtlas; Q9VW60; differential. DR Genevisible; Q9VW60; DM. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005622; C:intracellular; IBA:GOC. DR GO; GO:0005886; C: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; IDA:FlyBase. DR GO; GO:0019933; P:cAMP-mediated signaling; 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; IPR029787; Nucleotide_cyclase. DR Pfam; PF16214; AC_N; 1. DR Pfam; PF00211; Guanylate_cyc; 2. 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; Complete proteome; KW Glycoprotein; Lyase; Magnesium; Manganese; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; KW Transmembrane; Transmembrane helix. FT CHAIN 1 1307 Adenylate cyclase type 2. FT /FTId=PRO_0000195713. FT TRANSMEM 85 105 Helical. {ECO:0000255}. FT TRANSMEM 113 133 Helical. {ECO:0000255}. FT TRANSMEM 137 157 Helical. {ECO:0000255}. FT TRANSMEM 178 198 Helical. {ECO:0000255}. FT TRANSMEM 211 231 Helical. {ECO:0000255}. FT TOPO_DOM 232 828 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 829 849 Helical. {ECO:0000255}. FT TRANSMEM 851 871 Helical. {ECO:0000255}. FT TRANSMEM 900 920 Helical. {ECO:0000255}. FT TRANSMEM 963 983 Helical. {ECO:0000255}. FT TRANSMEM 987 1007 Helical. {ECO:0000255}. FT TRANSMEM 1024 1044 Helical. {ECO:0000255}. FT TOPO_DOM 1045 1307 Cytoplasmic. {ECO:0000255}. FT DOMAIN 317 444 Guanylate cyclase 1. FT {ECO:0000255|PROSITE-ProRule:PRU00099}. FT DOMAIN 1110 1255 Guanylate cyclase 2. FT {ECO:0000255|PROSITE-ProRule:PRU00099}. FT NP_BIND 322 327 ATP. {ECO:0000250|UniProtKB:P30803}. FT NP_BIND 364 366 ATP. {ECO:0000250|UniProtKB:P30803}. FT NP_BIND 1242 1244 ATP. {ECO:0000250|UniProtKB:P26769}. FT NP_BIND 1249 1253 ATP. {ECO:0000250|UniProtKB:P26769}. FT METAL 322 322 Magnesium 1; catalytic. FT {ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099}. FT METAL 322 322 Magnesium 2; catalytic. FT {ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099}. FT METAL 323 323 Magnesium 2; via carbonyl oxygen; FT catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU00099}. FT METAL 366 366 Magnesium 1; catalytic. FT {ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099}. FT METAL 366 366 Magnesium 2; catalytic. FT {ECO:0000250|UniProtKB:P30803, FT ECO:0000255|PROSITE-ProRule:PRU00099}. FT BINDING 410 410 ATP. {ECO:0000250|UniProtKB:P30803}. FT BINDING 1162 1162 ATP. {ECO:0000250|UniProtKB:P26769}. FT BINDING 1289 1289 ATP. {ECO:0000250|UniProtKB:P26769}. FT CARBOHYD 934 934 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 941 941 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 948 948 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1019 1019 N-linked (GlcNAc...). {ECO:0000255}. FT CONFLICT 538 538 V -> G (in Ref. 1; AAC62509). FT {ECO:0000305}. FT CONFLICT 679 679 A -> VSS (in Ref. 1; AAC62509). FT {ECO:0000305}. FT CONFLICT 1037 1037 I -> T (in Ref. 1; AAC62509). FT {ECO:0000305}. FT CONFLICT 1183 1183 T -> TSRSFA (in Ref. 4; AAM50201). FT {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 //