ID   ADCY2_RAT               Reviewed;        1090 AA.
AC   P26769;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   08-NOV-2023, entry version 182.
DE   RecName: Full=Adenylate cyclase type 2;
DE            EC=4.6.1.1 {ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:21596131};
DE   AltName: Full=ATP pyrophosphate-lyase 2;
DE   AltName: Full=Adenylate cyclase type II;
DE   AltName: Full=Adenylyl cyclase 2;
DE            Short=AC2 {ECO:0000303|PubMed:24363043};
GN   Name=Adcy2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=1719547; DOI=10.1073/pnas.88.22.10173;
RA   Feinstein P.G., Schrader K.A., Bakalyar H.A., Tang W.J., Krupinski J.,
RA   Gilman A.G., Reed R.R.;
RT   "Molecular cloning and characterization of a Ca2+/calmodulin-insensitive
RT   adenylyl cyclase from rat brain.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:10173-10177(1991).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=7761832; DOI=10.1126/science.7761832;
RA   Chen J., DeVivo M., Dingus J., Harry A., Li J., Sui J., Carty D.J.,
RA   Blank J.L., Exton J.H., Stoffel R.H.;
RT   "A region of adenylyl cyclase 2 critical for regulation by G protein beta
RT   gamma subunits.";
RL   Science 268:1166-1169(1995).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP   AND INTERACTION WITH THE G PROTEIN BETA AND GAMMA SUBUNIT COMPLEX.
RX   PubMed=21596131; DOI=10.1016/j.cellsig.2011.05.002;
RA   Boran A.D., Chen Y., Iyengar R.;
RT   "Identification of new Gbetagamma interaction sites in adenylyl cyclase
RT   2.";
RL   Cell. Signal. 23:1489-1495(2011).
RN   [4]
RP   PHOSPHORYLATION AT SER-490 AND SER-543, MUTAGENESIS OF SER-490 AND SER-543,
RP   CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY
RP   REGULATION.
RX   PubMed=22906005; DOI=10.1042/bj20120279;
RA   Shen J.X., Wachten S., Halls M.L., Everett K.L., Cooper D.M.;
RT   "Muscarinic receptors stimulate AC2 by novel phosphorylation sites, whereas
RT   Gbetagamma subunits exert opposing effects depending on the G-protein
RT   source.";
RL   Biochem. J. 447:393-405(2012).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=24363043; DOI=10.1007/s00210-013-0950-4;
RA   Bogard A.S., Birg A.V., Ostrom R.S.;
RT   "Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that
RT   selectively regulates IL-6 expression in airway smooth muscle cells:
RT   differential regulation of gene expression by AC isoforms.";
RL   Naunyn Schmiedebergs Arch. Pharmacol. 387:329-339(2014).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 871-1090 IN COMPLEX WITH
RP   FORSKOLIN.
RX   PubMed=9069282; DOI=10.1038/386247a0;
RA   Zhang G., Liu Y., Ruoho A.E., Hurley J.H.;
RT   "Structure of the adenylyl cyclase catalytic core.";
RL   Nature 386:247-253(1997).
RN   [8]
RP   ERRATUM OF PUBMED:9069282.
RA   Zhang G., Liu Y., Ruoho A.E., Hurley J.H.;
RL   Nature 388:204-204(1997).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 870-1081 OF CHIMERA WITH ADCY5 IN
RP   COMPLEX WITH GNAS, INTERACTION WITH GNAS, AND DOMAIN.
RX   PubMed=9417641; DOI=10.1126/science.278.5345.1907;
RA   Tesmer J.J.G., Sunahara R.K., Gilman A.G., Sprang S.R.;
RT   "Crystal structure of the catalytic domains of adenylyl cyclase in a
RT   complex with Gsalpha.GTPgammaS.";
RL   Science 278:1907-1916(1997).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 870-1081 OF CHIMERA WITH ADCY5 IN
RP   COMPLEX WITH GNAS AND ATP ANALOGS, INTERACTION WITH GNAS, DOMAIN, CATALYTIC
RP   ACTIVITY, FUNCTION, AND COFACTOR.
RX   PubMed=10427002; DOI=10.1126/science.285.5428.756;
RA   Tesmer J.J.G., Sunahara R.K., Johnson R.A., Gosselin G., Gilman A.G.,
RA   Sprang S.R.;
RT   "Two-metal-ion catalysis in adenylyl cyclase.";
RL   Science 285:756-760(1999).
RN   [11] {ECO:0007744|PDB:1CS4, ECO:0007744|PDB:1CUL}
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 874-1081 OF CHIMERA WITH ADCY5 IN
RP   COMPLEX WITH GNAS; MAGNESIUM AND ATP ANALOGS, INTERACTION WITH GNAS,
RP   DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX   PubMed=11087399; DOI=10.1021/bi0015562;
RA   Tesmer J.J., Dessauer C.W., Sunahara R.K., Murray L.D., Johnson R.A.,
RA   Gilman A.G., Sprang S.R.;
RT   "Molecular basis for P-site inhibition of adenylyl cyclase.";
RL   Biochemistry 39:14464-14471(2000).
RN   [12] {ECO:0007744|PDB:1TL7, ECO:0007744|PDB:1U0H}
RP   X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 870-1081 OF CHIMERA WITH ADCY5 IN
RP   COMPLEX WITH GNAS AND ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, INTERACTION
RP   WITH GNAS, AND DOMAIN.
RX   PubMed=15591060; DOI=10.1074/jbc.m409076200;
RA   Mou T.C., Gille A., Fancy D.A., Seifert R., Sprang S.R.;
RT   "Structural basis for the inhibition of mammalian membrane adenylyl cyclase
RT   by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate.";
RL   J. Biol. Chem. 280:7253-7261(2005).
RN   [13] {ECO:0007744|PDB:2GVD, ECO:0007744|PDB:2GVZ}
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 870-1081 OF CHIMERA WITH ADCY5 IN
RP   COMPLEX WITH GNAS AND ATP ANALOG, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   INTERACTION WITH GNAS, AND DOMAIN.
RX   PubMed=16766715; DOI=10.1124/mol.106.026427;
RA   Mou T.C., Gille A., Suryanarayana S., Richter M., Seifert R., Sprang S.R.;
RT   "Broad specificity of mammalian adenylyl cyclase for interaction with
RT   2',3'-substituted purine- and pyrimidine nucleotide inhibitors.";
RL   Mol. Pharmacol. 70:878-886(2006).
RN   [14] {ECO:0007744|PDB:3C14, ECO:0007744|PDB:3C15, ECO:0007744|PDB:3C16, ECO:0007744|PDB:3MAA}
RP   X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 870-1081 OF CHIMERA WITH ADCY5 IN
RP   COMPLEX WITH GNAS; FORSKOLIN; MAGNESIUM IONS AND ATP ANALOG, FUNCTION,
RP   CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH GNAS, AND DOMAIN.
RX   PubMed=19243146; DOI=10.1021/bi802122k;
RA   Mou T.C., Masada N., Cooper D.M., Sprang S.R.;
RT   "Structural basis for inhibition of mammalian adenylyl cyclase by
RT   calcium.";
RL   Biochemistry 48:3387-3397(2009).
CC   -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC       response to G-protein signaling (PubMed:22906005, PubMed:24363043,
CC       PubMed:10427002, PubMed:1719547, PubMed:7761832, PubMed:21596131,
CC       PubMed:11087399, PubMed:15591060, PubMed:19243146, PubMed:16766715).
CC       Down-stream signaling cascades mediate changes in gene expression
CC       patterns and lead to increased IL6 production (PubMed:24363043).
CC       Functions in signaling cascades downstream of the muscarinic
CC       acetylcholine receptors (PubMed:22906005).
CC       {ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399,
CC       ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715,
CC       ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:19243146,
CC       ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:22906005,
CC       ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:7761832}.
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:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399,
CC         ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715,
CC         ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:19243146,
CC         ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:22906005,
CC         ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:7761832};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399,
CC         ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:1719547,
CC         ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:7761832};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399,
CC         ECO:0000269|PubMed:16766715};
CC       Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC       (in vitro). {ECO:0000269|PubMed:16766715, ECO:0000305|PubMed:10427002};
CC   -!- ACTIVITY REGULATION: Activated by forskolin (PubMed:1719547,
CC       PubMed:22906005, PubMed:24363043). Is not activated by calmodulin
CC       (PubMed:1719547). Inhibited by calcium ions, already at micromolar
CC       concentration. Activated by the G protein alpha subunit GNAS
CC       (PubMed:1719547, PubMed:7761832, PubMed:21596131). Activated by the G
CC       protein beta and gamma subunit complex (PubMed:7761832,
CC       PubMed:21596131, PubMed:22906005). Phosphorylation by RAF1 results in
CC       its activation (By similarity). Phosphorylation by PKC activates the
CC       enzyme (PubMed:22906005). {ECO:0000250|UniProtKB:Q08462,
CC       ECO:0000269|PubMed:1719547, ECO:0000269|PubMed:21596131,
CC       ECO:0000269|PubMed:22906005, ECO:0000269|PubMed:24363043,
CC       ECO:0000269|PubMed:7761832}.
CC   -!- SUBUNIT: Interacts with RAF1 (By similarity). Interacts with GNAS
CC       (PubMed:9417641, PubMed:10427002, PubMed:11087399, PubMed:15591060,
CC       PubMed:16766715, PubMed:19243146). Interacts with the G protein beta
CC       and gamma subunit complex (PubMed:21596131).
CC       {ECO:0000250|UniProtKB:Q08462, ECO:0000269|PubMed:10427002,
CC       ECO:0000269|PubMed:11087399, ECO:0000269|PubMed:15591060,
CC       ECO:0000269|PubMed:16766715, ECO:0000269|PubMed:19243146,
CC       ECO:0000269|PubMed:21596131, ECO:0000269|PubMed:9417641}.
CC   -!- INTERACTION:
CC       P26769; Q99996-4: AKAP9; Xeno; NbExp=3; IntAct=EBI-1027877, EBI-15676518;
CC       P26769; Q08499-2: PDE4D; Xeno; NbExp=3; IntAct=EBI-1027877, EBI-8095525;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:1719547,
CC       ECO:0000269|PubMed:22906005}; Multi-pass membrane protein
CC       {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:1719547,
CC       ECO:0000269|PubMed:7761832}; Multi-pass membrane protein {ECO:0000305}.
CC       Cytoplasm {ECO:0000250|UniProtKB:Q08462}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain, olfactory epithelium and lung.
CC       {ECO:0000269|PubMed:1719547}.
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:0000269|PubMed:10427002, ECO:0000269|PubMed:11087399,
CC       ECO:0000269|PubMed:15591060, ECO:0000269|PubMed:16766715,
CC       ECO:0000269|PubMed:19243146, ECO:0000269|PubMed:9417641}.
CC   -!- PTM: Phosphorylated by RAF1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q08462}.
CC   -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC       family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR   EMBL; M80550; AAA40682.1; -; mRNA.
DR   PIR; A41541; A41541.
DR   RefSeq; NP_112269.1; NM_031007.1.
DR   PDB; 1AB8; X-ray; 2.20 A; A/B=871-1090.
DR   PDB; 1AZS; X-ray; 2.30 A; B=870-1081.
DR   PDB; 1CJK; X-ray; 3.00 A; B=870-1081.
DR   PDB; 1CJT; X-ray; 2.80 A; B=870-1081.
DR   PDB; 1CJU; X-ray; 2.80 A; B=870-1081.
DR   PDB; 1CJV; X-ray; 3.00 A; B=870-1081.
DR   PDB; 1CS4; X-ray; 2.50 A; B=870-1081.
DR   PDB; 1CUL; X-ray; 2.40 A; B=874-1081.
DR   PDB; 1TL7; X-ray; 2.80 A; B=870-1081.
DR   PDB; 1U0H; X-ray; 2.90 A; B=870-1081.
DR   PDB; 2GVD; X-ray; 2.90 A; B=870-1081.
DR   PDB; 2GVZ; X-ray; 3.27 A; B=870-1081.
DR   PDB; 3C14; X-ray; 2.68 A; B=870-1081.
DR   PDB; 3C15; X-ray; 2.78 A; B=870-1081.
DR   PDB; 3C16; X-ray; 2.87 A; B=870-1081.
DR   PDB; 3G82; X-ray; 3.11 A; B=870-1081.
DR   PDB; 3MAA; X-ray; 3.00 A; B=870-1081.
DR   PDBsum; 1AB8; -.
DR   PDBsum; 1AZS; -.
DR   PDBsum; 1CJK; -.
DR   PDBsum; 1CJT; -.
DR   PDBsum; 1CJU; -.
DR   PDBsum; 1CJV; -.
DR   PDBsum; 1CS4; -.
DR   PDBsum; 1CUL; -.
DR   PDBsum; 1TL7; -.
DR   PDBsum; 1U0H; -.
DR   PDBsum; 2GVD; -.
DR   PDBsum; 2GVZ; -.
DR   PDBsum; 3C14; -.
DR   PDBsum; 3C15; -.
DR   PDBsum; 3C16; -.
DR   PDBsum; 3G82; -.
DR   PDBsum; 3MAA; -.
DR   AlphaFoldDB; P26769; -.
DR   SMR; P26769; -.
DR   BioGRID; 249536; 1.
DR   DIP; DIP-164N; -.
DR   IntAct; P26769; 8.
DR   MINT; P26769; -.
DR   STRING; 10116.ENSRNOP00000038994; -.
DR   BindingDB; P26769; -.
DR   ChEMBL; CHEMBL2958; -.
DR   DrugCentral; P26769; -.
DR   GlyCosmos; P26769; 2 sites, No reported glycans.
DR   GlyGen; P26769; 2 sites.
DR   iPTMnet; P26769; -.
DR   PhosphoSitePlus; P26769; -.
DR   PaxDb; 10116-ENSRNOP00000038994; -.
DR   GeneID; 81636; -.
DR   KEGG; rno:81636; -.
DR   UCSC; RGD:619965; rat.
DR   AGR; RGD:619965; -.
DR   CTD; 108; -.
DR   RGD; 619965; Adcy2.
DR   eggNOG; KOG3619; Eukaryota.
DR   InParanoid; P26769; -.
DR   OrthoDB; 3686360at2759; -.
DR   PhylomeDB; P26769; -.
DR   BRENDA; 4.6.1.1; 5301.
DR   Reactome; R-RNO-163615; PKA activation.
DR   Reactome; R-RNO-170660; Adenylate cyclase activating pathway.
DR   Reactome; R-RNO-170670; Adenylate cyclase inhibitory pathway.
DR   Reactome; R-RNO-418597; G alpha (z) signalling events.
DR   Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR   EvolutionaryTrace; P26769; -.
DR   PRO; PR:P26769; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR   GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0004016; F:adenylate cyclase activity; IDA:UniProtKB.
DR   GO; GO:0008179; F:adenylate cyclase binding; IDA:BHF-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IPI:RGD.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0006171; P:cAMP biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR   GO; GO:1904322; P:cellular response to forskolin; IDA:UniProtKB.
DR   CDD; cd07302; CHD; 2.
DR   Gene3D; 3.30.70.1230; Nucleotide cyclase; 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; IPR009398; Adcy_conserved_dom.
DR   InterPro; IPR029787; Nucleotide_cyclase.
DR   PANTHER; PTHR45627; ADENYLATE CYCLASE TYPE 1; 1.
DR   PANTHER; PTHR45627:SF6; ADENYLATE CYCLASE TYPE 2; 1.
DR   Pfam; PF16214; AC_N; 1.
DR   Pfam; PF06327; Adcy_cons_dom; 1.
DR   Pfam; PF00211; Guanylate_cyc; 2.
DR   PIRSF; PIRSF039050; Ade_cyc; 1.
DR   SMART; SM00044; CYCc; 2.
DR   SUPFAM; SSF55073; Nucleotide cyclase; 2.
DR   PROSITE; PS00452; GUANYLATE_CYCLASE_1; 2.
DR   PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; cAMP biosynthesis; Cell membrane; Cytoplasm;
KW   Glycoprotein; Lyase; Magnesium; Manganese; Membrane; Metal-binding;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..1090
FT                   /note="Adenylate cyclase type 2"
FT                   /id="PRO_0000195686"
FT   TOPO_DOM        1..44
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        45..65
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        75..95
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        107..127
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        132..152
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        157..177
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        186..206
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        207..600
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        601..621
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        626..646
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        679..699
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        734..754
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        763..783
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        800..820
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        821..1090
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255, ECO:0000305"
FT   REGION          904..921
FT                   /note="Interaction with GNAS"
FT                   /evidence="ECO:0000269|PubMed:11087399"
FT   REGION          989..992
FT                   /note="Interaction with GNAS"
FT                   /evidence="ECO:0000269|PubMed:11087399"
FT   BINDING         294..299
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         294
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099,
FT                   ECO:0000305"
FT   BINDING         294
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                   ECO:0000269|PubMed:11087399, ECO:0000305"
FT   BINDING         295
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                   ECO:0000269|PubMed:11087399, ECO:0000305"
FT   BINDING         336..338
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         338
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099,
FT                   ECO:0000305"
FT   BINDING         338
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                   ECO:0000269|PubMed:11087399, ECO:0000305"
FT   BINDING         382
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         938
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305|PubMed:10427002,
FT                   ECO:0000305|PubMed:11087399, ECO:0000305|PubMed:15591060,
FT                   ECO:0000305|PubMed:16766715, ECO:0000305|PubMed:19243146"
FT   BINDING         1018..1020
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305|PubMed:10427002,
FT                   ECO:0000305|PubMed:11087399, ECO:0000305|PubMed:15591060,
FT                   ECO:0000305|PubMed:16766715, ECO:0000305|PubMed:19243146"
FT   BINDING         1025..1029
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:10427002,
FT                   ECO:0007744|PDB:1CJK, ECO:0007744|PDB:3MAA"
FT   BINDING         1065
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000305|PubMed:10427002,
FT                   ECO:0000305|PubMed:11087399, ECO:0000305|PubMed:15591060,
FT                   ECO:0000305|PubMed:16766715, ECO:0000305|PubMed:19243146"
FT   MOD_RES         490
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000269|PubMed:22906005"
FT   MOD_RES         543
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000269|PubMed:22906005"
FT   CARBOHYD        712
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        717
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         490
FT                   /note="S->A: Reduces activation by PKC. Abolishes
FT                   activation by PKC; when associated with A-543."
FT                   /evidence="ECO:0000269|PubMed:22906005"
FT   MUTAGEN         490
FT                   /note="S->D: Increases basal level of enzyme activity.
FT                   Abolishes activation by PKC; when associated with D-543."
FT                   /evidence="ECO:0000269|PubMed:22906005"
FT   MUTAGEN         543
FT                   /note="S->A: Reduces activation by PKC. Abolishes
FT                   activation by PKC; when associated with A-490."
FT                   /evidence="ECO:0000269|PubMed:22906005"
FT   MUTAGEN         543
FT                   /note="S->D: Increases basal level of enzyme activity.
FT                   Abolishes activation by PKC; when associated with D-490."
FT                   /evidence="ECO:0000269|PubMed:22906005"
FT   STRAND          879..891
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           895..898
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   TURN            903..908
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           909..923
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           924..927
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           929..931
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          934..940
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          943..948
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           967..987
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   TURN            988..991
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          997..1010
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          1012..1014
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          1016..1021
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           1022..1032
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          1039..1041
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   HELIX           1043..1052
FT                   /evidence="ECO:0007829|PDB:1AB8"
FT   STRAND          1056..1064
FT                   /evidence="ECO:0007829|PDB:1AZS"
FT   TURN            1065..1067
FT                   /evidence="ECO:0007829|PDB:1AZS"
FT   STRAND          1068..1075
FT                   /evidence="ECO:0007829|PDB:1AZS"
SQ   SEQUENCE   1090 AA;  123316 MW;  935CE44DF73199B3 CRC64;
     MRRRRYLRDR AEAAAAAAAG GGEGLQRSRD WLYESYYCMS QQHPLIVFLL LIVMGACLAL
     LAVFFALGLE VEDHVAFLIT VPTALAIFFA IFILVCIESV FKKLLRVFSL VIWICLVAMG
     YLFMCFGGTV SAWDQVSFFL FIIFVVYTML PFNMRDAIIA SILTSSSHTI VLSVYLSATP
     GAKEHLFWQI LANVIIFICG NLAGAYHKHL MELALQQTYR DTCNCIKSRI KLEFEKRQQE
     RLLLSLLPAH IAMEMKAEII QRLQGPKAGQ MENTNNFHNL YVKRHTNVSI LYADIVGFTR
     LASDCSPGEL VHMLNELFGK FDQIAKENEC MRIKILGDCY YCVSGLPISL PNHAKNCVKM
     GLDMCEAIKK VRDATGVDIN MRVGVHSGNV LCGVIGLQKW QYDVWSHDVT LANHMEAGGV
     PGRVHISSVT LEHLNGAYKV EEGDGEIRDP YLKQHLVKTY FVINPKGERR SPQHLFRPRH
     TLDGAKMRAS VRMTRYLESW GAAKPFAHLH HRDSMTTENG KISTTDVPMG QHNFQNRTLR
     TKSQKKRFEE ELNERMIQAI DGINAQKQWL KSEDIQRISL LFYNKNIEKE YRATALPAFK
     YYVTCACLIF LCIFIVQILV LPKTSILGFS FGAAFLSLIF ILFVCFAGQL LQCSKKASTS
     LMWLLKSSGI IANRPWPRIS LTIVTTAIIL TMAVFNMFFL SNSEETTLPT ANTSNANVSV
     PDNQASILHA RNLFFLPYFI YSCILGLISC SVFLRVNYEL KMLIMMVALV GYNTILLHTH
     AHVLDAYSQV LFQRPGIWKD LKTMGSVSLS IFFITLLVLG RQSEYYCRLD FLWKNKFKKE
     REEIETMENL NRVLLENVLP AHVAEHFLAR SLKNEELYHQ SYDCVCVMFA SIPDFKEFYT
     ESDVNKEGLE CLRLLNEIIA DFDDLLSKPK FSGVEKIKTI GSTYMAATGL SAIPSQEHAQ
     EPERQYMHIG TMVEFAYALV GKLDAINKHS FNDFKLRVGI NHGPVIAGVI GAQKPQYDIW
     GNTVNVASRM DSTGVLDKIQ VTEETSLILQ TLGYTCTCRG IINVKGKGDL KTYFVNTEMS
     RSLSQSNLAS
//