ID   ADCY9_HUMAN             Reviewed;        1353 AA.
AC   O60503; A7E2V5; A7E2X2; D3DUD1; O60273; Q4ZHT9; Q4ZIR5; Q9BWT4; Q9UGP2;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   13-DEC-2002, sequence version 4.
DT   27-MAR-2024, entry version 196.
DE   RecName: Full=Adenylate cyclase type 9 {ECO:0000303|PubMed:9628827};
DE            EC=4.6.1.1 {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827};
DE   AltName: Full=ATP pyrophosphate-lyase 9;
DE   AltName: Full=Adenylate cyclase type IX {ECO:0000303|PubMed:10987815};
DE            Short=ACIX {ECO:0000303|PubMed:10987815};
DE   AltName: Full=Adenylyl cyclase 9;
DE            Short=AC9 {ECO:0000303|PubMed:15879435};
GN   Name=ADCY9; Synonyms=KIAA0520;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, ACTIVITY
RP   REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Heart;
RX   PubMed=9628827; DOI=10.1006/geno.1998.5293;
RA   Hacker B.M., Tomlinson J.E., Wayman G.A., Sultana R., Chan G.,
RA   Villacres E., Disteche C., Storm D.R.;
RT   "Cloning, chromosomal mapping, and regulatory properties of the human type
RT   9 adenylyl cyclase (ADCY9).";
RL   Genomics 50:97-104(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP   SPECIFICITY, AND VARIANT MET-772.
RX   PubMed=12972952; DOI=10.1097/00008571-200309000-00002;
RA   Small K.M., Brown K.M., Theiss C.T., Seman C.A., Weiss S.T., Liggett S.B.;
RT   "An Ile to Met polymorphism in the catalytic domain of adenylyl cyclase
RT   type 9 confers reduced beta2-adrenergic receptor stimulation.";
RL   Pharmacogenetics 13:535-541(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP   LOCATION, AND VARIANT MET-772.
RX   PubMed=15879435; DOI=10.1093/hmg/ddi175;
RA   Tantisira K.G., Small K.M., Litonjua A.A., Weiss S.T., Liggett S.B.;
RT   "Molecular properties and pharmacogenetics of a polymorphism of adenylyl
RT   cyclase type 9 in asthma: interaction between beta-agonist and
RT   corticosteroid pathways.";
RL   Hum. Mol. Genet. 14:1671-1677(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT SER-1154.
RX   PubMed=10987815; DOI=10.1046/j.1471-4159.2000.0751358.x;
RA   Paterson J.M., Smith S.M., Simpson J., Grace O.C., Sosunov A.A., Bell J.E.,
RA   Antoni F.A.;
RT   "Characterisation of human adenylyl cyclase IX reveals inhibition by
RT   Ca(2+)/Calcineurin and differential mRNA plyadenylation.";
RL   J. Neurochem. 75:1358-1367(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Toyota T., Yamada K., Meerabux J., Hattori E., Saito K., Yoshitsugu K.,
RA   Shimizu H., Nankai M., Toru M., Detera-Wadleigh S.D., Yoshikawa T.;
RT   "Mutation screening, case control study and transmission disequilibrium
RT   analysis of adenylate cyclase type 9 (ADCY9) gene in functional
RT   psychoses.";
RL   Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-1154.
RC   TISSUE=Brain;
RX   PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA   Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA   Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. IX. The
RT   complete sequences of 100 new cDNA clones from brain which can code for
RT   large proteins in vitro.";
RL   DNA Res. 5:31-39(1998).
RN   [7]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [8]
RP   SEQUENCE REVISION.
RA   Ohara O., Nagase T., Kikuno R., Ishikawa K.;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-1154.
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1259, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1307, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1257 AND SER-1259, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Adenylyl cyclase that catalyzes the formation of the
CC       signaling molecule cAMP in response to activation of G protein-coupled
CC       receptors (PubMed:9628827, PubMed:12972952, PubMed:15879435,
CC       PubMed:10987815). Contributes to signaling cascades activated by CRH
CC       (corticotropin-releasing factor), corticosteroids and beta-adrenergic
CC       receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815,
CC       ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435,
CC       ECO:0000269|PubMed:9628827}.
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:10987815, ECO:0000269|PubMed:12972952,
CC         ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P30803};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:P30803};
CC       Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC       (in vitro). {ECO:0000250|UniProtKB:P30803};
CC   -!- ACTIVITY REGULATION: Insensitive to calcium/calmodulin, forskolin and
CC       somatostatin. Stimulated by beta-adrenergic receptor activation
CC       (PubMed:9628827). Activity is down-regulated by calcium/calcineurin
CC       (PubMed:10987815). {ECO:0000269|PubMed:10987815,
CC       ECO:0000269|PubMed:9628827}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10987815,
CC       ECO:0000269|PubMed:9628827}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Detected in skeletal muscle, pancreas, lung, heart,
CC       kidney, liver, brain and placenta (PubMed:9628827, PubMed:10987815).
CC       Expressed in multiple cells of the lung, with expression highest in
CC       airway smooth muscle (PubMed:12972952). {ECO:0000269|PubMed:10987815,
CC       ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:9628827}.
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:0000255|PROSITE-ProRule:PRU00099}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC24201.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=BAA25446.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF036927; AAC24201.1; ALT_FRAME; mRNA.
DR   EMBL; DQ008441; AAY27880.1; -; mRNA.
DR   EMBL; DQ005545; AAY21237.1; -; mRNA.
DR   EMBL; AJ133123; CAB65084.1; -; mRNA.
DR   EMBL; AY028959; AAK29464.1; -; Genomic_DNA.
DR   EMBL; AY028949; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028950; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028951; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028952; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028953; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028954; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028955; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028956; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AY028957; AAK29464.1; JOINED; Genomic_DNA.
DR   EMBL; AB011092; BAA25446.3; ALT_INIT; mRNA.
DR   EMBL; CH471112; EAW85331.1; -; Genomic_DNA.
DR   EMBL; CH471112; EAW85332.1; -; Genomic_DNA.
DR   EMBL; BC136657; AAI36658.1; -; mRNA.
DR   EMBL; BC136658; AAI36659.1; -; mRNA.
DR   EMBL; BC151207; AAI51208.1; -; mRNA.
DR   EMBL; BC151229; AAI51230.1; -; mRNA.
DR   CCDS; CCDS32382.1; -.
DR   RefSeq; NP_001107.2; NM_001116.3.
DR   AlphaFoldDB; O60503; -.
DR   SMR; O60503; -.
DR   BioGRID; 106628; 158.
DR   IntAct; O60503; 23.
DR   MINT; O60503; -.
DR   STRING; 9606.ENSP00000294016; -.
DR   BindingDB; O60503; -.
DR   ChEMBL; CHEMBL2655; -.
DR   DrugBank; DB02587; Colforsin.
DR   GlyCosmos; O60503; 3 sites, No reported glycans.
DR   GlyGen; O60503; 3 sites.
DR   iPTMnet; O60503; -.
DR   PhosphoSitePlus; O60503; -.
DR   SwissPalm; O60503; -.
DR   BioMuta; ADCY9; -.
DR   CPTAC; CPTAC-1229; -.
DR   CPTAC; CPTAC-1230; -.
DR   EPD; O60503; -.
DR   jPOST; O60503; -.
DR   MassIVE; O60503; -.
DR   MaxQB; O60503; -.
DR   PaxDb; 9606-ENSP00000294016; -.
DR   PeptideAtlas; O60503; -.
DR   ProteomicsDB; 49441; -.
DR   Pumba; O60503; -.
DR   Antibodypedia; 55436; 263 antibodies from 31 providers.
DR   DNASU; 115; -.
DR   Ensembl; ENST00000294016.8; ENSP00000294016.3; ENSG00000162104.10.
DR   GeneID; 115; -.
DR   KEGG; hsa:115; -.
DR   MANE-Select; ENST00000294016.8; ENSP00000294016.3; NM_001116.4; NP_001107.2.
DR   UCSC; uc002cvx.4; human.
DR   AGR; HGNC:240; -.
DR   CTD; 115; -.
DR   DisGeNET; 115; -.
DR   GeneCards; ADCY9; -.
DR   HGNC; HGNC:240; ADCY9.
DR   HPA; ENSG00000162104; Tissue enhanced (skeletal).
DR   MIM; 603302; gene.
DR   neXtProt; NX_O60503; -.
DR   OpenTargets; ENSG00000162104; -.
DR   PharmGKB; PA30; -.
DR   VEuPathDB; HostDB:ENSG00000162104; -.
DR   eggNOG; KOG3618; Eukaryota.
DR   GeneTree; ENSGT00940000155577; -.
DR   HOGENOM; CLU_001072_12_0_1; -.
DR   InParanoid; O60503; -.
DR   OMA; FTAMPPG; -.
DR   OrthoDB; 3686360at2759; -.
DR   PhylomeDB; O60503; -.
DR   TreeFam; TF313845; -.
DR   PathwayCommons; O60503; -.
DR   Reactome; R-HSA-163359; Glucagon signaling in metabolic regulation.
DR   Reactome; R-HSA-163615; PKA activation.
DR   Reactome; R-HSA-164378; PKA activation in glucagon signalling.
DR   Reactome; R-HSA-170660; Adenylate cyclase activating pathway.
DR   Reactome; R-HSA-170670; Adenylate cyclase inhibitory pathway.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-418597; G alpha (z) signalling events.
DR   Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR   Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR   Reactome; R-HSA-9634597; GPER1 signaling.
DR   Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR   Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR   SignaLink; O60503; -.
DR   SIGNOR; O60503; -.
DR   BioGRID-ORCS; 115; 17 hits in 1151 CRISPR screens.
DR   ChiTaRS; ADCY9; human.
DR   GeneWiki; ADCY9; -.
DR   GenomeRNAi; 115; -.
DR   Pharos; O60503; Tbio.
DR   PRO; PR:O60503; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; O60503; Protein.
DR   Bgee; ENSG00000162104; Expressed in secondary oocyte and 201 other cell types or tissues.
DR   ExpressionAtlas; O60503; baseline and differential.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0004016; F:adenylate cyclase activity; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0006171; P:cAMP biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; IPR029787; Nucleotide_cyclase.
DR   PANTHER; PTHR45627; ADENYLATE CYCLASE TYPE 1; 1.
DR   PANTHER; PTHR45627:SF8; ADENYLATE CYCLASE TYPE 9; 1.
DR   Pfam; PF00211; Guanylate_cyc; 2.
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.
DR   Genevisible; O60503; HS.
PE   1: Evidence at protein 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..1353
FT                   /note="Adenylate cyclase type 9"
FT                   /id="PRO_0000195708"
FT   TOPO_DOM        1..117
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        139..141
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        142..162
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        163..171
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        172..192
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        193..215
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        216..235
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        236..241
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        242..259
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        260..280
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        281..301
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        302..786
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        787..807
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        808..818
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        819..839
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        840..867
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        868..888
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        889..891
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        892..912
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        913..920
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        921..941
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        942..975
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        976..996
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        997..1353
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          394..521
FT                   /note="Guanylate cyclase 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   DOMAIN          1058..1198
FT                   /note="Guanylate cyclase 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   REGION          1..27
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          49..71
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          349..375
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          642..684
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1292..1326
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        654..684
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1306..1326
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         399..404
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         399
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   BINDING         399
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         400
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         441..443
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         443
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   BINDING         443
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         487
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         1108
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   BINDING         1185..1187
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   BINDING         1192..1196
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   BINDING         1232
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   MOD_RES         610
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P51830"
FT   MOD_RES         688
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P51830"
FT   MOD_RES         691
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P51830"
FT   MOD_RES         706
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         1257
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         1259
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1295
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P51830"
FT   MOD_RES         1307
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231"
FT   CARBOHYD        206
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        955
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        964
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         772
FT                   /note="I -> M (found in 37.5% of the Asian population, in
FT                   30% of the Caucasian population and in 16.3% of the
FT                   African-American population; reduced adenylyl cyclase
FT                   activity in response to stimulation of the beta-adregnergic
FT                   receptor by Mn(2+) agonists isoproteronol and NaF;
FT                   increased albuterol-stimulated adenylyl cyclase activity in
FT                   the presence of corticosteroid; dbSNP:rs2230739)"
FT                   /evidence="ECO:0000269|PubMed:12972952,
FT                   ECO:0000269|PubMed:15879435"
FT                   /id="VAR_023750"
FT   VARIANT         1154
FT                   /note="N -> S (in dbSNP:rs61731445)"
FT                   /evidence="ECO:0000269|PubMed:10987815,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9628581"
FT                   /id="VAR_070887"
FT   CONFLICT        493
FT                   /note="G -> R (in Ref. 4; CAB65084)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        884
FT                   /note="V -> A (in Ref. 4; CAB65084)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1308
FT                   /note="P -> R (in Ref. 4; CAB65084)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1353 AA;  150701 MW;  4CBF051EA49B5B7B CRC64;
     MASPPHQQLL HHHSTEVSCD SSGDSNSVRV KINPKQLSSN SHPKHCKYSI SSSCSSSGDS
     GGVPRRVGGG GRLRRQKKLP QLFERASSRW WDPKFDSVNL EEACLERCFP QTQRRFRYAL
     FYIGFACLLW SIYFAVHMRS RLIVMVAPAL CFLLVCVGFF LFTFTKLYAR HYAWTSLALT
     LLVFALTLAA QFQVLTPVSG RGDSSNLTAT ARPTDTCLSQ VGSFSMCIEV LFLLYTVMHL
     PLYLSLCLGV AYSVLFETFG YHFRDEACFP SPGAGALHWE LLSRGLLHGC IHAIGVHLFV
     MSQVRSRSTF LKVGQSIMHG KDLEVEKALK ERMIHSVMPR IIADDLMKQG DEESENSVKR
     HATSSPKNRK KKSSIQKAPI AFRPFKMQQI EEVSILFADI VGFTKMSANK SAHALVGLLN
     DLFGRFDRLC EETKCEKIST LGDCYYCVAG CPEPRADHAY CCIEMGLGMI KAIEQFCQEK
     KEMVNMRVGV HTGTVLCGIL GMRRFKFDVW SNDVNLANLM EQLGVAGKVH ISEATAKYLD
     DRYEMEDGKV IERLGQSVVA DQLKGLKTYL ISGQRAKESR CSCAEALLSG FEVIDGSQVS
     SGPRGQGTAS SGNVSDLAQT VKTFDNLKTC PSCGITFAPK SEAGAEGGAP QNGCQDEHKN
     STKASGGPNP KTQNGLLSPP QEEKLTNSQT SLCEILQEKG RWAGVSLDQS ALLPLRFKNI
     REKTDAHFVD VIKEDSLMKD YFFKPPINQF SLNFLDQELE RSYRTSYQEE VIKNSPVKTF
     ASPTFSSLLD VFLSTTVFLT LSTTCFLKYE AATVPPPPAA LAVFSAALLL EVLSLAVSIR
     MVFFLEDVMA CTKRLLEWIA GWLPRHCIGA ILVSLPALAV YSHVTSEYET NIHFPVFTGS
     AALIAVVHYC NFCQLSSWMR SSLATVVGAG PLLLLYVSLC PDSSVLTSPL DAVQNFSSER
     NPCNSSVPRD LRRPASLIGQ EVVLVFFLLL LLVWFLNREF EVSYRLHYHG DVEADLHRTK
     IQSMRDQADW LLRNIIPYHV AEQLKVSQTY SKNHDSGGVI FASIVNFSEF YEENYEGGKE
     CYRVLNELIG DFDELLSKPD YSSIEKIKTI GATYMAASGL NTAQAQDGSH PQEHLQILFE
     FAKEMMRVVD DFNNNMLWFN FKLRVGFNHG PLTAGVIGTT KLLYDIWGDT VNIASRMDTT
     GVECRIQVSE ESYRVLSKMG YDFDYRGTVN VKGKGQMKTY LYPKCTDHRV IPQHQLSISP
     DIRVQVDGSI GRSPTDEIAN LVPSVQYVDK TSLGSDSSTQ AKDAHLSPKR PWKEPVKAEE
     RGRFGKAIEK DDCDETGIEE ANELTKLNVS KSV
//