ADCY6_MOUSE
ID ADCY6_MOUSE Reviewed; 1165 AA.
AC Q01341;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Adenylate cyclase type 6;
DE EC=4.6.1.1 {ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:18071070, ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687, ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24363043};
DE AltName: Full=ATP pyrophosphate-lyase 6;
DE AltName: Full=Adenylate cyclase type VI;
DE AltName: Full=Adenylyl cyclase 6 {ECO:0000303|PubMed:18071070, ECO:0000303|PubMed:20466003};
DE Short=AC6 {ECO:0000303|PubMed:18071070, ECO:0000303|PubMed:20466003};
DE AltName: Full=Ca(2+)-inhibitable adenylyl cyclase;
GN Name=Adcy6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=1379717; DOI=10.1073/pnas.89.15.6716;
RA Yoshimura M., Cooper D.M.F.;
RT "Cloning and expression of a Ca(2+)-inhibitable adenylyl cyclase from NCB-
RT 20 cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6716-6720(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-1165.
RX PubMed=1332848; DOI=10.1210/endo.131.6.1332848;
RA Premont R.T., Jacobowitz O., Iyengar R.;
RT "Lowered responsiveness of the catalyst of adenylyl cyclase to stimulation
RT by GS in heterologous desensitization: a role for adenosine 3',5'-
RT monophosphate-dependent phosphorylation.";
RL Endocrinology 131:2774-2784(1992).
RN [3]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=17567809; DOI=10.1523/jneurosci.0342-07.2007;
RA Michalski N., Michel V., Bahloul A., Lefevre G., Barral J., Yagi H.,
RA Chardenoux S., Weil D., Martin P., Hardelin J.P., Sato M., Petit C.;
RT "Molecular characterization of the ankle-link complex in cochlear hair
RT cells and its role in the hair bundle functioning.";
RL J. Neurosci. 27:6478-6488(2007).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, ACTIVITY REGULATION, CATALYTIC ACTIVITY,
RP AND TISSUE SPECIFICITY.
RX PubMed=18071070; DOI=10.1161/circulationaha.107.730069;
RA Tang T., Gao M.H., Lai N.C., Firth A.L., Takahashi T., Guo T., Yuan J.X.,
RA Roth D.M., Hammond H.K.;
RT "Adenylyl cyclase type 6 deletion decreases left ventricular function via
RT impaired calcium handling.";
RL Circulation 117:61-69(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-573, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20371630; DOI=10.1096/fj.09-148007;
RA Kwon R.Y., Temiyasathit S., Tummala P., Quah C.C., Jacobs C.R.;
RT "Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6
RT and cyclic AMP in bone cells.";
RL FASEB J. 24:2859-2868(2010).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=20466003; DOI=10.1016/j.febslet.2010.05.004;
RA Chien C.L., Wu Y.S., Lai H.L., Chen Y.H., Jiang S.T., Shih C.M., Lin S.S.,
RA Chang C., Chern Y.;
RT "Impaired water reabsorption in mice deficient in the type VI adenylyl
RT cyclase (AC6).";
RL FEBS Lett. 584:2883-2890(2010).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20359598; DOI=10.1016/j.jacc.2009.11.066;
RA Tang T., Lai N.C., Hammond H.K., Roth D.M., Yang Y., Guo T., Gao M.H.;
RT "Adenylyl cyclase 6 deletion reduces left ventricular hypertrophy,
RT dilation, dysfunction, and fibrosis in pressure-overloaded female mice.";
RL J. Am. Coll. Cardiol. 55:1476-1486(2010).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP REGULATION.
RX PubMed=20864687; DOI=10.1681/asn.2010040409;
RA Rieg T., Tang T., Murray F., Schroth J., Insel P.A., Fenton R.A.,
RA Hammond H.K., Vallon V.;
RT "Adenylate cyclase 6 determines cAMP formation and aquaporin-2
RT phosphorylation and trafficking in inner medulla.";
RL J. Am. Soc. Nephrol. 21:2059-2068(2010).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH AKAP5; ADCY5; PDE4C AND PKD2.
RX PubMed=21670265; DOI=10.1073/pnas.1016214108;
RA Choi Y.H., Suzuki A., Hajarnis S., Ma Z., Chapin H.C., Caplan M.J.,
RA Pontoglio M., Somlo S., Igarashi P.;
RT "Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase
RT anchoring protein complex that is disrupted in cystic kidney diseases.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:10679-10684(2011).
RN [11]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=23753526; DOI=10.1113/jphysiol.2012.249698;
RA Sabbatini M.E., D'Alecy L., Lentz S.I., Tang T., Williams J.A.;
RT "Adenylyl cyclase 6 mediates the action of cyclic AMP-dependent
RT secretagogues in mouse pancreatic exocrine cells via protein kinase A
RT pathway activation.";
RL J. Physiol. (Lond.) 591:3693-3707(2013).
RN [12]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24277577; DOI=10.1096/fj.13-240432;
RA Lee K.L., Hoey D.A., Spasic M., Tang T., Hammond H.K., Jacobs C.R.;
RT "Adenylyl cyclase 6 mediates loading-induced bone adaptation in vivo.";
RL FASEB J. 28:1157-1165(2014).
RN [13]
RP DISRUPTION PHENOTYPE.
RX PubMed=24158982; DOI=10.1681/asn.2013010077;
RA Rees S., Kittikulsuth W., Roos K., Strait K.A., Van Hoek A., Kohan D.E.;
RT "Adenylyl cyclase 6 deficiency ameliorates polycystic kidney disease.";
RL J. Am. Soc. Nephrol. 25:232-237(2014).
RN [14]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY
RP REGULATION.
RX PubMed=24854272; DOI=10.1681/asn.2013101102;
RA Fenton R.A., Murray F., Dominguez Rieg J.A., Tang T., Levi M., Rieg T.;
RT "Renal phosphate wasting in the absence of adenylyl cyclase 6.";
RL J. Am. Soc. Nephrol. 25:2822-2834(2014).
RN [15]
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).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP
CC downstream of G protein-coupled receptors (PubMed:18071070,
CC PubMed:24363043). Functions in signaling cascades downstream of beta-
CC adrenergic receptors in the heart and in vascular smooth muscle cells
CC (PubMed:18071070). Functions in signaling cascades downstream of the
CC vasopressin receptor in the kidney and has a role in renal water
CC reabsorption (PubMed:20466003, PubMed:20864687). Functions in signaling
CC cascades downstream of PTH1R and plays a role in regulating renal
CC phosphate excretion (PubMed:24854272). Functions in signaling cascades
CC downstream of the VIP and SCT receptors in pancreas and contributes to
CC the regulation of pancreatic amylase and fluid secretion
CC (PubMed:23753526). Signaling mediates cAMP-dependent activation of
CC protein kinase PKA and promotes increased phosphorylation of various
CC proteins, including AKT (PubMed:18071070, PubMed:23753526). Plays a
CC role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and
CC storage, and is required for normal heart ventricular contractibility
CC (PubMed:18071070). May contribute to normal heart function
CC (PubMed:18071070, PubMed:20359598). Mediates vasodilatation after
CC activation of beta-adrenergic receptors by isoproterenol (By
CC similarity). Contributes to bone cell responses to mechanical stimuli
CC (PubMed:20371630, PubMed:24277577). {ECO:0000250|UniProtKB:O43306,
CC ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:18071070,
CC ECO:0000269|PubMed:20359598, ECO:0000269|PubMed:20371630,
CC ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687,
CC ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24277577,
CC ECO:0000269|PubMed:24363043, ECO:0000269|PubMed:24854272}.
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:1379717, ECO:0000269|PubMed:18071070,
CC ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687,
CC ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24363043,
CC ECO:0000269|PubMed:24854272};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O43306};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O43306};
CC Note=Binds 2 magnesium ions per subunit. Is also active with manganese
CC (in vitro). {ECO:0000250|UniProtKB:P30803};
CC -!- ACTIVITY REGULATION: Activated by forskolin (PubMed:18071070,
CC PubMed:20466003, PubMed:20864687, PubMed:23753526, PubMed:24363043).
CC Inhibited by calcium ions, already at micromolar concentrations
CC (PubMed:1379717, PubMed:18071070). Inhibited by adenosine, AMP and
CC their analogs (By similarity). Activated by GNAS. Is further activated
CC by the complex formed by GNB1 and GNG2 (By similarity). Phosphorylation
CC by RAF1 results in its activation (By similarity).
CC {ECO:0000250|UniProtKB:P30804, ECO:0000250|UniProtKB:Q03343,
CC ECO:0000269|PubMed:1379717, ECO:0000269|PubMed:18071070,
CC ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:20864687,
CC ECO:0000269|PubMed:23753526, ECO:0000269|PubMed:24363043}.
CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2
CC (PubMed:21670265). Interacts with RAF1. Interacts (via cytoplasmic N-
CC terminus) with GNAS, GNB1 and GNG2 (By similarity).
CC {ECO:0000250|UniProtKB:O43306, ECO:0000269|PubMed:21670265}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1379717,
CC ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:21670265}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:21670265}. Cell projection, cilium
CC {ECO:0000269|PubMed:20371630, ECO:0000269|PubMed:20466003,
CC ECO:0000269|PubMed:21670265}. Cell projection, stereocilium
CC {ECO:0000269|PubMed:17567809}.
CC -!- TISSUE SPECIFICITY: Detected in kidney tubules (PubMed:20466003).
CC Detected in primary bone cells with osteocyte morphology
CC (PubMed:24277577). Detected in heart (at protein level)
CC (PubMed:18071070). Highly expressed in heart (PubMed:1379717,
CC PubMed:18071070). Detected in kidney, pancreas acini and ducts
CC (PubMed:23753526). Expressed in cochlear outer and inner hair cells
CC (PubMed:17567809). Weakly detectable in brain, intestine, lung and
CC spleen (PubMed:1379717). {ECO:0000269|PubMed:1379717,
CC ECO:0000269|PubMed:17567809, ECO:0000269|PubMed:18071070,
CC ECO:0000269|PubMed:20466003, ECO:0000269|PubMed:23753526,
CC ECO:0000269|PubMed:24277577}.
CC -!- DEVELOPMENTAL STAGE: In the inner ear, between 16 dpc and P1, present
CC along the sterocilia of outer hair cells, but almost undetectable in
CC inner hair cell hair bundle. From P3 onward, expression in outer hair
CC cell bundles is restricted to their base and it is also expressed at
CC the base of inner hair cell stereocilia. {ECO:0000269|PubMed:17567809}.
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 -!- PTM: Phosphorylation by RAF1 increases enzyme activity. Phosphorylation
CC by PKA on Ser-659 inhibits the GNAS-mediated increase in catalytic
CC activity. Phosphorylation by PKC on Ser-553, Ser-659 and Thr-916
CC inhibits catalytic activity. {ECO:0000250|UniProtKB:Q03343}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, present no obvious phenotype and are fertile (PubMed:18071070,
CC PubMed:20466003, PubMed:23753526, PubMed:24277577). Their hearts
CC display a decrease in left ventricular pressure, both at the basal
CC level and after activation of beta-adrenergic receptors
CC (PubMed:18071070). Besides, their hearts show defects in sarcoplasmic
CC Ca(2+) uptake and storage, and decreased levels of protein
CC phosphorylation (PubMed:18071070). Male mice show increased mortality
CC after transversal aortic constriction (PubMed:20359598). In contrast,
CC female mice do not show increased mortality after transversal aortic
CC constriction, and develop less heart hypertrophy and fibrosis than
CC wild-type (PubMed:20359598). Compared to wild-type, mutant mice drink
CC more and produce greater volumes of urine with decreased osmolarity,
CC but there is no difference in the total quantity of excreted urinary
CC solutes and no difference in blood plasma composition (PubMed:20466003,
CC PubMed:20864687). The impaired urinary water homeostasis is due to
CC retention of AQP2 in intracellular vesicles and decreased AQP2 levels
CC at the cell membrane (PubMed:20466003). Mutant mice display increased
CC urinary inorganic phosphate excretion, but normal plasma phosphate
CC levels (PubMed:24854272). Mutant mice display increased plasma levels
CC of PTH and FGF23, the two principal regulators of urinary phosphate
CC excretion (PubMed:24854272). Mutant mice display no obvious skeleton
CC defects, but display less bone formation after load stress than wild-
CC type (PubMed:24277577). Mutant mice lacking both Adcy6 and Pkd1 survive
CC longer and have less severe polycystic kidney disease than mice lacking
CC only Pkd1 (PubMed:24158982). {ECO:0000269|PubMed:18071070,
CC ECO:0000269|PubMed:20359598, ECO:0000269|PubMed:20466003,
CC ECO:0000269|PubMed:20864687, ECO:0000269|PubMed:23753526,
CC ECO:0000269|PubMed:24158982, ECO:0000269|PubMed:24277577,
CC ECO:0000269|PubMed:24854272}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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; M93422; AAA37174.1; -; mRNA.
DR EMBL; M96653; AAA37182.1; -; mRNA.
DR PIR; A49201; A49201.
DR RefSeq; NP_031431.2; NM_007405.2.
DR AlphaFoldDB; Q01341; -.
DR SMR; Q01341; -.
DR BioGRID; 197975; 1.
DR STRING; 10090.ENSMUSP00000093939; -.
DR GlyGen; Q01341; 3 sites.
DR iPTMnet; Q01341; -.
DR PhosphoSitePlus; Q01341; -.
DR SwissPalm; Q01341; -.
DR jPOST; Q01341; -.
DR MaxQB; Q01341; -.
DR PaxDb; Q01341; -.
DR PRIDE; Q01341; -.
DR ProteomicsDB; 285724; -.
DR DNASU; 11512; -.
DR GeneID; 11512; -.
DR KEGG; mmu:11512; -.
DR CTD; 112; -.
DR MGI; MGI:87917; Adcy6.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; Q01341; -.
DR OrthoDB; 215180at2759; -.
DR PhylomeDB; Q01341; -.
DR BRENDA; 4.6.1.1; 3474.
DR Reactome; R-MMU-163615; PKA activation.
DR Reactome; R-MMU-170660; Adenylate cyclase activating pathway.
DR Reactome; R-MMU-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-MMU-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-MMU-418597; G alpha (z) signalling events.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR BioGRID-ORCS; 11512; 7 hits in 71 CRISPR screens.
DR ChiTaRS; Adcy6; mouse.
DR PRO; PR:Q01341; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q01341; protein.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:BHF-UCL.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0031528; C:microvillus membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0032420; C:stereocilium; IEA:UniProtKB-SubCell.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008294; F:calcium- and calmodulin-responsive adenylate cyclase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; ISS:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; IPI:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0000149; F:SNARE binding; ISO:MGI.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISO:MGI.
DR GO; GO:0006171; P:cAMP biosynthetic process; IMP:UniProtKB.
DR GO; GO:0071870; P:cellular response to catecholamine stimulus; ISO:MGI.
DR GO; GO:1904322; P:cellular response to forskolin; IMP:UniProtKB.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISO:MGI.
DR GO; GO:1904117; P:cellular response to vasopressin; IMP:UniProtKB.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0072660; P:maintenance of protein location in plasma membrane; ISO:MGI.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:ParkinsonsUK-UCL.
DR GO; GO:0035811; P:negative regulation of urine volume; IMP:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; IMP:UniProtKB.
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; IPR009398; Adcy_conserved_dom.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF16214; AC_N; 1.
DR Pfam; PF06327; DUF1053; 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 1: Evidence at protein level;
KW ATP-binding; cAMP biosynthesis; Cell membrane; Cell projection; Cilium;
KW Glycoprotein; Lyase; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1165
FT /note="Adenylate cyclase type 6"
FT /id="PRO_0000195700"
FT TOPO_DOM 1..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 304..670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 671..688
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 699..715
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 740..756
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 757..816
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 817..833
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 836..852
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 894..910
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 911..1165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 382..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 382
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 382
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 383
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 424..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 426
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 426
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 470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1028
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1102..1104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1109..1113
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43306"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 916
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 790
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 875
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 47
FT /note="K -> N (in Ref. 2; AAA37182)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="G -> A (in Ref. 2; AAA37182)"
FT /evidence="ECO:0000305"
FT CONFLICT 508..509
FT /note="GR -> RAG (in Ref. 2; AAA37182)"
FT /evidence="ECO:0000305"
FT CONFLICT 737
FT /note="V -> G (in Ref. 2; AAA37182)"
FT /evidence="ECO:0000305"
FT CONFLICT 881
FT /note="L -> Q (in Ref. 2; AAA37182)"
FT /evidence="ECO:0000305"
FT CONFLICT 990
FT /note="V -> M (in Ref. 2; AAA37182)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1165 AA; 130319 MW; 24EE1BB45DF1E87E CRC64;
MSWFSGLLVP KVDERKTAWG ERNGQKRPRH ANRASGFCAP RYMSCLKNAE PPSPTPAAHT
RCPWQDEAFI RRAGPGRGVE LGLRSVALGF DDTEVTTPMG TAEVAPDTSP RSGPSCWHRL
VQVFQSKQFR SAKLERLYQR YFFQMNQSSL TLLMAVLVLL MAVLLTFHAA PAQPQPAYVA
LLTCASVLFV VLMVVCNRHS FRQDSMWVVS YVVLGILAAV QVGGALAANP HSPSAGLWCP
VFFVYITYTL LPIRMRAAVL SGLGLSTLHL ILAWQLNSSD PFLWKQLGAN VVLFLCTNAI
GVCTHYPAEV SQRQAFQETR GYIQARLHLQ HENRQQERLL LSVLPQHVAM EMKEDINTKK
EDMMFHKIYI QKHDNVSILF ADIEGFTSLA SQCTAQELVM TLNELFARFD KLAAENHCLR
IKILGDCYYC VSGLPEARAD HAHCCVEMGV DMIEAISLVR EVTGVNVNMR VGIHSGRVHC
GVLGLRKWQF DVWSNDVTLA NHMEAGGGRR IHITRATLQY LNGDYEVEPG RGGERNAYLK
EQCIETFLIL GASQKRKEEK AMLAKLQRTR ANSMEGLMPR WVPDRAFSRT KDSKAFRQMG
IDDSSKDNRG AQDALNPEDE VDEFLGRAID ARSIDQLRKD HVRRFLLTFQ REDLEKKYSR
KVDPRFGAYV ACALLVFCFI CFIQLLVFPY STLILGIYAA IFLLLLVTVL ICAVCSCGSF
FPKALQRLSR NIVRSRVHST AVGIFSVLLV FISAIANMFT CNHTPIRTCA ARMLNLTPAD
VTACHLQQLN YSLGLDAPLC EGTAPTCSFP EYFVGNVLLS LLASSVFLHI SSIGKLAMTF
ILGFTYLVLL LLGPPAAIFD NYDLLLGVHG LASSNETFDG LDCPAVGRVA LKYMTPVILL
VFALALYLHA QQVESTARLD FLWKLQATGE KEEMEELQAY NRRLLHNILP KDVAAHFLAR
ERRNDELYYQ SCECVAVMFA SIANFSEFYV ELEANNEGVE CLRLLNEIIA DFDEIISEER
FRQLEKIKTI GSTYMAASGL NASTYDQVGR SHITALADYA MRLMEQMKHI NEHSFNNFQM
KIGLNMGPVV AGVIGARKPQ YDIWGNTVNV SSRMDSTGVP DRIQVTTDLY QVLAAKGYQL
ECRGVVKVKG KGEMTTYFLN GGPSS
