ADCY6_HUMAN
ID ADCY6_HUMAN Reviewed; 1168 AA.
AC O43306; Q9NR75; Q9UDB0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Adenylate cyclase type 6;
DE EC=4.6.1.1 {ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:17916776};
DE AltName: Full=ATP pyrophosphate-lyase 6;
DE AltName: Full=Adenylate cyclase type VI;
DE AltName: Full=Adenylyl cyclase 6 {ECO:0000303|PubMed:17916776};
DE AltName: Full=Ca(2+)-inhibitable adenylyl cyclase;
GN Name=ADCY6; Synonyms=KIAA0422;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Thyroid;
RX PubMed=10978539; DOI=10.1016/s0167-4781(00)00187-1;
RA Wicker R., Catalan A.G., Cailleux A.-F., Starenki D., Stengel D.,
RA Sarasin A., Suarez H.G.;
RT "Cloning and expression of human adenylyl cyclase type VI in normal thyroid
RT tissues.";
RL Biochim. Biophys. Acta 1493:279-283(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retina;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1040-1103.
RX PubMed=8476432; DOI=10.1006/bbrc.1993.1415;
RA Hellevuo K., Yoshimura M., Kao M., Hoffman P.L., Cooper D.M.F.,
RA Tabakoff B.;
RT "A novel adenylyl cyclase sequence cloned from the human erythroleukemia
RT cell line.";
RL Biochem. Biophys. Res. Commun. 192:311-318(1993).
RN [6]
RP INTERACTION WITH RAF1.
RX PubMed=15385642; DOI=10.1124/mol.66.4.921;
RA Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.;
RT "Raf kinase activation of adenylyl cyclases: isoform-selective
RT regulation.";
RL Mol. Pharmacol. 66:921-928(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [8]
RP IDENTIFICATION BY 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-576, 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 [10]
RP IDENTIFICATION BY 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).
RN [11]
RP VARIANT SER-674, CHARACTERIZATION OF VARIANT SER-674, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17916776; DOI=10.1161/atvbaha.107.145557;
RA Gros R., Van Uum S., Hutchinson-Jaffe A., Ding Q., Pickering J.G.,
RA Hegele R.A., Feldman R.D.;
RT "Increased enzyme activity and beta-adrenergic mediated vasodilation in
RT subjects expressing a single-nucleotide variant of human adenylyl cyclase
RT 6.";
RL Arterioscler. Thromb. Vasc. Biol. 27:2657-2663(2007).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH GNAS; GNB1 AND GNG2.
RX PubMed=17110384; DOI=10.1074/jbc.m607522200;
RA Gao X., Sadana R., Dessauer C.W., Patel T.B.;
RT "Conditional stimulation of type V and VI adenylyl cyclases by G protein
RT betagamma subunits.";
RL J. Biol. Chem. 282:294-302(2007).
RN [13]
RP INVOLVEMENT IN LCCS8, AND VARIANT LCCS8 CYS-1116.
RX PubMed=24319099; DOI=10.1093/hmg/ddt618;
RA Laquerriere A., Maluenda J., Camus A., Fontenas L., Dieterich K.,
RA Nolent F., Zhou J., Monnier N., Latour P., Gentil D., Heron D.,
RA Desguerres I., Landrieu P., Beneteau C., Delaporte B., Bellesme C.,
RA Baumann C., Capri Y., Goldenberg A., Lyonnet S., Bonneau D., Estournet B.,
RA Quijano-Roy S., Francannet C., Odent S., Saint-Frison M.H., Sigaudy S.,
RA Figarella-Branger D., Gelot A., Mussini J.M., Lacroix C.,
RA Drouin-Garraud V., Malinge M.C., Attie-Bitach T., Bessieres B.,
RA Bonniere M., Encha-Razavi F., Beaufrere A.M., Khung-Savatovsky S.,
RA Perez M.J., Vasiljevic A., Mercier S., Roume J., Trestard L.,
RA Saugier-Veber P., Cordier M.P., Layet V., Legendre M.,
RA Vigouroux-Castera A., Lunardi J., Bayes M., Jouk P.S., Rigonnot L.,
RA Granier M., Sternberg D., Warszawski J., Gut I., Gonzales M., Tawk M.,
RA Melki J.;
RT "Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis
RT multiplex congenita with axoglial defects.";
RL Hum. Mol. Genet. 23:2279-2289(2014).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP
CC downstream of G protein-coupled receptors (PubMed:17916776,
CC PubMed:17110384). Functions in signaling cascades downstream of beta-
CC adrenergic receptors in the heart and in vascular smooth muscle cells
CC (PubMed:17916776). Functions in signaling cascades downstream of the
CC vasopressin receptor in the kidney and has a role in renal water
CC reabsorption. Functions in signaling cascades downstream of PTH1R and
CC plays a role in regulating renal phosphate excretion. Functions in
CC signaling cascades downstream of the VIP and SCT receptors in pancreas
CC and contributes to the regulation of pancreatic amylase and fluid
CC secretion (By similarity). Signaling mediates cAMP-dependent activation
CC of protein kinase PKA. This promotes increased phosphorylation of
CC various proteins, including AKT. Plays a role in regulating cardiac
CC sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for
CC normal heart ventricular contractibility. May contribute to normal
CC heart function (By similarity). Mediates vasodilatation after
CC activation of beta-adrenergic receptors by isoproterenol
CC (PubMed:17916776). Contributes to bone cell responses to mechanical
CC stimuli (By similarity). {ECO:0000250|UniProtKB:Q01341,
CC ECO:0000250|UniProtKB:Q03343, ECO:0000269|PubMed:17110384,
CC ECO:0000269|PubMed:17916776}.
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:17110384, ECO:0000269|PubMed:17916776};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15385642};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15385642};
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:17916776,
CC PubMed:17110384). Inhibited by calcium ions, already at micromolar
CC concentrations (By similarity). Inhibited by adenosine, AMP and their
CC analogs (By similarity). Activated by GNAS (PubMed:17110384). Is
CC further activated by the complex formed by GNB1 and GNG2
CC (PubMed:17110384). Phosphorylation by RAF1 results in its activation
CC (By similarity). {ECO:0000250|UniProtKB:P30804,
CC ECO:0000250|UniProtKB:Q01341, ECO:0000250|UniProtKB:Q03343,
CC ECO:0000269|PubMed:17916776}.
CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By
CC similarity). Interacts with RAF1 (PubMed:15385642). Interacts (via
CC cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (PubMed:17110384).
CC {ECO:0000250|UniProtKB:Q01341, ECO:0000269|PubMed:15385642,
CC ECO:0000269|PubMed:17110384}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17110384};
CC Multi-pass membrane protein {ECO:0000305}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q01341}. Cell projection, stereocilium
CC {ECO:0000250|UniProtKB:Q01341}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43306-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43306-2; Sequence=VSP_000244;
CC -!- TISSUE SPECIFICITY: Detected in peripheral blood mononuclear leukocytes
CC (at protein level) (PubMed:17916776). Detected in thyroid
CC (PubMed:10978539). {ECO:0000269|PubMed:10978539}.
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 at Ser-662 inhibits the GNAS-mediated increase in catalytic
CC activity. Phosphorylation by PKC at Ser-556, Ser-662 and Thr-919
CC inhibits catalytic activity. {ECO:0000250|UniProtKB:Q03343}.
CC -!- DISEASE: Lethal congenital contracture syndrome 8 (LCCS8) [MIM:616287]:
CC A form of lethal congenital contracture syndrome, an autosomal
CC recessive disorder characterized by degeneration of anterior horn
CC neurons, extreme skeletal muscle atrophy and congenital non-progressive
CC joint contractures. The contractures can involve the upper or lower
CC limbs and/or the vertebral column, leading to various degrees of
CC flexion or extension limitations evident at birth. LCCS8 is an axoglial
CC form of arthrogryposis multiplex congenita, characterized by congenital
CC distal joint contractures, reduced fetal movements, and severe motor
CC paralysis leading to death early in the neonatal period.
CC {ECO:0000269|PubMed:24319099}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA24852.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF250226; AAF82478.1; -; mRNA.
DR EMBL; AB007882; BAA24852.2; ALT_INIT; mRNA.
DR EMBL; BC064923; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS8767.1; -. [O43306-1]
DR RefSeq; NP_056085.1; NM_015270.4. [O43306-1]
DR RefSeq; XP_006719273.1; XM_006719210.3. [O43306-1]
DR AlphaFoldDB; O43306; -.
DR SMR; O43306; -.
DR BioGRID; 106625; 53.
DR IntAct; O43306; 24.
DR MINT; O43306; -.
DR STRING; 9606.ENSP00000311405; -.
DR BindingDB; O43306; -.
DR ChEMBL; CHEMBL2097167; -.
DR GuidetoPHARMACOLOGY; 1283; -.
DR GlyGen; O43306; 1 site.
DR iPTMnet; O43306; -.
DR PhosphoSitePlus; O43306; -.
DR SwissPalm; O43306; -.
DR BioMuta; ADCY6; -.
DR EPD; O43306; -.
DR jPOST; O43306; -.
DR MassIVE; O43306; -.
DR MaxQB; O43306; -.
DR PaxDb; O43306; -.
DR PeptideAtlas; O43306; -.
DR PRIDE; O43306; -.
DR ProteomicsDB; 48880; -. [O43306-1]
DR ProteomicsDB; 48881; -. [O43306-2]
DR Antibodypedia; 4336; 191 antibodies from 28 providers.
DR DNASU; 112; -.
DR Ensembl; ENST00000307885.4; ENSP00000311405.4; ENSG00000174233.12. [O43306-1]
DR Ensembl; ENST00000357869.8; ENSP00000350536.4; ENSG00000174233.12. [O43306-1]
DR Ensembl; ENST00000550422.5; ENSP00000446730.1; ENSG00000174233.12. [O43306-2]
DR GeneID; 112; -.
DR KEGG; hsa:112; -.
DR MANE-Select; ENST00000357869.8; ENSP00000350536.4; NM_015270.5; NP_056085.1.
DR UCSC; uc001rsh.5; human. [O43306-1]
DR CTD; 112; -.
DR DisGeNET; 112; -.
DR GeneCards; ADCY6; -.
DR HGNC; HGNC:237; ADCY6.
DR HPA; ENSG00000174233; Low tissue specificity.
DR MalaCards; ADCY6; -.
DR MIM; 600294; gene.
DR MIM; 616287; phenotype.
DR neXtProt; NX_O43306; -.
DR OpenTargets; ENSG00000174233; -.
DR Orphanet; 2680; Hypomyelination neuropathy-arthrogryposis syndrome.
DR PharmGKB; PA27; -.
DR VEuPathDB; HostDB:ENSG00000174233; -.
DR eggNOG; KOG3619; Eukaryota.
DR GeneTree; ENSGT00940000155687; -.
DR HOGENOM; CLU_001072_2_0_1; -.
DR InParanoid; O43306; -.
DR OMA; CEGTMPT; -.
DR OrthoDB; 215180at2759; -.
DR PhylomeDB; O43306; -.
DR TreeFam; TF313845; -.
DR PathwayCommons; O43306; -.
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-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-400042; Adrenaline,noradrenaline inhibits insulin secretion.
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; O43306; -.
DR SIGNOR; O43306; -.
DR BioGRID-ORCS; 112; 12 hits in 1070 CRISPR screens.
DR ChiTaRS; ADCY6; human.
DR GeneWiki; ADCY6; -.
DR GenomeRNAi; 112; -.
DR Pharos; O43306; Tchem.
DR PRO; PR:O43306; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O43306; protein.
DR Bgee; ENSG00000174233; Expressed in apex of heart and 127 other tissues.
DR ExpressionAtlas; O43306; baseline and differential.
DR Genevisible; O43306; HS.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032420; C:stereocilium; IEA:UniProtKB-SubCell.
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:0019901; F:protein kinase binding; ISS:BHF-UCL.
DR GO; GO:0005080; F:protein kinase C 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:0097746; P:blood vessel diameter maintenance; IMP:UniProtKB.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0071870; P:cellular response to catecholamine stimulus; IDA:BHF-UCL.
DR GO; GO:1904322; P:cellular response to forskolin; IDA:UniProtKB.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IDA:BHF-UCL.
DR GO; GO:1904117; P:cellular response to vasopressin; ISS:UniProtKB.
DR GO; GO:0007212; P:dopamine receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:ParkinsonsUK-UCL.
DR GO; GO:0035811; P:negative regulation of urine volume; ISS:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; ISS: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 Alternative splicing; ATP-binding; cAMP biosynthesis; Cell membrane;
KW Cell projection; Cilium; Disease variant; Glycoprotein; Lyase; Magnesium;
KW Manganese; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..1168
FT /note="Adenylate cyclase type 6"
FT /id="PRO_0000195699"
FT TOPO_DOM 1..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..255
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..275
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 306..673
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 674..691
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 702..718
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 743..759
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 760..819
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 820..836
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 839..855
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 897..913
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 914..1168
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 384..389
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 384
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 384
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 385
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 426..428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 428
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 428
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 472
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1031
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1105..1107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1112..1116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 576
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 919
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT CARBOHYD 793
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 762..814
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9455477"
FT /id="VSP_000244"
FT VARIANT 674
FT /note="A -> S (no effect on basal enzyme activity, but
FT increased enzyme activity upon activation via G-proteins or
FT forskolin; dbSNP:rs3730071)"
FT /id="VAR_048249"
FT VARIANT 1116
FT /note="R -> C (in LCCS8; dbSNP:rs786204798)"
FT /evidence="ECO:0000269|PubMed:24319099"
FT /id="VAR_073434"
SQ SEQUENCE 1168 AA; 130615 MW; 127BB6E67F73AA61 CRC64;
MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA EPPSPTPAGP
PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA GGTAEVAPDA VPRSGRSCWR
RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS SLTLLMAVLV LLTAVLLAFH AAPARPQPAY
VALLACAAAL FVGLMVVCNR HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW
CPVFFVYIAY TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN
VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV AMEMKEDINT
KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL VMTLNELFAR FDKLAAENHC
LRIKILGDCY YCVSGLPEAR ADHAHCCVEM GVDMIEAISL VREVTGVNVN MRVGIHSGRV
HCGVLGLRKW QFDVWSNDVT LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA
YLKEQHIETF LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR
QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL TFQREDLEKK
YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI YASIFLLLLI TVLICAVYSC
GSLFPKALQR LSRSIVRSRA HSTAVGIFSV LLVFTSAIAN MFTCNHTPIR SCAARMLNLT
PADITACHLQ QLNYSLGLDA PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA
MIFVLGLIYL VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV
ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN ILPKDVAAHF
LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE GVECLRLLNE IIADFDEIIS
EERFRQLEKI KTIGSTYMAA SGLNASTYDQ VGRSHITALA DYAMRLMEQM KHINEHSFNN
FQMKIGLNMG PVVAGVIGAR KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG
YQLECRGVVK VKGKGEMTTY FLNGGPSS
