ADCY3_HUMAN
ID ADCY3_HUMAN Reviewed; 1144 AA.
AC O60266; B3KT86; Q53T54; Q9UDB1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Adenylate cyclase type 3;
DE EC=4.6.1.1 {ECO:0000250|UniProtKB:Q8VHH7};
DE AltName: Full=ATP pyrophosphate-lyase 3;
DE AltName: Full=Adenylate cyclase type III;
DE Short=AC-III;
DE AltName: Full=Adenylate cyclase, olfactive type;
DE AltName: Full=Adenylyl cyclase 3 {ECO:0000305};
DE Short=AC3 {ECO:0000303|PubMed:9920776};
GN Name=ADCY3; Synonyms=KIAA0511;
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), VARIANT PRO-107, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9920776; DOI=10.1006/bbrc.1998.9983;
RA Yang B., He B., Abdel-Halim S.M., Tibell A., Brendel M.D., Bretzel R.G.,
RA Efendic S., Hillert J.;
RT "Molecular cloning of a full-length cDNA for human type 3 adenylyl cyclase
RT and its expression in human islets.";
RL Biochem. Biophys. Res. Commun. 254:548-551(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Substantia nigra;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [LARGE SCALE MRNA] OF 212-1144 (ISOFORM 1).
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 984-1060 (ISOFORM 1/2).
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 [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11549699; DOI=10.1210/jcem.86.9.7837;
RA Cote M., Guillon G., Payet M.D., Gallo-Payet N.;
RT "Expression and regulation of adenylyl cyclase isoforms in the human
RT adrenal gland.";
RL J. Clin. Endocrinol. Metab. 86:4495-4503(2001).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=15705663; DOI=10.1210/me.2004-0318;
RA Livera G., Xie F., Garcia M.A., Jaiswal B., Chen J., Law E., Storm D.R.,
RA Conti M.;
RT "Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility
RT and spermatozoon function.";
RL Mol. Endocrinol. 19:1277-1290(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-525, AND IDENTIFICATION BY
RP 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 POLYMORPHISM, INVOLVEMENT IN BMIQ19, AND INVOLVEMENT IN OBESITY.
RX PubMed=29311636; DOI=10.1038/s41588-017-0022-7;
RA Grarup N., Moltke I., Andersen M.K., Dalby M., Vitting-Seerup K., Kern T.,
RA Mahendran Y., Joersboe E., Larsen C.V.L., Dahl-Petersen I.K., Gilly A.,
RA Suveges D., Dedoussis G., Zeggini E., Pedersen O., Andersson R.,
RA Bjerregaard P., Joergensen M.E., Albrechtsen A., Hansen T.;
RT "Loss-of-function variants in ADCY3 increase risk of obesity and type 2
RT diabetes.";
RL Nat. Genet. 50:172-174(2018).
RN [11]
RP POLYMORPHISM, INVOLVEMENT IN BMIQ19, INVOLVEMENT IN OBESITY, VARIANT
RP OBESITY PHE-1118 DEL, AND VARIANT ILE-64.
RX PubMed=29311637; DOI=10.1038/s41588-017-0023-6;
RA Saeed S., Bonnefond A., Tamanini F., Mirza M.U., Manzoor J., Janjua Q.M.,
RA Din S.M., Gaitan J., Milochau A., Durand E., Vaillant E., Haseeb A.,
RA De Graeve F., Rabearivelo I., Sand O., Queniat G., Boutry R., Schott D.A.,
RA Ayesha H., Ali M., Khan W.I., Butt T.A., Rinne T., Stumpel C.,
RA Abderrahmani A., Lang J., Arslan M., Froguel P.;
RT "Loss-of-function mutations in ADCY3 cause monogenic severe obesity.";
RL Nat. Genet. 50:175-179(2018).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling. Participates in signaling cascades
CC triggered by odorant receptors via its function in cAMP biosynthesis.
CC Required for the perception of odorants. Required for normal sperm
CC motility and normal male fertility. Plays a role in regulating insulin
CC levels and body fat accumulation in response to a high fat diet.
CC {ECO:0000250|UniProtKB:Q8VHH7}.
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:0000250|UniProtKB:Q8VHH7};
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: Activated by forskolin. After forskolin treatment,
CC activity is further increased by calcium/calmodulin. In the absence of
CC forskolin, calcium/calmodulin has little effect on enzyme activity.
CC {ECO:0000250|UniProtKB:P21932}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11549699};
CC Multi-pass membrane protein {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:11549699}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q8VHH7}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P21932}. Note=Also detected in the cytoplasm,
CC close to lipid droplets. {ECO:0000269|PubMed:11549699}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60266-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60266-2; Sequence=VSP_055813, VSP_055814, VSP_055815;
CC -!- TISSUE SPECIFICITY: Detected in zona glomerulosa and zona fasciculata
CC in the adrenal gland (at protein level) (PubMed:11549699). Expressed in
CC brain, heart, kidney, liver, lung, pancreas islets, placenta, and
CC skeletal muscle (PubMed:9920776). Detected in testis (PubMed:15705663).
CC {ECO:0000269|PubMed:11549699, ECO:0000269|PubMed:15705663,
CC ECO:0000269|PubMed:9920776}.
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 modules have no catalytic activity, but when they are
CC brought together, enzyme activity is restored. The active site is at
CC the interface of the two modules. {ECO:0000250|UniProtKB:P30803}.
CC -!- PTM: Sumoylated. Sumoylation is required for targeting ot olfactory
CC cilia. {ECO:0000250|UniProtKB:P21932}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8VHH7}.
CC -!- PTM: Rapidly phosphorylated after stimulation by odorants or forskolin.
CC Phosphorylation by CaMK2 at Ser-1076 down-regulates enzyme activity.
CC {ECO:0000250|UniProtKB:Q8VHH7}.
CC -!- POLYMORPHISM: Genetic variations at the ADCY3 locus define the body
CC mass index quantitative trait locus 19 (BMIQ19) [MIM:617885]. Variance
CC in body mass index is a susceptibility factor for obesity.
CC {ECO:0000269|PubMed:29311636, ECO:0000269|PubMed:29311637}.
CC -!- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by
CC an increase of body weight beyond the limitation of skeletal and
CC physical requirements, as the result of excessive accumulation of body
CC fat. {ECO:0000269|PubMed:29311636, ECO:0000269|PubMed:29311637}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; AF033861; AAD13403.1; -; mRNA.
DR EMBL; AK095173; BAG52998.1; -; mRNA.
DR EMBL; AC012073; AAY14787.1; -; Genomic_DNA.
DR EMBL; BC126235; AAI26236.1; -; mRNA.
DR EMBL; AB011083; BAA25437.1; -; mRNA.
DR CCDS; CCDS1715.1; -. [O60266-1]
DR RefSeq; NP_001307542.1; NM_001320613.1.
DR RefSeq; NP_004027.2; NM_004036.4. [O60266-1]
DR AlphaFoldDB; O60266; -.
DR SMR; O60266; -.
DR BioGRID; 106623; 79.
DR IntAct; O60266; 13.
DR MINT; O60266; -.
DR STRING; 9606.ENSP00000260600; -.
DR BindingDB; O60266; -.
DR ChEMBL; CHEMBL2097167; -.
DR GlyGen; O60266; 1 site.
DR iPTMnet; O60266; -.
DR PhosphoSitePlus; O60266; -.
DR BioMuta; ADCY3; -.
DR EPD; O60266; -.
DR jPOST; O60266; -.
DR MassIVE; O60266; -.
DR MaxQB; O60266; -.
DR PaxDb; O60266; -.
DR PeptideAtlas; O60266; -.
DR PRIDE; O60266; -.
DR ProteomicsDB; 3671; -.
DR ProteomicsDB; 49298; -. [O60266-1]
DR Antibodypedia; 4130; 148 antibodies from 26 providers.
DR DNASU; 109; -.
DR Ensembl; ENST00000260600.9; ENSP00000260600.5; ENSG00000138031.15. [O60266-1]
DR Ensembl; ENST00000679454.1; ENSP00000505261.1; ENSG00000138031.15. [O60266-1]
DR GeneID; 109; -.
DR KEGG; hsa:109; -.
DR MANE-Select; ENST00000679454.1; ENSP00000505261.1; NM_004036.5; NP_004027.2.
DR UCSC; uc002rfs.5; human. [O60266-1]
DR CTD; 109; -.
DR DisGeNET; 109; -.
DR GeneCards; ADCY3; -.
DR HGNC; HGNC:234; ADCY3.
DR HPA; ENSG00000138031; Low tissue specificity.
DR MalaCards; ADCY3; -.
DR MIM; 600291; gene.
DR MIM; 601665; phenotype.
DR MIM; 617885; phenotype.
DR neXtProt; NX_O60266; -.
DR OpenTargets; ENSG00000138031; -.
DR PharmGKB; PA164741137; -.
DR VEuPathDB; HostDB:ENSG00000138031; -.
DR eggNOG; KOG3619; Eukaryota.
DR GeneTree; ENSGT00940000156549; -.
DR HOGENOM; CLU_001072_2_4_1; -.
DR InParanoid; O60266; -.
DR OrthoDB; 154265at2759; -.
DR PhylomeDB; O60266; -.
DR TreeFam; TF313845; -.
DR PathwayCommons; O60266; -.
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-381753; Olfactory Signaling 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; O60266; -.
DR SIGNOR; O60266; -.
DR BioGRID-ORCS; 109; 18 hits in 1067 CRISPR screens.
DR ChiTaRS; ADCY3; human.
DR GeneWiki; ADCY3; -.
DR GenomeRNAi; 109; -.
DR Pharos; O60266; Tbio.
DR PRO; PR:O60266; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O60266; protein.
DR Bgee; ENSG00000138031; Expressed in tibial nerve and 199 other tissues.
DR ExpressionAtlas; O60266; baseline and differential.
DR Genevisible; O60266; HS.
DR GO; GO:0060170; C:ciliary membrane; ISS:ARUK-UCL.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004016; F:adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007340; P:acrosome reaction; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006171; P:cAMP biosynthetic process; ISS:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0008355; P:olfactory learning; ISS:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007338; P:single fertilization; 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; IPR029787; Nucleotide_cyclase.
DR Pfam; PF16214; AC_N; 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; Calmodulin-binding; cAMP biosynthesis;
KW Cell membrane; Cell projection; Cytoplasm; Glycoprotein; Golgi apparatus;
KW Isopeptide bond; Lyase; Magnesium; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Obesity; Olfaction; Phosphoprotein; Reference proteome;
KW Repeat; Sensory transduction; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..1144
FT /note="Adenylate cyclase type 3"
FT /id="PRO_0000195687"
FT TOPO_DOM 1..79
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..632
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 633..653
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 664..684
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 708..728
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 754..774
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 775..795
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 833..853
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 854..1144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 504..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..544
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 324..329
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 324
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 324
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 325
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 366..368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 368
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 368
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 412
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 975
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1062..1064
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1069..1073
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 525
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHH7"
FT MOD_RES 1076
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q8VHH7"
FT CARBOHYD 736
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 465
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO3)"
FT /evidence="ECO:0000250|UniProtKB:P21932"
FT VAR_SEQ 1..389
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055813"
FT VAR_SEQ 452
FT /note="G -> GGSKIEERLYSCVVAPTLRLRWE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055814"
FT VAR_SEQ 725..770
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055815"
FT VARIANT 64
FT /note="N -> I (in dbSNP:rs541941351)"
FT /evidence="ECO:0000269|PubMed:29311637"
FT /id="VAR_080791"
FT VARIANT 107
FT /note="S -> P (in dbSNP:rs11676272)"
FT /evidence="ECO:0000269|PubMed:9920776"
FT /id="VAR_048248"
FT VARIANT 1118
FT /note="Missing (in OBESITY; risk factor;
FT dbSNP:rs750852737)"
FT /evidence="ECO:0000269|PubMed:29311637"
FT /id="VAR_080792"
SQ SEQUENCE 1144 AA; 128960 MW; B75D39DD0A8ACA12 CRC64;
MPRNQGFSEP EYSAEYSAEY SVSLPSDPDR GVGRTHEISV RNSGSCLCLP RFMRLTFVPE
SLENLYQTYF KRQRHETLLV LVVFAALFDC YVVVMCAVVF SSDKLASLAV AGIGLVLDII
LFVLCKKGLL PDRVTRRVLP YVLWLLITAQ IFSYLGLNFA RAHAASDTVG WQVFFVFSFF
ITLPLSLSPI VIISVVSCVV HTLVLGVTVA QQQQEELKGM QLLREILANV FLYLCAIAVG
IMSYYMADRK HRKAFLEARQ SLEVKMNLEE QSQQQENLML SILPKHVADE MLKDMKKDES
QKDQQQFNTM YMYRHENVSI LFADIVGFTQ LSSACSAQEL VKLLNELFAR FDKLAAKYHQ
LRIKILGDCY YCICGLPDYR EDHAVCSILM GLAMVEAISY VREKTKTGVD MRVGVHTGTV
LGGVLGQKRW QYDVWSTDVT VANKMEAGGI PGRVHISQST MDCLKGEFDV EPGDGGSRCD
YLEEKGIETY LIIASKPEVK KTATQNGLNG SALPNGAPAS SKSSSPALIE TKEPNGSAHS
SGSTSEKPEE QDAQADNPSF PNPRRRLRLQ DLADRVVDAS EDEHELNQLL NEALLERESA
QVVKKRNTFL LSMRFMDPEM ETRYSVEKEK QSGAAFSCSC VVLLCTALVE ILIDPWLMTN
YVTFMVGEIL LLILTICSLA AIFPRAFPKK LVAFSTWIDR TRWARNTWAM LAIFILVMAN
VVDMLSCLQY YTGPSNATAG METEGSCLEN PKYYNYVAVL SLIATIMLVQ VSHMVKLTLM
LLVAGAVATI NLYAWRPVFD EYDHKRFREH DLPMVALEQM QGFNPGLNGT DRLPLVPSKY
SMTVMVFLMM LSFYYFSRHV EKLARTLFLW KIEVHDQKER VYEMRRWNEA LVTNMLPEHV
ARHFLGSKKR DEELYSQTYD EIGVMFASLP NFADFYTEES INNGGIECLR FLNEIISDFD
SLLDNPKFRV ITKIKTIGST YMAASGVTPD VNTNGFASSN KEDKSERERW QHLADLADFA
LAMKDTLTNI NNQSFNNFML RIGMNKGGVL AGVIGARKPH YDIWGNTVNV ASRMESTGVM
GNIQVVEETQ VILREYGFRF VRRGPIFVKG KGELLTFFLK GRDKLATFPN GPSVTLPHQV
VDNS
