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 24-JAN-2024, entry version 213. 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}. 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; 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.ENSP00000384484; -. DR BindingDB; O60266; -. DR ChEMBL; CHEMBL3164; -. DR DrugBank; DB02587; Colforsin. DR GlyCosmos; O60266; 1 site, No reported glycans. DR GlyGen; O60266; 1 site. DR iPTMnet; O60266; -. DR PhosphoSitePlus; O60266; -. DR SwissPalm; O60266; -. DR BioMuta; ADCY3; -. DR EPD; O60266; -. DR jPOST; O60266; -. DR MassIVE; O60266; -. DR MaxQB; O60266; -. DR PaxDb; 9606-ENSP00000260600; -. DR PeptideAtlas; O60266; -. DR ProteomicsDB; 3671; -. DR ProteomicsDB; 49298; -. [O60266-1] DR Antibodypedia; 4130; 173 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 AGR; HGNC:234; -. 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; 3686360at2759; -. 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; 20 hits in 1148 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 200 other cell types or tissues. DR ExpressionAtlas; O60266; baseline and differential. 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: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; Nucleotide cyclase; 2. DR InterPro; IPR001054; A/G_cyclase. DR InterPro; IPR018297; A/G_cyclase_CS. DR InterPro; IPR032628; AC_N. DR InterPro; IPR030672; Adcy. DR InterPro; IPR029787; Nucleotide_cyclase. DR PANTHER; PTHR45627; ADENYLATE CYCLASE TYPE 1; 1. DR PANTHER; PTHR45627:SF12; ADENYLATE CYCLASE TYPE 3; 1. 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; Nucleotide cyclase; 2. DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 2. DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2. DR Genevisible; O60266; HS. 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 //