ID   ADCY2_HUMAN             Reviewed;        1091 AA.
AC   Q08462; B7Z2C1; Q2NKL8; Q9UDB2; Q9UPU2;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2006, sequence version 5.
DT   10-FEB-2021, entry version 188.
DE   RecName: Full=Adenylate cyclase type 2;
DE            EC=4.6.1.1 {ECO:0000269|PubMed:15385642};
DE   AltName: Full=ATP pyrophosphate-lyase 2;
DE   AltName: Full=Adenylate cyclase type II;
DE   AltName: Full=Adenylyl cyclase 2;
GN   Name=ADCY2; Synonyms=KIAA1060;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RA   Guo J.H., Yu L.;
RT   "Molecular cloning of human adenylyl cyclase gene.";
RL   Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Amygdala;
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=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-147.
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 205-1091 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA   Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIV. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 6:197-205(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 616-1091 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=1427768; DOI=10.1007/bf00210755;
RA   Stengel D., Parma J., Gannage M.-H., Roeckel N., Mattei M.-G., Barouki R.,
RA   Hanoune J.;
RT   "Different chromosomal localization of two adenylyl cyclase genes expressed
RT   in human brain.";
RL   Hum. Genet. 90:126-130(1992).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 948-1017 (ISOFORM 1), AND TISSUE SPECIFICITY.
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   [8]
RP   TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
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   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP   PHOSPHORYLATION BY RAF1, SUBCELLULAR LOCATION, AND 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   [10]
RP   SUBCELLULAR LOCATION.
RX   PubMed=21228062; DOI=10.1124/jpet.110.177923;
RA   Bogard A.S., Xu C., Ostrom R.S.;
RT   "Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2,
RT   4, and 6 in distinct membrane microdomains.";
RL   J. Pharmacol. Exp. Ther. 337:209-217(2011).
CC   -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC       response to G-protein signaling (PubMed:15385642). Down-stream
CC       signaling cascades mediate changes in gene expression patterns and lead
CC       to increased IL6 production. Functions in signaling cascades downstream
CC       of the muscarinic acetylcholine receptors (By similarity).
CC       {ECO:0000250|UniProtKB:P26769, ECO:0000269|PubMed:15385642}.
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:15385642};
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:P26769};
CC   -!- ACTIVITY REGULATION: Activated by forskolin (PubMed:15385642). Is not
CC       activated by calmodulin. Inhibited by calcium ions, already at
CC       micromolar concentration. Activated by the G protein alpha subunit
CC       GNAS. Activated by the G protein beta and gamma subunit complex (By
CC       similarity). Phosphorylation by RAF1 results in its activation
CC       (PubMed:15385642). Phosphorylation by PKC activates the enzyme (By
CC       similarity). {ECO:0000250|UniProtKB:P26769,
CC       ECO:0000269|PubMed:15385642}.
CC   -!- SUBUNIT: Interacts with RAF1 (PubMed:15385642). Interacts with GNAS.
CC       Interacts with the G protein beta and gamma subunit complex (By
CC       similarity). {ECO:0000250|UniProtKB:P26769,
CC       ECO:0000269|PubMed:15385642}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15385642}; Multi-
CC       pass membrane protein {ECO:0000305}. Cell membrane
CC       {ECO:0000269|PubMed:11549699, ECO:0000269|PubMed:21228062}; Multi-pass
CC       membrane protein {ECO:0000305}. Cytoplasm
CC       {ECO:0000269|PubMed:11549699}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q08462-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q08462-2; Sequence=VSP_055811, VSP_055812;
CC   -!- TISSUE SPECIFICITY: Detected in zona glomerulosa and zona fasciculata
CC       in the adrenal gland (at protein level) (PubMed:11549699). Expressed in
CC       brain, especially in caudate nucleus, cerebellum and hippocampus.
CC       {ECO:0000269|PubMed:11549699, ECO:0000269|PubMed:8476432}.
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: Phosphorylated by RAF1. {ECO:0000269|PubMed:15385642}.
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; AF410885; AAP97285.1; -; mRNA.
DR   EMBL; AK294555; BAH11807.1; -; mRNA.
DR   EMBL; AC010346; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC010437; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC024577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC093305; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC113366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC111743; AAI11744.1; -; mRNA.
DR   EMBL; AB028983; BAA83012.1; -; mRNA.
DR   EMBL; X74210; CAA52282.1; -; mRNA.
DR   EMBL; L21993; AAA64923.1; -; mRNA.
DR   CCDS; CCDS3872.2; -. [Q08462-1]
DR   PIR; I37136; I37136.
DR   RefSeq; NP_065433.2; NM_020546.2. [Q08462-1]
DR   SMR; Q08462; -.
DR   BioGRID; 106622; 12.
DR   DIP; DIP-422N; -.
DR   IntAct; Q08462; 2.
DR   MINT; Q08462; -.
DR   STRING; 9606.ENSP00000342952; -.
DR   BindingDB; Q08462; -.
DR   ChEMBL; CHEMBL3760; -.
DR   DrugBank; DB06843; 2',5'-DIDEOXY-ADENOSINE 3'-MONOPHOSPHATE.
DR   DrugBank; DB09121; Aurothioglucose.
DR   DrugBank; DB02587; Colforsin.
DR   GlyGen; Q08462; 2 sites.
DR   iPTMnet; Q08462; -.
DR   PhosphoSitePlus; Q08462; -.
DR   BioMuta; ADCY2; -.
DR   DMDM; 118572617; -.
DR   jPOST; Q08462; -.
DR   MassIVE; Q08462; -.
DR   MaxQB; Q08462; -.
DR   PaxDb; Q08462; -.
DR   PeptideAtlas; Q08462; -.
DR   PRIDE; Q08462; -.
DR   ProteomicsDB; 58613; -. [Q08462-1]
DR   ProteomicsDB; 6429; -.
DR   Antibodypedia; 22409; 170 antibodies.
DR   Ensembl; ENST00000338316; ENSP00000342952; ENSG00000078295. [Q08462-1]
DR   GeneID; 108; -.
DR   KEGG; hsa:108; -.
DR   UCSC; uc003jdz.2; human. [Q08462-1]
DR   CTD; 108; -.
DR   DisGeNET; 108; -.
DR   GeneCards; ADCY2; -.
DR   HGNC; HGNC:233; ADCY2.
DR   HPA; ENSG00000078295; Group enriched (brain, skeletal muscle).
DR   MIM; 103071; gene.
DR   neXtProt; NX_Q08462; -.
DR   OpenTargets; ENSG00000078295; -.
DR   PharmGKB; PA24561; -.
DR   VEuPathDB; HostDB:ENSG00000078295.15; -.
DR   eggNOG; KOG3619; Eukaryota.
DR   GeneTree; ENSGT00940000156424; -.
DR   HOGENOM; CLU_001072_2_5_1; -.
DR   InParanoid; Q08462; -.
DR   OMA; MFFLEDN; -.
DR   PhylomeDB; Q08462; -.
DR   TreeFam; TF313845; -.
DR   BRENDA; 4.6.1.1; 2681.
DR   PathwayCommons; Q08462; -.
DR   Reactome; R-HSA-163359; Glucagon signaling in metabolic regulation.
DR   Reactome; R-HSA-163615; PKA activation.
DR   Reactome; R-HSA-164378; PKA activation in glucagon signalling.
DR   Reactome; R-HSA-170660; Adenylate cyclase activating pathway.
DR   Reactome; R-HSA-170670; Adenylate cyclase inhibitory pathway.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   Reactome; R-HSA-418597; G alpha (z) signalling events.
DR   Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR   Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR   Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR   Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR   SIGNOR; Q08462; -.
DR   BioGRID-ORCS; 108; 2 hits in 874 CRISPR screens.
DR   ChiTaRS; ADCY2; human.
DR   GeneWiki; ADCY2; -.
DR   GenomeRNAi; 108; -.
DR   Pharos; Q08462; Tbio.
DR   PRO; PR:Q08462; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q08462; protein.
DR   Bgee; ENSG00000078295; Expressed in frontal cortex and 212 other tissues.
DR   ExpressionAtlas; Q08462; baseline and differential.
DR   Genevisible; Q08462; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0045121; C:membrane raft; ISS:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0004016; F:adenylate cyclase activity; ISS:BHF-UCL.
DR   GO; GO:0008179; F:adenylate cyclase binding; ISS:BHF-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR   GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR   GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:Reactome.
DR   GO; GO:0034199; P:activation of protein kinase A activity; TAS:Reactome.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISS:BHF-UCL.
DR   GO; GO:0006171; P:cAMP biosynthetic process; ISS:BHF-UCL.
DR   GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR   GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR   GO; GO:0071377; P:cellular response to glucagon stimulus; TAS:Reactome.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0003091; P:renal water homeostasis; TAS:Reactome.
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   Cytoplasm; Glycoprotein; Lyase; Magnesium; Manganese; Membrane;
KW   Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Repeat; Transmembrane; Transmembrane helix.
FT   CHAIN           1..1091
FT                   /note="Adenylate cyclase type 2"
FT                   /id="PRO_0000195684"
FT   TOPO_DOM        1..45
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        46..66
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..96
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        108..128
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        133..153
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        159..179
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        187..207
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        208..601
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        602..622
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        628..652
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        680..701
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        734..755
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        763..780
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        801..821
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        822..1091
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   NP_BIND         295..300
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   NP_BIND         337..339
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   NP_BIND         1019..1021
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   NP_BIND         1026..1030
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   REGION          905..922
FT                   /note="Interaction with GNAS"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   REGION          990..993
FT                   /note="Interaction with GNAS"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   METAL           295
FT                   /note="Magnesium 1; catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   METAL           295
FT                   /note="Magnesium 2; catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   METAL           296
FT                   /note="Magnesium 2; via carbonyl oxygen; catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   METAL           339
FT                   /note="Magnesium 1; catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   METAL           339
FT                   /note="Magnesium 2; catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   BINDING         383
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P30803"
FT   BINDING         939
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   BINDING         1066
FT                   /note="ATP"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   MOD_RES         491
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   MOD_RES         544
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000250|UniProtKB:P26769"
FT   CARBOHYD        713
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        716
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..59
FT                   /note="MWQEAMRRRRYLRDRSEEAAGGGDGLPRSRDWLYESYYCMSQQHPLIVFLLL
FT                   IVMGSCL -> MDLRWARDLHLREASRSVAFTTLRLGAVTTGLLTFREPGDKEKSGKGL
FT                   GKRWRIQREES (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055811"
FT   VAR_SEQ         60..239
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_055812"
FT   VARIANT         147
FT                   /note="V -> L (in dbSNP:rs13166360)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_029012"
FT   VARIANT         163
FT                   /note="V -> I (in dbSNP:rs34043481)"
FT                   /id="VAR_048247"
FT   CONFLICT        188..207
FT                   /note="VWQILANVIIFICGNLAGAY -> GLADPGQCDHFHLWEPGXTN (in
FT                   Ref. 1; AAP97285)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        675
FT                   /note="R -> Q (in Ref. 6; CAA52282/AAA64923)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1091 AA;  123603 MW;  41FD8BC607C075D1 CRC64;
     MWQEAMRRRR YLRDRSEEAA GGGDGLPRSR DWLYESYYCM SQQHPLIVFL LLIVMGSCLA
     LLAVFFALGL EVEDHVAFLI TVPTALAIFF AIFILVCIES VFKKLLRLFS LVIWICLVAM
     GYLFMCFGGT VSPWDQVSFF LFIIFVVYTM LPFNMRDAII ASVLTSSSHT IVLSVCLSAT
     PGGKEHLVWQ ILANVIIFIC GNLAGAYHKH LMELALQQTY QDTCNCIKSR IKLEFEKRQQ
     ERLLLSLLPA HIAMEMKAEI IQRLQGPKAG QMENTNNFHN LYVKRHTNVS ILYADIVGFT
     RLASDCSPGE LVHMLNELFG KFDQIAKENE CMRIKILGDC YYCVSGLPIS LPNHAKNCVK
     MGLDMCEAIK KVRDATGVDI NMRVGVHSGN VLCGVIGLQK WQYDVWSHDV TLANHMEAGG
     VPGRVHISSV TLEHLNGAYK VEEGDGDIRD PYLKQHLVKT YFVINPKGER RSPQHLFRPR
     HTLDGAKMRA SVRMTRYLES WGAAKPFAHL HHRDSMTTEN GKISTTDVPM GQHNFQNRTL
     RTKSQKKRFE EELNERMIQA IDGINAQKQW LKSEDIQRIS LLFYNKVLEK EYRATALPAF
     KYYVTCACLI FFCIFIVQIL VLPKTSVLGI SFGAAFLLLA FILFVCFAGQ LLQCSKKASP
     LLMWLLKSSG IIANRPWPRI SLTIITTAII LMMAVFNMFF LSDSEETIPP TANTTNTSFS
     ASNNQVAILR AQNLFFLPYF IYSCILGLIS CSVFLRVNYE LKMLIMMVAL VGYNTILLHT
     HAHVLGDYSQ VLFERPGIWK DLKTMGSVSL SIFFITLLVL GRQNEYYCRL DFLWKNKFKK
     EREEIETMEN LNRVLLENVL PAHVAEHFLA RSLKNEELYH QSYDCVCVMF ASIPDFKEFY
     TESDVNKEGL ECLRLLNEII ADFDDLLSKP KFSGVEKIKT IGSTYMAATG LSAVPSQEHS
     QEPERQYMHI GTMVEFAFAL VGKLDAINKH SFNDFKLRVG INHGPVIAGV IGAQKPQYDI
     WGNTVNVASR MDSTGVLDKI QVTEETSLVL QTLGYTCTCR GIINVKGKGD LKTYFVNTEM
     SRSLSQSNVA S
//