ID ADCY2_MOUSE Reviewed; 1090 AA.
AC Q80TL1; Q8CFU6;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 2.
DT 08-NOV-2023, entry version 140.
DE RecName: Full=Adenylate cyclase type 2;
DE EC=4.6.1.1;
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling. Down-stream signaling cascades mediate
CC changes in gene expression patterns and lead to increased IL6
CC production. Functions in signaling cascades downstream of the
CC muscarinic acetylcholine receptors. {ECO:0000250|UniProtKB:P26769}.
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:P26769};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P26769};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P26769};
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. Is not activated by
CC calmodulin. Inhibited by calcium ions, already at micromolar
CC concentration. Activated by the G protein alpha subunit GNAS. Activated
CC by the G protein beta and gamma subunit complex. Phosphorylation by
CC RAF1 results in its activation (By similarity). Phosphorylation by PKC
CC activates the enzyme (By similarity). {ECO:0000250|UniProtKB:P26769,
CC ECO:0000250|UniProtKB:Q08462}.
CC -!- SUBUNIT: Interacts with RAF1 (By similarity). Interacts with GNAS.
CC Interacts with the G protein beta and gamma subunit complex (By
CC similarity). {ECO:0000250|UniProtKB:P26769,
CC ECO:0000250|UniProtKB:Q08462}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P26769}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:P26769}. Cell membrane
CC {ECO:0000250|UniProtKB:P26769}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P26769}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q08462}.
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:0000250|UniProtKB:Q08462}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65714.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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; AK122432; BAC65714.1; ALT_INIT; mRNA.
DR EMBL; BC037107; AAH37107.1; -; mRNA.
DR AlphaFoldDB; Q80TL1; -.
DR SMR; Q80TL1; -.
DR STRING; 10090.ENSMUSP00000022013; -.
DR GlyCosmos; Q80TL1; 3 sites, No reported glycans.
DR GlyGen; Q80TL1; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q80TL1; -.
DR PhosphoSitePlus; Q80TL1; -.
DR SwissPalm; Q80TL1; -.
DR EPD; Q80TL1; -.
DR MaxQB; Q80TL1; -.
DR PaxDb; 10090-ENSMUSP00000022013; -.
DR ProteomicsDB; 296066; -.
DR AGR; MGI:99676; -.
DR MGI; MGI:99676; Adcy2.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; Q80TL1; -.
DR PhylomeDB; Q80TL1; -.
DR BRENDA; 4.6.1.1; 3474.
DR Reactome; R-MMU-163615; PKA activation.
DR Reactome; R-MMU-170660; Adenylate cyclase activating pathway.
DR Reactome; R-MMU-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-MMU-418597; G alpha (z) signalling events.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR ChiTaRS; Adcy2; mouse.
DR PRO; PR:Q80TL1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q80TL1; Protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0004016; F:adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0008179; F:adenylate cyclase binding; IPI:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0006171; P:cAMP biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; 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; IPR009398; Adcy_conserved_dom.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR PANTHER; PTHR45627; ADENYLATE CYCLASE TYPE 1; 1.
DR PANTHER; PTHR45627:SF6; ADENYLATE CYCLASE TYPE 2; 1.
DR Pfam; PF16214; AC_N; 1.
DR Pfam; PF06327; Adcy_cons_dom; 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.
PE 1: Evidence at protein level;
KW ATP-binding; cAMP biosynthesis; Cell membrane; Cytoplasm; Glycoprotein;
KW Lyase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1090
FT /note="Adenylate cyclase type 2"
FT /id="PRO_0000195685"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..600
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 601..621
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 626..646
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 679..699
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 734..754
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 763..783
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 800..820
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 821..1090
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 904..921
FT /note="Interaction with GNAS"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT REGION 989..992
FT /note="Interaction with GNAS"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 294..299
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 294
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 294
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 295
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 336..338
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 338
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 338
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 382
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 938
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1018..1020
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1025..1029
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1065
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 490
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 543
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT CARBOHYD 712
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 717
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 723
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1090 AA; 123270 MW; 461CDF5E6C828CCB CRC64;
MRRRRYLRDR AEAAAAAAAG GGEGLQRSRD WLYESYYCMS QQHPLIVFLL LIVMGACLAL
LAVFFALGLE VEDHVAFLIT VPTALAIFFA IFILVCIESV FKKLLRVFSL VIWICLVAMG
YLFMCFGGTV SAWDQVSFFL FIIFVVYTML PFNMRDAIIA SVLTSSSHTI VLSVYLSATP
GAKEHLFWQI LANVIIFICG NLAGAYHKHL MELALQQTYR DTCNCIKSRI KLEFEKRQQE
RLLLSLLPAH IAMEMKAEII QRLQGPKAGQ MENTNNFHNL YVKRHTNVSI LYADIVGFTR
LASDCSPGEL VHMLNELFGK FDQIAKENEC MRIKILGDCY YCVSGLPISL PNHAKNCVKM
GLDMCEAIKK VRDATGVDIN MRVGVHSGNV LCGVIGLQKW QYDVWSHDVT LANHMEAGGV
PGRVHISSVT LEHLNGAYKV EEGDGEIRDP YLKQHLVKTY FVINPKGERR SPQHLFRPRH
TLDGAKMRAS VRMTRYLESW GAAKPFAHLH HRDSMTTENG KISTTDVPMG QHNFQNRTLR
TKSQKKRFEE ELNERMIQAI DGINAQKQWL KSEDIQRISL FFYNKNIEKE YRATALPAFK
YYVTCACLIF LCIFIVQILV LPKTSILGFS FGAAFLSLIF ILFVCFAGQL LQCSKKASAS
LLWLLKSSGI IANRPWPRIS LTIVTTAIIL TMAVFNMFFL SNSEETTLPT ANASNANVSV
PDNQTAILHA RNLFFLPYFI YSCILGLISC SVFLRVNYEL KMLIMMVALV GYNIILLHTH
AHVLDAYSQV LFQRPGIWKD LKTMGSVSLS IFFITLLVLG RQSEYYCRLD FLWKNKFKKE
REEIETMENL NRVLLENVLP AHVAEHFLAR SLKNEELYHQ SYDCVCVMFA SIPDFKEFYT
ESDVNKEGLE CLRLLNEIIA DFDDLLSKPK FSGVEKIKTI GSTYMAATGL SAVPSQEHAQ
EPERQYMHIG TMVEFAYALV GKLDAINKHS FNDFKLRVGI NHGPVIAGVI GAQKPQYDIW
GNTVNVASRM DSTGVLDKIQ VTEETSLILQ TLGYTCTCRG IINVKGKGDL KTYFVNTEMS
RSLSQSNLAS
//
