ADCY9_MOUSE
ID ADCY9_MOUSE Reviewed; 1353 AA.
AC P51830; Q61279;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Adenylate cyclase type 9;
DE EC=4.6.1.1 {ECO:0000269|PubMed:8662814};
DE AltName: Full=ATP pyrophosphate-lyase 9;
DE AltName: Full=Adenylate cyclase type IX;
DE AltName: Full=Adenylyl cyclase 9;
DE Short=AC9 {ECO:0000303|PubMed:8662814};
DE AltName: Full=Adenylyl cyclase type 10;
DE Short=ACTP10;
GN Name=Adcy9;
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 [MRNA], CATALYTIC ACTIVITY, FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=8662814; DOI=10.1074/jbc.271.23.13900;
RA Premont R.T., Matsuoka I., Mattei M.-G., Pouille Y., Defer N., Hanoune J.;
RT "Identification and characterization of a widely expressed form of adenylyl
RT cyclase.";
RL J. Biol. Chem. 271:13900-13907(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7575502; DOI=10.1006/bbrc.1995.2385;
RA Paterson J.M., Smith S.M., Harmar A.J., Antoni F.A.;
RT "Control of a novel adenylyl cyclase by calcineurin.";
RL Biochem. Biophys. Res. Commun. 214:1000-1008(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1106-1193.
RX PubMed=7528319; DOI=10.1016/0076-6879(94)38011-2;
RA Premont R.T.;
RT "Identification of adenylyl cyclases by amplification using degenerate
RT primers.";
RL Methods Enzymol. 238:116-127(1994).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-613 AND SER-1332, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-610; SER-613; SER-688;
RP SER-691; SER-706; SER-1295 AND SER-1332, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, and
RC Testis;
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: Adenylyl cyclase that catalyzes the formation of the
CC signaling molecule cAMP in response to activation of G protein-coupled
CC receptors. Contributes to signaling cascades activated by CRH
CC (corticotropin-releasing factor), corticosteroids and by beta-
CC adrenergic receptors. {ECO:0000250|UniProtKB:O60503,
CC ECO:0000269|PubMed:8662814}.
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:O60503};
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: Insensitive to calcium/calmodulin, forskolin and
CC somatostatin. Stimulated by beta-adrenergic receptor activation.
CC Activity is down-regulated by calcium/calcineurin.
CC {ECO:0000250|UniProtKB:O60503}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8662814};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in brain, spleen, lung, liver and testis
CC (at protein level). Detected in brain, especially in hippocampus,
CC cerebellum and neocortex. Found in decreasing order in skeletal muscle,
CC heart, adrenal gland, ovary and brain; and to a lesser extent, in
CC kidney, liver, testis, lung, thymus and spleen.
CC {ECO:0000269|PubMed:8662814}.
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 -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; U30602; AAC52603.1; -; mRNA.
DR EMBL; Z50190; CAA90570.1; -; mRNA.
DR CCDS; CCDS27917.1; -.
DR PIR; JC4279; JC4279.
DR RefSeq; NP_033754.2; NM_009624.3.
DR AlphaFoldDB; P51830; -.
DR SMR; P51830; -.
DR BioGRID; 197978; 3.
DR STRING; 10090.ENSMUSP00000113498; -.
DR GlyGen; P51830; 3 sites.
DR iPTMnet; P51830; -.
DR PhosphoSitePlus; P51830; -.
DR SwissPalm; P51830; -.
DR jPOST; P51830; -.
DR MaxQB; P51830; -.
DR PaxDb; P51830; -.
DR PeptideAtlas; P51830; -.
DR PRIDE; P51830; -.
DR ProteomicsDB; 285685; -.
DR Antibodypedia; 55436; 238 antibodies from 31 providers.
DR DNASU; 11515; -.
DR Ensembl; ENSMUST00000005719; ENSMUSP00000005719; ENSMUSG00000005580.
DR Ensembl; ENSMUST00000117801; ENSMUSP00000113498; ENSMUSG00000005580.
DR GeneID; 11515; -.
DR KEGG; mmu:11515; -.
DR UCSC; uc007xzr.2; mouse.
DR CTD; 115; -.
DR MGI; MGI:108450; Adcy9.
DR VEuPathDB; HostDB:ENSMUSG00000005580; -.
DR eggNOG; KOG3618; Eukaryota.
DR GeneTree; ENSGT00940000155577; -.
DR InParanoid; P51830; -.
DR OMA; PYIQTYL; -.
DR OrthoDB; 430975at2759; -.
DR PhylomeDB; P51830; -.
DR TreeFam; TF313845; -.
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 BioGRID-ORCS; 11515; 0 hits in 70 CRISPR screens.
DR ChiTaRS; Adcy9; mouse.
DR PRO; PR:P51830; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P51830; protein.
DR Bgee; ENSMUSG00000005580; Expressed in CA3 field of hippocampus and 239 other tissues.
DR ExpressionAtlas; P51830; baseline and differential.
DR Genevisible; P51830; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
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; IPR029787; Nucleotide_cyclase.
DR Pfam; PF00211; Guanylate_cyc; 2.
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 ATP-binding; cAMP biosynthesis; Cell membrane; Glycoprotein; Lyase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1353
FT /note="Adenylate cyclase type 9"
FT /id="PRO_0000195709"
FT TOPO_DOM 1..117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..141
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..215
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..241
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 242..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..280
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 281..301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 302..786
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 787..807
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 808..818
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 819..839
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 840..867
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 868..888
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 889..891
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 892..912
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 913..920
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 921..941
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 942..975
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 976..996
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 997..1353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 596..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 641..685
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1290..1314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 601..615
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..685
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 399..404
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 399
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 399
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 400
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 441..443
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 443
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 443
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 487
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1185..1187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1192..1196
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1232
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 610
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 706
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60503"
FT MOD_RES 1259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60503"
FT MOD_RES 1295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60503"
FT MOD_RES 1332
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 955
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 964
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 893
FT /note="H -> Q (in Ref. 2; CAA90570)"
FT /evidence="ECO:0000305"
FT CONFLICT 1192
FT /note="N -> D (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1305
FT /note="R -> H (in Ref. 2; CAA90570)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1353 AA; 150954 MW; C65736A8304F689E CRC64;
MASSPHQQLL HHHSTEVSCD SSGDSNSVRV KINPKQLSSN THPKHCKYSI SSSCSSSGDS
GGLPRRVGGG GRLRRQKKLP QLFERASSRW WDPKFDSMNL EEACLERCFP QTQRRFRYAL
FYVGFACLLW SIYFAVHMKS KVIVMVVPAL CFLVVCVGFF LFTFTKLYAR HYAWTSLALT
LLVFALTLAA QFQVWTPLSG RVDSSNHTLT ATPADTCLSQ VGSFSICIEV LLLLYTVMQL
PLYLSLFLGV VYSVLFETFG YHFRNEDCYP SPGPGALHWE LLSRALLHVC IHAIGIHLFV
MSQVRSRSTF LKVGQSIMHG KDLEVEKALK ERMIHSVMPR IIADDLMKQG DEESENSVKR
HATSSPKNRK KKSSIQKAPI AFRPFKMQQI EEVSILFADI VGFTKMSANK SAHALVGLLN
DLFGRFDRLC EQTKCEKIST LGDCYYCVAG CPEPRADHAY CCIEMGLGMI KAIEQFCQEK
KEMVNMRVGV HTGTVLCGIL GMRRFKFDVW SNDVNLANLM EQLGVAGKVH ISEATAKYLD
DRYEMEDGRV IERLGQSVVA DQLKGLKTYL ISGQRAKESH CSCAEALLSG FEVIDDSRES
SGPRGQGTAS PGSVSDLAQT VKTFDNLKTC PSCGITFAPK SEAGAEGGTV QNGCQDEPKT
STKASGGPNS KTQNGLLSPP AEEKLTNSQT SLCEILQEKG RWAGVSLDQS ALLPLRFKNI
REKTDAHFVD VIKEDSLMKD YFFKPPINQF SLNFLDQELE RSYRTSYQEE VIKNSPVKTF
ASATFSSLLD VFLSTTVFLI LSITCFLKYG ATATPPPPAA LAVFGADLLL EVLSLIVSIR
MVFFLEDVMT CTKWLLEWIA GWLPRHCIGA ILVSLPALAV YSHITSEFET NIHVTMFTGS
AVLVAVVHYC NFCQLSSWMR SSLATIVGAG LLLLLHISLC QDSSIVMSPL DSAQNFSAQR
NPCNSSVLQD GRRPASLIGK ELILTFFLLL LLVWFLNREF EVSYRLHYHG DVEADLHRTK
IQSMRDQADW LLRNIIPYHV AEQLKVSQTY SKNHDSGGVI FASIVNFSEF YEENYEGGKE
CYRVLNELIG DFDELLSKPD YNSIEKIKTI GATYMAASGL NTAQCQEGGH PQEHLRILFE
FAKEMMRVVD DFNNNMLWFN FKLRVGFNHG PLTAGVIGTT KLLYDIWGDT VNIASRMDTT
GVECRIQVSE ESYRVLSKMG YDFDYRGTVN VKGKGQMKTY LYPKCTDNGV VPQHQLSISP
DIRVQVDGSI GRSPTDEIAN LVPSVQYSDK ASLGSDDSTQ AKEARLSSKR SWREPVKAEE
RFPFGKAIEK DSCEDIGVEE ASELSKLNVS KSV
