ADCY1_BOVIN
ID ADCY1_BOVIN Reviewed; 1134 AA.
AC P19754;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Adenylate cyclase type 1;
DE EC=4.6.1.1 {ECO:0000269|PubMed:19029295, ECO:0000269|PubMed:2022671, ECO:0000269|PubMed:2472670};
DE AltName: Full=ATP pyrophosphate-lyase 1;
DE AltName: Full=Adenylate cyclase type I;
DE AltName: Full=Adenylyl cyclase 1 {ECO:0000305};
DE Short=AC1 {ECO:0000303|PubMed:19029295};
DE AltName: Full=Ca(2+)/calmodulin-activated adenylyl cyclase {ECO:0000305};
GN Name=ADCY1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=2472670; DOI=10.1126/science.2472670;
RA Krupinski J., Coussen F., Bakalyar H.A., Tang W.-J., Feinstein P.G.,
RA Orth K., Slaughter C., Reed R.R., Gilman A.G.;
RT "Adenylyl cyclase amino acid sequence: possible channel- or transporter-
RT like structure.";
RL Science 244:1558-1564(1989).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP AND GLYCOSYLATION.
RX PubMed=2022671; DOI=10.1016/s0021-9258(18)93016-4;
RA Tang W.J., Krupinski J., Gilman A.G.;
RT "Expression and characterization of calmodulin-activated (type I)
RT adenylylcyclase.";
RL J. Biol. Chem. 266:8595-8603(1991).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP MUTAGENESIS OF PHE-503, AND INTERACTION WITH CALM.
RX PubMed=19029295; DOI=10.1074/jbc.m807359200;
RA Masada N., Ciruela A., Macdougall D.A., Cooper D.M.;
RT "Distinct mechanisms of regulation by Ca2+/calmodulin of type 1 and 8
RT adenylyl cyclases support their different physiological roles.";
RL J. Biol. Chem. 284:4451-4463(2009).
RN [4]
RP 3D-STRUCTURE MODELING OF 295-450; 861-936 AND 950-1045.
RX PubMed=9391039; DOI=10.1073/pnas.94.25.13414;
RA Liu Y., Ruoho A.E., Rao V.D., Hurley J.H.;
RT "Catalytic mechanism of the adenylyl and guanylyl cyclases: modeling and
RT mutational analysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13414-13419(1997).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling (PubMed:2472670, PubMed:2022671.
CC PubMed:19029295). Mediates responses to increased cellular
CC Ca(2+)/calmodulin levels (PubMed:2022671, PubMed:19029295). May be
CC involved in regulatory processes in the central nervous system. May
CC play a role in memory and learning. Plays a role in the regulation of
CC the circadian rhythm of daytime contrast sensitivity probably by
CC modulating the rhythmic synthesis of cyclic AMP in the retina (By
CC similarity). {ECO:0000250|UniProtKB:O88444,
CC ECO:0000269|PubMed:19029295, ECO:0000269|PubMed:2022671,
CC ECO:0000269|PubMed:2472670}.
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:19029295, ECO:0000269|PubMed:2022671,
CC ECO:0000269|PubMed:2472670};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:2022671};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:2022671};
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 calcium/calmodulin (PubMed:2022671,
CC PubMed:19029295). Activated by forskolin (PubMed:2472670). Activated by
CC the G protein alpha subunit GNAS (PubMed:2022671). Inhibited by the G
CC protein beta and gamma subunit complex (PubMed:2022671). Inhibited by
CC the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP
CC (PubMed:2022671). {ECO:0000269|PubMed:19029295,
CC ECO:0000269|PubMed:2022671, ECO:0000269|PubMed:2472670}.
CC -!- SUBUNIT: Interacts with CALM. {ECO:0000269|PubMed:19029295}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:2022671,
CC ECO:0000269|PubMed:2472670}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:2022671, ECO:0000305|PubMed:2472670}. Cell membrane
CC {ECO:0000269|PubMed:19029295, ECO:0000269|PubMed:2022671}; Multi-pass
CC membrane protein {ECO:0000305|PubMed:2022671}. Cytoplasm
CC {ECO:0000250|UniProtKB:O88444}. Membrane raft
CC {ECO:0000269|PubMed:19029295}. Note=Expressed in the cytoplasm of
CC supporting cells and hair cells of the cochlea vestibule, as well as to
CC the cochlear hair cell nuclei and stereocilia.
CC {ECO:0000250|UniProtKB:O88444}.
CC -!- TISSUE SPECIFICITY: Detected in brain cortex (at protein level).
CC Detected in brain. {ECO:0000269|PubMed:2472670}.
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:P30803}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:2022671}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M25579; AAA79957.1; -; mRNA.
DR PIR; A41350; A41350.
DR RefSeq; NP_776654.1; NM_174229.2.
DR AlphaFoldDB; P19754; -.
DR SMR; P19754; -.
DR STRING; 9913.ENSBTAP00000012528; -.
DR BindingDB; P19754; -.
DR ChEMBL; CHEMBL3549; -.
DR DrugCentral; P19754; -.
DR iPTMnet; P19754; -.
DR PaxDb; P19754; -.
DR PRIDE; P19754; -.
DR Ensembl; ENSBTAT00000012528; ENSBTAP00000012528; ENSBTAG00000009520.
DR GeneID; 281601; -.
DR KEGG; bta:281601; -.
DR CTD; 107; -.
DR VEuPathDB; HostDB:ENSBTAG00000009520; -.
DR VGNC; VGNC:25642; ADCY1.
DR eggNOG; KOG3619; Eukaryota.
DR GeneTree; ENSGT00940000154872; -.
DR InParanoid; P19754; -.
DR OMA; ERRMCPY; -.
DR OrthoDB; 594476at2759; -.
DR BRENDA; 4.6.1.1; 908.
DR PRO; PR:P19754; -.
DR Proteomes; UP000009136; Chromosome 4.
DR Bgee; ENSBTAG00000009520; Expressed in retina and 37 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0004016; F:adenylate cyclase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008294; F:calcium- and calmodulin-responsive adenylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; IMP:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0150076; P:neuroinflammatory response; ISS:UniProtKB.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
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 ATP-binding; Biological rhythms; Calmodulin-binding; cAMP biosynthesis;
KW Cell membrane; Cytoplasm; Direct protein sequencing; Glycoprotein; Lyase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1134
FT /note="Adenylate cyclase type 1"
FT /id="PRO_0000195681"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 66..86
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..174
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 216..236
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 237..612
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 613..633
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 637..657
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 676..696
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 697..726
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 727..747
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 755..775
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 777..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 798..1134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 305..432
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 871..1013
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 495..522
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000305"
FT REGION 1027..1050
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250"
FT REGION 1088..1134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 310..315
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 310
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 310
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 311
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 352..354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 354
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 354
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 398
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 923
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1000..1002
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1007..1011
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1047
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88444"
FT CARBOHYD 706
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 503
FT /note="F->A: Impairs interaction with CALM and responses to
FT Ca(2+)/calmodulin."
FT /evidence="ECO:0000269|PubMed:19029295"
SQ SEQUENCE 1134 AA; 123979 MW; CC4A10BCE224DFF3 CRC64;
MAGAPRGRGG GGGGGGAGES GGAERAAGPG GRRGLRACDE EFACPELEAL FRGYTLRLEQ
AATLKALAVL SLLAGALALA ELLGAPGPAP GLAKGSHPVH CVLFLALLVV TNVRSLQVPQ
LQQVGQLALL FSLTFALLCC PFALGGPAGA HAGAAAVPAT ADQGVWQLLL VTFVSYALLP
VRSLLAIGFG LVVAASHLLV TATLVPAKRP RLWRTLGANA LLFLGVNVYG IFVRILAERA
QRKAFLQARN CIEDRLRLED ENEKQERLLM SLLPRNVAME MKEDFLKPPE RIFHKIYIQR
HDNVSILFAD IVGFTGLASQ CTAQELVKLL NELFGKFDEL ATENHCRRIK ILGDCYYCVS
GLTQPKTDHA HCCVEMGLDM IDTITSVAEA TEVDLNMRVG LHTGRVLCGV LGLRKWQYDV
WSNDVTLANV MEAAGLPGKV HITKTTLACL NGDYEVEPGH GHERNSFLKT HNIETFFIVP
SHRRKIFPGL ILSDIKPAKR MKFKTVCYLL VQLMHCRKMF KAEIPFSNVM TCEDDDKRRA
LRTASEKLRN RSSFSTNVVQ TTPGTRVNRY IGRLLEARQM ELEMADLNFF TLKYKQAERE
RKYHQLQDEY FTSAVVLALI LAALFGLVYL LIIPQSVAVL LLLVFCICFL VACVLYLHIT
RVQCFPGCLT IQIRTVLCIF IVVLIYSVAQ GCVVGCLPWS WSSSPNGSLV VLSSGGRDPV
LPVPPCESAP HALLCGLVGT LPLAIFLRVS SLPKMILLAV LTTSYILVLE LSGYTKAMGA
GAISGRSFEP IMAILLFSCT LALHARQVDV KLRLDYLWAA QAEEERDDME KVKLDNKRIL
FNLLPAHVAQ HFLMSNPRNM DLYYQSYSQV GVMFASIPNF NDFYIELDGN NMGVECLRLL
NEIIADFDEL MDKDFYKDLE KIKTIGSTYM AAVGLAPTAG TKAKKCISSH LSTLADFAIE
MFDVLDEINY QSYNDFVLRV GINVGPVVAG VIGARRPQYD IWGNTVNVAS RMDSTGVQGR
IQVTEEVHRL LRRGSYRFVC RGKVSVKGKG EMLTYFLEGR TDGNGSQTRS LNSERKMYPF
GRAGLQTRLA AGHPPVPPAA GLPVGAGPGA LQGSGLAPGP PGQHLPPGAS GKEA
