ADCY5_RAT
ID ADCY5_RAT Reviewed; 1262 AA.
AC Q04400;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Adenylate cyclase type 5;
DE EC=4.6.1.1 {ECO:0000269|PubMed:1409703};
DE AltName: Full=ATP pyrophosphate-lyase 5;
DE AltName: Full=Adenylate cyclase type V;
DE AltName: Full=Adenylyl cyclase 5;
GN Name=Adcy5;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Heart, Kidney, and Liver;
RA Premont R.T.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 164-1262, CATALYTIC ACTIVITY, FUNCTION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=1409703; DOI=10.1073/pnas.89.20.9809;
RA Premont R.T., Chen J., Ma H.-W., Ponnapalli M., Iyengar R.;
RT "Two members of a widely expressed subfamily of hormone-stimulated adenylyl
RT cyclases.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:9809-9813(1992).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling (PubMed:1409703). Mediates signaling
CC downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in
CC response to increased blood glucose levels and contributes to the
CC regulation of Ca(2+)-dependent insulin secretion.
CC {ECO:0000250|UniProtKB:O95622, ECO:0000269|PubMed:1409703}.
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:1409703};
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. Activated by GNAS.
CC Activity is further increased by interaction with the G protein beta
CC and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is
CC not activated by calmodulin. Inhibited by adenosine and ATP analogs.
CC Inhibited by calcium ions, already at micromolar concentrations (By
CC similarity). Phosphorylation by RAF1 results in its activation (By
CC similarity). {ECO:0000250|UniProtKB:O95622,
CC ECO:0000250|UniProtKB:P30803}.
CC -!- SUBUNIT: Interacts with GNAS, GNB1 and GNG2 (By similarity). Part of a
CC complex containing AKAP5, ADCY6, PDE4C and PKD2 (By similarity).
CC Interacts with RAF1 (By similarity). {ECO:0000250|UniProtKB:O95622,
CC ECO:0000250|UniProtKB:P84309}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P30803};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P30803}. Cell
CC projection, cilium {ECO:0000250|UniProtKB:P84309}.
CC -!- TISSUE SPECIFICITY: Detected in brain and kidney.
CC {ECO:0000269|PubMed:1409703}.
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: Phosphorylated by RAF1. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M96159; AAB39764.1; -; mRNA.
DR RefSeq; NP_072122.1; NM_022600.1.
DR AlphaFoldDB; Q04400; -.
DR SMR; Q04400; -.
DR BioGRID; 249116; 1.
DR STRING; 10116.ENSRNOP00000046488; -.
DR BindingDB; Q04400; -.
DR ChEMBL; CHEMBL2880; -.
DR DrugCentral; Q04400; -.
DR GlyGen; Q04400; 3 sites.
DR SwissPalm; Q04400; -.
DR PaxDb; Q04400; -.
DR PRIDE; Q04400; -.
DR GeneID; 64532; -.
DR KEGG; rno:64532; -.
DR UCSC; RGD:71014; rat.
DR CTD; 111; -.
DR RGD; 71014; Adcy5.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; Q04400; -.
DR OrthoDB; 215180at2759; -.
DR BRENDA; 4.6.1.1; 5301.
DR Reactome; R-RNO-163615; PKA activation.
DR Reactome; R-RNO-170660; Adenylate cyclase activating pathway.
DR Reactome; R-RNO-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-RNO-400042; Adrenaline,noradrenaline inhibits insulin secretion.
DR Reactome; R-RNO-418597; G alpha (z) signalling events.
DR Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR PRO; PR:Q04400; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:RGD.
DR GO; GO:0008179; F:adenylate cyclase binding; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008294; F:calcium- and calmodulin-responsive adenylate cyclase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; ISO:RGD.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0007195; P:adenylate cyclase-inhibiting dopamine receptor signaling pathway; ISO:RGD.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:RGD.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:0001973; P:G protein-coupled adenosine receptor signaling pathway; ISO:RGD.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0043278; P:response to morphine; IEP:RGD.
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; 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 ATP-binding; cAMP biosynthesis; Cell membrane; Cell projection; Cilium;
KW Glycoprotein; Lyase; Magnesium; Membrane; Metal-binding; Methylation;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1262
FT /note="Adenylate cyclase type 5"
FT /id="PRO_0000195697"
FT TOPO_DOM 1..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..263
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 396..763
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 764..784
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 790..810
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 837..857
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 858..910
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 911..931
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 936..956
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 985..1005
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1006..1262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 470..597
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 1072..1211
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 1..196
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 104..118
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 475..480
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 475
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 475
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 476
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 517..519
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 519
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 519
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 563
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1124
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1198..1200
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1205..1209
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1245
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 23
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P84309"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P84309"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P84309"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43306"
FT MOD_RES 755
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 1012
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT CARBOHYD 871
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 888
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 973
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1262 AA; 139179 MW; 8B147E201C5DF601 CRC64;
MSGSKSVSPP GYAAQTAASP APRGGPEHRA AWGEADSRAN GYPHAPGGST RGSTKRSGGA
VTPQQQQRLA SRWRGGDDDE DPPLSGDDPL VGGFGFSFRS KSAWQERGGD DGGRGSRRQR
RGAAGGGSTR APPAGGSGSS AAAAAAAGGT EVRPRSVEVG LEERRGKGRA AEELEPGTGT
VEDGDGSEDG GSSVASGSGT GTVLSLGACC LALLQIFRSK KFPSDKLERL YQRYFFRLNQ
SSLTMLMAVL VLVCLVMLAF HAARPPLQVV YLAVLAAAVG VILIMAVLCN RAAFHQDHMG
LACYALIAVV LAVQVVGLLL PQPRSASEGI WWTVFFIYTI YTLLPVRMRA AVLSGVLLSA
LHLAISLHTN AQDQFLLKQL VSNVLIFSCT NIVGVCTHYP AEVSQRQAFQ ETRECIQARL
HSQRENQQQE RLLLSVLPRH VAMEMKADIN AKQEDMMFHK IYIQKHDNVS ILFADIEGFT
SLASQCTAQE LVMTLNELFA RFDKLAAENH CLRIKILGDC YYCVSGLPEA RADHAHCCVE
MGMDMIEAIS SVREVTGVNV NMRVGIHSGR VHCGVLGLRK WQFDVWSNDV TLANHMEAGG
KAGRIHITKA TLNYLNGDYE VEPGCGGERN AYLKEHSIET FLILRCTQKR KEEKAMIAKM
NRQRTNSIGH NPPHWGAERP FYNHLGGNQV SKEMKRMGFE DPKDKNAQES ANPEDEVDEF
LGRAIDARSI DRLRSEHVRK FLLTFREPDL EKKYSKQVDD RFGAYVACAS LVFLFICFVQ
ITIVPHSLFM LSFYLSCFLL LALVVFISVI YACVKLFPTP LQTLSRKIVR SKKNSTLVGV
FTITLVFLSA FVNMFMCNSK NLVGCLAEEH NITVNQVNAC HVMESAFNYS LGDEQGFCGS
PQSNCNFPEY FTYSVLLSLL ACSVFLQISC IGKLVLMLAI ELIYVLIVEV PGVTLFDNAD
LLVTANAIDF SNNGTSQCPE HATKVALKVV TPIIISVFVL ALYLHAQQVE STARLDFLWK
LQATEEKEEM EELQAYNRRL LHNILPKDVA AHFLARERRN DELYYQSCEC VAVMFASIAN
FSEFYVELEA NNEGVECLRL LNEIIADFDE IISEDRFRQL EKIKTIGSTY MAASGLNDST
YDKAGKTHIK ALADFAMKLM DQMKYINEHS FNNFQMKIGL NIGPVVAGVI GARKPQYDIW
GNTVNVASRM DSTGVPDRIQ VTTDMYQVLA ANTYQLECRG VVKVKGKGEM MTYFLNGGPP
LS
