ADCY5_RABIT
ID ADCY5_RABIT Reviewed; 1264 AA.
AC P40144;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Adenylate cyclase type 5;
DE EC=4.6.1.1 {ECO:0000250|UniProtKB:O95622};
DE AltName: Full=ATP pyrophosphate-lyase 5;
DE AltName: Full=Adenylate cyclase type V;
DE AltName: Full=Adenylyl cyclase 5;
GN Name=ADCY5;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Myocardium;
RX PubMed=8307190; DOI=10.1016/0014-5793(94)80279-3;
RA Wallach J., Droste M., Kluxen F.-W., Pfeuffer T., Frank R.;
RT "Molecular cloning and expression of a novel type V adenylyl cyclase from
RT rabbit myocardium.";
RL FEBS Lett. 338:257-263(1994).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling. Mediates signaling downstream of
CC ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to
CC increased blood glucose levels and contributes to the regulation of
CC Ca(2+)-dependent insulin secretion. {ECO:0000250|UniProtKB:O95622}.
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:O95622};
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: Myocardial tissue. {ECO:0000269|PubMed:8307190}.
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: The N-terminus is blocked. {ECO:0000269|PubMed:8307190}.
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; Z29371; CAA82562.1; -; mRNA.
DR PIR; S41603; S41603.
DR RefSeq; NP_001076097.1; NM_001082628.1.
DR AlphaFoldDB; P40144; -.
DR SMR; P40144; -.
DR STRING; 9986.ENSOCUP00000013017; -.
DR PRIDE; P40144; -.
DR GeneID; 100009315; -.
DR KEGG; ocu:100009315; -.
DR CTD; 111; -.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; P40144; -.
DR OrthoDB; 215180at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004016; F:adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP 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; ISS:UniProtKB.
DR GO; GO:0006171; P:cAMP biosynthetic process; ISS:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
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 CDD; cd07302; CHD; 1.
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 Direct protein sequencing; Glycoprotein; Lyase; Magnesium; Membrane;
KW Metal-binding; Methylation; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..1264
FT /note="Adenylate cyclase type 5"
FT /id="PRO_0000195696"
FT TOPO_DOM 1..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 331..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..765
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 766..786
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 797..816
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 839..859
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 860..912
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 913..933
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 938..958
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 987..1006
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1007..1264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 472..599
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 1074..1213
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 1..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..73
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..120
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..180
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 477..482
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 477
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 477
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 478
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 519..521
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 521
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 521
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 565
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1126
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1200..1202
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1207..1211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1247
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 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P84309"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P84309"
FT MOD_RES 669
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43306"
FT MOD_RES 757
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 1014
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT CARBOHYD 873
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 890
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 975
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1264 AA; 139624 MW; 1787EB42A0C2FDF6 CRC64;
MSGSKGVSPP GYAAQTAAAP ASRGGPEHRS AWGEADSRAN GYPHAPGGSA RGSTKKPGGA
VTPQQQQQQQ RLASRWRGDD DDEPPLSGDD PLAGGFGFSF RSKSAWQERG GDDCGRGSRR
QRRGAAGGGS TRAPPAGGGC GGGSAAAAAA AGGTEVRPRS VELGLEERRG KGRAVDELEA
GAVEGGEGAE DGGSSADSSN GPGAVLSLGA CCLALLQIFR SKKFPSDKLE RLYQRYFFRL
NQSSLTMLMA VLVLVCLVML AFHAARPPLQ LPYLAVLAAA VGVILVMAVL CNRAAFHQDH
MGLACYALIA VVLAVQVVGL LLPQPRSASE GIWWTVFFIY TIYTLLPVRM RAAVLSGVLL
STLHLAIALR TNAQDRFLLK QLVSNVLIFS CTNIVGVCTH YPAEVSQRQA FQETRECIQA
RLHSQRENQQ QERLLLSVLP RHVAMEMKAD INAKQEDMMF HKIYIQKHDN VSILFADIEG
FTSLASQCTA QELVMTLNEL FARFDKLAAE NHCLRIKILG DCYYCVSGLP EARADHAHCC
VEMGMDMIEA ISLVREVTGV NVNMRVGIHS GRVHCGVLGL RKWQFDVWSN DVTLANHMEA
GGKAGRIHIT KATLNYLNGD YEVEPGCGGE RNAYLKEHSI ETFLILRCTQ KRKEEKAMIA
KMNRQRTNSI GHNPPHWGAE RPFYNHLGGN QVSKEMKRMG FEDPKDKNAQ ESTNPEDEVD
EFLGRAIDAR SIDRLRSEHV RRFLLTFREP DLEKKYSKQV DDRFGAYVAC ASLVFLFICC
VQITIVPHSM FMLSFYLACF LLLTLVVFVS MIYSCVKLFP RPLQSLSRKI VRSKMNSTLV
GVFTITLVFL SAFVNMFMCN SKDLLDCLAA EHNISVIHVN ACHVVESAFN YSLGNEQGFC
GNSRPNCNFP EYFTYSVLLS LLACSVFLQI SCIGKLVLML AIELTYVLIV EVPRVTLFDN
ADLLVTANAI DISSNGTSQC PEHATKVALK VVTPIIISVF VLALYLHAQQ VESTARLDFL
WKLQATEEKE EMEELQAYNR RLLHNILPKD VAAHFLARER RNDELYYQSC ECVAVMFASI
ANFSEFYVEL EANNEGVECL RLLNEIIADF DEIISEDRFR QLEKIKTIGS TYMAASGLND
STYDKVGKTH IKALADFAMK LMDQMKYINE HSFNNFQMKI GLNIGPVVAG VIGARKPQYD
IWGNTVNVAS RMDSTGVPDR IQVTTDMYQV LAANTYQLEC RGVVKVKGKG EMMTYFLNGG
PPLS
