ADCY6_CANLF
ID ADCY6_CANLF Reviewed; 1165 AA.
AC P30804;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Adenylate cyclase type 6;
DE EC=4.6.1.1 {ECO:0000269|PubMed:1528892, ECO:0000269|PubMed:17110384};
DE AltName: Full=ATP pyrophosphate-lyase 6;
DE AltName: Full=Adenylate cyclase type VI;
DE AltName: Full=Adenylyl cyclase 6;
DE AltName: Full=Ca(2+)-inhibitable adenylyl cyclase;
GN Name=ADCY6;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, COFACTOR,
RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=1528892; DOI=10.1073/pnas.89.18.8774;
RA Katsushika S., Chen L., Kawabe J., Nilakantan R., Halnon N.J., Homcy C.J.,
RA Ishikawa Y.;
RT "Cloning and characterization of a sixth adenylyl cyclase isoform: types V
RT and VI constitute a subgroup within the mammalian adenylyl cyclase
RT family.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8774-8778(1992).
RN [2]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17110384; DOI=10.1074/jbc.m607522200;
RA Gao X., Sadana R., Dessauer C.W., Patel T.B.;
RT "Conditional stimulation of type V and VI adenylyl cyclases by G protein
RT betagamma subunits.";
RL J. Biol. Chem. 282:294-302(2007).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP
CC downstream of G protein-coupled receptors (PubMed:1528892,
CC PubMed:17110384). Functions in signaling cascades downstream of the
CC vasopressin receptor in the kidney and has a role in renal water
CC reabsorption. Functions in signaling cascades downstream of PTH1R and
CC plays a role in regulating renal phosphate excretion. Functions in
CC signaling cascades downstream of the VIP and SCT receptors in pancreas
CC and contributes to the regulation of pancreatic amylase and fluid
CC secretion (By similarity). Signaling mediates cAMP-dependent activation
CC of protein kinase PKA (By similarity). This promotes increased
CC phosphorylation of various proteins, including AKT. Plays a role in
CC regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage,
CC and is required for normal heart ventricular contractibility. May
CC contribute to normal heart function (By similarity). Mediates
CC vasodilatation after activation of beta-adrenergic receptors by
CC isoproterenol (By similarity). Contributes to bone cell responses to
CC mechanical stimuli (By similarity). {ECO:0000250|UniProtKB:O43306,
CC ECO:0000250|UniProtKB:Q01341, ECO:0000250|UniProtKB:Q03343,
CC ECO:0000269|PubMed:1528892, ECO:0000269|PubMed:17110384}.
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:1528892, ECO:0000269|PubMed:17110384};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O43306};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:1528892};
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. Inhibited by calcium ions,
CC already at micromolar concentrations. Inhibited by adenosine, AMP and
CC their analogs (PubMed:1528892). Activated by GNAS (PubMed:17110384). Is
CC further activated by the complex formed by GNB1 and GNG2
CC (PubMed:17110384). Phosphorylation by RAF1 results in its activation
CC (By similarity). {ECO:0000250|UniProtKB:Q03343,
CC ECO:0000269|PubMed:1528892, ECO:0000269|PubMed:17110384}.
CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By
CC similarity). Interacts with RAF1. Interacts (via cytoplasmic N-
CC terminus) with GNAS, GNB1 and GNG2 (By similarity).
CC {ECO:0000250|UniProtKB:O43306, ECO:0000250|UniProtKB:Q01341}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1528892,
CC ECO:0000269|PubMed:17110384}; Multi-pass membrane protein
CC {ECO:0000305}. Cell projection, cilium {ECO:0000250|UniProtKB:Q01341}.
CC Cell projection, stereocilium {ECO:0000250|UniProtKB:Q01341}.
CC -!- TISSUE SPECIFICITY: Detected in brain and heart.
CC {ECO:0000269|PubMed:1528892}.
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: Phosphorylation by RAF1 increases enzyme activity. Phosphorylation
CC by PKA on Ser-659 inhibits the GNAS-mediated increase in catalytic
CC activity. Phosphorylation by PKC on Ser-553, Ser-659 and Thr-916
CC inhibits catalytic activity. {ECO:0000250|UniProtKB:Q03343}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M94968; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A46180; A46180.
DR AlphaFoldDB; P30804; -.
DR SMR; P30804; -.
DR STRING; 9615.ENSCAFP00000039800; -.
DR PaxDb; P30804; -.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; P30804; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0032420; C:stereocilium; 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:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0006171; P:cAMP biosynthetic process; ISS:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:1904117; P:cellular response to vasopressin; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0035811; P:negative regulation of urine volume; ISS:UniProtKB.
DR GO; GO:0003091; P:renal water homeostasis; ISS:UniProtKB.
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; Manganese; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1165
FT /note="Adenylate cyclase type 6"
FT /id="PRO_0000195698"
FT TOPO_DOM 1..149
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 150..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 287..303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 304..670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 671..688
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 699..715
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 740..756
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 757..816
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 817..833
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 836..852
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 894..910
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 911..1165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 382..387
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 382
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 382
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 383
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 424..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 426
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 426
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 470
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 1028
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1102..1104
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1109..1113
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43306"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43306"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT MOD_RES 916
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q03343"
FT CARBOHYD 790
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 875
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1165 AA; 130324 MW; BA9D2D329120615E CRC64;
MSWFSGLLVP KVDERKTAWG ERNGQKRPRR GTRTSGFCTP RYMSCLRDAQ PPSPTPAAPP
RCPWQDEAFI RRGGPGKGTE LGLRAVALGF EDTEAMSAVG AAGGGPDVTP GSRRSCWRRL
AQVFQSKQFR SAKLERLYQR YFFQMNQSSL TLLMAVLVLL TAVLLAFHAA PARPQPAYVA
LLACAATLFV ALMVVCNRHS FRQDSMWVVS YVVLGILAAV QVGGALAANP RSPSVGLWCP
VFFVYITYTL LPIRMRAAVF SGLGLSTLHL ILAWQLNRGD AFLWKQLGAN MLLFLCTNVI
GICTHYPAEV SQRQAFQETR GYIQARLHLP DENRQQERLL LSVLPQHVAM EMKEDINTKK
EDMMFHKIYI QKHDNVSILF ADIEGFTSLA SQCTAQELVM TLNELFARFD KLAAENHCLR
IKILGDCYYC VSGLPEARAD HAHCCVEMGV DMIEAISLVR EVTGVNVNMR VGIHSGRVHC
GVLGLRKWQF DVWSNDVTLA NHMEAARAGR IHITRATLQY LNGDYEVEPG RGGERNAYLK
EQHIETFLIL GASQKRKEEK AMLAKLQRTR ANSMEGLMPR WVPDRAFSRT KDSKAFRQMG
IDDSSKDNRG AQDALNPEDE VDEFLGRAID ARSIDQLRKD HVRRFLLTFQ REDLEKKYSR
KVDPRFGAYV ACALLVFCFI CFIQLLVFPH STVMLGIYAS IFVLLLITVL TCAVYSCGSL
FPKALRRLSR SIVRSRAHST VVGIFSVLLV FTSAIANMFT CNHTPIRTCA ARMLNVTPAD
ITACHLQQLN YSLGLDAPLC EGTAPTCSFP EYFVGNMLLS LLASSVFLHI SSIGKLAMIF
VLGLIYLVLL LLGPPSTIFD NYDLLLGVHG LASSNDTFDG LDCPAAGRVA LKYMTPVILL
VFALALYLHA QQVESTARLD FLWKLQATGE KEEMEELQAY NRRLLHNILP KDVAAHFLAR
ERRNDELYYQ SCECVAVMFA SIANFSEFYV ELEANNEGVE CLRLLNEIIA DFDEIISEER
FRQLEKIKTI GSTYMAASGL NASTYDQAGR SHITALADYA MRLMEQMKHI NEHSFNNFQM
KIGLNMGPVV AGVIGARKPQ YDIWGNTVNV SSRMDSTGVP DRIQVTTDLY QVLAAKRYQL
ECRGVVKVKG KGEMTTYFLN GGPPS
