ADCY3_RAT
ID ADCY3_RAT Reviewed; 1144 AA.
AC P21932;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Adenylate cyclase type 3;
DE EC=4.6.1.1 {ECO:0000269|PubMed:1633161, ECO:0000269|PubMed:2255909, ECO:0000269|PubMed:24363043};
DE AltName: Full=ATP pyrophosphate-lyase 3;
DE AltName: Full=Adenylate cyclase type III {ECO:0000303|PubMed:2255909};
DE Short=AC-III;
DE AltName: Full=Adenylate cyclase, olfactive type;
DE AltName: Full=Adenylyl cyclase 3;
DE Short=AC3;
GN Name=Adcy3;
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], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Olfactory epithelium;
RX PubMed=2255909; DOI=10.1126/science.2255909;
RA Bakalyar H.A., Reed R.R.;
RT "Identification of a specialized adenylyl cyclase that may mediate odorant
RT detection.";
RL Science 250:1403-1406(1990).
RN [2]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=1633161; DOI=10.1021/bi00143a019;
RA Choi E.J., Xia Z., Storm D.R.;
RT "Stimulation of the type III olfactory adenylyl cyclase by calcium and
RT calmodulin.";
RL Biochemistry 31:6492-6498(1992).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=15705663; DOI=10.1210/me.2004-0318;
RA Livera G., Xie F., Garcia M.A., Jaiswal B., Chen J., Law E., Storm D.R.,
RA Conti M.;
RT "Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility
RT and spermatozoon function.";
RL Mol. Endocrinol. 19:1277-1290(2005).
RN [4]
RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=24363043; DOI=10.1007/s00210-013-0950-4;
RA Bogard A.S., Birg A.V., Ostrom R.S.;
RT "Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that
RT selectively regulates IL-6 expression in airway smooth muscle cells:
RT differential regulation of gene expression by AC isoforms.";
RL Naunyn Schmiedebergs Arch. Pharmacol. 387:329-339(2014).
RN [5]
RP SUMOYLATION, MUTAGENESIS OF LYS-465, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=25908845; DOI=10.1242/jcs.164673;
RA McIntyre J.C., Joiner A.M., Zhang L., Iniguez-Lluhi J., Martens J.R.;
RT "SUMOylation regulates ciliary localization of olfactory signaling
RT proteins.";
RL J. Cell Sci. 128:1934-1945(2015).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling (PubMed:2255909, PubMed:1633161,
CC PubMed:24363043). Participates in signaling cascades triggered by
CC odorant receptors via its function in cAMP biosynthesis
CC (PubMed:2255909). Required for the perception of odorants. Required for
CC normal sperm motility and normal male fertility. Plays a role in
CC regulating insulin levels and body fat accumulation in response to a
CC high fat diet (By similarity). {ECO:0000250|UniProtKB:Q8VHH7,
CC ECO:0000269|PubMed:1633161, ECO:0000269|PubMed:2255909,
CC ECO:0000269|PubMed:24363043}.
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:1633161, ECO:0000269|PubMed:2255909,
CC ECO:0000269|PubMed:24363043};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:2255909};
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 (PubMed:2255909,
CC PubMed:1633161, PubMed:24363043). After forskolin treatment, activity
CC is further increased by calcium/calmodulin (PubMed:1633161). In the
CC absence of forskolin, calcium/calmodulin has little effect on enzyme
CC activity (PubMed:1633161). {ECO:0000269|PubMed:1633161,
CC ECO:0000269|PubMed:2255909, ECO:0000269|PubMed:24363043}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15705663,
CC ECO:0000269|PubMed:1633161}; Multi-pass membrane protein {ECO:0000305}.
CC Golgi apparatus {ECO:0000269|PubMed:15705663}. Cell projection, cilium
CC {ECO:0000269|PubMed:2255909, ECO:0000269|PubMed:25908845}. Cytoplasm
CC {ECO:0000250|UniProtKB:O60266}.
CC -!- TISSUE SPECIFICITY: Detected on cilia on the olfactory epithelium (at
CC protein level) (PubMed:2255909, PubMed:25908845). Detected on cilia on
CC the olfactory epithelium. {ECO:0000269|PubMed:2255909}.
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 modules have no catalytic activity, but when they are
CC brought together, enzyme activity is restored. The active site is at
CC the interface of the two modules. {ECO:0000250|UniProtKB:P30803}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:2255909}.
CC -!- PTM: Sumoylated. Sumoylation is required for targeting ot olfactory
CC cilia. {ECO:0000269|PubMed:25908845}.
CC -!- PTM: Rapidly phosphorylated after stimulation by odorants or forskolin.
CC Phosphorylation by CaMK2 at Ser-1076 down-regulates enzyme activity.
CC {ECO:0000250|UniProtKB:Q8VHH7}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M55075; AAA40677.1; -; mRNA.
DR PIR; A39833; A39833.
DR RefSeq; NP_570135.2; NM_130779.2.
DR AlphaFoldDB; P21932; -.
DR SMR; P21932; -.
DR BioGRID; 249093; 1.
DR STRING; 10116.ENSRNOP00000005389; -.
DR BindingDB; P21932; -.
DR ChEMBL; CHEMBL2095179; -.
DR DrugCentral; P21932; -.
DR GlyGen; P21932; 1 site.
DR PhosphoSitePlus; P21932; -.
DR PaxDb; P21932; -.
DR GeneID; 64508; -.
DR KEGG; rno:64508; -.
DR CTD; 109; -.
DR RGD; 71009; Adcy3.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; P21932; -.
DR OrthoDB; 154265at2759; -.
DR PhylomeDB; P21932; -.
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-418597; G alpha (z) signalling events.
DR Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR PRO; PR:P21932; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0060170; C:ciliary membrane; ISO:RGD.
DR GO; GO:0005929; C:cilium; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
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; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:UniProtKB.
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:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007340; P:acrosome reaction; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; IDA:UniProtKB.
DR GO; GO:0030317; P:flagellated sperm motility; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0008355; P:olfactory learning; ISS:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; ISO:RGD.
DR GO; GO:0007338; P:single fertilization; 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; 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; Calmodulin-binding; cAMP biosynthesis; Cell membrane;
KW Cell projection; Cytoplasm; Glycoprotein; Golgi apparatus; Isopeptide bond;
KW Lyase; Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Olfaction; Phosphoprotein; Reference proteome; Repeat;
KW Sensory transduction; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..1144
FT /note="Adenylate cyclase type 3"
FT /id="PRO_0000195689"
FT TOPO_DOM 1..79
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 80..100
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 105..125
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 631..651
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 662..682
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 706..726
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 TRANSMEM 833..853
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 854..1144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 504..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 526..546
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 324..329
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 324
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 324
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 325
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 366..368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 368
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 368
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 412
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 975
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1062..1064
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1069..1073
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60266"
FT MOD_RES 578
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHH7"
FT MOD_RES 1076
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q8VHH7"
FT CARBOHYD 734
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 465
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO3)"
FT /evidence="ECO:0000269|PubMed:25908845"
FT MUTAGEN 465
FT /note="K->R: Abolishes sumoylation. Abolishes location at
FT cilia in the olfactory epithelium."
FT /evidence="ECO:0000269|PubMed:25908845"
SQ SEQUENCE 1144 AA; 128936 MW; 21098D028DDBAB55 CRC64;
MTEDQGFSDP EYSAEYSAEY SVSLPSDPDR GVGRTHEISV RNSGSCLCLP RFMRLTFVPE
SLENLYQTYF KRQRHETLLV LVVFAALFDC YVVVMCAVVF SSDKLAPLMV AGVGLVLDII
LFVLCKKGLL PDRVSRKVVP YLLWLLITAQ IFSYLGLNFS RAHAASDTVG WQAFFVFSFF
ITLPLSLSPI VIISVVSCVV HTLVLGVTVA QQQQDELEGM QLLREILANV FLYLCAIIVG
IMSYYMADRK HRKAFLEARQ SLEVKMNLEE QSQQQENLML SILPKHVADE MLKDMKKDES
QKDQQQFNTM YMYRHENVSI LFADIVGFTQ LSSACSAQEL VKLLNELFAR FDKLAAKYHQ
LRIKILGDCY YCICGLPDYR EDHAVCSILM GLAMVEAISY VREKTKTGVD MRVGVHTGTV
LGGVLGQKRW QYDVWSTDVT VANKMEAGGI PGRVHISQST MDCLKGEFDV EPGDGGSRCD
YLDEKGIETY LIIASKPEVK KTAQNGLNGS ALPNGAPASK PSSPALIETK EPNGSAHASG
STSEEAEEQE AQADNPSFPN PRRRLRLQDL ADRVVDASED EHELNQLLNE ALLERESAQV
VKKRNTFLLT MRFMDPEMET RYSVEKEKQS GAAFSCSCVV LFCTAMVEIL IDPWLMTNYV
TFVVGEVLLL ILTICSMAAI FPRAFPKKLV AFSSWIDRTR WARNTWAMLA IFILVMANVV
DMLSCLQYYM GPYNVTTGIE LDGGCMENPK YYNYVAVLSL IATIMLVQVS HMVKLTLMLL
VTGAVTAINL YAWCPVFDEY DHKRFQEKDS PMVALEKMQV LSTPGLNGTD SRLPLVPSKY
SMTVMMFVMM LSFYYFSRHV EKLARTLFLW KIEVHDQKER VYEMRRWNEA LVTNMLPEHV
ARHFLGSKKR DEELYSQSYD EIGVMFASLP NFADFYTEES INNGGIECLR FLNEIISDFD
SLLDNPKFRV ITKIKTIGST YMAASGVTPD VNTNGFTSSS KEEKSDKERW QHLADLADFA
LAMKDTLTNI NNQSFNNFML RIGMNKGGVL AGVIGARKPH YDIWGNTVNV ASRMESTGVM
GNIQVVEETQ VILREYGFRF VRRGPIFVKG KGELLTFFLK GRDRPAAFPN GSSVTLPHQV
VDNP
