ADCY4_RAT
ID ADCY4_RAT Reviewed; 1064 AA.
AC P26770;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Adenylate cyclase type 4;
DE EC=4.6.1.1 {ECO:0000269|PubMed:1946437};
DE AltName: Full=ATP pyrophosphate-lyase 4;
DE AltName: Full=Adenylate cyclase type IV;
DE AltName: Full=Adenylyl cyclase 4;
GN Name=Adcy4;
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], CATALYTIC ACTIVITY, FUNCTION, COFACTOR,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=1946437; DOI=10.1073/pnas.88.22.10178;
RA Gao B., Gilman A.G.;
RT "Cloning and expression of a widely distributed (type IV) adenylyl
RT cyclase.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10178-10182(1991).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517 AND THR-533, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling. {ECO:0000269|PubMed:1946437}.
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:1946437};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:1946437};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:1946437};
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. Insensitive to
CC calcium/calmodulin. Stimulated by GNAS and by the G-protein beta and
CC gamma subunit complex. {ECO:0000269|PubMed:1946437}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1946437};
CC Multi-pass membrane protein {ECO:0000305}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8NFM4}.
CC -!- TISSUE SPECIFICITY: Widely distributed. {ECO:0000269|PubMed:1946437}.
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 -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M80633; AAA40665.1; -; mRNA.
DR PIR; A41542; A41542.
DR AlphaFoldDB; P26770; -.
DR SMR; P26770; -.
DR STRING; 10116.ENSRNOP00000027719; -.
DR BindingDB; P26770; -.
DR ChEMBL; CHEMBL2095179; -.
DR DrugCentral; P26770; -.
DR GlyGen; P26770; 2 sites.
DR iPTMnet; P26770; -.
DR PhosphoSitePlus; P26770; -.
DR PaxDb; P26770; -.
DR PRIDE; P26770; -.
DR UCSC; RGD:2034; rat.
DR RGD; 2034; Adcy4.
DR eggNOG; KOG3619; Eukaryota.
DR InParanoid; P26770; -.
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:P26770; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005080; F:protein kinase C binding; ISO:RGD.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA: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; Cytoplasm; Glycoprotein;
KW Lyase; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1064
FT /note="Adenylate cyclase type 4"
FT /id="PRO_0000195692"
FT TOPO_DOM 1..28
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 29..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..162
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 191..582
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 583..604
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 608..630
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 661..684
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 685..707
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 708..733
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 741..761
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 788..804
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 805..1064
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 498..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..520
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 278..283
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 278
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 278
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 279
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 320..322
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 322
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 322
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
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30803"
FT BINDING 914
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 994..996
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1001..1005
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1041
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 533
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 694
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 701
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1064 AA; 118799 MW; 5A2A0B895B5A0DA8 CRC64;
MARLFSPRPP PSEDLFYETY YSLSQQYPLL ILLLVIVLCA IVALPAVAWA SGRELTSDPS
FLTTVLCALG GFSLLLGLAS REQQLQRWTR PLSGLIWAAL LALGYGFLFT GGVVSAWDQV
SFFLFIIFTV YAMLPLGMRD AAAAGVISSL SHLLVLGLYL GWRPESQRDL LPQLAANAVL
FLCGNVVGAY HKALMERALR ATFREALSSL HSRRRLDTEK KHQEHLLLSI LPAYLAREMK
AEIMARLQAG QSSRPENTNN FHSLYVKRHQ GVSVLYADIV GFTRLASECS PKELVLMLNE
LFGKFDQIAK EHECMRIKIL GDCYYCVSGL PLSLPDHAIN CVRMGLDMCR AIRKLRVATG
VDINMRVGVH SGSVLCGVIG LQKWQYDVWS HDVTLANHME AGGVPGRVHI TGATLALLAG
AYAVERADME HRDPYLRELG EPTYLVIDPW AEEEDEKGTE RGLLSSLEGH TMRPSLLMTR
YLESWGAAKP FAHLSHVDSP ASTSTPLPEK AFSPQWSLDR SRTPRGLHDE LDTGDAKFFQ
VIEQLNSQKQ WKQSKDFNLL TLYFREKEME KQYRLSALPA FKYYAACTFL VFLSNFTIQM
LVTTRPPALA TTYSITFLLF LLLLFVCFSE HLTKCVQKGP KMLHWLPALS VLVATRPGLR
VALGTATILL VFTMAVVSLL FLPVSSDCPF LAPNVSSVAF NTSWELPASL PLISIPYSMH
CCVLGFLSCS LFLHMSFELK LLLLLLWLVA SCSLFLHSHA WLSDCLIARL YQGSLGSRPG
VLKEPKLMGA IYFFIFFFTL LVLARQNEYY CRLDFLWKKK LRQEREETET MENVLPAHVA
PQLIGQNRRN EDLYHQSYEC VCVLFASIPD FKEFYSESNI NHEGLECLRL LNEIIADFDE
LLSKPKFSGV EKIKTIGSTY MAATGLNATP GQDTQQDAER SCSHLGTMVE FAVALGSKLG
VINKHSFNNF RLRVGLNHGP VVAGVIGAQK PQYDIWGNTV NVASRMESTG VLGKIQVTEE
TARALQSLGY TCYSRGVIKV KGKGQLCTYF LNTDLTRTGS PSAS
