ADCY4_MOUSE
ID ADCY4_MOUSE Reviewed; 1077 AA.
AC Q91WF3;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Adenylate cyclase type 4;
DE EC=4.6.1.1 {ECO:0000250|UniProtKB:P26770};
DE AltName: Full=ATP pyrophosphate-lyase 4;
DE AltName: Full=Adenylate cyclase type IV;
DE AltName: Full=Adenylyl cyclase 4;
GN Name=Adcy4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RA Rui X., Schimmer B.P.;
RT "Sequence of mouse adenylyl cyclase type IV.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 355-366, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP in
CC response to G-protein signaling. {ECO:0000250|UniProtKB:P26770}.
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:P26770};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P26770};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P26770};
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:0000250|UniProtKB:P26770}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P26770};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P26770}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8NFM4}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF442771; AAL38004.1; -; mRNA.
DR EMBL; BC015299; AAH15299.1; -; mRNA.
DR CCDS; CCDS27130.1; -.
DR RefSeq; NP_536683.1; NM_080435.1.
DR RefSeq; XP_006518386.1; XM_006518323.1.
DR RefSeq; XP_006518387.1; XM_006518324.1.
DR AlphaFoldDB; Q91WF3; -.
DR SMR; Q91WF3; -.
DR BioGRID; 222367; 3.
DR STRING; 10090.ENSMUSP00000130530; -.
DR GlyGen; Q91WF3; 2 sites.
DR iPTMnet; Q91WF3; -.
DR PhosphoSitePlus; Q91WF3; -.
DR MaxQB; Q91WF3; -.
DR PaxDb; Q91WF3; -.
DR PRIDE; Q91WF3; -.
DR ProteomicsDB; 285761; -.
DR Antibodypedia; 3908; 239 antibodies from 26 providers.
DR DNASU; 104110; -.
DR Ensembl; ENSMUST00000002398; ENSMUSP00000002398; ENSMUSG00000022220.
DR Ensembl; ENSMUST00000170223; ENSMUSP00000130530; ENSMUSG00000022220.
DR GeneID; 104110; -.
DR KEGG; mmu:104110; -.
DR UCSC; uc007uat.1; mouse.
DR CTD; 196883; -.
DR MGI; MGI:99674; Adcy4.
DR VEuPathDB; HostDB:ENSMUSG00000022220; -.
DR eggNOG; KOG3619; Eukaryota.
DR GeneTree; ENSGT00940000159445; -.
DR HOGENOM; CLU_001072_2_5_1; -.
DR InParanoid; Q91WF3; -.
DR OMA; NCPFRAP; -.
DR OrthoDB; 363718at2759; -.
DR PhylomeDB; Q91WF3; -.
DR TreeFam; TF313845; -.
DR BRENDA; 4.6.1.1; 3474.
DR Reactome; R-MMU-163615; PKA activation.
DR Reactome; R-MMU-170660; Adenylate cyclase activating pathway.
DR Reactome; R-MMU-170670; Adenylate cyclase inhibitory pathway.
DR Reactome; R-MMU-418597; G alpha (z) signalling events.
DR Reactome; R-MMU-5610787; Hedgehog 'off' state.
DR BioGRID-ORCS; 104110; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q91WF3; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q91WF3; protein.
DR Bgee; ENSMUSG00000022220; Expressed in external carotid artery and 156 other tissues.
DR ExpressionAtlas; Q91WF3; baseline and differential.
DR Genevisible; Q91WF3; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0004016; F:adenylate cyclase activity; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:MGI.
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; IDA:MGI.
DR GO; GO:0006171; P:cAMP biosynthetic process; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
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;
KW Direct protein sequencing; Glycoprotein; Lyase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..1077
FT /note="Adenylate cyclase type 4"
FT /id="PRO_0000195691"
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..717
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 718..738
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 746..766
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 793..809
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 810..1077
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 502..524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..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 927
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1007..1009
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1014..1018
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P26769"
FT BINDING 1054
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:0000250|UniProtKB:P26770"
FT MOD_RES 533
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P26770"
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 1077 AA; 120380 MW; 03EA262D05F4B36D CRC64;
MARLFSPRPP PSEDLFYETY YSLSQQYPLL ILLLVIVLCA LVALPAVAWA SGRELTSDPS
FLTTVLCALG GFSLLLGLAS REQQLQRWTR PLSGLIWVAL LALGYGFLFT GGVVSAWDQV
SFFLFIIFTV YAMLPLGMRD AAAAGVISSL SHLLVLGLYL GWQPESQRAL LPQLAANAVL
FLCGNVVGAY HKALMERALR ATFREALSSL HSRRRLDTEK KHQEHLLLSI LPAYLAREMK
AEIMARLQAG QRSRPENTNN FHSLYVKRHQ GVSVLYADIV GFTRLASECS PKELVLMLNE
LFGKFDQIAK EHECMRIKIL GDCYYCVSGL PLSLPDHAIN CVRMGLDMCR AIRKLRVATG
VDINMRVGVH SGSVLCGVIG LQKWQYDVWS HDVTLANHME AGGVPGRVHI TGATLALLAG
AYAVERADTE HRDPYLRELG EPTYLVIDPR AEEEDEKGTA KGLLSSLEGH TMRPSLLMTR
YLESWGAAKP FAHLSHLDSP VSTSTPLPEK AFSPQWSLDR SRTPRGLDDE LDTGDAKFFQ
VIEQLNSQKQ WKQSKDFNLL TLYFREKEME KQYRLSALPA FKYYAACTFL VFLSNFTIQM
LVTTRPPALI ITYSITFLLF FLLLFVCFSE HLTKCVQKGP KMLHWLPALS VLVATRPGFR
VALGTATILL VFTMAIASLL FLPVSSDCLF LASNVSSVTF NASWEMPGSL PLISIPLISI
PYSMHCCVLG FLSCSLFLHM SFELKLLLLL LWLVASCSLF LHSHAWLSDC LIARLYQSPS
DSRPGVLKEP KLMGAIYFFI FFFTLLVLAR QNEYYCRLDF LWKKKLRQER EETETMENLT
RLLLENVLPA HVAPQFIGQN RRNEDLYHQS YECVCVLFAS VPDFKEFYSE SNINHEGLEC
LRLLNEIIAD FDELLSKPKF SGVEKIKTIG STYMAATGLN ATSGQDTQQD SERSCSHLGT
MVEFAVALGS KLGVINKHSF NNFRLRVGLN HGPVVAGVIG AQKPQYDIWG NTVNVASRME
STGVLGKIQV TEETARALQS LGYTCYSRGS IKVKGKGELC TYFLNTDLTR TGSPSAS
