PDE4C_RAT
ID PDE4C_RAT Reviewed; 536 AA.
AC P14644;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4C;
DE EC=3.1.4.53 {ECO:0000250|UniProtKB:Q08493};
DE AltName: Full=DPDE1;
DE Flags: Fragment;
GN Name=Pde4c {ECO:0000312|RGD:727918}; Synonyms=Dpde1;
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].
RX PubMed=7958996; DOI=10.1016/0378-1119(94)90155-4;
RA Bolger G.B., Rodgers L., Riggs M.;
RT "Differential CNS expression of alternative mRNA isoforms of the mammalian
RT genes encoding cAMP-specific phosphodiesterases.";
RL Gene 149:237-244(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 153-511.
RC TISSUE=Testis;
RX PubMed=2546153; DOI=10.1073/pnas.86.14.5325;
RA Swinnen J.V., Joseph D.R., Conti M.;
RT "Molecular cloning of rat homologues of the Drosophila melanogaster dunce
RT cAMP phosphodiesterase: evidence for a family of genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5325-5329(1989).
CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key
CC regulator of many important physiological processes.
CC {ECO:0000250|UniProtKB:Q08493}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165,
CC ChEBI:CHEBI:456215; EC=3.1.4.53;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000250|UniProtKB:Q08493};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q08493};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q07343};
CC Note=Binds 2 divalent metal cations per subunit (By similarity). Site 2
CC has a preference for magnesium and/or manganese ions (By similarity).
CC {ECO:0000250|UniProtKB:Q07343, ECO:0000250|UniProtKB:Q08493};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000250|UniProtKB:Q08493}.
CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, ADCY6 and PKD2.
CC {ECO:0000250|UniProtKB:Q3UEI1}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q3UEI1}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE4 subfamily. {ECO:0000305}.
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DR EMBL; L27061; AAA56858.1; -; mRNA.
DR EMBL; M25347; AAA41847.1; -; mRNA.
DR PIR; I67945; I67945.
DR AlphaFoldDB; P14644; -.
DR SMR; P14644; -.
DR STRING; 10116.ENSRNOP00000026457; -.
DR BindingDB; P14644; -.
DR ChEMBL; CHEMBL2094267; -.
DR DrugCentral; P14644; -.
DR PaxDb; P14644; -.
DR RGD; 727918; Pde4c.
DR eggNOG; KOG3689; Eukaryota.
DR InParanoid; P14644; -.
DR PhylomeDB; P14644; -.
DR Reactome; R-RNO-180024; DARPP-32 events.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR UniPathway; UPA00762; UER00747.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR040844; PDE4_UCR.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF18100; PDE4_UCR; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 2: Evidence at transcript level;
KW cAMP; Cell projection; Cilium; Hydrolase; Magnesium; Manganese;
KW Metal-binding; Phosphoprotein; Reference proteome; Zinc.
FT CHAIN <1..536
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase 4C"
FT /id="PRO_0000198813"
FT DOMAIN 178..507
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 49..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 254
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 254
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 254
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 258
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 258
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 294
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 295
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 295
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 295
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 295
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 412
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 412
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08493"
FT BINDING 463
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 463
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 466
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 466
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UEI1"
FT CONFLICT 218
FT /note="R -> S (in Ref. 2; AAA41847)"
FT /evidence="ECO:0000305"
FT CONFLICT 507
FT /note="S -> N (in Ref. 2; AAA41847)"
FT /evidence="ECO:0000305"
FT NON_TER 1
SQ SEQUENCE 536 AA; 60064 MW; 87D12BE2C46642F3 CRC64;
NSSRTSSAAS DLHGEDMIVT PFAQVLASLR TVRSNVAALA HGAGSATRQA LLGTPPQSSQ
QAAPAEESGL QLAQETLEEL DWCLEQLETL QTRRSVGEMA SNKFKRMLNR ELTHLSETSR
SGNQVSEYIS QTFLDQQAEV ELPAPPTEDH PWPMAQITGL RKSCHTSLPT AAIPRFGVQT
DQEEQLAKEL EDTNKWGLDV FKVAELSGNR PLTAVIFRVL QERDLLKTFQ IPADTLLRYL
LTLEGHYHSN VAYHNSIHAA DVVQSAHVLL GTPALEAVFT DLEVLAAIFA CAIHDVDHPG
VSNQFLINTN SELALMYNDS SVLENHHLAV GFKLLQGENC DIFQNLSTKQ KLSLRRMVID
MVLATDMSKH MSLLADLKTM VETKKVTSLG VLLLDNYSDR IQVLQSLVHC ADLSNPAKPL
PLYRQWTERI MAEFFQQGDR ERESGLDISP MCDKHTASVE KSQVGFIDYI AHPLWETWAD
LVHPDAQELL DTLEDNREWY QSRVPCSPPH AIGPDRFKFE LTLEETEEEE EEDERH
