PDE4D_RAT
ID PDE4D_RAT Reviewed; 803 AA.
AC P14270; A1E347; A1EC59; F1M1H7; O35470; Q6TRI0; Q8CG04; Q8CG06;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 4.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4D;
DE EC=3.1.4.53;
DE AltName: Full=DPDE3;
GN Name=Pde4d;
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] (ISOFORM 31), AND INDUCTION.
RC TISSUE=Testis;
RX PubMed=2554303; DOI=10.1073/pnas.86.21.8197;
RA Swinnen J.V., Joseph D.R., Conti M.;
RT "The mRNA encoding a high-affinity cAMP phosphodiesterase is regulated by
RT hormones and cAMP.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8197-8201(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 31; 32 AND 33).
RX PubMed=8034568; DOI=10.1016/s0021-9258(17)32297-4;
RA Sette C., Vicini E., Conti M.;
RT "The ratPDE3/IVd phosphodiesterase gene codes for multiple proteins
RT differentially activated by cAMP-dependent protein kinase.";
RL J. Biol. Chem. 269:18271-18274(1994).
RN [3]
RP SEQUENCE REVISION TO 6.
RA Conti M.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 31 AND 32).
RC STRAIN=Wistar;
RX PubMed=8276818; DOI=10.1016/s0021-9258(17)42355-6;
RA Monaco L., Vicini E., Conti M.;
RT "Structure of two rat genes coding for closely related rolipram-sensitive
RT cAMP phosphodiesterases. Multiple mRNA variants originate from alternative
RT splicing and multiple start sites.";
RL J. Biol. Chem. 269:347-357(1994).
RN [5]
RP ERRATUM OF PUBMED:8276818.
RA Monaco L., Vicini E., Conti M.;
RL J. Biol. Chem. 269:20806-20806(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Jin S.-L.C., Kuo W.-P., Conti M.;
RT "Characterization of a cAMP-specific phosphodiesterase variant (PDE4D4)
RT expressed in the rat brain.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 6 AND 7).
RC STRAIN=Sprague-Dawley;
RX PubMed=12834813; DOI=10.1016/s0898-6568(03)00042-1;
RA Wang D., Deng C., Bugaj-Gaweda B., Kwan M., Gunwaldsen C., Leonard C.,
RA Xin X., Hu Y., Unterbeck A., De Vivo M.;
RT "Cloning and characterization of novel PDE4D isoforms PDE4D6 and PDE4D7.";
RL Cell. Signal. 15:883-891(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 8), BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=17261351; DOI=10.1016/j.bbagen.2006.12.006;
RA Levallet G., Levallet J., Bonnamy P.J.;
RT "Alterations in proteoglycan synthesis selectively impair FSH-induced
RT particulate cAMP-phosphodiesterase 4 (PDE4) activation in immature rat
RT Sertoli cells.";
RL Biochim. Biophys. Acta 1770:638-648(2007).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9).
RA Gaweda B., De Vivo M., Wang D.;
RT "Novel PDE4D isoform, PDE4D9.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE OF 224-672.
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).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 226-803 (ISOFORM 33), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 253-803 (ISOFORM 31).
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 [13]
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=10187850; DOI=10.1074/jbc.274.15.10557;
RA Liu H., Maurice D.H.;
RT "Phosphorylation-mediated activation and translocation of the cyclic AMP-
RT specific phosphodiesterase PDE4D3 by cyclic AMP-dependent protein kinase
RT and mitogen-activated protein kinases. A potential mechanism allowing for
RT the coordinated regulation of PDE4D activity and targeting.";
RL J. Biol. Chem. 274:10557-10565(1999).
RN [14]
RP INTERACTION WITH PDE4DIP.
RX PubMed=11134006; DOI=10.1074/jbc.m006546200;
RA Verde I., Pahlke G., Salanova M., Zhang G., Wang S., Coletti D.,
RA Onuffer J., Jin S.-L.C., Conti M.;
RT "Myomegalin is a novel protein of the Golgi/centrosome that interacts with
RT a cyclic nucleotide phosphodiesterase.";
RL J. Biol. Chem. 276:11189-11198(2001).
RN [15]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH THE CENTROSOME (ISOFORM 33).
RX PubMed=11285255; DOI=10.1074/jbc.c000911200;
RA Tasken K.A., Collas P., Kemmner W.A., Witczak O., Conti M., Tasken K.;
RT "Phosphodiesterase 4D and protein kinase a type II constitute a signaling
RT unit in the centrosomal area.";
RL J. Biol. Chem. 276:21999-22002(2001).
RN [16]
RP ALTERNATIVE SPLICING (ISOFORMS 4; 5; 6; 7; 8; 9; 31; 32 AND 33).
RX PubMed=15717866; DOI=10.1042/bj20050030;
RA Richter W., Jin S.L., Conti M.;
RT "Splice variants of the cyclic nucleotide phosphodiesterase PDE4D are
RT differentially expressed and regulated in rat tissue.";
RL Biochem. J. 388:803-811(2005).
RN [17]
RP INTERACTION WITH SHANK2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17244609; DOI=10.1074/jbc.m610857200;
RA Lee J.H., Richter W., Namkung W., Kim K.H., Kim E., Conti M., Lee M.G.;
RT "Dynamic regulation of cystic fibrosis transmembrane conductance regulator
RT by competitive interactions of molecular adaptors.";
RL J. Biol. Chem. 282:10414-10422(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-137, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-52 AND SER-56 (ISOFORM 5), AND IDENTIFICATION BY
RP 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: Hydrolyzes the second messenger cAMP, which is a key
CC regulator of many important physiological processes.
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:Q08499};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000250|UniProtKB:Q08499};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q08499};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions. {ECO:0000250|UniProtKB:Q08499};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q08499};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q07343};
CC Note=Binds 2 divalent metal cations per subunit. Site 2 has a
CC preference for magnesium and/or manganese ions.
CC {ECO:0000250|UniProtKB:Q08499};
CC -!- ACTIVITY REGULATION: Activated by phosphatidic acid (By similarity).
CC Inhibited by rolipram. {ECO:0000250, ECO:0000269|PubMed:17261351}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=18 pmol/min/mg enzyme for cAMP (in the absence of follicle-
CC stimulating hormone (FSH)) {ECO:0000269|PubMed:17261351};
CC Vmax=5 pmol/min/mg enzyme for cAMP (in the presence of follicle-
CC stimulating hormone (FSH)) {ECO:0000269|PubMed:17261351};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1.
CC -!- SUBUNIT: Homodimer for the long isoforms. Isoforms with truncated N-
CC termini are monomeric. Binds ARRB2. Isoform 33 is part of a ternary
CC complex containing PRKAR2A, PRKAR2B and AKAP9. Identified in a complex
CC composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1)
CC (By similarity). Interacts with PDE4DIP. Isoform 5 interacts (via N-
CC terminal region) with SHANK2 (via proline-rich region); the interaction
CC is increased in a PKA-dependent manner. Isoform 33, isoform 4, isoform
CC 7, isoform 8 and isoform 9 but not isoform 32 and isoform 6 interact
CC with SHANK2. Isoform 31 interacts weakly with SHANK2. {ECO:0000250,
CC ECO:0000269|PubMed:11134006, ECO:0000269|PubMed:17244609}.
CC -!- INTERACTION:
CC P14270; P08588: ADRB1; Xeno; NbExp=2; IntAct=EBI-8333209, EBI-991009;
CC P14270-8; Q9QX74: Shank2; NbExp=4; IntAct=EBI-9032440, EBI-397902;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane. Cytoplasm. Membrane.
CC Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome. Note=Found in the soluble fraction,
CC associated with membranes, and associated with the cytoskeleton and the
CC centrosome. Colocalized with SHANK2 to the apical membrane of colonic
CC crypt cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=4; Synonyms=PDE4D4;
CC IsoId=P14270-5; Sequence=Displayed;
CC Name=33; Synonyms=PDE4D3, PDE3.3;
CC IsoId=P14270-1; Sequence=VSP_012398, VSP_012399;
CC Name=31; Synonyms=PDE3.1;
CC IsoId=P14270-2; Sequence=VSP_004581;
CC Name=32; Synonyms=PDE3.2;
CC IsoId=P14270-3; Sequence=VSP_004582;
CC Name=5; Synonyms=PDE4D5;
CC IsoId=P14270-8; Sequence=VSP_053485;
CC Name=6; Synonyms=PDE4D6;
CC IsoId=P14270-7; Sequence=VSP_012404, VSP_012405;
CC Name=7; Synonyms=PDE4D7;
CC IsoId=P14270-4; Sequence=VSP_012400, VSP_012401;
CC Name=8; Synonyms=PDE4D8;
CC IsoId=P14270-9; Sequence=VSP_053486;
CC Name=9; Synonyms=PDE4D9;
CC IsoId=P14270-6; Sequence=VSP_012402, VSP_012403;
CC -!- TISSUE SPECIFICITY: Expressed in epithelial cells. Isoform 33, isoform
CC 4, isoform 5 and isoform 9 are expressed in brain. Isoform 33, isoform
CC 5, isoform 8 and isoform 9 are expressed in heart (at protein level).
CC Isoform 4 and isoform 6 are strongly expressed in cortex and
CC cerebellum. Isoform 7 is strongly expressed in cortex and testis;
CC weakly expressed in kidney, lung, spleen and cerebellum. Isoform 8 is
CC strongly expressed in lung, heart and liver. Isoform 31, isoform 32,
CC isoform 33, isoform 5 and isoform 9 are widely distributed.
CC {ECO:0000269|PubMed:17244609, ECO:0000269|PubMed:17261351}.
CC -!- INDUCTION: Up-regulated by cAMP and follicle-stimulating hormone.
CC {ECO:0000269|PubMed:2554303}.
CC -!- PTM: Isoform 1 and isoform 9 are rapidly activated by PKA through
CC phosphorylation. Long isoforms that share a conserved PKA
CC phosphorylation site in the N-terminus are also activated.
CC {ECO:0000269|PubMed:10187850}.
CC -!- PTM: Sumoylation of long isoforms by PIAS4 augments their activation by
CC PKA phosphorylation and represses their inhibition by ERK
CC phosphorylation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE4 subfamily. {ECO:0000305}.
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; U09455; AAA20401.1; -; mRNA.
DR EMBL; U09457; AAB81869.1; -; mRNA.
DR EMBL; U09456; AAA20393.1; -; mRNA.
DR EMBL; U01280; AAA18925.1; -; Unassigned_DNA.
DR EMBL; U01278; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01282; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01283; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01284; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01285; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01286; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01287; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01279; AAA18925.1; JOINED; Unassigned_DNA.
DR EMBL; U01280; AAA18924.1; -; Unassigned_DNA.
DR EMBL; U01278; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01282; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01283; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01284; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01285; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01286; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01287; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; U01279; AAA18924.1; JOINED; Unassigned_DNA.
DR EMBL; AF031373; AAB95266.1; -; mRNA.
DR EMBL; AF536974; AAN10116.1; -; mRNA.
DR EMBL; EF102484; ABK97408.1; -; mRNA.
DR EMBL; EF121818; ABL14108.1; -; mRNA.
DR EMBL; AF536979; AAN10121.1; -; mRNA.
DR EMBL; AY388961; AAQ90405.1; -; mRNA.
DR EMBL; AABR06012736; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012737; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012739; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012740; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012743; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012744; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012745; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012746; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012747; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012748; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012749; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012751; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012756; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012757; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012758; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012759; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06012760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; L27059; AAA56857.1; -; mRNA.
DR EMBL; L27060; AAC26969.1; -; mRNA.
DR PIR; B53109; B53109.
DR PIR; I61259; I61259.
DR RefSeq; NP_001106799.1; NM_001113328.1.
DR RefSeq; NP_001106800.1; NM_001113329.1. [P14270-4]
DR RefSeq; NP_001106803.1; NM_001113332.1. [P14270-8]
DR RefSeq; NP_001106805.1; NM_001113334.1. [P14270-9]
DR RefSeq; NP_058728.1; NM_017032.1. [P14270-1]
DR RefSeq; XP_008758943.1; XM_008760721.1. [P14270-6]
DR RefSeq; XP_008758944.1; XM_008760722.2. [P14270-7]
DR RefSeq; XP_008758945.1; XM_008760723.1. [P14270-3]
DR AlphaFoldDB; P14270; -.
DR SMR; P14270; -.
DR BioGRID; 246765; 5.
DR IntAct; P14270; 3.
DR MINT; P14270; -.
DR STRING; 10116.ENSRNOP00000067171; -.
DR BindingDB; P14270; -.
DR ChEMBL; CHEMBL2712; -.
DR DrugCentral; P14270; -.
DR iPTMnet; P14270; -.
DR PhosphoSitePlus; P14270; -.
DR PaxDb; P14270; -.
DR PRIDE; P14270; -.
DR Ensembl; ENSRNOT00000066384; ENSRNOP00000063446; ENSRNOG00000042536. [P14270-9]
DR Ensembl; ENSRNOT00000067546; ENSRNOP00000062384; ENSRNOG00000042536. [P14270-7]
DR Ensembl; ENSRNOT00000110594; ENSRNOP00000076534; ENSRNOG00000042536. [P14270-4]
DR Ensembl; ENSRNOT00000111781; ENSRNOP00000094176; ENSRNOG00000042536. [P14270-6]
DR Ensembl; ENSRNOT00000113369; ENSRNOP00000093090; ENSRNOG00000042536. [P14270-8]
DR GeneID; 24627; -.
DR KEGG; rno:24627; -.
DR CTD; 5144; -.
DR RGD; 3281; Pde4d.
DR VEuPathDB; HostDB:ENSRNOG00000042536; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000155674; -.
DR HOGENOM; CLU_005940_5_3_1; -.
DR InParanoid; P14270; -.
DR OrthoDB; 904682at2759; -.
DR PhylomeDB; P14270; -.
DR BRENDA; 3.1.4.53; 5301.
DR Reactome; R-RNO-180024; DARPP-32 events.
DR Reactome; R-RNO-418555; G alpha (s) signalling events.
DR SABIO-RK; P14270; -.
DR UniPathway; UPA00762; UER00747.
DR PRO; PR:P14270; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000042536; Expressed in quadriceps femoris and 18 other tissues.
DR ExpressionAtlas; P14270; baseline and differential.
DR Genevisible; P14270; RN.
DR GO; GO:0034704; C:calcium channel complex; ISO:RGD.
DR GO; GO:0005813; C:centrosome; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0030016; C:myofibril; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0034705; C:potassium channel complex; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISO:RGD.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISO:RGD.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0051117; F:ATPase binding; ISO:RGD.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; IPI:BHF-UCL.
DR GO; GO:0030552; F:cAMP binding; ISO:RGD.
DR GO; GO:0004112; F:cyclic-nucleotide phosphodiesterase activity; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:1901363; F:heterocyclic compound binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0086024; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in positive regulation of heart rate; IC:BHF-UCL.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0007568; P:aging; ISO:RGD.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:RGD.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0061028; P:establishment of endothelial barrier; IDA:UniProtKB.
DR GO; GO:0050900; P:leukocyte migration; ISO:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0007613; P:memory; IMP:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:RGD.
DR GO; GO:0045822; P:negative regulation of heart contraction; ISO:RGD.
DR GO; GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:1901898; P:negative regulation of relaxation of cardiac muscle; ISO:RGD.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISO:RGD.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:RGD.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:RGD.
DR GO; GO:0043949; P:regulation of cAMP-mediated signaling; IMP:RGD.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IMP:BHF-UCL.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0002027; P:regulation of heart rate; ISO:RGD.
DR GO; GO:0010880; P:regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISO:RGD.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; ISO:RGD.
DR GO; GO:0010469; P:regulation of signaling receptor activity; IMP:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006939; P:smooth muscle contraction; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
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 PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; cAMP; Cell membrane; Cytoplasm; Cytoskeleton;
KW Hydrolase; Isopeptide bond; Magnesium; Manganese; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..803
FT /note="cAMP-specific 3',5'-cyclic phosphodiesterase 4D"
FT /id="PRO_0000198816"
FT DOMAIN 381..710
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 1..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 338..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 705..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 732..803
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..87
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..357
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 753..772
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 773..787
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 457
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 457
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 457
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 497
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 498
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 498
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 498
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q07343"
FT BINDING 498
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 498
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 615
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 615
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 618
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 666
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 666
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 669
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT BINDING 669
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08499"
FT CROSSLNK 382
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..297
FT /note="Missing (in isoform 32)"
FT /evidence="ECO:0000303|PubMed:8034568"
FT /id="VSP_004582"
FT VAR_SEQ 1..286
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:12834813"
FT /id="VSP_012404"
FT VAR_SEQ 1..264
FT /note="MEAEGSSVPARAGSHEGSDSSGGAALKAPKHLWRHEQHHQYPLRQPQFRLLH
FT PHHHLPPPPPPSPQPQLQPPPPPPLPPPPPPPGATRGRYASSGASRVRHRGYSDTERYL
FT YCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRRFDVDNGTSAGRSPLDPMTSPGSG
FT LILQANFVHSQRRESFLYRSDSDYDLSPKSMSRNSSIASDIHGDDLIVTPFAQVLASLR
FT TVRNNFAALTNLQDRAPSKRSPMCNQPSINKATIT -> MKEQPSCAGTGHPSMAGYGR
FT MAPFELAGGPVKRLRTESPFPCLFA (in isoform 31)"
FT /evidence="ECO:0000303|PubMed:2554303,
FT ECO:0000303|PubMed:7958996, ECO:0000303|PubMed:8034568"
FT /id="VSP_004581"
FT VAR_SEQ 1..147
FT /note="MEAEGSSVPARAGSHEGSDSSGGAALKAPKHLWRHEQHHQYPLRQPQFRLLH
FT PHHHLPPPPPPSPQPQLQPPPPPPLPPPPPPPGATRGRYASSGASRVRHRGYSDTERYL
FT YCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MAQQTTSPDTLTVPEVDNP
FT HVPNPWLNEDLVKSLRENLLQHEKSKTARKSVSPKLSPVISPRNSPRLLRRMLLSSNIP
FT KQRRFTVAHTC (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:17261351"
FT /id="VSP_053485"
FT VAR_SEQ 1..147
FT /note="MEAEGSSVPARAGSHEGSDSSGGAALKAPKHLWRHEQHHQYPLRQPQFRLLH
FT PHHHLPPPPPPSPQPQLQPPPPPPLPPPPPPPGATRGRYASSGASRVRHRGYSDTERYL
FT YCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MAFVWDPLGVTVPGPSPRT
FT RTRLRFSKSYS (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:17261351"
FT /id="VSP_053486"
FT VAR_SEQ 1..131
FT /note="Missing (in isoform 33)"
FT /evidence="ECO:0000303|PubMed:7958996,
FT ECO:0000303|PubMed:8034568"
FT /id="VSP_012398"
FT VAR_SEQ 1..125
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_012402"
FT VAR_SEQ 1..56
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:12834813"
FT /id="VSP_012400"
FT VAR_SEQ 57..147
FT /note="LPPPPPPSPQPQLQPPPPPPLPPPPPPPGATRGRYASSGASRVRHRGYSDTE
FT RYLYCRAMDRTSYAVETGHRPGLKKSRMSWPSSFQGLRR -> MERNTCDVLSRSKSAS
FT EETLHSCNDEEDPFRGMEPYLVRRLSSRSIQLPPLAFRQLEQTDLRSESENIPRPTSLP
FT LKILPLIAVTSADSTG (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:12834813"
FT /id="VSP_012401"
FT VAR_SEQ 126..147
FT /note="GHRPGLKKSRMSWPSSFQGLRR -> MSIIMKPRSRSTSSLRTTEAVC (in
FT isoform 9)"
FT /evidence="ECO:0000303|Ref.9"
FT /id="VSP_012403"
FT VAR_SEQ 132..147
FT /note="KKSRMSWPSSFQGLRR -> MMHVNTFPFRRHSWIC (in isoform
FT 33)"
FT /evidence="ECO:0000303|PubMed:7958996,
FT ECO:0000303|PubMed:8034568"
FT /id="VSP_012399"
FT VAR_SEQ 287..301
FT /note="ETLQTRHSVSEMASN -> MPEANYLLSVSWGYI (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:12834813"
FT /id="VSP_012405"
FT CONFLICT 226
FT /note="A -> N (in Ref. 12; AAA56857)"
FT /evidence="ECO:0000305"
FT CONFLICT 357
FT /note="S -> P (in Ref. 9; AAQ90405)"
FT /evidence="ECO:0000305"
FT CONFLICT 480..486
FT /note="Missing (in Ref. 4; AAA18924/AAA18925)"
FT /evidence="ECO:0000305"
FT CONFLICT 641
FT /note="G -> E (in Ref. 12; AAC26969)"
FT /evidence="ECO:0000305"
FT CONFLICT 757
FT /note="C -> Y (in Ref. 12; AAA56857)"
FT /evidence="ECO:0000305"
FT MOD_RES P14270-8:52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES P14270-8:56
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 803 AA; 90552 MW; 13E28B257556496D CRC64;
MEAEGSSVPA RAGSHEGSDS SGGAALKAPK HLWRHEQHHQ YPLRQPQFRL LHPHHHLPPP
PPPSPQPQLQ PPPPPPLPPP PPPPGATRGR YASSGASRVR HRGYSDTERY LYCRAMDRTS
YAVETGHRPG LKKSRMSWPS SFQGLRRFDV DNGTSAGRSP LDPMTSPGSG LILQANFVHS
QRRESFLYRS DSDYDLSPKS MSRNSSIASD IHGDDLIVTP FAQVLASLRT VRNNFAALTN
LQDRAPSKRS PMCNQPSINK ATITEEAYQK LASETLEELD WCLDQLETLQ TRHSVSEMAS
NKFKRMLNRE LTHLSEMSRS GNQVSEYISN TFLDKQHEVE IPSPTQKEKE KKKRPMSQIS
GVKKLMHSSS LTNSCIPRFG VKTEQEDVLA KELEDVNKWG LHVFRIAELS GNRPLTVIMH
TIFQERDLLK TFKIPVDTLI TYLMTLEDHY HADVAYHNNI HAADVVQSTH VLLSTPALEA
VFTDLEILAA IFASAIHDVD HPGVSNQFLI NTNSELALMY NDSSVLENHH LAVGFKLLQE
ENCDIFQNLT KKQRQSLRKM AIDIVLATDM SKHMNLLADL KTMVETKKVT SSGVLLLDNY
SDRIQVLQNM VHCADLSNPT KPLQLYRQWT DRIMEEFFRQ GDRERERGME ISPMCDKHNA
SVEKSQVGFI DYIVHPLWET WADLVHPDAQ DILDTLEDNR EWYQSTIPQS PSPAPDDQED
GRQGQTEKFQ FELTLEEDGE SDTEKDSGSQ VEEDTSCSDS KTLCTQDSES TEIPLDEQVE
EEAVAEEESQ PQTGVADDCC PDT
