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 27-MAR-2024, entry version 188. DE RecName: Full=3',5'-cyclic-AMP phosphodiesterase 4D {ECO:0000305}; DE EC=3.1.4.53; DE AltName: Full=DPDE3; DE AltName: Full=cAMP-specific phosphodiesterase 4D {ECO:0000305}; 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 CC follicle-stimulating hormone (FSH)) {ECO:0000269|PubMed:17261351}; CC Vmax=5 pmol/min/mg enzyme for cAMP (in the presence of CC follicle-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_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.ENSRNOP00000015138; -. DR BindingDB; P14270; -. DR ChEMBL; CHEMBL2712; -. DR DrugCentral; P14270; -. DR iPTMnet; P14270; -. DR PhosphoSitePlus; P14270; -. DR PaxDb; 10116-ENSRNOP00000067171; -. DR Ensembl; ENSRNOT00000066384.5; ENSRNOP00000063446.2; ENSRNOG00000042536.5. [P14270-9] DR Ensembl; ENSRNOT00000067546.4; ENSRNOP00000062384.2; ENSRNOG00000042536.5. [P14270-7] DR Ensembl; ENSRNOT00000110594.1; ENSRNOP00000076534.1; ENSRNOG00000042536.5. [P14270-4] DR Ensembl; ENSRNOT00000111781.1; ENSRNOP00000094176.1; ENSRNOG00000042536.5. [P14270-6] DR Ensembl; ENSRNOT00000113369.1; ENSRNOP00000093090.1; ENSRNOG00000042536.5. [P14270-8] DR GeneID; 24627; -. DR KEGG; rno:24627; -. DR AGR; RGD:3281; -. 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 OMA; FNTDEGG; -. DR OrthoDB; 240889at2759; -. 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 cell types or tissues. DR ExpressionAtlas; P14270; baseline and differential. DR GO; GO:0034704; C:calcium channel complex; ISO:RGD. DR GO; GO:0005813; C:centrosome; IDA:RGD. DR GO; GO:0005829; C:cytosol; ISO: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: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; ISO:RGD. 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:0005246; F:calcium channel regulator activity; ISO:RGD. 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:0030545; F:signaling receptor regulator activity; IMP:BHF-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD. DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0019933; P:cAMP-mediated signaling; ISO:RGD. 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:0071372; P:cellular response to follicle-stimulating hormone 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: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:1990266; P:neutrophil migration; ISO:RGD. DR GO; GO:0001542; P:ovulation from ovarian follicle; ISO:RGD. DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:RGD. DR GO; GO:0010460; P:positive regulation of heart rate; IMP:BHF-UCL. 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:0032729; P:positive regulation of type II interferon production; ISO:RGD. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:RGD. DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISO: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:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; ISO: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: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 Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1. 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 PANTHER; PTHR11347:SF91; CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4D; 1. DR PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1. DR Pfam; PF18100; PDE4_UCR; 1. DR Pfam; PF00233; PDEase_I; 1. DR PRINTS; PR00387; PDIESTERASE1. DR SUPFAM; SSF101447; Formin homology 2 domain (FH2 domain); 1. DR SUPFAM; SSF109604; HD-domain/PDEase-like; 1. DR PROSITE; PS00126; PDEASE_I_1; 1. DR PROSITE; PS51845; PDEASE_I_2; 1. DR Genevisible; P14270; RN. 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="3',5'-cyclic-AMP 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 //