ID PDE4C_HUMAN Reviewed; 712 AA. AC Q08493; B3KTC4; Q9UN44; Q9UN45; Q9UN46; Q9UPJ6; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 27-MAR-2002, sequence version 2. DT 24-JAN-2024, entry version 191. DE RecName: Full=3',5'-cyclic-AMP phosphodiesterase 4C {ECO:0000305}; DE EC=3.1.4.53 {ECO:0000269|PubMed:7843419}; DE AltName: Full=DPDE1; DE AltName: Full=PDE21; DE AltName: Full=cAMP-specific phosphodiesterase 4C {ECO:0000305}; GN Name=PDE4C {ECO:0000312|HGNC:HGNC:8782}; Synonyms=DPDE1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4C1), TISSUE SPECIFICITY, FUNCTION, RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES. RC TISSUE=Substantia nigra; RX PubMed=7843419; DOI=10.1016/0014-5793(94)01460-i; RA Engels P., Sullivan M., Mueller T., Luebbert H.; RT "Molecular cloning and functional expression in yeast of a human cAMP- RT specific phosphodiesterase subtype (PDE IV-C)."; RL FEBS Lett. 358:305-310(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS PDE4C1; PDE4C2 AND PDE4C3). RX PubMed=10574328; DOI=10.1016/s0898-6568(99)00037-6; RA Sullivan M., Olsen A.S., Houslay M.D.; RT "Genomic organisation of the human cyclic AMP-specific phosphodiesterase RT PDE4C gene and its chromosomal localisation to 19p13.1, between RAB3A and RT JUND."; RL Cell. Signal. 11:735-742(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE4C1). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 462-712. RX PubMed=8413254; DOI=10.1128/mcb.13.10.6558-6571.1993; RA Bolger G., Michaeli T., Martins T., St John T., Steiner B., Rodgers L., RA Riggs M., Wigler M., Ferguson K.; RT "A family of human phosphodiesterases homologous to the dunce learning and RT memory gene product of Drosophila melanogaster are potential targets for RT antidepressant drugs."; RL Mol. Cell. Biol. 13:6558-6571(1993). RN [7] {ECO:0007744|PDB:2QYM} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 306-663 IN COMPLEX WITH ZINC AND RP MAGNESIUM, FUNCTION, AND COFACTOR. RX PubMed=17727341; DOI=10.1042/bj20070970; RA Wang H., Peng M.-S., Chen Y., Geng J., Robinson H., Houslay M.D., Cai J., RA Ke H.; RT "Structures of the four subfamilies of phosphodiesterase-4 provide insight RT into the selectivity of their inhibitors."; RL Biochem. J. 408:193-201(2007). CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key CC regulator of many important physiological processes. CC {ECO:0000269|PubMed:17727341, ECO:0000269|PubMed:7843419}. 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:0000269|PubMed:7843419}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278; CC Evidence={ECO:0000305|PubMed:7843419}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:17727341}; CC Note=Binds 2 divalent metal cations per subunit. Site 1 may CC preferentially bind zinc ions. {ECO:0000269|PubMed:17727341}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:17727341}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:Q07343}; CC Note=Binds 2 divalent metal cations per subunit (PubMed:17727341). Site CC 2 has a preference for magnesium and/or manganese ions (By similarity). CC {ECO:0000250|UniProtKB:Q07343, ECO:0000269|PubMed:17727341}; CC -!- ACTIVITY REGULATION: Inhibited by rolipram. CC {ECO:0000269|PubMed:7843419}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.5 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:7843419}; CC Vmax=37 nmol/min/mg enzyme {ECO:0000269|PubMed:7843419}; CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from CC 3',5'-cyclic AMP: step 1/1. {ECO:0000305|PubMed:7843419}. CC -!- SUBUNIT: Part of a complex containing AKAP5, ADCY5, ADCY6 and PKD2. CC {ECO:0000250|UniProtKB:Q3UEI1}. CC -!- INTERACTION: CC Q08493-2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-12169289, EBI-742054; CC Q08493-2; O15499: GSC2; NbExp=3; IntAct=EBI-12169289, EBI-19954058; CC Q08493-2; P26718: KLRK1; NbExp=3; IntAct=EBI-12169289, EBI-458344; CC Q08493-2; P50221: MEOX1; NbExp=3; IntAct=EBI-12169289, EBI-2864512; CC Q08493-2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12169289, EBI-16439278; CC Q08493-2; Q9UJX0: OSGIN1; NbExp=3; IntAct=EBI-12169289, EBI-9057006; CC Q08493-2; P26367: PAX6; NbExp=3; IntAct=EBI-12169289, EBI-747278; CC Q08493-2; P30626: SRI; NbExp=3; IntAct=EBI-12169289, EBI-750459; CC Q08493-2; P59817: ZNF280A; NbExp=3; IntAct=EBI-12169289, EBI-8489342; CC Q08493-3; P30626: SRI; NbExp=3; IntAct=EBI-10225541, EBI-750459; CC -!- SUBCELLULAR LOCATION: Cell projection, cilium CC {ECO:0000250|UniProtKB:Q3UEI1}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=PDE4C1; CC IsoId=Q08493-1; Sequence=Displayed; CC Name=PDE4C2; CC IsoId=Q08493-2; Sequence=VSP_004575; CC Name=PDE4C3; CC IsoId=Q08493-3; Sequence=VSP_004574; CC Name=PDE4C4; CC IsoId=Q08493-4; Sequence=Not described; CC Name=PDE4C5; CC IsoId=Q08493-5; Sequence=Not described; CC Name=PDE4C6; CC IsoId=Q08493-6; Sequence=Not described; CC Name=PDE4C7; CC IsoId=Q08493-7; Sequence=Not described; CC -!- TISSUE SPECIFICITY: Expressed in various tissues but not in cells of CC the immune system. {ECO:0000269|PubMed:7843419}. 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; Z46632; CAA86601.1; -; mRNA. DR EMBL; AF157816; AAD47053.1; -; Genomic_DNA. DR EMBL; AF157811; AAD47053.1; JOINED; Genomic_DNA. DR EMBL; AF157814; AAD47053.1; JOINED; Genomic_DNA. DR EMBL; AF157815; AAD47053.1; JOINED; Genomic_DNA. DR EMBL; AF157816; AAD47054.1; -; Genomic_DNA. DR EMBL; AF157812; AAD47054.1; JOINED; Genomic_DNA. DR EMBL; AF157814; AAD47054.1; JOINED; Genomic_DNA. DR EMBL; AF157815; AAD47054.1; JOINED; Genomic_DNA. DR EMBL; AF157816; AAD47055.1; -; Genomic_DNA. DR EMBL; AF157814; AAD47055.1; JOINED; Genomic_DNA. DR EMBL; AF157815; AAD47055.1; JOINED; Genomic_DNA. DR EMBL; AK095384; BAG53036.1; -; mRNA. DR EMBL; AC005759; AAC83047.1; -; Genomic_DNA. DR EMBL; CH471106; EAW84677.1; -; Genomic_DNA. DR EMBL; L20968; AAA03591.1; -; mRNA. DR CCDS; CCDS12373.1; -. [Q08493-1] DR CCDS; CCDS42523.1; -. [Q08493-3] DR CCDS; CCDS46016.1; -. [Q08493-2] DR PIR; S71626; S71626. DR RefSeq; NP_000914.2; NM_000923.5. [Q08493-1] DR RefSeq; NP_001092288.1; NM_001098818.3. [Q08493-3] DR RefSeq; NP_001092289.1; NM_001098819.3. [Q08493-2] DR RefSeq; NP_001317101.1; NM_001330172.1. [Q08493-1] DR RefSeq; XP_011526358.1; XM_011528056.2. DR PDB; 2QYM; X-ray; 1.90 A; A=306-663. DR PDBsum; 2QYM; -. DR AlphaFoldDB; Q08493; -. DR SMR; Q08493; -. DR BioGRID; 111169; 10. DR IntAct; Q08493; 9. DR STRING; 9606.ENSP00000347689; -. DR BindingDB; Q08493; -. DR ChEMBL; CHEMBL291; -. DR DrugBank; DB01427; Amrinone. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB05219; Crisaborole. DR DrugBank; DB00651; Dyphylline. DR DrugBank; DB06246; Exisulind. DR DrugBank; DB05266; Ibudilast. DR DrugBank; DB01088; Iloprost. DR DrugBank; DB01791; Piclamilast. DR DrugBank; DB01656; Roflumilast. DR DrugBank; DB01954; Rolipram. DR DrugBank; DB09283; Trapidil. DR DrugCentral; Q08493; -. DR GuidetoPHARMACOLOGY; 1302; -. DR GlyGen; Q08493; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q08493; -. DR PhosphoSitePlus; Q08493; -. DR BioMuta; PDE4C; -. DR DMDM; 20141263; -. DR EPD; Q08493; -. DR jPOST; Q08493; -. DR MassIVE; Q08493; -. DR MaxQB; Q08493; -. DR PaxDb; 9606-ENSP00000347689; -. DR PeptideAtlas; Q08493; -. DR ProteomicsDB; 58615; -. [Q08493-1] DR ProteomicsDB; 58616; -. [Q08493-2] DR ProteomicsDB; 58617; -. [Q08493-3] DR Antibodypedia; 27961; 241 antibodies from 31 providers. DR DNASU; 5143; -. DR Ensembl; ENST00000262805.17; ENSP00000262805.10; ENSG00000105650.23. [Q08493-3] DR Ensembl; ENST00000447275.7; ENSP00000402091.1; ENSG00000105650.23. [Q08493-2] DR Ensembl; ENST00000594465.7; ENSP00000470210.1; ENSG00000105650.23. [Q08493-1] DR Ensembl; ENST00000594617.7; ENSP00000469696.1; ENSG00000105650.23. [Q08493-1] DR GeneID; 5143; -. DR KEGG; hsa:5143; -. DR MANE-Select; ENST00000262805.17; ENSP00000262805.10; NM_001098818.4; NP_001092288.1. [Q08493-3] DR UCSC; uc002nii.5; human. [Q08493-1] DR AGR; HGNC:8782; -. DR CTD; 5143; -. DR DisGeNET; 5143; -. DR GeneCards; PDE4C; -. DR HGNC; HGNC:8782; PDE4C. DR HPA; ENSG00000105650; Tissue enhanced (tongue). DR MIM; 600128; gene. DR neXtProt; NX_Q08493; -. DR OpenTargets; ENSG00000105650; -. DR PharmGKB; PA264; -. DR VEuPathDB; HostDB:ENSG00000105650; -. DR eggNOG; KOG3689; Eukaryota. DR GeneTree; ENSGT00940000162285; -. DR HOGENOM; CLU_005940_5_3_1; -. DR InParanoid; Q08493; -. DR OMA; WTERVMA; -. DR OrthoDB; 240889at2759; -. DR PhylomeDB; Q08493; -. DR TreeFam; TF314638; -. DR BRENDA; 3.1.4.53; 2681. DR PathwayCommons; Q08493; -. DR Reactome; R-HSA-180024; DARPP-32 events. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR SignaLink; Q08493; -. DR SIGNOR; Q08493; -. DR UniPathway; UPA00762; UER00747. DR BioGRID-ORCS; 5143; 27 hits in 1152 CRISPR screens. DR ChiTaRS; PDE4C; human. DR EvolutionaryTrace; Q08493; -. DR GeneWiki; PDE4C; -. DR GenomeRNAi; 5143; -. DR Pharos; Q08493; Tclin. DR PRO; PR:Q08493; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q08493; Protein. DR Bgee; ENSG00000105650; Expressed in apex of heart and 96 other cell types or tissues. DR ExpressionAtlas; Q08493; baseline and differential. DR GO; GO:0005929; C:cilium; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. 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; IDA:UniProtKB. 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:0007165; P:signal transduction; IBA:GO_Central. DR CDD; cd00077; HDc; 1. DR Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 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 PANTHER; PTHR11347:SF135; CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4C; 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 SMART; SM00471; HDc; 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; Q08493; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; cAMP; Cell projection; Cilium; KW Hydrolase; Manganese; Metal-binding; Phosphoprotein; Reference proteome; KW Zinc. FT CHAIN 1..712 FT /note="3',5'-cyclic-AMP phosphodiesterase 4C" FT /id="PRO_0000198811" FT DOMAIN 312..641 FT /note="PDEase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192" FT REGION 1..31 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 45..64 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 181..200 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 636..655 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 664..712 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 185..199 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 664..680 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 388 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 388 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:Q08499" FT BINDING 388 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 392 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 392 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:17727341, FT ECO:0007744|PDB:2QYM" FT BINDING 428 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:17727341, FT ECO:0007744|PDB:2QYM" FT BINDING 429 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 429 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:17727341, FT ECO:0007744|PDB:2QYM" FT BINDING 429 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 429 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:17727341, FT ECO:0007744|PDB:2QYM" FT BINDING 429 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 546 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 546 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:17727341, FT ECO:0007744|PDB:2QYM" FT BINDING 597 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:Q08499" FT BINDING 597 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT BINDING 600 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:Q08499" FT BINDING 600 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000250|UniProtKB:Q07343" FT MOD_RES 73 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3UEI1" FT MOD_RES 641 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3UEI1" FT VAR_SEQ 1..106 FT /note="Missing (in isoform PDE4C2)" FT /evidence="ECO:0000305" FT /id="VSP_004575" FT VAR_SEQ 1..81 FT /note="MENLGVGEGAEACSRLSRSRGRHSMTRAPKHLWRQPRRPIRIQQRFYSDPDK FT SAGCRERDLSPRPELRKSRLSWPVSSCRR -> MQGPPAPAPVPGPGSPRGSPRGSPGL FT FRKLLVNQSIRLQRRFTVAHPLC (in isoform PDE4C3)" FT /evidence="ECO:0000305" FT /id="VSP_004574" FT VARIANT 131 FT /note="S -> L (in dbSNP:rs10413646)" FT /id="VAR_050473" FT VARIANT 289 FT /note="R -> Q (in dbSNP:rs34503849)" FT /id="VAR_050474" FT VARIANT 344 FT /note="R -> Q (in dbSNP:rs2229228)" FT /id="VAR_034374" FT VARIANT 344 FT /note="R -> W (in dbSNP:rs11879710)" FT /id="VAR_061497" FT CONFLICT 204 FT /note="K -> N (in Ref. 2; AAD47053/AAD47054)" FT /evidence="ECO:0000305" FT CONFLICT 211 FT /note="D -> Y (in Ref. 2; AAD47053/AAD47054)" FT /evidence="ECO:0000305" FT CONFLICT 339..340 FT /note="EL -> DV (in Ref. 1; CAA86601)" FT /evidence="ECO:0000305" FT CONFLICT 444..446 FT /note="NSE -> K (in Ref. 4; AAC83047)" FT /evidence="ECO:0000305" FT CONFLICT 446..447 FT /note="EL -> DV (in Ref. 1; CAA86601)" FT /evidence="ECO:0000305" FT HELIX 317..323 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 324..326 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 334..340 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 345..356 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 359..362 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 367..379 FT /evidence="ECO:0007829|PDB:2QYM" FT STRAND 385..389 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 390..404 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 407..409 FT /evidence="ECO:0007829|PDB:2QYM" FT TURN 410..412 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 415..427 FT /evidence="ECO:0007829|PDB:2QYM" FT TURN 428..431 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 435..437 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 456..467 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 468..470 FT /evidence="ECO:0007829|PDB:2QYM" FT TURN 476..479 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 482..497 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 501..503 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 504..516 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 531..546 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 549..551 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 554..569 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 600..603 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 605..616 FT /evidence="ECO:0007829|PDB:2QYM" FT TURN 617..620 FT /evidence="ECO:0007829|PDB:2QYM" FT HELIX 621..630 FT /evidence="ECO:0007829|PDB:2QYM" SQ SEQUENCE 712 AA; 79902 MW; 1932116C9CE0322C CRC64; MENLGVGEGA EACSRLSRSR GRHSMTRAPK HLWRQPRRPI RIQQRFYSDP DKSAGCRERD LSPRPELRKS RLSWPVSSCR RFDLENGLSC GRRALDPQSS PGLGRIMQAP VPHSQRRESF LYRSDSDYEL SPKAMSRNSS VASDLHGEDM IVTPFAQVLA SLRTVRSNVA ALARQQCLGA AKQGPVGNPS SSNQLPPAED TGQKLALETL DELDWCLDQL ETLQTRHSVG EMASNKFKRI LNRELTHLSE TSRSGNQVSE YISRTFLDQQ TEVELPKVTA EEAPQPMSRI SGLHGLCHSA SLSSATVPRF GVQTDQEEQL AKELEDTNKW GLDVFKVAEL SGNRPLTAII FSIFQERDLL KTFQIPADTL ATYLLMLEGH YHANVAYHNS LHAADVAQST HVLLATPALE AVFTDLEILA ALFASAIHDV DHPGVSNQFL INTNSELALM YNDASVLENH HLAVGFKLLQ AENCDIFQNL SAKQRLSLRR MVIDMVLATD MSKHMNLLAD LKTMVETKKV TSLGVLLLDN YSDRIQVLQN LVHCADLSNP TKPLPLYRQW TDRIMAEFFQ QGDRERESGL DISPMCDKHT ASVEKSQVGF IDYIAHPLWE TWADLVHPDA QDLLDTLEDN REWYQSKIPR SPSDLTNPER DGPDRFQFEL TLEEAEEEDE EEEEEGEETA LAKEALELPD TELLSPEAGP DPGDLPLDNQ RT //