ID PDE4B_HUMAN Reviewed; 736 AA. AC Q07343; A5YW33; O15443; Q13945; Q5TEK4; Q5TEK5; Q5TEK6; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 27-MAR-2024, entry version 214. DE RecName: Full=3',5'-cyclic-AMP phosphodiesterase 4B {ECO:0000305}; DE EC=3.1.4.53 {ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:17519386, ECO:0000269|PubMed:8392015, ECO:0000269|PubMed:9371714}; DE AltName: Full=DPDE4; DE AltName: Full=PDE32; DE AltName: Full=cAMP-specific phosphodiesterase 4B {ECO:0000305}; GN Name=PDE4B {ECO:0000312|HGNC:HGNC:8781}; Synonyms=DPDE4; 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 PDE4B2), CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION. RX PubMed=8392015; DOI=10.1016/0378-1119(93)90274-7; RA Obernolte R., Bhakta S., Alvarez R., Bach C., Mulkins M., Jarnagin K., RA Shelton E.R.; RT "The cDNA of a human lymphocyte cyclic-AMP phosphodiesterase (PDE IV) RT reveals a multigene family."; RL Gene 129:239-247(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PDE4B1 AND PDE4B2). RC TISSUE=Brain; 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B3), CATALYTIC ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=9371714; DOI=10.1042/bj3280549; RA Huston E., Lumb S., Russell A., Catterall C., Ross A.H., Steele M.R., RA Bolger G.B., Perry M.J., Owens R.J., Houslay M.D.; RT "Molecular cloning and transient expression in COS7 cells of a novel human RT PDE4B cAMP-specific phosphodiesterase, HSPDE4B3."; RL Biochem. J. 328:549-558(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B2). RC TISSUE=Brain; RX PubMed=8384210; DOI=10.1016/s0021-9258(18)53275-0; RA McLaughlin M.M., Cieslinski L.B., Burman M., Torphy T.J., Livi G.P.; RT "A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human RT brain. Cloning and expression of cDNA, biochemical characterization of RT recombinant protein, and tissue distribution of mRNA."; RL J. Biol. Chem. 268:6470-6476(1993). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PDE4B5), TISSUE SPECIFICITY (ISOFORM RP PDE4B5), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM RP PDE4B5), ACTIVITY REGULATION, SUBCELLULAR LOCATION (ISOFORM PDE4B5), AND RP INTERACTION WITH DISC1 (ISOFORM PDE4B5). RX PubMed=17519386; DOI=10.1124/jpet.107.122218; RA Cheung Y.F., Kan Z., Garrett-Engele P., Gall I., Murdoch H., Baillie G.S., RA Camargo L.M., Johnson J.M., Houslay M.D., Castle J.C.; RT "PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 RT variant whose isoform-specifying N-terminal region is identical to that of RT cAMP phosphodiesterase-4D6 (PDE4D6)."; RL J. Pharmacol. Exp. Ther. 322:600-609(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS PDE4B1; PDE4B3 AND RP PDE4B5). RC TISSUE=Hippocampus, and Thalamus; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PDE4B1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] {ECO:0007744|PDB:1F0J} RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 324-700 IN COMPLEX WITH ZINC AND RP MAGNESIUM, FUNCTION, AND COFACTOR. RX PubMed=10846163; DOI=10.1126/science.288.5472.1822; RA Xu R.X., Hassell A.M., Vanderwall D., Lambert M.H., Holmes W.D., RA Luther M.A., Rocque W.J., Milburn M.V., Zhao Y., Ke H., Nolte R.T.; RT "Atomic structure of PDE4: insights into phosphodiesterase mechanism and RT specificity."; RL Science 288:1822-1825(2000). RN [11] {ECO:0007744|PDB:1RO6, ECO:0007744|PDB:1RO9, ECO:0007744|PDB:1ROR} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 324-700 IN COMPLEX WITH AMP; RP ZINC; MANGANESE; MAGNESIUM AND THE INHIBITOR ROLIPRAM, FUNCTION, COFACTOR, RP AND ACTIVE SITE. RX PubMed=15003452; DOI=10.1016/j.jmb.2004.01.040; RA Xu R.X., Rocque W.J., Lambert M.H., Vanderwall D.E., Luther M.A., RA Nolte R.T.; RT "Crystal structures of the catalytic domain of phosphodiesterase 4B RT complexed with AMP, 8-Br-AMP, and rolipram."; RL J. Mol. Biol. 337:355-365(2004). RN [12] {ECO:0007744|PDB:1TB5} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 324-700 IN COMPLEX WITH AMP; ZINC RP AND MAGNESIUM, MUTAGENESIS OF 567-ASN--TYR-575; ASN-567; TYR-575 AND RP TYR-652, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15260978; DOI=10.1016/j.molcel.2004.07.005; RA Zhang K.Y.J., Card G.L., Suzuki Y., Artis D.R., Fong D., Gillette S., RA Hsieh D., Neiman J., West B.L., Zhang C., Milburn M.V., Kim S.-H., RA Schlessinger J., Bollag G.; RT "A glutamine switch mechanism for nucleotide selectivity by RT phosphodiesterases."; RL Mol. Cell 15:279-286(2004). RN [13] {ECO:0007744|PDB:1XLX, ECO:0007744|PDB:1XLZ, ECO:0007744|PDB:1XM4, ECO:0007744|PDB:1XM6, ECO:0007744|PDB:1XMU, ECO:0007744|PDB:1XMY, ECO:0007744|PDB:1XN0, ECO:0007744|PDB:1XOS, ECO:0007744|PDB:1XOT} RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 324-700 IN COMPLEX WITH ZINC; RP MAGNESIUM AND INHIBITORS. RX PubMed=15576036; DOI=10.1016/j.str.2004.10.004; RA Card G.L., England B.P., Suzuki Y., Fong D., Powell B., Lee B., Luu C., RA Tabrizizad M., Gillette S., Ibrahim P.N., Artis D.R., Bollag G., RA Milburn M.V., Kim S.-H., Schlessinger J., Zhang K.Y.J.; RT "Structural basis for the activity of drugs that inhibit RT phosphodiesterases."; RL Structure 12:2233-2247(2004). RN [14] {ECO:0007744|PDB:1Y2H, ECO:0007744|PDB:1Y2J} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 324-700 IN COMPLEX WITH ZINC; RP MAGNESIUM AND INHIBITORS. RX PubMed=15685167; DOI=10.1038/nbt1059; RA Card G.L., Blasdel L., England B.P., Zhang C., Suzuki Y., Gillette S., RA Fong D., Ibrahim P.N., Artis D.R., Bollag G., Milburn M.V., Kim S.-H., RA Schlessinger J., Zhang K.Y.J.; RT "A family of phosphodiesterase inhibitors discovered by cocrystallography RT and scaffold-based drug design."; RL Nat. Biotechnol. 23:201-207(2005). RN [15] {ECO:0007744|PDB:2QYL} RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 324-659 IN COMPLEX WITH ZINC AND RP THE INHIBITOR NVP. 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). RN [16] {ECO:0007744|PDB:3D3P} RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 324-675 IN COMPLEX WITH ZINC; RP MAGNESIUM AND INHIBITOR. RX PubMed=18539455; DOI=10.1016/j.bmcl.2008.05.052; RA Hamblin J.N., Angell T.D.R., Ballantine S.P., Cook C.M., Cooper A.W.J., RA Dawson J., Delves C.J., Jones P.S., Lindvall M., Lucas F.S., Mitchell C.J., RA Neu M.Y., Ranshaw L.E., Solanke Y.E., Somers D.O., Wiseman J.O.; RT "Pyrazolopyridines as a novel structural class of potent and selective PDE4 RT inhibitors."; RL Bioorg. Med. Chem. Lett. 18:4237-4241(2008). CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key CC regulator of many important physiological processes (PubMed:15260978). CC May be involved in mediating central nervous system effects of CC therapeutic agents ranging from antidepressants to antiasthmatic and CC anti-inflammatory agents. {ECO:0000269|PubMed:10846163, CC ECO:0000269|PubMed:15003452, ECO:0000269|PubMed:15260978}. 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:15260978, ECO:0000269|PubMed:17519386, CC ECO:0000269|PubMed:8392015, ECO:0000269|PubMed:9371714}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278; CC Evidence={ECO:0000305|PubMed:15260978, ECO:0000305|PubMed:17519386, CC ECO:0000305|PubMed:8392015, ECO:0000305|PubMed:9371714}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:10846163, ECO:0000269|PubMed:15003452}; CC Note=Binds 2 divalent metal cations per subunit. Site 1 may CC preferentially bind zinc ions. {ECO:0000269|PubMed:10846163, CC ECO:0000269|PubMed:15003452}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:10846163, ECO:0000269|PubMed:15003452}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000269|PubMed:15003452}; CC Note=Binds 2 divalent metal cations per subunit. Site 2 has a CC preference for magnesium and/or manganese ions. CC {ECO:0000269|PubMed:10846163, ECO:0000269|PubMed:15003452}; CC -!- ACTIVITY REGULATION: Inhibited by rolipram. CC {ECO:0000269|PubMed:17519386}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform PDE4B2]: CC Kinetic parameters: CC KM=15 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:8392015}; CC KM=2.6 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:8392015}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform PDE4B1]: CC Kinetic parameters: CC KM=2 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:8392015}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform PDE4B3]: CC Kinetic parameters: CC KM=1.5 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:8392015}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform PDE4B5]: CC Kinetic parameters: CC KM=5.8 uM for 3',5'-cyclic AMP {ECO:0000269|PubMed:17519386}; CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from CC 3',5'-cyclic AMP: step 1/1. {ECO:0000305|PubMed:15260978, CC ECO:0000305|PubMed:8392015, ECO:0000305|PubMed:9371714}. CC -!- SUBUNIT: [Isoform PDE4B5]: Interacts with DISC1. CC {ECO:0000269|PubMed:17519386}. CC -!- SUBCELLULAR LOCATION: [Isoform PDE4B5]: Cytoplasm CC {ECO:0000269|PubMed:17519386}. Cell membrane CC {ECO:0000269|PubMed:17519386}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=PDE4B1 {ECO:0000303|PubMed:9371714}; CC IsoId=Q07343-1; Sequence=Displayed; CC Name=PDE4B2 {ECO:0000303|PubMed:9371714}; CC IsoId=Q07343-2; Sequence=VSP_004572; CC Name=PDE4B3 {ECO:0000303|PubMed:9371714}; CC IsoId=Q07343-3; Sequence=VSP_004571; CC Name=PDE4B5 {ECO:0000303|PubMed:17519386}; CC IsoId=Q07343-4; Sequence=VSP_047723, VSP_047724; CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, lung and skeletal muscle CC (PubMed:17519386). Expressed in white blood cells (PubMed:8392015). CC {ECO:0000269|PubMed:17519386, ECO:0000269|PubMed:8392015}. CC -!- TISSUE SPECIFICITY: [Isoform PDE4B5]: Brain-specific isoform. CC {ECO:0000269|PubMed:17519386}. CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. CC PDE4 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35643.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; L12686; AAA35643.1; ALT_INIT; mRNA. DR EMBL; L20966; AAA03589.1; -; mRNA. DR EMBL; L20971; AAA03593.1; -; mRNA. DR EMBL; U85048; AAB96381.1; -; mRNA. DR EMBL; M97515; AAA36426.1; -; mRNA. DR EMBL; EF595686; ABQ85407.1; -; mRNA. DR EMBL; AK289969; BAF82658.1; -; mRNA. DR EMBL; AK290006; BAF82695.1; -; mRNA. DR EMBL; AK290206; BAF82895.1; -; mRNA. DR EMBL; AL592285; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL357273; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL109926; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL359701; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL513493; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590783; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591487; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX06524.1; -; Genomic_DNA. DR EMBL; BC101480; AAI01481.1; -; mRNA. DR EMBL; BC105040; AAI05041.1; -; mRNA. DR CCDS; CCDS30742.1; -. [Q07343-3] DR CCDS; CCDS30743.1; -. [Q07343-2] DR CCDS; CCDS632.1; -. [Q07343-1] DR CCDS; CCDS72802.1; -. [Q07343-4] DR PIR; I61354; I61354. DR RefSeq; NP_001032416.1; NM_001037339.2. [Q07343-2] DR RefSeq; NP_001032417.1; NM_001037340.2. [Q07343-3] DR RefSeq; NP_001032418.1; NM_001037341.1. [Q07343-1] DR RefSeq; NP_001284369.1; NM_001297440.1. DR RefSeq; NP_001284370.1; NM_001297441.1. DR RefSeq; NP_001284371.1; NM_001297442.1. [Q07343-4] DR RefSeq; NP_002591.2; NM_002600.3. [Q07343-1] DR PDB; 1F0J; X-ray; 1.77 A; A/B=324-700. DR PDB; 1RO6; X-ray; 2.00 A; A/B=324-700. DR PDB; 1RO9; X-ray; 2.13 A; A/B=324-700. DR PDB; 1ROR; X-ray; 2.00 A; A/B=324-700. DR PDB; 1TB5; X-ray; 2.15 A; A/B=324-700. DR PDB; 1XLX; X-ray; 2.19 A; A/B=324-700. DR PDB; 1XLZ; X-ray; 2.06 A; A/B=324-700. DR PDB; 1XM4; X-ray; 2.31 A; A/B=324-700. DR PDB; 1XM6; X-ray; 1.92 A; A/B=324-700. DR PDB; 1XMU; X-ray; 2.30 A; A/B=324-700. DR PDB; 1XMY; X-ray; 2.40 A; A/B=324-700. DR PDB; 1XN0; X-ray; 2.31 A; A/B=324-700. DR PDB; 1XOS; X-ray; 2.28 A; A=324-700. DR PDB; 1XOT; X-ray; 2.34 A; A/B=324-700. DR PDB; 1Y2H; X-ray; 2.40 A; A/B=324-700. DR PDB; 1Y2J; X-ray; 2.55 A; A/B=324-700. DR PDB; 2CHM; X-ray; 1.60 A; A=450-475. DR PDB; 2QYL; X-ray; 1.95 A; A=324-659. DR PDB; 3D3P; X-ray; 1.75 A; A=324-675. DR PDB; 3FRG; X-ray; 1.70 A; A=324-675. DR PDB; 3G45; X-ray; 2.63 A; A/B=241-289, A/B=305-659. DR PDB; 3GWT; X-ray; 1.75 A; A=324-675. DR PDB; 3HC8; X-ray; 1.79 A; A=451-474. DR PDB; 3HDZ; X-ray; 1.80 A; A=451-474. DR PDB; 3HMV; X-ray; 2.23 A; A/B=324-700. DR PDB; 3KKT; X-ray; 2.48 A; A/B=324-700. DR PDB; 3LY2; X-ray; 2.60 A; A/B/C/D/E/F/G/H=324-659. DR PDB; 3O0J; X-ray; 1.95 A; A=334-656. DR PDB; 3O56; X-ray; 2.42 A; A=324-675. DR PDB; 3O57; X-ray; 2.00 A; A=324-675. DR PDB; 3W5E; X-ray; 2.30 A; A/B=324-700. DR PDB; 3WD9; X-ray; 2.50 A; A/B=324-700. DR PDB; 4KP6; X-ray; 1.50 A; A=324-659. DR PDB; 4MYQ; X-ray; 1.90 A; A=324-691. DR PDB; 4NW7; X-ray; 2.15 A; A=324-691. DR PDB; 4WZI; X-ray; 2.58 A; A/B=122-736. DR PDB; 4X0F; X-ray; 3.22 A; A/B=122-736. DR PDB; 5K6J; X-ray; 1.86 A; A=334-656. DR PDB; 5LAQ; X-ray; 2.40 A; A=241-289, A=305-659. DR PDB; 5OHJ; X-ray; 1.60 A; A/B=241-659. DR PDB; 6BOJ; X-ray; 1.70 A; A/B/C/D=663-673. DR PDB; 8OEG; X-ray; 1.89 A; A=241-659. DR PDBsum; 1F0J; -. DR PDBsum; 1RO6; -. DR PDBsum; 1RO9; -. DR PDBsum; 1ROR; -. DR PDBsum; 1TB5; -. DR PDBsum; 1XLX; -. DR PDBsum; 1XLZ; -. DR PDBsum; 1XM4; -. DR PDBsum; 1XM6; -. DR PDBsum; 1XMU; -. DR PDBsum; 1XMY; -. DR PDBsum; 1XN0; -. DR PDBsum; 1XOS; -. DR PDBsum; 1XOT; -. DR PDBsum; 1Y2H; -. DR PDBsum; 1Y2J; -. DR PDBsum; 2CHM; -. DR PDBsum; 2QYL; -. DR PDBsum; 3D3P; -. DR PDBsum; 3FRG; -. DR PDBsum; 3G45; -. DR PDBsum; 3GWT; -. DR PDBsum; 3HC8; -. DR PDBsum; 3HDZ; -. DR PDBsum; 3HMV; -. DR PDBsum; 3KKT; -. DR PDBsum; 3LY2; -. DR PDBsum; 3O0J; -. DR PDBsum; 3O56; -. DR PDBsum; 3O57; -. DR PDBsum; 3W5E; -. DR PDBsum; 3WD9; -. DR PDBsum; 4KP6; -. DR PDBsum; 4MYQ; -. DR PDBsum; 4NW7; -. DR PDBsum; 4WZI; -. DR PDBsum; 4X0F; -. DR PDBsum; 5K6J; -. DR PDBsum; 5LAQ; -. DR PDBsum; 5OHJ; -. DR PDBsum; 6BOJ; -. DR PDBsum; 8OEG; -. DR AlphaFoldDB; Q07343; -. DR SMR; Q07343; -. DR BioGRID; 111168; 65. DR CORUM; Q07343; -. DR ELM; Q07343; -. DR IntAct; Q07343; 7. DR STRING; 9606.ENSP00000342637; -. DR BindingDB; Q07343; -. DR ChEMBL; CHEMBL275; -. DR DrugBank; DB04149; (R)-Rolipram. DR DrugBank; DB03606; (S)-Rolipram. DR DrugBank; DB03807; 1-(2-Chlorophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester. DR DrugBank; DB06909; 1-ethyl-N-(phenylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide. DR DrugBank; DB01959; 3,5-Dimethyl-1-(3-Nitrophenyl)-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester. DR DrugBank; DB08299; 4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid. DR DrugBank; DB03349; 8-Bromo-Adenosine-5'-Monophosphate. DR DrugBank; DB00131; Adenosine phosphate. DR DrugBank; DB01427; Amrinone. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB03849; Cilomilast. DR DrugBank; DB05219; Crisaborole. DR DrugBank; DB01647; Daxalipram. DR DrugBank; DB00651; Dyphylline. DR DrugBank; DB00824; Enprofylline. DR DrugBank; DB02660; Filaminast. DR DrugBank; DB05266; Ibudilast. DR DrugBank; DB01088; Iloprost. DR DrugBank; DB01113; Papaverine. DR DrugBank; DB01791; Piclamilast. DR DrugBank; DB01656; Roflumilast. DR DrugBank; DB01954; Rolipram. DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine. DR DrugBank; DB01412; Theobromine. DR DrugBank; DB00277; Theophylline. DR DrugBank; DB09283; Trapidil. DR DrugCentral; Q07343; -. DR GuidetoPHARMACOLOGY; 1301; -. DR GlyGen; Q07343; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q07343; -. DR PhosphoSitePlus; Q07343; -. DR SwissPalm; Q07343; -. DR BioMuta; PDE4B; -. DR DMDM; 729163; -. DR EPD; Q07343; -. DR jPOST; Q07343; -. DR MassIVE; Q07343; -. DR MaxQB; Q07343; -. DR PaxDb; 9606-ENSP00000332116; -. DR PeptideAtlas; Q07343; -. DR ProteomicsDB; 58512; -. [Q07343-1] DR ProteomicsDB; 58513; -. [Q07343-2] DR ProteomicsDB; 58514; -. [Q07343-3] DR ProteomicsDB; 65061; -. DR ProteomicsDB; 768; -. DR Pumba; Q07343; -. DR Antibodypedia; 1172; 571 antibodies from 35 providers. DR DNASU; 5142; -. DR Ensembl; ENST00000329654.8; ENSP00000332116.4; ENSG00000184588.18. [Q07343-1] DR Ensembl; ENST00000341517.9; ENSP00000342637.4; ENSG00000184588.18. [Q07343-1] DR Ensembl; ENST00000371045.9; ENSP00000360084.5; ENSG00000184588.18. [Q07343-2] DR Ensembl; ENST00000423207.6; ENSP00000392947.2; ENSG00000184588.18. [Q07343-3] DR Ensembl; ENST00000480109.2; ENSP00000432592.1; ENSG00000184588.18. [Q07343-4] DR GeneID; 5142; -. DR KEGG; hsa:5142; -. DR MANE-Select; ENST00000341517.9; ENSP00000342637.4; NM_002600.4; NP_002591.2. DR UCSC; uc001dcp.4; human. [Q07343-1] DR AGR; HGNC:8781; -. DR CTD; 5142; -. DR DisGeNET; 5142; -. DR GeneCards; PDE4B; -. DR HGNC; HGNC:8781; PDE4B. DR HPA; ENSG00000184588; Tissue enhanced (bone). DR MIM; 600127; gene. DR neXtProt; NX_Q07343; -. DR OpenTargets; ENSG00000184588; -. DR PharmGKB; PA33129; -. DR VEuPathDB; HostDB:ENSG00000184588; -. DR eggNOG; KOG3689; Eukaryota. DR GeneTree; ENSGT00940000155190; -. DR HOGENOM; CLU_005940_5_3_1; -. DR InParanoid; Q07343; -. DR OMA; MMKERCG; -. DR OrthoDB; 240889at2759; -. DR PhylomeDB; Q07343; -. DR TreeFam; TF314638; -. DR BRENDA; 3.1.4.53; 2681. DR PathwayCommons; Q07343; -. DR Reactome; R-HSA-180024; DARPP-32 events. [Q07343-3] DR SignaLink; Q07343; -. DR SIGNOR; Q07343; -. DR UniPathway; UPA00762; UER00747. DR BioGRID-ORCS; 5142; 13 hits in 1168 CRISPR screens. DR ChiTaRS; PDE4B; human. DR EvolutionaryTrace; Q07343; -. DR GeneWiki; PDE4B; -. DR GenomeRNAi; 5142; -. DR Pharos; Q07343; Tclin. DR PRO; PR:Q07343; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q07343; Protein. DR Bgee; ENSG00000184588; Expressed in corpus callosum and 204 other cell types or tissues. DR ExpressionAtlas; Q07343; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0060076; C:excitatory synapse; IEA:Ensembl. DR GO; GO:0000930; C:gamma-tubulin complex; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl. DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISS:BHF-UCL. DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL. DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IDA:BHF-UCL. DR GO; GO:0005246; F:calcium channel regulator activity; ISS:BHF-UCL. DR GO; GO:0030552; F:cAMP binding; IGI:BHF-UCL. DR GO; GO:0043015; F:gamma-tubulin binding; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0044325; F:transmembrane transporter binding; ISS:BHF-UCL. DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0071872; P:cellular response to epinephrine stimulus; ISS:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:BHF-UCL. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS:BHF-UCL. DR GO; GO:0050900; P:leukocyte migration; ISS:BHF-UCL. DR GO; GO:0071878; P:negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:1901898; P:negative regulation of relaxation of cardiac muscle; ISS:BHF-UCL. DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:BHF-UCL. DR GO; GO:0001780; P:neutrophil homeostasis; ISS:BHF-UCL. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:BHF-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; IMP:BHF-UCL. DR GO; GO:1902514; P:regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISS:BHF-UCL. DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:BHF-UCL. 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:SF108; CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4B; 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; Q07343; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; cAMP; Cell membrane; Cytoplasm; KW Hydrolase; Membrane; Metal-binding; Phosphoprotein; Reference proteome; KW Zinc. FT CHAIN 1..736 FT /note="3',5'-cyclic-AMP phosphodiesterase 4B" FT /id="PRO_0000198809" FT DOMAIN 330..659 FT /note="PDEase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192" FT REGION 51..78 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 189..209 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 282..301 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 685..736 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 716..736 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 406 FT /note="Proton donor" FT /evidence="ECO:0000305|PubMed:15003452, FT ECO:0007744|PDB:1ROR" FT BINDING 406 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:Q08499" FT BINDING 406 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0000269|PubMed:15260978, ECO:0007744|PDB:1ROR, FT ECO:0007744|PDB:1TB5" FT BINDING 410 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0007744|PDB:1ROR" FT BINDING 410 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, FT ECO:0000269|PubMed:15685167, ECO:0000269|PubMed:17727341, FT ECO:0000269|PubMed:18539455, ECO:0007744|PDB:1RO6, FT ECO:0007744|PDB:1RO9, ECO:0007744|PDB:1ROR, FT ECO:0007744|PDB:1TB5, ECO:0007744|PDB:1XLX, FT ECO:0007744|PDB:1XLZ, ECO:0007744|PDB:1XM4, FT ECO:0007744|PDB:1XM6, ECO:0007744|PDB:1XMU, FT ECO:0007744|PDB:1XMY, ECO:0007744|PDB:1XN0, FT ECO:0007744|PDB:1XOS, ECO:0007744|PDB:1XOT, FT ECO:0007744|PDB:1Y2H, ECO:0007744|PDB:1Y2J, FT ECO:0007744|PDB:2QYL, ECO:0007744|PDB:3D3P" FT BINDING 446 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:10846163, FT ECO:0000269|PubMed:15003452, ECO:0000269|PubMed:15576036, FT ECO:0000269|PubMed:15685167, ECO:0000269|PubMed:17727341, FT ECO:0000269|PubMed:18539455, ECO:0007744|PDB:1F0J, FT ECO:0007744|PDB:1RO6, ECO:0007744|PDB:1RO9, FT ECO:0007744|PDB:1ROR, ECO:0007744|PDB:1XLX, FT ECO:0007744|PDB:1XLZ, ECO:0007744|PDB:1XM4, FT ECO:0007744|PDB:1XM6, ECO:0007744|PDB:1XMU, FT ECO:0007744|PDB:1XMY, ECO:0007744|PDB:1XN0, FT ECO:0007744|PDB:1XOS, ECO:0007744|PDB:1XOT, FT ECO:0007744|PDB:1Y2H, ECO:0007744|PDB:1Y2J, FT ECO:0007744|PDB:2QYL, ECO:0007744|PDB:3D3P" FT BINDING 447 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0000269|PubMed:15260978, ECO:0007744|PDB:1ROR, FT ECO:0007744|PDB:1TB5" FT BINDING 447 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:10846163, FT ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, FT ECO:0000269|PubMed:15685167, ECO:0000269|PubMed:18539455, FT ECO:0007744|PDB:1F0J, ECO:0007744|PDB:1TB5, FT ECO:0007744|PDB:1XLX, ECO:0007744|PDB:1XLZ, FT ECO:0007744|PDB:1XM4, ECO:0007744|PDB:1XM6, FT ECO:0007744|PDB:1XMU, ECO:0007744|PDB:1XMY, FT ECO:0007744|PDB:1XN0, ECO:0007744|PDB:1XOS, FT ECO:0007744|PDB:1XOT, ECO:0007744|PDB:1Y2H, FT ECO:0007744|PDB:1Y2J, ECO:0007744|PDB:3D3P" FT BINDING 447 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0007744|PDB:1RO6" FT BINDING 447 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:10846163, FT ECO:0000269|PubMed:15003452, ECO:0000269|PubMed:15260978, FT ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:15685167, FT ECO:0000269|PubMed:17727341, ECO:0000269|PubMed:18539455, FT ECO:0007744|PDB:1F0J, ECO:0007744|PDB:1RO6, FT ECO:0007744|PDB:1RO9, ECO:0007744|PDB:1ROR, FT ECO:0007744|PDB:1TB5, ECO:0007744|PDB:1XLX, FT ECO:0007744|PDB:1XLZ, ECO:0007744|PDB:1XM4, FT ECO:0007744|PDB:1XM6, ECO:0007744|PDB:1XMU, FT ECO:0007744|PDB:1XMY, ECO:0007744|PDB:1XN0, FT ECO:0007744|PDB:1XOS, ECO:0007744|PDB:1XOT, FT ECO:0007744|PDB:1Y2H, ECO:0007744|PDB:1Y2J, FT ECO:0007744|PDB:2QYL, ECO:0007744|PDB:3D3P" FT BINDING 447 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0007744|PDB:1ROR" FT BINDING 564 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0007744|PDB:1ROR" FT BINDING 564 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:10846163, FT ECO:0000269|PubMed:15003452, ECO:0000269|PubMed:15260978, FT ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:15685167, FT ECO:0000269|PubMed:18539455, ECO:0007744|PDB:1F0J, FT ECO:0007744|PDB:1RO6, ECO:0007744|PDB:1RO9, FT ECO:0007744|PDB:1ROR, ECO:0007744|PDB:1TB5, FT ECO:0007744|PDB:1XLX, ECO:0007744|PDB:1XLZ, FT ECO:0007744|PDB:1XM4, ECO:0007744|PDB:1XM6, FT ECO:0007744|PDB:1XMU, ECO:0007744|PDB:1XMY, FT ECO:0007744|PDB:1XN0, ECO:0007744|PDB:1XOS, FT ECO:0007744|PDB:1XOT, ECO:0007744|PDB:1Y2H, FT ECO:0007744|PDB:1Y2J, ECO:0007744|PDB:3D3P" FT BINDING 615 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:Q08499" FT BINDING 615 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000269|PubMed:15003452, FT ECO:0000269|PubMed:15260978, ECO:0007744|PDB:1ROR, FT ECO:0007744|PDB:1TB5" FT BINDING 618 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:Q08499" FT BINDING 618 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000305|PubMed:15003452, FT ECO:0000305|PubMed:15260978, ECO:0007744|PDB:1ROR, FT ECO:0007744|PDB:1TB5" FT MOD_RES 290 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14646" FT MOD_RES 659 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14646" FT MOD_RES 661 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14646" FT VAR_SEQ 1..211 FT /note="MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQL FT PPLSQRQSERARTPEGDGISRPTTLPLTTLPSIAITTVSQECFDVENGPSPGRSPLDPQ FT ASSSAGLVLHATFPGHSQRRESFLYRSDSDYDLSPKAMSRNSSLPSEQHGDDLIVTPFA FT QVLASLRSVRNNFTILTNLHGTSNKRSPAASQPPVSRVNPQ -> MKEHGGTFSSTGIS FT GGSGDSAMDSLQPLQPNYMPVCLFA (in isoform PDE4B2)" FT /evidence="ECO:0000303|PubMed:8384210, FT ECO:0000303|PubMed:8392015, ECO:0000303|PubMed:8413254" FT /id="VSP_004572" FT VAR_SEQ 1..93 FT /note="MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQL FT PPLSQRQSERARTPEGDGISRPTTLPLTTLPSIAITTVSQE -> MTAKDSSKELTASE FT PEVCIKTFKEQMHLELELPRLPGNRPTSPKISPRSSPRNSPCFFRKLLVNKSIRQRRRF FT TVAHT (in isoform PDE4B3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9371714" FT /id="VSP_004571" FT VAR_SEQ 1..15 FT /note="MKKSRSVMTVMADDN -> MPEANYLLSVSWGYI (in isoform FT PDE4B5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17519386" FT /id="VSP_047723" FT VAR_SEQ 16..248 FT /note="Missing (in isoform PDE4B5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17519386" FT /id="VSP_047724" FT VARIANT 703 FT /note="S -> C (in dbSNP:rs2227297)" FT /id="VAR_034373" FT MUTAGEN 567..575 FT /note="NPTKSLELY->HPTKSLELH: Increases substrate FT selectivity for cGMP." FT /evidence="ECO:0000269|PubMed:15260978" FT MUTAGEN 567 FT /note="N->A: Changes substrate selectivity from FT cAMP-specific to dual cAMP and cGMP binding and hydrolysis; FT when associated with Q-575 and W-652." FT /evidence="ECO:0000269|PubMed:15260978" FT MUTAGEN 575 FT /note="Y->Q: Changes substrate selectivity from FT cAMP-specific to dual cAMP and cGMP binding and hydrolysis; FT when associated with A-567 and W-652." FT /evidence="ECO:0000269|PubMed:15260978" FT MUTAGEN 652 FT /note="Y->W: Changes substrate selectivity from FT cAMP-specific to dual cAMP and cGMP binding and hydrolysis; FT when associated with A-567 and Q-575." FT /evidence="ECO:0000269|PubMed:15260978" FT HELIX 168..183 FT /evidence="ECO:0007829|PDB:4WZI" FT HELIX 217..235 FT /evidence="ECO:0007829|PDB:4WZI" FT HELIX 239..264 FT /evidence="ECO:0007829|PDB:4WZI" FT HELIX 266..279 FT /evidence="ECO:0007829|PDB:4WZI" FT HELIX 324..327 FT /evidence="ECO:0007829|PDB:5OHJ" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:5OHJ" FT TURN 332..334 FT /evidence="ECO:0007829|PDB:1XMU" FT HELIX 335..342 FT /evidence="ECO:0007829|PDB:4KP6" FT TURN 343..346 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 352..358 FT /evidence="ECO:0007829|PDB:4KP6" FT TURN 359..361 FT /evidence="ECO:0007829|PDB:1RO6" FT HELIX 363..374 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 377..380 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 385..397 FT /evidence="ECO:0007829|PDB:4KP6" FT STRAND 403..407 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 408..422 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 425..427 FT /evidence="ECO:0007829|PDB:4KP6" FT TURN 428..430 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 433..445 FT /evidence="ECO:0007829|PDB:4KP6" FT TURN 446..449 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 455..460 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 464..468 FT /evidence="ECO:0007829|PDB:4KP6" FT TURN 469..471 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 474..486 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 490..492 FT /evidence="ECO:0007829|PDB:3FRG" FT TURN 494..497 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 500..515 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 519..521 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 522..534 FT /evidence="ECO:0007829|PDB:4KP6" FT STRAND 542..544 FT /evidence="ECO:0007829|PDB:8OEG" FT HELIX 549..564 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 567..569 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 572..595 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 602..604 FT /evidence="ECO:0007829|PDB:3FRG" FT TURN 606..608 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 611..621 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 623..633 FT /evidence="ECO:0007829|PDB:4KP6" FT TURN 634..638 FT /evidence="ECO:0007829|PDB:4KP6" FT HELIX 639..654 FT /evidence="ECO:0007829|PDB:4KP6" FT STRAND 656..658 FT /evidence="ECO:0007829|PDB:1RO6" FT STRAND 659..662 FT /evidence="ECO:0007829|PDB:3KKT" FT HELIX 664..666 FT /evidence="ECO:0007829|PDB:3KKT" FT HELIX 671..677 FT /evidence="ECO:0007829|PDB:1F0J" SQ SEQUENCE 736 AA; 83343 MW; 208FCE9CD40EF5EB CRC64; MKKSRSVMTV MADDNVKDYF ECSLSKSYSS SSNTLGIDLW RGRRCCSGNL QLPPLSQRQS ERARTPEGDG ISRPTTLPLT TLPSIAITTV SQECFDVENG PSPGRSPLDP QASSSAGLVL HATFPGHSQR RESFLYRSDS DYDLSPKAMS RNSSLPSEQH GDDLIVTPFA QVLASLRSVR NNFTILTNLH GTSNKRSPAA SQPPVSRVNP QEESYQKLAM ETLEELDWCL DQLETIQTYR SVSEMASNKF KRMLNRELTH LSEMSRSGNQ VSEYISNTFL DKQNDVEIPS PTQKDREKKK KQQLMTQISG VKKLMHSSSL NNTSISRFGV NTENEDHLAK ELEDLNKWGL NIFNVAGYSH NRPLTCIMYA IFQERDLLKT FRISSDTFIT YMMTLEDHYH SDVAYHNSLH AADVAQSTHV LLSTPALDAV FTDLEILAAI FAAAIHDVDH PGVSNQFLIN TNSELALMYN DESVLENHHL AVGFKLLQEE HCDIFMNLTK KQRQTLRKMV IDMVLATDMS KHMSLLADLK TMVETKKVTS SGVLLLDNYT DRIQVLRNMV HCADLSNPTK SLELYRQWTD RIMEEFFQQG DKERERGMEI SPMCDKHTAS VEKSQVGFID YIVHPLWETW ADLVQPDAQD ILDTLEDNRN WYQSMIPQSP SPPLDEQNRD CQGLMEKFQF ELTLDEEDSE GPEKEGEGHS YFSSTKTLCV IDPENRDSLG ETDIDIATED KSPVDT //