PDE4B_HUMAN
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 03-AUG-2022, entry version 205.
DE RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4B;
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;
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};
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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 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 AlphaFoldDB; Q07343; -.
DR SMR; Q07343; -.
DR BioGRID; 111168; 64.
DR CORUM; Q07343; -.
DR ELM; Q07343; -.
DR IntAct; Q07343; 7.
DR STRING; 9606.ENSP00000332116; -.
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 iPTMnet; Q07343; -.
DR PhosphoSitePlus; Q07343; -.
DR BioMuta; PDE4B; -.
DR DMDM; 729163; -.
DR EPD; Q07343; -.
DR jPOST; Q07343; -.
DR MassIVE; Q07343; -.
DR MaxQB; Q07343; -.
DR PaxDb; Q07343; -.
DR PeptideAtlas; Q07343; -.
DR PRIDE; Q07343; -.
DR ProteomicsDB; 58512; -. [Q07343-1]
DR ProteomicsDB; 58513; -. [Q07343-2]
DR ProteomicsDB; 58514; -. [Q07343-3]
DR ProteomicsDB; 65061; -.
DR ProteomicsDB; 768; -.
DR Antibodypedia; 1172; 513 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 CTD; 5142; -.
DR DisGeNET; 5142; -.
DR GeneCards; PDE4B; -.
DR HGNC; HGNC:8781; PDE4B.
DR HPA; ENSG00000184588; Tissue enhanced (bone marrow, brain).
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 OMA; EQSTHGH; -.
DR OrthoDB; 199083at2759; -.
DR PhylomeDB; Q07343; -.
DR TreeFam; TF314638; -.
DR BRENDA; 3.1.4.53; 2681.
DR PathwayCommons; Q07343; -.
DR Reactome; R-HSA-180024; DARPP-32 events.
DR SignaLink; Q07343; -.
DR SIGNOR; Q07343; -.
DR UniPathway; UPA00762; UER00747.
DR BioGRID-ORCS; 5142; 8 hits in 1079 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 202 other tissues.
DR ExpressionAtlas; Q07343; baseline and differential.
DR Genevisible; Q07343; HS.
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:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
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:0140199; P:negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; IEA:Ensembl.
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:0032729; P:positive regulation of interferon-gamma production; IMP:BHF-UCL.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:BHF-UCL.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; ISS:BHF-UCL.
DR GO; GO:1901841; P:regulation of high voltage-gated calcium channel activity; 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; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR043371; PDE4.
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; PTHR11347:SF108; 1.
DR Pfam; PF18100; PDE4_UCR; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 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="cAMP-specific 3',5'-cyclic 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 cAMP-
FT specific to dual cAMP and cGMP binding and hydrolysis; when
FT associated with Q-575 and W-652."
FT /evidence="ECO:0000269|PubMed:15260978"
FT MUTAGEN 575
FT /note="Y->Q: Changes substrate selectivity from cAMP-
FT specific to dual cAMP and cGMP binding and hydrolysis; when
FT associated with A-567 and W-652."
FT /evidence="ECO:0000269|PubMed:15260978"
FT MUTAGEN 652
FT /note="Y->W: Changes substrate selectivity from cAMP-
FT specific to dual cAMP and cGMP binding and hydrolysis; when
FT 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 540..542
FT /evidence="ECO:0007829|PDB:2QYL"
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
