PDE4_DICDI
ID PDE4_DICDI Reviewed; 1039 AA.
AC Q86H13; Q54HY3; Q54HY4;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=cAMP-specific 3',5'-cAMP phosphodiesterase 4;
DE EC=3.1.4.53 {ECO:0000269|PubMed:16644729};
DE AltName: Full=Phosphodiesterase 4;
DE Short=DdPDE4 {ECO:0000303|PubMed:16644729};
DE Flags: Precursor;
GN Name=Pde4; ORFNames=DDB_G0289121;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 283-1039, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION, DEVELOPMENTAL STAGE,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16644729; DOI=10.1074/jbc.m600040200;
RA Bader S., Kortholt A., Snippe H., Van Haastert P.J.M.;
RT "DdPDE4, a novel cAMP-specific phosphodiesterase at the surface of
RT dictyostelium cells.";
RL J. Biol. Chem. 281:20018-20026(2006).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=12429832; DOI=10.1091/mbc.e02-05-0302;
RA Bosgraaf L., Russcher H., Snippe H., Bader S., Wind J.,
RA Van Haastert P.J.M.;
RT "Identification and characterization of two unusual cGMP-stimulated
RT phosphodiesterases in dictyostelium.";
RL Mol. Biol. Cell 13:3878-3889(2002).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=17040207; DOI=10.1042/bj20061153;
RA Bader S., Kortholt A., Van Haastert P.J.M.;
RT "Seven Dictyostelium discoideum phosphodiesterases degrade three pools of
RT cAMP and cGMP.";
RL Biochem. J. 402:153-161(2007).
CC -!- FUNCTION: Phosphodiesterase specific for extracellular cAMP. Involved
CC in the degradation of extracellular cAMP specifically during
CC multicellular development. {ECO:0000269|PubMed:16644729}.
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:16644729};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000269|PubMed:16644729};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250};
CC Note=Binds 2 divalent metal cations per subunit. Site 1 may
CC preferentially bind zinc ions, while site 2 has a preference for
CC magnesium and/or manganese ions. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by 3-isobutyl-1-methylxanthine (IBMX).
CC {ECO:0000269|PubMed:16644729}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for cAMP (catalytic domain expressed in vegetative AX2
CC cells) {ECO:0000269|PubMed:16644729};
CC Vmax=4200 pmol/min/mg enzyme with cAMP as substrate
CC {ECO:0000269|PubMed:16644729};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16644729};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Low expression during growth and cell aggregation
CC (up to 6 hours), maximally increases after 9 hours of starvation,
CC during the mound stage. Remains expressed at significant levels during
CC the other stages of multicellular development.
CC {ECO:0000269|PubMed:16644729}.
CC -!- DISRUPTION PHENOTYPE: Null cells show a reduction of phosphodiesterase
CC activity on the cell surface. Aggregation speed is similar, but from
CC the mound stage until fruiting body formation it is slower. Aggregates
CC largely remain as mounds; after 15 hours (compared to slugs in wild
CC type cells), after 20 hours (compared to culmination state in wild type
CC cells) and after 27 hours (compared to completion of fruiting body
CC formation in wild type cells). Thus, slug formation and culmination
CC appear to be affected. These processes were not only slower but also
CC less slugs and fruiting bodies are formed.
CC {ECO:0000269|PubMed:16644729}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO59486.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAL62868.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=EAL62884.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY211984; AAO59486.1; ALT_INIT; mRNA.
DR EMBL; AAFI02000130; EAL62868.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AAFI02000130; EAL62884.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_636379.1; XM_631287.1.
DR RefSeq; XP_636380.1; XM_631288.1.
DR AlphaFoldDB; Q86H13; -.
DR SMR; Q86H13; -.
DR STRING; 44689.DDB0216197; -.
DR PaxDb; Q86H13; -.
DR PRIDE; Q86H13; -.
DR EnsemblProtists; EAL62868; EAL62868; DDB_G0289121.
DR EnsemblProtists; EAL62884; EAL62884; DDB_G0289153.
DR GeneID; 8626980; -.
DR GeneID; 8626981; -.
DR KEGG; ddi:DDB_G0289121; -.
DR KEGG; ddi:DDB_G0289153; -.
DR dictyBase; DDB_G0289121; pde4.
DR eggNOG; KOG3688; Eukaryota.
DR eggNOG; KOG3689; Eukaryota.
DR InParanoid; Q86H13; -.
DR PhylomeDB; Q86H13; -.
DR BRENDA; 3.1.4.53; 1939.
DR Reactome; R-DDI-180024; DARPP-32 events.
DR Reactome; R-DDI-418555; G alpha (s) signalling events.
DR SABIO-RK; Q86H13; -.
DR PRO; PR:Q86H13; -.
DR Proteomes; UP000002195; Chromosome 5.
DR GO; GO:0005576; C:extracellular region; TAS:dictyBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:dictyBase.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IMP:dictyBase.
DR GO; GO:0004114; F:3',5'-cyclic-nucleotide phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031000; P:response to caffeine; IDA:dictyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0030587; P:sorocarp development; IMP:dictyBase.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 1.10.1300.10; -; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 1: Evidence at protein level;
KW cAMP; cAMP-binding; Cell membrane; Coiled coil; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Nucleotide-binding; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..1039
FT /note="cAMP-specific 3',5'-cAMP phosphodiesterase 4"
FT /id="PRO_0000363970"
FT TOPO_DOM 30..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..256
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 278..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 284..304
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..310
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..356
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 378..1039
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 533..973
FT /note="PDEase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT REGION 40..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 116..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 738..835
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 978..1033
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 384..414
FT /evidence="ECO:0000255"
FT ACT_SITE 609
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 613
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 648
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 649
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 649
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT BINDING 861
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 430
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 500
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 769
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 791
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 795
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 804
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 809
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 823
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 826
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 874
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 944
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1018
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1023
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 284
FT /note="Y -> D (in Ref. 2; AAO59486)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1039 AA; 119447 MW; 29817E88B3B3ADD6 CRC64;
MFNNNNNDKI NNTMMSNNPS GQIINLESID CNSNLSNTTS IKDSNNNNNN NNNNNNNINN
NINKINPNID RKVLDDFNSK SIKIIDNKLN KKNSKKNLYS KEVDDDINKI NLNKKIIPNE
TNSNNSNNNN NNSNNNNNNN NNNNNFNYNN NINSNNNIIN NNNNINNNSN NNNNNNNNNS
ISLYVDTQEK SKKKVNAESL RGPIIFQNFI LYTFFLIVIG TAEGTSWAPE IRVANFVPYC
VMCVVLLEFN RLHKKPLLRI IFPLYTSNIP FAYMCIFSRE ARKYVLISLL FFASCLCIFL
QSGIPDLRKH IVIFCIIFMI NYGCCILFMD WFYIDTTGTK PYRGRILATK IHWGEEATIL
VSMALLGCIF IVLEKFIKSY ARCVAEQHYQ IQCLQKEKEK LQTEINISLK KLDLDTPIEK
IMDILRSMIN TSESENDKKQ LIKVIAVLGS NKLYDPDFKF ETCTDDAEVY SWLQSMLNRE
VGYSNVNNNN NMMMIENNNN NTIINNNLIE PTSPNFSKKL TSSDLIPRIR SMPEITDQGI
QELIINNFLE WDFPVFQLSE ITDGNPLFYM SYFLFSRHKF FEKFKIGIDC FKNFMRKIES
GYDSTNPYHN SIHATDVLHN LNYFIEKSFG KFLTDIELFS MILAAIIHDF KHPGVNNHFQ
INSKSRLALK YNDKSILENY HLHQAFIIMN EPESGILLKL SDSVRKEIRE TIIALVLSTD
MAKHFNLVGR FKSMANSFPT TTNTQQPSSS SSSSSSTTIP TSTITPTPNS TTSTTTTTTT
TTTTTNNNNN NNSNNNSLNN IINNCSSSNG SMGASGADNS NSNNTNNSNS NNQNQCGSSI
FLNSNKKDRL LLMKISIKCA DISNPSKPWN LYTNWSNRVT SEFYKQGDKE KESNMDVSAF
MDRNKPATTK CQINFINIFV APIYEIWSHH FPQFKLCYQN ILSNLSRLEI EQQQQLQLQQ
QQQQQLQQQQ QQQQQIHQQQ QQQLHHHQQQ QQFQHQQHQQ QLQHQHQQQL NNQNQNQNQS
NSNNSNSFGL TQSNYLIVV
