ID F6R8A4_MONDO Unreviewed; 690 AA.
AC F6R8A4;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 11-DEC-2019, sequence version 3.
DT 27-MAR-2024, entry version 77.
DE RecName: Full=Phosphodiesterase {ECO:0000256|RuleBase:RU363067};
DE EC=3.1.4.- {ECO:0000256|RuleBase:RU363067};
GN Name=PDE4D {ECO:0000313|Ensembl:ENSMODP00000024412.4};
OS Monodelphis domestica (Gray short-tailed opossum).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Didelphimorphia; Didelphidae; Monodelphis.
OX NCBI_TaxID=13616 {ECO:0000313|Ensembl:ENSMODP00000024412.4, ECO:0000313|Proteomes:UP000002280};
RN [1] {ECO:0000313|Ensembl:ENSMODP00000024412.4, ECO:0000313|Proteomes:UP000002280}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=17495919; DOI=10.1038/nature05805;
RA Mikkelsen T.S., Wakefield M.J., Aken B., Amemiya C.T., Chang J.L., Duke S.,
RA Garber M., Gentles A.J., Goodstadt L., Heger A., Jurka J., Kamal M.,
RA Mauceli E., Searle S.M., Sharpe T., Baker M.L., Batzer M.A., Benos P.V.,
RA Belov K., Clamp M., Cook A., Cuff J., Das R., Davidow L., Deakin J.E.,
RA Fazzari M.J., Glass J.L., Grabherr M., Greally J.M., Gu W., Hore T.A.,
RA Huttley G.A., Kleber M., Jirtle R.L., Koina E., Lee J.T., Mahony S.,
RA Marra M.A., Miller R.D., Nicholls R.D., Oda M., Papenfuss A.T., Parra Z.E.,
RA Pollock D.D., Ray D.A., Schein J.E., Speed T.P., Thompson K.,
RA VandeBerg J.L., Wade C.M., Walker J.A., Waters P.D., Webber C.,
RA Weidman J.R., Xie X., Zody M.C., Baldwin J., Abdouelleil A., Abdulkadir J.,
RA Abebe A., Abera B., Abreu J., Acer S.C., Aftuck L., Alexander A., An P.,
RA Anderson E., Anderson S., Arachi H., Azer M., Bachantsang P., Barry A.,
RA Bayul T., Berlin A., Bessette D., Bloom T., Bloom T., Boguslavskiy L.,
RA Bonnet C., Boukhgalter B., Bourzgui I., Brown A., Cahill P., Channer S.,
RA Cheshatsang Y., Chuda L., Citroen M., Collymore A., Cooke P., Costello M.,
RA D'Aco K., Daza R., De Haan G., DeGray S., DeMaso C., Dhargay N., Dooley K.,
RA Dooley E., Doricent M., Dorje P., Dorjee K., Dupes A., Elong R., Falk J.,
RA Farina A., Faro S., Ferguson D., Fisher S., Foley C.D., Franke A.,
RA Friedrich D., Gadbois L., Gearin G., Gearin C.R., Giannoukos G., Goode T.,
RA Graham J., Grandbois E., Grewal S., Gyaltsen K., Hafez N., Hagos B.,
RA Hall J., Henson C., Hollinger A., Honan T., Huard M.D., Hughes L.,
RA Hurhula B., Husby M.E., Kamat A., Kanga B., Kashin S., Khazanovich D.,
RA Kisner P., Lance K., Lara M., Lee W., Lennon N., Letendre F., LeVine R.,
RA Lipovsky A., Liu X., Liu J., Liu S., Lokyitsang T., Lokyitsang Y.,
RA Lubonja R., Lui A., MacDonald P., Magnisalis V., Maru K., Matthews C.,
RA McCusker W., McDonough S., Mehta T., Meldrim J., Meneus L., Mihai O.,
RA Mihalev A., Mihova T., Mittelman R., Mlenga V., Montmayeur A., Mulrain L.,
RA Navidi A., Naylor J., Negash T., Nguyen T., Nguyen N., Nicol R., Norbu C.,
RA Norbu N., Novod N., O'Neill B., Osman S., Markiewicz E., Oyono O.L.,
RA Patti C., Phunkhang P., Pierre F., Priest M., Raghuraman S., Rege F.,
RA Reyes R., Rise C., Rogov P., Ross K., Ryan E., Settipalli S., Shea T.,
RA Sherpa N., Shi L., Shih D., Sparrow T., Spaulding J., Stalker J.,
RA Stange-Thomann N., Stavropoulos S., Stone C., Strader C., Tesfaye S.,
RA Thomson T., Thoulutsang Y., Thoulutsang D., Topham K., Topping I.,
RA Tsamla T., Vassiliev H., Vo A., Wangchuk T., Wangdi T., Weiand M.,
RA Wilkinson J., Wilson A., Yadav S., Young G., Yu Q., Zembek L., Zhong D.,
RA Zimmer A., Zwirko Z., Jaffe D.B., Alvarez P., Brockman W., Butler J.,
RA Chin C., Gnerre S., MacCallum I., Graves J.A., Ponting C.P., Breen M.,
RA Samollow P.B., Lander E.S., Lindblad-Toh K.;
RT "Genome of the marsupial Monodelphis domestica reveals innovation in non-
RT coding sequences.";
RL Nature 447:167-177(2007).
RN [2] {ECO:0000313|Ensembl:ENSMODP00000024412.4}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00033681};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25278;
CC Evidence={ECO:0000256|ARBA:ARBA00033681};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000256|RuleBase:RU363067};
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:0000256|RuleBase:RU363067};
CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from
CC 3',5'-cyclic AMP: step 1/1. {ECO:0000256|ARBA:ARBA00004703}.
CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC PDE4 subfamily. {ECO:0000256|ARBA:ARBA00009517}.
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DR RefSeq; XP_007486423.1; XM_007486361.2.
DR AlphaFoldDB; F6R8A4; -.
DR STRING; 13616.ENSMODP00000024412; -.
DR Ensembl; ENSMODT00000024845.4; ENSMODP00000024412.4; ENSMODG00000019569.4.
DR GeneID; 100032166; -.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000155674; -.
DR HOGENOM; CLU_005940_5_2_1; -.
DR InParanoid; F6R8A4; -.
DR OMA; FNTDEGG; -.
DR OrthoDB; 240889at2759; -.
DR TreeFam; TF314638; -.
DR UniPathway; UPA00762; UER00747.
DR Proteomes; UP000002280; Chromosome 3.
DR Bgee; ENSMODG00000019569; Expressed in heart and 17 other cell types or tissues.
DR GO; GO:0034704; C:calcium channel complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IBA:GO_Central.
DR GO; GO:0051117; F:ATPase binding; IBA:GO_Central.
DR GO; GO:0030552; F:cAMP binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0097110; F:scaffold protein binding; IEA:Ensembl.
DR GO; GO:0044325; F:transmembrane transporter binding; IBA:GO_Central.
DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IBA:GO_Central.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of type II interferon production; IEA:Ensembl.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IBA:GO_Central.
DR GO; GO:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl.
DR Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1.
DR InterPro; IPR040844; PDE4_UCR.
DR InterPro; IPR023088; PDEase.
DR InterPro; IPR002073; PDEase_catalytic_dom.
DR InterPro; IPR036971; PDEase_catalytic_dom_sf.
DR InterPro; IPR023174; PDEase_CS.
DR PANTHER; PTHR11347:SF91; CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE 4D; 1.
DR PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR Pfam; PF18100; PDE4_UCR; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SUPFAM; SSF109604; HD-domain/PDEase-like; 1.
DR PROSITE; PS00126; PDEASE_I_1; 1.
DR PROSITE; PS51845; PDEASE_I_2; 1.
PE 3: Inferred from homology;
KW cAMP {ECO:0000256|ARBA:ARBA00023149};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU363067};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR623088-3};
KW Reference proteome {ECO:0000313|Proteomes:UP000002280}.
FT DOMAIN 264..593
FT /note="PDEase"
FT /evidence="ECO:0000259|PROSITE:PS51845"
FT REGION 221..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 588..690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..240
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 603..618
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 636..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..679
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 340
FT /note="Proton donor"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-1"
FT BINDING 340..344
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
FT BINDING 344
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 381
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 498
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
FT BINDING 498
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 549
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
SQ SEQUENCE 690 AA; 78042 MW; FABDD17176E65A9E CRC64;
MAFVSDPLGA SIPRLSPRAK MRMCFSKSYS FDVDNGTSSG RSPLDPMTSP GSGLILQANF
VHSQRRESFL YRSDSDYDLS PKSMSRNSSI ASDIHGDDLI VTPFAQVLAS LRTVRNNFAA
LTNLQDRAPN KRSPMCNQPS INKATITEEA YQKLASETLE ELDWCLDQLE TLQTRHSVSE
MASNKFKRML NRELTHLSEM SRSGNQVSEF ISSTFLDKQH EVEIPSPTQK EKEKKKRPMS
QISGVKKLMH SSSLTNSSIP RFGVKTDQED GLAKELEDVN KWGLHVFKIA EFSGNRPLTV
IMHTIFQERD LLKTFKIPVD TLITYLMTLE DHYHADVAYH NNIHAADVVQ STHVLLSTPA
LEAVFTDLEI LAAIFASAIH DVDHPGVSNQ FLINTNSELA LMYNDSSVLE NHHLAVGFKL
LQEENCDIFQ NLTKKQRQSL RKMVIDIVLA TDMSKHMNLL ADLKTMVETK KVTSSGVLLL
DNYSDRIQVL QNMVHCADLS NPTKPLQLYR QWTDRIMEEF FRQGDRERER GMEISPMCDK
HNASVEKSQV GFIDYIVHPL WETWADLVHP DAQDILDTLE DNREWYQSTI PQSPSPAPDD
QEEGRQGQTE KFQFELTLEE DGESDTEKDS GSPVEEDTSC SDSKTLCTQD SESTEIPLDE
QVEEEAVGEE EEEEDPAEPC AIENEHSPDT
//
