ID Q7KYS4_HUMAN Unreviewed; 606 AA. AC Q7KYS4; DT 05-JUL-2004, integrated into UniProtKB/TrEMBL. DT 05-JUL-2004, sequence version 1. DT 12-OCT-2022, entry version 111. DE RecName: Full=Phosphodiesterase {ECO:0000256|RuleBase:RU363067}; DE EC=3.1.4.- {ECO:0000256|RuleBase:RU363067}; 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 {ECO:0000313|EMBL:AAC51915.1}; RN [1] {ECO:0000313|EMBL:AAC51915.1} RP NUCLEOTIDE SEQUENCE. RC TISSUE=Glioblastoma {ECO:0000313|EMBL:AAC51915.1}; RX PubMed=9429761; DOI=10.1016/S0898-6568(97)00072-7; RA Owens R.J., Lumb S., Rees-Milton K., Russell A., Baldock D., Lang V., RA Crabbe T., Ballesteros M., Perry M.J.; RT "Molecular cloning and expression of a human phosphodiesterase 4C."; RL Cell. Signal. 9:575-585(1997). 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=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000256|ARBA:ARBA00001946}; 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}. 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; U88712; AAC51915.1; -; mRNA. DR RefSeq; NP_001092289.1; NM_001098819.3. DR PeptideAtlas; Q7KYS4; -. DR PRIDE; Q7KYS4; -. DR DNASU; 5143; -. DR GeneID; 5143; -. DR CTD; 5143; -. DR PharmGKB; PA264; -. DR UniPathway; UPA00762; UER00747. DR BioGRID-ORCS; 5143; 25 hits in 1067 CRISPR screens. DR GenomeRNAi; 5143; -. DR Genevisible; Q7KYS4; HS. DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR CDD; cd00077; HDc; 1. DR Gene3D; 1.10.1300.10; -; 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 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 2: Evidence at transcript level; 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}. FT DOMAIN 206..535 FT /note="PDEase" FT /evidence="ECO:0000259|PROSITE:PS51845" FT REGION 75..94 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 530..549 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 557..606 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 79..93 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 557..574 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 282 FT /note="Proton donor" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-1" FT BINDING 282..286 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" FT BINDING 286 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 322 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 323 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" FT BINDING 323 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 323 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 440 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" FT BINDING 440 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3" FT BINDING 491 FT /ligand="AMP" FT /ligand_id="ChEBI:CHEBI:456215" FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2" SQ SEQUENCE 606 AA; 67719 MW; AC14D9401F5CCDCE CRC64; MQAPVPHSQR RESFLYRSDS DYELSPKAMS RNSSVASDLH GEDMIVTPFA QVLASLRTVR SNVAALARQQ CLGAAKQGPV GNPSSSNQLP PAEDTGQKLA LETLDELDWC LDQLETLQTR HSVGEMASNK FKRILNRELT HLSETSRSGN QVSEYISRTF LDQQTEVELP KVTAEEAPQP MSRISGLHGL CHSASLSSAT VPRFGVQTDQ EEQLAKELED TNKWGLDVFK VAELSGNQPL TAIIFSIFQE RDLLKTFQIP ADTLATYLLM LEGHYHANVA YHNSLHAADV AQSTHVLLAT PALEAVFTDL EILAALFASA IHDVDHPGVS NQFLINTNSE LALMYNDASV LENHHLAVGF KLLQAENCDI FQNLSAKQRL SLRRMVIDMV LATDMSKHMN LLADLKTMVE TKKVTSLGVL LLDNYSDRIQ VLQNLVHCAD LSNPTKPLPL YRQWTDRIMA EFFQQGDRER ESGLDISPMC DKHTASVEKS QVGFIDYIAH PLWETWADLV HPDAQDLLDT LEDNREWYQS KIPRSPSDLT NPERDGPDRF QFELTLEEAE EEDEEEEEEG EETALAKEAL ELPDTELLSP EAGPAPGDLP LDNQRT //