ID G1U4Q4_RABIT Unreviewed; 936 AA.
AC G1U4Q4;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 11-DEC-2019, sequence version 2.
DT 27-MAR-2024, entry version 70.
DE RecName: Full=Phosphodiesterase {ECO:0000256|RuleBase:RU363067};
DE EC=3.1.4.- {ECO:0000256|RuleBase:RU363067};
GN Name=PDE2A {ECO:0000313|Ensembl:ENSOCUP00000024379.2};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986 {ECO:0000313|Ensembl:ENSOCUP00000024379.2, ECO:0000313|Proteomes:UP000001811};
RN [1] {ECO:0000313|Ensembl:ENSOCUP00000024379.2, ECO:0000313|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke inbred {ECO:0000313|Ensembl:ENSOCUP00000024379.2,
RC ECO:0000313|Proteomes:UP000001811};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSOCUP00000024379.2}
RP IDENTIFICATION.
RC STRAIN=Thorbecke {ECO:0000313|Ensembl:ENSOCUP00000024379.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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 -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family.
CC {ECO:0000256|RuleBase:RU363067}.
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DR EMBL; AAGW02008149; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02008150; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02008151; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G1U4Q4; -.
DR SMR; G1U4Q4; -.
DR STRING; 9986.ENSOCUP00000024379; -.
DR PaxDb; 9986-ENSOCUP00000024379; -.
DR Ensembl; ENSOCUT00000023739.2; ENSOCUP00000024379.2; ENSOCUG00000014917.4.
DR eggNOG; KOG3689; Eukaryota.
DR GeneTree; ENSGT00940000159817; -.
DR HOGENOM; CLU_006980_3_0_1; -.
DR InParanoid; G1U4Q4; -.
DR TreeFam; TF316499; -.
DR Proteomes; UP000001811; Chromosome 1.
DR Bgee; ENSOCUG00000014917; Expressed in frontal cortex and 17 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0030552; F:cAMP binding; IEA:Ensembl.
DR GO; GO:0030553; F:cGMP binding; ISS:UniProtKB.
DR GO; GO:0004118; F:cGMP-stimulated cyclic-nucleotide phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR GO; GO:0042301; F:phosphate ion binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0030911; F:TPR domain binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:1904613; P:cellular response to 2,3,7,8-tetrachlorodibenzodioxine; IEA:Ensembl.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0071321; P:cellular response to cGMP; ISS:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; ISS:UniProtKB.
DR GO; GO:0036006; P:cellular response to macrophage colony-stimulating factor stimulus; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0046069; P:cGMP catabolic process; ISS:UniProtKB.
DR GO; GO:0019934; P:cGMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISS:UniProtKB.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISS:UniProtKB.
DR GO; GO:0043949; P:regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0010752; P:regulation of cGMP-mediated signaling; IEA:Ensembl.
DR CDD; cd00077; HDc; 1.
DR Gene3D; 3.30.450.40; -; 2.
DR Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1.
DR InterPro; IPR003018; GAF.
DR InterPro; IPR029016; GAF-like_dom_sf.
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 PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1.
DR PANTHER; PTHR11347:SF102; PHOSPHODIESTERASE; 1.
DR Pfam; PF01590; GAF; 1.
DR Pfam; PF13185; GAF_2; 1.
DR Pfam; PF00233; PDEase_I; 1.
DR PRINTS; PR00387; PDIESTERASE1.
DR SMART; SM00065; GAF; 2.
DR SMART; SM00471; HDc; 1.
DR SUPFAM; SSF55781; GAF domain-like; 3.
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 cGMP {ECO:0000256|ARBA:ARBA00022535};
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:UP000001811}.
FT DOMAIN 573..897
FT /note="PDEase"
FT /evidence="ECO:0000259|PROSITE:PS51845"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 651
FT /note="Proton donor"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-1"
FT BINDING 651..655
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
FT BINDING 655
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 691
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 692
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
FT BINDING 692
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 692
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 803
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
FT BINDING 803
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-3"
FT BINDING 854
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000256|PIRSR:PIRSR623088-2"
SQ SEQUENCE 936 AA; 104550 MW; 695E4FB532C614A3 CRC64;
MHGQSLHCHC PGSASQDPLA QEPEPPGSRA GRLEDALLSL GSVIDLAGLQ HAIKEALSAV
LPRVETVYTY LLDEECRLVC EDPWHELPQE GKVREAVVSQ KRLSCNGLGS SDLPGKPLAR
LVAPLAPDTQ VLVLPLLDKE AGAVAAVILV HCGQLSDSEE WSLQAVEKHT LVALRRMRAL
QQRGLGQAPG TGAGAGAGAV QNTPVEAAED QQGGAAYTDH DRKILHLCGE LYDPDAASLQ
LKVLQYLQQE TQAAHCCLLL VSEDNLQLSC KVIGDKVLGE EISFPLTTGR LGQVVQDKKS
IQLEDLPSED VQQLQSMLGC EVQTMLCVPV ISRATDQVVA LACAFNKLGG ALFTEQDEQV
IQHCFHYTGT VLTSTLAFQK EQKLKCECQA LLQVAKNLFT HLDDVSVLLQ EIITEARNLS
NAEICSVFLL DQNELVAKVF DGGVVDDESY EIRIPADQGI AGHVATTGQI LNIPDAYAHP
LFYRGVDDST GFRTRNILCF PIKNENQEVI GVAELVNKIN GPWFSKFDED LATAFSIYCG
ISIAHSLLYK KVNEAQYRSH LANEMMMYHM KVSDDEYTKL LHDGIQPVAS IDSNFANFTY
TPRSLPEDDT SMAILSMLQD MNFINNYKID CPTLARFCLM VKKGYRDPPY HNWMHAFSVS
HFCYLLYKNL ELTNYLEDIE IFALFISCMC HDLDHRGTNN SFQVASKSVL AALYSSEGSV
MERHHFAQAI AILNTHGCNI FDHFSRKDYQ RMLDLMRDII LATDLAHHLR IFKDLQKMAE
VGYDRTNKQH HRLLLCLLMT SCDLSDQTKG WKTTRKIAEL IYKEFFSQGD LEKAMGNRPM
EMMDREKAYI PELQISFMEH IAMPIYKLLQ DLFPKAAELY ERVASNREHW TKVSHKFTIR
GLPSNNSLDF LDEEYEVPGL DGTRAPVNGC CSLDTE
//
