PDE_MACLB
ID PDE_MACLB Reviewed; 851 AA.
AC W8E7D1;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=Venom phosphodiesterase {ECO:0000303|PubMed:25079051};
DE Short=PDE {ECO:0000303|PubMed:25079051};
DE Short=VLPDE {ECO:0000303|PubMed:25079051};
DE EC=3.6.1.- {ECO:0000269|PubMed:25079051};
DE Flags: Precursor;
OS Macrovipera lebetina (Levantine viper) (Vipera lebetina).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Macrovipera.
OX NCBI_TaxID=8709;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=25079051; DOI=10.1016/j.biochi.2014.07.020;
RA Trummal K., Aaspollu A., Tonismaegi K., Samel M., Subbi J., Siigur J.,
RA Siigur E.;
RT "Phosphodiesterase from Vipera lebetina venom - structure and
RT characterization.";
RL Biochimie 106:48-55(2014).
CC -!- FUNCTION: Hydrolyzes ADP with high activity (PubMed:25079051). Shows
CC weak or no activity on 5'-AMP, 5'-GMP, 3'-AMP, ATP, cAMP, and cGMP
CC (PubMed:25079051). Is devoid of monophosphatase and proteinase
CC activities (PubMed:25079051). Dose-dependently inhibits platelet
CC aggregation induced by ADP (IC(50)=0.99 uM) and collagen (IC(50)=1.4
CC uM) (PubMed:25079051). {ECO:0000269|PubMed:25079051}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP + H2O = AMP + H(+) + phosphate; Xref=Rhea:RHEA:61436,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:25079051};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250|UniProtKB:J3SEZ3};
CC Note=Binds 2 divalent metal cations per subunit.
CC {ECO:0000250|UniProtKB:J3SEZ3};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.5-9.0. {ECO:0000269|PubMed:25079051};
CC Temperature dependence:
CC Optimum temperature is 60 degrees Celsius.
CC {ECO:0000269|PubMed:25079051};
CC -!- SUBUNIT: Monomer cleaved in two subunits; disulfide-linked. Is
CC synthesized as a single-chain protein and is subsequently cleaved to
CC form a two-subunit protein held together with disulfide bonds
CC (PubMed:25079051). {ECO:0000269|PubMed:25079051}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:25079051}.
CC -!- TISSUE SPECIFICITY: Expressed by venom gland.
CC {ECO:0000305|PubMed:25079051}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; KF408295; AHJ80885.1; -; mRNA.
DR AlphaFoldDB; W8E7D1; -.
DR SMR; W8E7D1; -.
DR PRIDE; W8E7D1; -.
DR BRENDA; 3.1.15.1; 6665.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0043262; F:adenosine-diphosphatase activity; IEA:RHEA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.570.10; -; 1.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR001604; DNA/RNA_non-sp_Endonuclease.
DR InterPro; IPR044929; DNA/RNA_non-sp_Endonuclease_sf.
DR InterPro; IPR020821; Extracellular_endonuc_su_A.
DR InterPro; IPR044925; His-Me_finger_sf.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR InterPro; IPR036024; Somatomedin_B-like_dom_sf.
DR InterPro; IPR001212; Somatomedin_B_dom.
DR Pfam; PF01223; Endonuclease_NS; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR Pfam; PF01033; Somatomedin_B; 2.
DR SMART; SM00892; Endonuclease_NS; 1.
DR SMART; SM00477; NUC; 1.
DR SMART; SM00201; SO; 2.
DR SUPFAM; SSF53649; SSF53649; 1.
DR SUPFAM; SSF54060; SSF54060; 1.
DR SUPFAM; SSF90188; SSF90188; 2.
DR PROSITE; PS00524; SMB_1; 2.
DR PROSITE; PS50958; SMB_2; 2.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Metal-binding;
KW Platelet aggregation inhibiting toxin; Repeat; Secreted; Signal; Toxin.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:25079051"
FT CHAIN 24..851
FT /note="Venom phosphodiesterase"
FT /evidence="ECO:0000305|PubMed:25079051"
FT /id="PRO_5004907664"
FT DOMAIN 30..73
FT /note="SMB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DOMAIN 74..118
FT /note="SMB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT MOTIF 58..60
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 185
FT /note="AMP-threonine intermediate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 147
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 185
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 271
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 305
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 309
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 309
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 352
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 353
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT BINDING 462
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT SITE 421..422
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:25079051"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 405
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 512
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 594
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 745
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 34..51
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 34..38
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 38..69
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 49..62
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 49..51
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 55..61
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 62..69
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 78..95
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 78..83
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 83..113
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 93..106
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 93..95
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 99..105
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 106..113
FT /note="Alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00350"
FT DISULFID 124..170
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 132..344
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 360..457
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 408..793
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 541..599
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 554..654
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 556..639
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
FT DISULFID 762..772
FT /evidence="ECO:0000250|UniProtKB:A0A2D0TC04"
SQ SEQUENCE 851 AA; 96181 MW; 8EF74A1D5EB83EFA CRC64;
MIQQKVLFIS LVAVALGLGL GLGLKESVEP QVSCRYRCNE TFSKMASGCS CDDKCTERQA
CCQDYEDTCV LPTQSWSCSK LRCSEKRMAN VLCSCSEDCL EKKDCCTDYK SICKGETSWL
KDQCASSSAA QCPSGFEQSP LILFSMDGFR AGYLETWDSL MPNINKLKTC GTHAKYMRAV
YPTKTFVNHY TIVTGLYPES HGIIDNNIYD VTLNLNFSLS APTMTNPAWW GGQPIWHTVT
YQGLKAATYF WPGSEVKING SYPTIYKVYN KSIPFEARVT EVLKWLDLPK AERPDFVTLY
IEEPDTTGHK FGPVSGEIIM ALQMADRTLG MLMEGLKQRN LHNCVNLILL ADHGMEQISC
NRLEYMTDYF DKVDFFMYEG PAPRIRSKNV PKDFYTFDSE GIVRNLTCQK PKQYFKAYLA
KDLPKRLHYV NNIRIDKVNL MVDQQWMAVR NKNYNRCNGG THGYDNEFKS MQAIFLAHGP
GFKGKNEVTS FENIEVYNLM CDLLKLKPAP NNGTHGSLNH LLKNPFYNPS PAKEQTSPLS
CPFGPVPSPD VSGCKCSSIT DLGKVNERLN LNNQAKTESE AHNLPYGRPQ VLQNHSKYCL
LHQAKYISAY SQDVLMPLWS SYTINKSPPT SVPPSASDCL RLDVRIPAAQ SQTCSNYQPD
LTITPGFLYP PNFGSSNFEQ YDALITSNLV PMFKGFTRLW NYFHGTLLPK YARERNGLNV
ISGPIFDYNY DGHFDSYDTI KEYVNDTKIP IPTHFFVVLT SCENQINTPL NCPGSLKVLS
FILPHRPDNS ESCADTSPDN LWVEERIQTH TARVRDVELL TGLNFYSGLK QPLPETLQLK
TFLPIFVNPV N
