MPPD2_RAT
ID MPPD2_RAT Reviewed; 294 AA.
AC B1WBP0; Q8CFG1;
DT 13-OCT-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Metallophosphoesterase MPPED2;
DE EC=3.1.-.- {ECO:0000269|PubMed:19004815, ECO:0000269|PubMed:21824479};
DE AltName: Full=239FB {ECO:0000303|PubMed:19004815};
DE AltName: Full=Fetal brain protein 239 homolog;
DE AltName: Full=Metallophosphoesterase domain-containing protein 2;
GN Name=Mpped2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-283.
RC TISSUE=Hippocampus;
RA Chen D., Saugstad J., Henshall D., Minami M., Simon R.P.;
RT "Molecular cloning and characterization of a rat novel A18 hnRNP protein
RT binding gene.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP HOMODIMERIZATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-65; HIS-67;
RP ASP-86; ASN-117; HIS-118 AND GLY-252.
RX PubMed=19004815; DOI=10.1074/jbc.m805996200;
RA Tyagi R., Shenoy A.R., Visweswariah S.S.;
RT "Characterization of an evolutionarily conserved metallophosphoesterase
RT that is expressed in the fetal brain and associated with the WAGR
RT syndrome.";
RL J. Biol. Chem. 284:5217-5228(2009).
RN [5] {ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4, ECO:0007744|PDB:3RL5}
RP X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS) OF WILD-TYPE AND MUTANTS ARG-67 AND
RP HIS-252 IN COMPLEX WITH MANGANESE AND GMP, FUNCTION, COFACTOR, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-67; PHE-183 AND
RP GLY-252.
RX PubMed=21824479; DOI=10.1016/j.jmb.2011.07.060;
RA Dermol U., Janardan V., Tyagi R., Visweswariah S.S., Podobnik M.;
RT "Unique utilization of a phosphoprotein phosphatase fold by a mammalian
RT phosphodiesterase associated with WAGR syndrome.";
RL J. Mol. Biol. 412:481-494(2011).
CC -!- FUNCTION: Displays low metallophosphoesterase activity (in vitro)
CC (PubMed:19004815, PubMed:21824479). May play a role in the development
CC of the nervous system (Probable). {ECO:0000269|PubMed:19004815,
CC ECO:0000269|PubMed:21824479, ECO:0000305}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:19004815, ECO:0000269|PubMed:21824479};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:19004815};
CC -!- ACTIVITY REGULATION: Inhibited by nmolar levels of AMP and GMP.
CC {ECO:0000269|PubMed:21824479}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 mM for p-nitrophenyl phenyphosphonate
CC {ECO:0000269|PubMed:19004815};
CC KM=1.5 mM for manganese {ECO:0000269|PubMed:19004815};
CC Vmax=8 umol/min/mg enzyme with p-nitrophenyl phenyphosphonate as
CC substrate {ECO:0000269|PubMed:19004815};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19004815}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal brain (at protein level).
CC detected in fetal and adult brain. {ECO:0000269|PubMed:19004815}.
CC -!- MISCELLANEOUS: This protein has a low affinity for cofactor and
CC demonstrates very restricted substrate specificity. The enzyme may need
CC additional interacting proteins to show full activity, or may be losing
CC its activity and acquiring the role of a scaffolding protein.
CC {ECO:0000305|PubMed:19004815}.
CC -!- SIMILARITY: Belongs to the UPF0046 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM09960.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; CH473949; EDL79739.1; -; Genomic_DNA.
DR EMBL; CH473949; EDL79741.1; -; Genomic_DNA.
DR EMBL; CH473949; EDL79742.1; -; Genomic_DNA.
DR EMBL; BC161828; AAI61828.1; -; mRNA.
DR EMBL; AY093422; AAM09960.1; ALT_SEQ; mRNA.
DR RefSeq; NP_942073.2; NM_198778.2.
DR RefSeq; XP_006234742.1; XM_006234680.3.
DR RefSeq; XP_006234743.1; XM_006234681.3.
DR RefSeq; XP_006234744.1; XM_006234682.3.
DR RefSeq; XP_006234745.1; XM_006234683.3.
DR RefSeq; XP_008760326.1; XM_008762104.2.
DR RefSeq; XP_017447394.1; XM_017591905.1.
DR RefSeq; XP_017447395.1; XM_017591906.1.
DR PDB; 3RL3; X-ray; 1.42 A; A=1-294.
DR PDB; 3RL4; X-ray; 1.29 A; A=1-294.
DR PDB; 3RL5; X-ray; 1.26 A; A=1-294.
DR PDBsum; 3RL3; -.
DR PDBsum; 3RL4; -.
DR PDBsum; 3RL5; -.
DR AlphaFoldDB; B1WBP0; -.
DR SMR; B1WBP0; -.
DR STRING; 10116.ENSRNOP00000062716; -.
DR PaxDb; B1WBP0; -.
DR PRIDE; B1WBP0; -.
DR Ensembl; ENSRNOT00000065168; ENSRNOP00000062716; ENSRNOG00000004863.
DR GeneID; 362185; -.
DR KEGG; rno:362185; -.
DR UCSC; RGD:735060; rat.
DR CTD; 744; -.
DR RGD; 735060; Mpped2.
DR eggNOG; KOG3947; Eukaryota.
DR GeneTree; ENSGT00390000007681; -.
DR HOGENOM; CLU_041441_1_0_1; -.
DR InParanoid; B1WBP0; -.
DR OMA; HYLEYES; -.
DR OrthoDB; 1301937at2759; -.
DR PhylomeDB; B1WBP0; -.
DR TreeFam; TF314305; -.
DR EvolutionaryTrace; B1WBP0; -.
DR PRO; PR:B1WBP0; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000004863; Expressed in frontal cortex and 16 other tissues.
DR Genevisible; B1WBP0; RN.
DR GO; GO:0016208; F:AMP binding; IDA:UniProtKB.
DR GO; GO:0019002; F:GMP binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IDA:UniProtKB.
DR Gene3D; 3.60.21.10; -; 1.
DR InterPro; IPR024201; Calcineurin-like_Pesterase.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR Pfam; PF00149; Metallophos; 1.
DR PIRSF; PIRSF035808; Pdiesterase_Brain_239; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cobalt; Hydrolase; Manganese; Metal-binding;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..294
FT /note="Metallophosphoesterase MPPED2"
FT /id="PRO_0000386546"
FT BINDING 65
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 67
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 86
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 86
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 117..118
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 117
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 213
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 225..226
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 254..255
FT /ligand="GMP"
FT /ligand_id="ChEBI:CHEBI:58115"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT BINDING 254
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21824479,
FT ECO:0007744|PDB:3RL3, ECO:0007744|PDB:3RL4"
FT MUTAGEN 65
FT /note="D->A: Loss of phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:19004815"
FT MUTAGEN 67
FT /note="H->A,R: Loss of phosphodiesterase activity. Disrupts
FT metal cofactor binding."
FT /evidence="ECO:0000269|PubMed:19004815"
FT MUTAGEN 86
FT /note="D->A: Loss of phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:19004815"
FT MUTAGEN 117
FT /note="N->A: Loss of phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:19004815"
FT MUTAGEN 118
FT /note="H->A: Loss of phosphodiesterase activity."
FT /evidence="ECO:0000269|PubMed:19004815"
FT MUTAGEN 183
FT /note="F->A: Decreased affinity for manganese. Decreased
FT inhibition by AMP and GMP."
FT /evidence="ECO:0000269|PubMed:19004815,
FT ECO:0000269|PubMed:21824479"
FT MUTAGEN 252
FT /note="G->H: Increased affinity for manganese. Decreased
FT inhibition by AMP and GMP."
FT /evidence="ECO:0000269|PubMed:19004815,
FT ECO:0000269|PubMed:21824479"
FT CONFLICT 123
FT /note="D -> E (in Ref. 3; AAM09960)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="S -> C (in Ref. 3; AAM09960)"
FT /evidence="ECO:0000305"
FT TURN 17..20
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 22..33
FT /evidence="ECO:0007829|PDB:3RL5"
FT TURN 38..40
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 93..104
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 124..130
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:3RL5"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 163..169
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:3RL4"
FT HELIX 194..200
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 233..241
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:3RL5"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:3RL5"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:3RL5"
SQ SEQUENCE 294 AA; 33336 MW; FEAE6DD0537C21E5 CRC64;
MAHGIPSQGK VTITVDEYSS NPTQAFTHYN INQSRFQPPH VHMVDPIPYD TPKPAGHTRF
VCISDTHSRT DGIQMPYGDI LLHTGDFTEL GLPSEVKKFN DWLGNLPYEY KIVIAGNHEL
TFDKEFMADL VKQDYYRFPS VSKLKPEDFD NVQSLLTNSI YLQDSEVTVK GFRIYGAPWT
PWFNGWGFNL PRGQSLLDKW NLIPEGTDIL MTHGPPLGFR DWVPKELQRV GCVELLNTVQ
RRVRPKLHVF GGIHEGYGTM TDGYTTYINA STCTVSFQPT NPPIIFDLPN PQGS
