ENPP5_MOUSE
ID ENPP5_MOUSE Reviewed; 477 AA.
AC Q9EQG7; A9C479; Q921P7;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 5;
DE Short=E-NPP 5;
DE Short=NPP-5;
DE EC=3.1.-.-;
DE Flags: Precursor;
GN Name=Enpp5 {ECO:0000312|MGI:MGI:1933830};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:AAG49143.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000269|PubMed:11027689};
RX PubMed=11027689; DOI=10.1074/jbc.m007552200;
RA Gijsbers R., Ceulemans H., Stalmans W., Bollen M.;
RT "Structural and catalytic similarities between nucleotide
RT pyrophosphatases/phosphodiesterases and alkaline phosphatases.";
RL J. Biol. Chem. 276:1361-1368(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=12927778; DOI=10.1016/s0006-291x(03)01454-2;
RA Ohe Y., Ohnishi H., Okazawa H., Tomizawa K., Kobayashi H., Okawa K.,
RA Matozaki T.;
RT "Characterization of nucleotide pyrophosphatase-5 as an oligomannosidic
RT glycoprotein in rat brain.";
RL Biochem. Biophys. Res. Commun. 308:719-725(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6] {ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO}
RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 25-430 OF WILD-TYPE AND MUTANT
RP ALA-72 IN COMPLEX WITH AMP, FUNCTION, MUTAGENESIS OF THR-72; TYR-73 AND
RP GLU-159, ACTIVE SITE, METAL-BINDING SITES, AND COFACTOR.
RX PubMed=28898552; DOI=10.1111/febs.14266;
RA Gorelik A., Randriamihaja A., Illes K., Nagar B.;
RT "A key tyrosine substitution restricts nucleotide hydrolysis by the
RT ectoenzyme NPP5.";
RL FEBS J. 284:3718-3726(2017).
CC -!- FUNCTION: Can hydrolyze NAD but cannot hydrolyze nucleotide di- and
CC triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May
CC play a role in neuronal cell communication (By similarity).
CC {ECO:0000250|UniProtKB:P84039, ECO:0000269|PubMed:28898552}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:28898552};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:28898552};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed abundantly in the brain and kidney, and
CC at lower levels in the liver. {ECO:0000269|PubMed:12927778}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P84039}.
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
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DR EMBL; AF233377; AAG49143.1; -; mRNA.
DR EMBL; CT030230; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC138977; AAI38978.1; -; mRNA.
DR EMBL; BC138978; AAI38979.1; -; mRNA.
DR CCDS; CCDS28802.1; -.
DR PIR; A59390; A59390.
DR RefSeq; NP_001162091.1; NM_001168620.2.
DR RefSeq; NP_001316548.1; NM_001329619.1.
DR RefSeq; NP_114392.1; NM_032003.3.
DR PDB; 5VEN; X-ray; 1.69 A; A/B=25-430.
DR PDB; 5VEO; X-ray; 1.53 A; A=25-430.
DR PDBsum; 5VEN; -.
DR PDBsum; 5VEO; -.
DR AlphaFoldDB; Q9EQG7; -.
DR SMR; Q9EQG7; -.
DR STRING; 10090.ENSMUSP00000024756; -.
DR GlyConnect; 2276; 6 N-Linked glycans (5 sites).
DR GlyGen; Q9EQG7; 9 sites, 6 N-linked glycans (5 sites).
DR PhosphoSitePlus; Q9EQG7; -.
DR MaxQB; Q9EQG7; -.
DR PaxDb; Q9EQG7; -.
DR PRIDE; Q9EQG7; -.
DR ProteomicsDB; 277877; -.
DR Antibodypedia; 2350; 161 antibodies from 24 providers.
DR DNASU; 83965; -.
DR Ensembl; ENSMUST00000024756; ENSMUSP00000024756; ENSMUSG00000023960.
DR Ensembl; ENSMUST00000154166; ENSMUSP00000122767; ENSMUSG00000023960.
DR GeneID; 83965; -.
DR KEGG; mmu:83965; -.
DR UCSC; uc008cpr.2; mouse.
DR CTD; 59084; -.
DR MGI; MGI:1933830; Enpp5.
DR VEuPathDB; HostDB:ENSMUSG00000023960; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000160562; -.
DR HOGENOM; CLU_017594_1_2_1; -.
DR InParanoid; Q9EQG7; -.
DR OMA; DEYVSRD; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q9EQG7; -.
DR TreeFam; TF330032; -.
DR BRENDA; 3.6.1.9; 3474.
DR BioGRID-ORCS; 83965; 3 hits in 70 CRISPR screens.
DR ChiTaRS; Enpp5; mouse.
DR PRO; PR:Q9EQG7; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9EQG7; protein.
DR Bgee; ENSMUSG00000023960; Expressed in seminal vesicle and 210 other tissues.
DR ExpressionAtlas; Q9EQG7; baseline and differential.
DR Genevisible; Q9EQG7; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISA:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000210; F:NAD+ diphosphatase activity; ISO:MGI.
DR GO; GO:0004551; F:nucleotide diphosphatase activity; ISA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007154; P:cell communication; ISO:MGI.
DR GO; GO:0009166; P:nucleotide catabolic process; ISA:MGI.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR Pfam; PF01663; Phosphodiest; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix;
KW Zinc.
FT SIGNAL 1..24
FT /evidence="ECO:0000250|UniProtKB:P84039"
FT CHAIN 25..477
FT /note="Ectonucleotide pyrophosphatase/phosphodiesterase
FT family member 5"
FT /id="PRO_0000036402"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 72
FT /note="Nucleophile"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 36
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 195
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEN, ECO:0007744|PDB:5VEO"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 72
FT /note="T->A: Catalytically inactive."
FT /evidence="ECO:0000305|PubMed:28898552"
FT MUTAGEN 73
FT /note="Y->F: Can hydrolyze nucleotides, with about fourfold
FT higher rates for adenine versus uridine and no strong
FT preference for diphosphates or triphosphates."
FT /evidence="ECO:0000269|PubMed:28898552"
FT MUTAGEN 159
FT /note="E->S: No effect on its ability to hydrolyze NAD."
FT /evidence="ECO:0000269|PubMed:28898552"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 40..44
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 72..81
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 85..88
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:5VEO"
FT TURN 98..101
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:5VEO"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 123..129
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:5VEO"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 163..174
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 181..187
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 191..197
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 204..224
FT /evidence="ECO:0007829|PDB:5VEO"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 267..274
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:5VEO"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:5VEO"
FT STRAND 361..369
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 373..380
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 392..395
FT /evidence="ECO:0007829|PDB:5VEO"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:5VEO"
SQ SEQUENCE 477 AA; 54387 MW; 98845AF8B725FD61 CRC64;
MIPEFLLASC TLATLCHSAP FSLQPEEQKV LVVSFDGFRW DYLYKVPTPH FHYIMKNGVH
VNQVTNVFIT KTYPNHYTLV TGLFAENHGI VANDMFDPIL NKSFSLEHMD IYDSKFWEEA
TPIWITNQRA GHASGAAMWP GADVKIHDSF PTYYLPYNES VSFEDRVAKI IEWFTAKDPI
NLGFLYWEEP DDTGHDVGPD SPLMGSVISD VDHKLGYLIK MLKRAKLWNN VNLIVTSDHG
MTQCSKQRVI ELDRYLDKEH YTLIDHSPVA AILPKEGKFD EVYDALAGAH PNLTVYKKEE
IPERWHYKHN DRVQPIVAVA DEGWYILQNK SDDFLLGNHG YDNALAEMHP IFLAHGPAFR
KNFTKEAMNS TDLYSLLCHL LNLTALPHNG SFWNVQDLLS SATPKPIPYT QSTTLLLGSD
KPGEDEQEES YPYYIGVSLG SIIAMVFFVV LIKHLIRSQV HTLQYRQVEV AQPLLQA
