ENPP5_HUMAN
ID ENPP5_HUMAN Reviewed; 477 AA.
AC Q9UJA9; Q5TFV2; Q6UX49;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
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|HGNC:HGNC:13717}; ORFNames=UNQ550/PRO1107;
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;
RN [1] {ECO:0000312|EMBL:AAQ88878.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-6 AND VAL-171.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAH27615.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis {ECO:0000269|PubMed:15489334};
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 [5] {ECO:0007744|PDB:5VEM}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 25-430, ACTIVE SITE,
RP 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. Lacks lysopholipase D activity. May play a role in
CC neuronal cell communication. {ECO:0000250|UniProtKB:P84039,
CC ECO:0000250|UniProtKB:Q9EQG7}.
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 -!- 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; AY358514; AAQ88878.1; -; mRNA.
DR EMBL; AL035701; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04293.1; -; Genomic_DNA.
DR EMBL; BC027615; AAH27615.1; -; mRNA.
DR CCDS; CCDS4915.1; -.
DR PIR; A59391; A59391.
DR RefSeq; NP_001277001.1; NM_001290072.1.
DR RefSeq; NP_001277002.1; NM_001290073.1.
DR RefSeq; NP_067547.1; NM_021572.5.
DR RefSeq; XP_005249317.1; XM_005249260.3.
DR RefSeq; XP_011513088.1; XM_011514786.2.
DR PDB; 5VEM; X-ray; 2.60 A; A/B/C=25-430.
DR PDBsum; 5VEM; -.
DR AlphaFoldDB; Q9UJA9; -.
DR SMR; Q9UJA9; -.
DR BioGRID; 121860; 5.
DR STRING; 9606.ENSP00000360436; -.
DR GlyGen; Q9UJA9; 8 sites.
DR iPTMnet; Q9UJA9; -.
DR PhosphoSitePlus; Q9UJA9; -.
DR BioMuta; ENPP5; -.
DR DMDM; 50401201; -.
DR EPD; Q9UJA9; -.
DR jPOST; Q9UJA9; -.
DR MassIVE; Q9UJA9; -.
DR MaxQB; Q9UJA9; -.
DR PaxDb; Q9UJA9; -.
DR PeptideAtlas; Q9UJA9; -.
DR PRIDE; Q9UJA9; -.
DR ProteomicsDB; 84616; -.
DR Antibodypedia; 2350; 161 antibodies from 24 providers.
DR DNASU; 59084; -.
DR Ensembl; ENST00000230565.3; ENSP00000230565.3; ENSG00000112796.10.
DR Ensembl; ENST00000371383.7; ENSP00000360436.1; ENSG00000112796.10.
DR GeneID; 59084; -.
DR KEGG; hsa:59084; -.
DR MANE-Select; ENST00000371383.7; ENSP00000360436.1; NM_001290072.2; NP_001277001.1.
DR UCSC; uc003oxz.2; human.
DR CTD; 59084; -.
DR DisGeNET; 59084; -.
DR GeneCards; ENPP5; -.
DR HGNC; HGNC:13717; ENPP5.
DR HPA; ENSG00000112796; Tissue enriched (epididymis).
DR MIM; 617001; gene.
DR neXtProt; NX_Q9UJA9; -.
DR OpenTargets; ENSG00000112796; -.
DR PharmGKB; PA27795; -.
DR VEuPathDB; HostDB:ENSG00000112796; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000160562; -.
DR HOGENOM; CLU_017594_1_2_1; -.
DR InParanoid; Q9UJA9; -.
DR OMA; DEYVSRD; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q9UJA9; -.
DR TreeFam; TF330032; -.
DR PathwayCommons; Q9UJA9; -.
DR BioGRID-ORCS; 59084; 8 hits in 1065 CRISPR screens.
DR GenomeRNAi; 59084; -.
DR Pharos; Q9UJA9; Tbio.
DR PRO; PR:Q9UJA9; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9UJA9; protein.
DR Bgee; ENSG00000112796; Expressed in corpus epididymis and 161 other tissues.
DR Genevisible; Q9UJA9; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0000210; F:NAD+ diphosphatase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007154; P:cell communication; ISS:UniProtKB.
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_0000036401"
FT TRANSMEM 432..452
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 72
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:28898552,
FT ECO:0007744|PDB:5VEM"
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:5VEM"
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:5VEM"
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:5VEM"
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:5VEM"
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:5VEM"
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:5VEM"
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:5VEM"
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 VARIANT 6
FT /note="L -> I (in dbSNP:rs3806995)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_020248"
FT VARIANT 39
FT /note="R -> P (in dbSNP:rs34109856)"
FT /id="VAR_033918"
FT VARIANT 69
FT /note="I -> V (in dbSNP:rs34432940)"
FT /id="VAR_052940"
FT VARIANT 171
FT /note="I -> V (in dbSNP:rs6926570)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_024693"
FT VARIANT 283
FT /note="Y -> C (in dbSNP:rs16874326)"
FT /id="VAR_052941"
FT CONFLICT 25
FT /note="P -> L (in Ref. 1; AAQ88878)"
FT /evidence="ECO:0000305"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 72..79
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 85..88
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:5VEM"
FT TURN 98..101
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:5VEM"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 123..129
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:5VEM"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 163..175
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 181..187
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 191..197
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 204..224
FT /evidence="ECO:0007829|PDB:5VEM"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 252..255
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 267..274
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 279..287
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 352..356
FT /evidence="ECO:0007829|PDB:5VEM"
FT STRAND 361..369
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 373..381
FT /evidence="ECO:0007829|PDB:5VEM"
FT HELIX 392..398
FT /evidence="ECO:0007829|PDB:5VEM"
SQ SEQUENCE 477 AA; 54666 MW; 6F776FD68E6536C7 CRC64;
MTSKFLLVSF ILAALSLSTT FSLQPDQQKV LLVSFDGFRW DYLYKVPTPH FHYIMKYGVH
VKQVTNVFIT KTYPNHYTLV TGLFAENHGI VANDMFDPIR NKSFSLDHMN IYDSKFWEEA
TPIWITNQRA GHTSGAAMWP GTDVKIHKRF PTHYMPYNES VSFEDRVAKI IEWFTSKEPI
NLGLLYWEDP DDMGHHLGPD SPLMGPVISD IDKKLGYLIQ MLKKAKLWNT LNLIITSDHG
MTQCSEERLI ELDQYLDKDH YTLIDQSPVA AILPKEGKFD EVYEALTHAH PNLTVYKKED
VPERWHYKYN SRIQPIIAVA DEGWHILQNK SDDFLLGNHG YDNALADMHP IFLAHGPAFR
KNFSKEAMNS TDLYPLLCHL LNITAMPHNG SFWNVQDLLN SAMPRVVPYT QSTILLPGSV
KPAEYDQEGS YPYFIGVSLG SIIVIVFFVI FIKHLIHSQI PALQDMHAEI AQPLLQA
