ENPP4_MOUSE
ID ENPP4_MOUSE Reviewed; 456 AA.
AC Q8BTJ4; Q3TZS2; Q69ZX0; Q8K1L3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Bis(5'-adenosyl)-triphosphatase enpp4;
DE EC=3.6.1.29;
DE AltName: Full=AP3A hydrolase;
DE Short=AP3Aase;
DE AltName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 4;
DE Short=E-NPP 4;
DE Short=NPP-4;
DE Flags: Precursor;
GN Name=Enpp4; Synonyms=Kiaa0879;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C3H/HeJ, and NOD; TISSUE=Brain, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-279.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, and Testis;
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).
CC -!- FUNCTION: Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into
CC AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to
CC induce proliferation of vascular smooth muscle cells. Acts as a
CC procoagulant, mediating platelet aggregation at the site of nascent
CC thrombus via release of ADP from Ap3A and activation of ADP receptors
CC (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + P(1),P(3)-bis(5'-adenosyl) triphosphate = ADP + AMP + 2
CC H(+); Xref=Rhea:RHEA:13893, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58529, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC EC=3.6.1.29;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BTJ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BTJ4-2; Sequence=VSP_032370;
CC -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32326.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK173048; BAD32326.1; ALT_INIT; Transcribed_RNA.
DR EMBL; AK157622; BAE34135.1; -; mRNA.
DR EMBL; AK090098; BAC41090.1; -; mRNA.
DR EMBL; BC027749; AAH27749.2; -; mRNA.
DR CCDS; CCDS28803.1; -. [Q8BTJ4-1]
DR RefSeq; NP_950181.2; NM_199016.2. [Q8BTJ4-1]
DR RefSeq; XP_006524193.2; XM_006524130.3.
DR RefSeq; XP_006524197.1; XM_006524134.2.
DR AlphaFoldDB; Q8BTJ4; -.
DR SMR; Q8BTJ4; -.
DR STRING; 10090.ENSMUSP00000024757; -.
DR GlyConnect; 2156; 5 N-Linked glycans (2 sites).
DR GlyGen; Q8BTJ4; 5 sites, 5 N-linked glycans (2 sites).
DR iPTMnet; Q8BTJ4; -.
DR PhosphoSitePlus; Q8BTJ4; -.
DR EPD; Q8BTJ4; -.
DR MaxQB; Q8BTJ4; -.
DR PaxDb; Q8BTJ4; -.
DR PeptideAtlas; Q8BTJ4; -.
DR PRIDE; Q8BTJ4; -.
DR ProteomicsDB; 275910; -. [Q8BTJ4-1]
DR ProteomicsDB; 275911; -. [Q8BTJ4-2]
DR Antibodypedia; 2757; 123 antibodies from 21 providers.
DR DNASU; 224794; -.
DR Ensembl; ENSMUST00000024757; ENSMUSP00000024757; ENSMUSG00000023961. [Q8BTJ4-1]
DR Ensembl; ENSMUST00000143137; ENSMUSP00000114429; ENSMUSG00000023961. [Q8BTJ4-1]
DR GeneID; 224794; -.
DR KEGG; mmu:224794; -.
DR UCSC; uc008cpu.1; mouse. [Q8BTJ4-1]
DR CTD; 22875; -.
DR MGI; MGI:2682634; Enpp4.
DR VEuPathDB; HostDB:ENSMUSG00000023961; -.
DR eggNOG; KOG2645; Eukaryota.
DR GeneTree; ENSGT00940000158831; -.
DR HOGENOM; CLU_017594_1_2_1; -.
DR InParanoid; Q8BTJ4; -.
DR OMA; FTCIIII; -.
DR OrthoDB; 999163at2759; -.
DR PhylomeDB; Q8BTJ4; -.
DR TreeFam; TF330032; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 224794; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q8BTJ4; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8BTJ4; protein.
DR Bgee; ENSMUSG00000023961; Expressed in substantia nigra and 218 other tissues.
DR Genevisible; Q8BTJ4; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0047710; F:bis(5'-adenosyl)-triphosphatase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0030194; P:positive regulation of blood coagulation; ISO:MGI.
DR GO; GO:0046130; P:purine ribonucleoside catabolic process; ISO:MGI.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR InterPro; IPR029879; ENPP4.
DR InterPro; IPR002591; Phosphodiest/P_Trfase.
DR PANTHER; PTHR10151:SF79; PTHR10151:SF79; 1.
DR Pfam; PF01663; Phosphodiest; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Blood coagulation; Cell membrane; Disulfide bond;
KW Glycoprotein; Hemostasis; Hydrolase; Membrane; Metal-binding;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..456
FT /note="Bis(5'-adenosyl)-triphosphatase enpp4"
FT /id="PRO_0000324796"
FT TOPO_DOM 19..410
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..431
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 432..456
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 73
FT /note="AMP-threonine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 37
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 73
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 196
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 389
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 257..290
FT /evidence="ECO:0000250"
FT DISULFID 397..404
FT /evidence="ECO:0000250"
FT VAR_SEQ 157..189
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_032370"
FT CONFLICT 88
FT /note="S -> N (in Ref. 3; AAH27749)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="I -> V (in Ref. 2; BAE34135)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 456 AA; 51611 MW; 7B94928E4EACAD91 CRC64;
MFNMKILVIP LFWGLVTGYK GNSSDSSAPR LLLVSFDGFR ADYLKSYDLP HLQNFIKEGV
LVEHVKNVFI TKTFPNHYSI VTGLYEESHG IVANSMYDSV TKKHFSESND KDPFWWNGAE
PIWVTNQLQE NRSSAAAMWP GTDVPIHNIT ASYFMNYSSS VSFKERLGNV TTWLSSSNPP
VTFAALYWEE PDVSGHKYGP EDKENMRRVL KEVDDLIGDI VLKLKVLGLW DSLNVIITSD
HGMAQCSKNR LIDLDSCIDR SNYSVIDLTP VAAILPKINV TEVYDKLKRC NPHMNVYLKE
AIPNRFYYQH SSRIQPIILV AEEGWTITLN KSSFKLGDHG YDNSLPSMHP FLAAHGPAFR
KGYRQSTINT VDIYPMMCHI LGLKPHPNNG TLSHTKCLLV DQWCINLPEA IGIVVSALLV
LTMLTGLMIF MRSRASTSRP FSRLQLQEDD DDPLID
