ENTP4_MOUSE
ID ENTP4_MOUSE Reviewed; 613 AA.
AC Q9DBT4;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Ectonucleoside triphosphate diphosphohydrolase 4;
DE Short=NTPDase 4;
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q9Y227};
DE EC=3.6.1.6 {ECO:0000250|UniProtKB:Q9Y227};
DE AltName: Full=Lysosomal apyrase-like protein of 70 kDa;
DE AltName: Full=Uridine-diphosphatase;
DE Short=UDPase;
DE EC=3.6.1.42 {ECO:0000250|UniProtKB:Q9Y227};
GN Name=Entpd4; Synonyms=Lalp70, Lysal1;
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 1).
RC STRAIN=C57BL/6J; TISSUE=Lung;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Mammary gland;
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 ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=10858452; DOI=10.1074/jbc.m001245200;
RA Biederbick A., Kosan C., Kunz J., Elsaesser H.-P.;
RT "First apyrase splice variants have different enzymatic properties.";
RL J. Biol. Chem. 275:19018-19024(2000).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue;
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: [Isoform 1]: Catalyzes the hydrolysis of nucleoside
CC triphosphates and diphosphates in a calcium- or magnesium-dependent
CC manner, with a preference for pyrimidines. Preferentially hydrolyzes
CC UTP and TTP on UTP and TTP. AMP, ADP, ATP and UMP are not substrates.
CC Preferentially activated by Ca(2+) over Mg(2+).
CC {ECO:0000250|UniProtKB:Q9Y227}.
CC -!- FUNCTION: [Isoform 2]: Has a broad substrate specificity with the
CC ability of cleaving all nucleotide di- and triphosphates with the
CC exception of adenosine di- and triphosphate (ADP and ATP).
CC Preferentially hydrolyzes CTP, UDP, CDP, GTP and GDP. Can use either
CC Ca(2+) or Mg(2+) equally. {ECO:0000250|UniProtKB:Q9Y227}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23681;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-diphosphate + H2O = a ribonucleoside 5'-
CC phosphate + H(+) + phosphate; Xref=Rhea:RHEA:36799,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:58043; EC=3.6.1.6;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36800;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + UDP = H(+) + phosphate + UMP; Xref=Rhea:RHEA:64876,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57865, ChEBI:CHEBI:58223; EC=3.6.1.6;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64877;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + UTP = H(+) + phosphate + UDP; Xref=Rhea:RHEA:64900,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:46398, ChEBI:CHEBI:58223;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64901;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + H2O = CDP + H(+) + phosphate; Xref=Rhea:RHEA:29387,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37563,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58069;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29388;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP + H2O = GMP + H(+) + phosphate; Xref=Rhea:RHEA:22156,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58115, ChEBI:CHEBI:58189; EC=3.6.1.42;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22157;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + TTP = H(+) + phosphate + TDP; Xref=Rhea:RHEA:65580,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:61417, ChEBI:CHEBI:63527;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65581;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9Y227};
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000250|UniProtKB:Q9Y227}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9Y227}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9Y227}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9Y227}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9Y227}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LALP70 {ECO:0000303|PubMed:10858452};
CC IsoId=Q9DBT4-1; Sequence=Displayed;
CC Name=2; Synonyms=LALP70V {ECO:0000303|PubMed:10858452};
CC IsoId=Q9DBT4-2; Sequence=VSP_003615;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10858452}.
CC -!- SIMILARITY: Belongs to the GDA1/CD39 NTPase family. {ECO:0000305}.
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DR EMBL; AK004761; BAB23542.1; -; mRNA.
DR EMBL; BC006924; AAH06924.1; -; mRNA.
DR EMBL; BC043134; AAH43134.1; -; mRNA.
DR CCDS; CCDS27240.1; -. [Q9DBT4-1]
DR RefSeq; NP_080450.1; NM_026174.3. [Q9DBT4-1]
DR RefSeq; XP_003688976.1; XM_003688928.3.
DR RefSeq; XP_003688977.1; XM_003688929.4.
DR RefSeq; XP_006519516.1; XM_006519453.2.
DR AlphaFoldDB; Q9DBT4; -.
DR SMR; Q9DBT4; -.
DR STRING; 10090.ENSMUSP00000138944; -.
DR GlyGen; Q9DBT4; 2 sites.
DR PhosphoSitePlus; Q9DBT4; -.
DR EPD; Q9DBT4; -.
DR MaxQB; Q9DBT4; -.
DR PaxDb; Q9DBT4; -.
DR PRIDE; Q9DBT4; -.
DR ProteomicsDB; 275458; -. [Q9DBT4-1]
DR ProteomicsDB; 275459; -. [Q9DBT4-2]
DR DNASU; 67464; -.
DR Ensembl; ENSMUST00000064831; ENSMUSP00000065046; ENSMUSG00000095463. [Q9DBT4-1]
DR Ensembl; ENSMUST00000184973; ENSMUSP00000138944; ENSMUSG00000095463. [Q9DBT4-1]
DR Ensembl; ENSMUST00000185072; ENSMUSP00000139202; ENSMUSG00000022066. [Q9DBT4-1]
DR GeneID; 67464; -.
DR KEGG; mmu:67464; -.
DR UCSC; uc007umi.2; mouse. [Q9DBT4-1]
DR UCSC; uc007umk.2; mouse. [Q9DBT4-2]
DR CTD; 9583; -.
DR MGI; MGI:1914714; Entpd4.
DR VEuPathDB; HostDB:ENSMUSG00000022066; -.
DR VEuPathDB; HostDB:ENSMUSG00000095463; -.
DR eggNOG; KOG1386; Eukaryota.
DR GeneTree; ENSGT01050000244974; -.
DR HOGENOM; CLU_010246_6_0_1; -.
DR InParanoid; Q9DBT4; -.
DR OMA; QDEIGPP; -.
DR OrthoDB; 1337265at2759; -.
DR PhylomeDB; Q9DBT4; -.
DR TreeFam; TF354343; -.
DR Reactome; R-MMU-8850843; Phosphate bond hydrolysis by NTPDase proteins.
DR BioGRID-ORCS; 100862375; 0 hits in 3 CRISPR screens.
DR BioGRID-ORCS; 67464; 0 hits in 38 CRISPR screens.
DR ChiTaRS; Entpd4; mouse.
DR PRO; PR:Q9DBT4; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9DBT4; protein.
DR Bgee; ENSMUSG00000022066; Expressed in proximal tubule and 58 other tissues.
DR ExpressionAtlas; Q9DBT4; baseline.
DR Genevisible; Q9DBT4; MM.
DR GO; GO:0000421; C:autophagosome membrane; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0043273; F:CTPase activity; ISS:UniProtKB.
DR GO; GO:0036384; F:cytidine-diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0004382; F:guanosine-diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0017110; F:nucleoside-diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0017111; F:nucleoside-triphosphatase activity; ISS:UniProtKB.
DR GO; GO:0045134; F:uridine-diphosphatase activity; ISS:UniProtKB.
DR GO; GO:0046036; P:CTP metabolic process; ISS:UniProtKB.
DR GO; GO:0046712; P:GDP catabolic process; ISS:UniProtKB.
DR GO; GO:0034656; P:nucleobase-containing small molecule catabolic process; ISS:UniProtKB.
DR GO; GO:0009134; P:nucleoside diphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0006256; P:UDP catabolic process; ISS:UniProtKB.
DR InterPro; IPR000407; GDA1_CD39_NTPase.
DR PANTHER; PTHR11782; PTHR11782; 1.
DR Pfam; PF01150; GDA1_CD39; 1.
DR PROSITE; PS01238; GDA1_CD39_NTPASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Hydrolase; Lysosome; Magnesium; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..613
FT /note="Ectonucleoside triphosphate diphosphohydrolase 4"
FT /id="PRO_0000209912"
FT TOPO_DOM 1..33
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..559
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9Y227"
FT TRANSMEM 560..580
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 581..613
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 222
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O35795"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 368..395
FT /evidence="ECO:0000250|UniProtKB:Q9Y227"
FT DISULFID 461..490
FT /evidence="ECO:0000250|UniProtKB:Q9Y227"
FT VAR_SEQ 287..294
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003615"
SQ SEQUENCE 613 AA; 69746 MW; DE528F512ABEF52F CRC64;
MGRIGISCLF PASWHFSISP VGCPRILNTN LRQIVVISIL AAAVSLLYFS VVIIRSKYGW
LSKDKKFQRY LARVTDVEAT DTNNPSVNYG IVVDCGSSGS RIFVYCWPRH NGNPHDLLDI
RQMRDKNRKP VVMKIKPGIS EFATSPEKVS DYISPLLSFA AEHVPRAKHK ETPLYILCTA
GMRVLPESQQ KAILEDLLTD IPVHYDFLFS DSHAEVISGK QEGVYAWIGI NFVLGRFEHI
EEDDEAVVEV NIPGSESSEA IVRKRTAGVL DMGGVSTQIA YEVPQTVSFA SSQQEEVAKN
LLAEFNLGCD VHQTEHVYRV YVATFLGFGG NAARQRYEDR LFASTVQKNR LLGKQTGLTP
DAPLLDPCLP LDIKDEIQQN GQTLYLQGTG DFDLCRETLQ PFMNKTNETQ TSLNGVYQPP
IHFQNSEFYG FSEFYYCTED VLRMGGDYNA ARFTQAAKDY CATKWSILRE RFDRGLYASH
ADLHRLKYQC FKSAWMFEVF HKGFSFPVTY KNLKTALQVY DKEVQWTLGA ILYRTRFLPL
RDIRQEVFRA GHAHWRGVSF VYNHYLFSGC FLVVLLSILL YLLRLRRIHR RAPRTGSLWM
EEGLPSQKGP GPL
