5NT3A_HUMAN
ID 5NT3A_HUMAN Reviewed; 336 AA.
AC Q9H0P0; A8K253; B2RAA5; B8ZZC4; Q6IPZ1; Q6NXS6; Q7L3G6; Q9P0P5; Q9UC42;
AC Q9UC43; Q9UC44; Q9UC45;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Cytosolic 5'-nucleotidase 3A {ECO:0000305|PubMed:15968458, ECO:0000305|PubMed:24603684};
DE EC=3.1.3.5 {ECO:0000269|PubMed:15968458, ECO:0000269|PubMed:24603684};
DE AltName: Full=7-methylguanosine phosphate-specific 5'-nucleotidase {ECO:0000305|PubMed:24603684};
DE Short=7-methylguanosine nucleotidase;
DE EC=3.1.3.91 {ECO:0000269|PubMed:24603684};
DE AltName: Full=Cytosolic 5'-nucleotidase 3;
DE AltName: Full=Cytosolic 5'-nucleotidase III;
DE Short=cN-III;
DE AltName: Full=Pyrimidine 5'-nucleotidase 1;
DE Short=P5'N-1;
DE Short=P5N-1;
DE Short=PN-I;
DE AltName: Full=Uridine 5'-monophosphate hydrolase 1;
DE AltName: Full=p36;
GN Name=NT5C3A; Synonyms=NT5C3, P5N1, UMPH1; ORFNames=HSPC233;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PROTEIN SEQUENCE OF 92-111;
RP 131-155; 226-240; 268-296 AND 313-332.
RC TISSUE=Placenta;
RX PubMed=10942414;
RA Amici A., Emanuelli M., Raffaelli N., Ruggieri S., Saccucci F., Magni G.;
RT "Human erythrocyte pyrimidine 5'-nucleotidase, PN-I, is identical to p36, a
RT protein associated to lupus inclusion formation in response to alpha-
RT interferon.";
RL Blood 96:1596-1598(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND
RP VARIANT P5ND VAL-137.
RX PubMed=11369620; DOI=10.1182/blood.v97.11.3327;
RA Marinaki A.M., Escuredo E., Duley J.A., Simmonds H.A., Amici A.,
RA Naponelli V., Magni G., Seip M., Ben-Bassat I., Harley E.H., Thein S.L.,
RA Rees D.C.;
RT "Genetic basis of hemolytic anemia caused by pyrimidine 5' nucleotidase
RT deficiency.";
RL Blood 97:3327-3332(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain cortex, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, Lung, Muscle, and Prostate;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 29-336 (ISOFORM 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [10]
RP PROTEIN SEQUENCE OF 83-95; 131-147; 226-240; 268-296 AND 311-329,
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8557639; DOI=10.1074/jbc.271.20.11595;
RA Rich S.A., Bose M., Tempst P., Rudofsky U.H.;
RT "Purification, microsequencing, and immunolocalization of p36, a new
RT interferon-alpha-induced protein that is associated with human lupus
RT inclusions.";
RL J. Biol. Chem. 271:1118-1126(1996).
RN [11]
RP CHARACTERIZATION OF P5ND VAL-137; PRO-181; SER-229 AND ARG-280.
RX PubMed=15604219; DOI=10.1182/blood-2004-10-3895;
RA Chiarelli L.R., Bianchi P., Fermo E., Galizzi A., Iadarola P., Mattevi A.,
RA Zanella A., Valentini G.;
RT "Functional analysis of pyrimidine 5'-nucleotidase mutants causing
RT nonspherocytic hemolytic anemia.";
RL Blood 105:3340-3345(2005).
RN [12]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY,
RP CHARACTERIZATION OF VARIANTS P5ND SER-229 AND ARG-280, AND MUTAGENESIS OF
RP ASP-88; PHE-89; ASP-90; GLU-135; ASP-232; PHE-233 AND ASP-234.
RX PubMed=15968458; DOI=10.1007/s00018-005-5135-y;
RA Amici A., Ciccioli K., Naponelli V., Raffaelli N., Magni G.;
RT "Evidence for essential catalytic determinants for human erythrocyte
RT pyrimidine 5'-nucleotidase.";
RL Cell. Mol. Life Sci. 62:1613-1620(2005).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24603684; DOI=10.1371/journal.pone.0090915;
RA Monecke T., Buschmann J., Neumann P., Wahle E., Ficner R.;
RT "Crystal structures of the novel cytosolic 5'-nucleotidase IIIB explain its
RT preference for m7GMP.";
RL PLoS ONE 9:90915-90915(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.67 ANGSTROMS) OF 64-336 IN COMPLEX WITH PHOSPHATE
RP AND MAGNESIUM IONS, ACTIVE SITE, AND METAL BINDING.
RX PubMed=17405878; DOI=10.1074/jbc.m700917200;
RA Wallden K., Stenmark P., Nyman T., Flodin S., Graeslund S., Loppnau P.,
RA Bianchi V., Nordlund P.;
RT "Crystal structure of human cytosolic 5'-nucleotidase II: insights into
RT allosteric regulation and substrate recognition.";
RL J. Biol. Chem. 282:17828-17836(2007).
RN [17]
RP VARIANT P5ND SER-229.
RX PubMed=12930399; DOI=10.1046/j.1365-2141.2003.04532.x;
RA Bianchi P., Fermo E., Alfinito F., Vercellati C., Baserga M., Ferraro F.,
RA Guzzo I., Rotoli B., Zanella A.;
RT "Molecular characterization of six unrelated Italian patients affected by
RT pyrimidine 5'-nucleotidase deficiency.";
RL Br. J. Haematol. 122:847-851(2003).
RN [18]
RP VARIANTS P5ND PRO-181 AND ARG-280, IDENTIFICATION OF ISOFORM 4, TISSUE
RP SPECIFICITY, AND CHARACTERIZATION OF VARIANTS P5ND PRO-181 AND ARG-280.
RX PubMed=15238149; DOI=10.1111/j.1365-2141.2004.05029.x;
RA Kanno H., Takizawa T., Miwa S., Fujii H.;
RT "Molecular basis of Japanese variants of pyrimidine 5'-nucleotidase
RT deficiency.";
RL Br. J. Haematol. 126:265-271(2004).
RN [19]
RP VARIANTS P5ND PRO-181; ARG-207 AND THR-297.
RX PubMed=16461318;
RA Manco L., Relvas L., Silva Pinto C., Pereira J., Almeida A.B.,
RA Ribeiro M.L.;
RT "Molecular characterization of five Portuguese patients with pyrimidine 5'-
RT nucleotidase deficient hemolytic anemia showing three new P5'N-I
RT mutations.";
RL Haematologica 91:266-267(2006).
RN [20]
RP CHARACTERIZATION OF VARIANTS P5ND ARG-113; ARG-207 AND THR-297.
RX PubMed=18499901; DOI=10.1016/j.bcmd.2007.10.005;
RA Chiarelli L.R., Morera S.M., Galizzi A., Fermo E., Zanella A.,
RA Valentini G.;
RT "Molecular basis of pyrimidine 5'-nucleotidase deficiency caused by 3 newly
RT identified missense mutations (c.187T>C, c.469G>C and c.740T>C) and a
RT tabulation of known mutations.";
RL Blood Cells Mol. Dis. 40:295-301(2008).
RN [21]
RP VARIANT P5ND GLY-95.
RX PubMed=25153905; DOI=10.1016/j.bcmd.2014.05.009;
RA Dos Santos A., Dantas L.E., Traina F., Albuquerque D.M., Chaim E.A.,
RA Saad S.T.;
RT "Pyrimidine-5'-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3
RT gene associated with pyrimidine-5'-nucleotidase type I deficiency and
RT influence of Gilbert's Syndrome on clinical expression.";
RL Blood Cells Mol. Dis. 53:246-252(2014).
CC -!- FUNCTION: Nucleotidase which shows specific activity towards cytidine
CC monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP)
CC (PubMed:24603684). CMP seems to be the preferred substrate
CC (PubMed:15968458). {ECO:0000269|PubMed:15968458,
CC ECO:0000269|PubMed:24603684}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(7)-methyl-GMP = N(7)-methylguanosine + phosphate;
CC Xref=Rhea:RHEA:37107, ChEBI:CHEBI:15377, ChEBI:CHEBI:20794,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58285; EC=3.1.3.91;
CC Evidence={ECO:0000269|PubMed:24603684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP + H2O = cytidine + phosphate; Xref=Rhea:RHEA:29367,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17562, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:60377; EC=3.1.3.91;
CC Evidence={ECO:0000269|PubMed:15968458};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-phosphate + H2O = a ribonucleoside +
CC phosphate; Xref=Rhea:RHEA:12484, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:18254, ChEBI:CHEBI:43474, ChEBI:CHEBI:58043; EC=3.1.3.5;
CC Evidence={ECO:0000269|PubMed:15968458};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 uM for m(7)GMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:24603684};
CC KM=66 uM for CMP {ECO:0000269|PubMed:15968458};
CC KM=80 uM for CMP (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:24603684};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:17405878}.
CC -!- INTERACTION:
CC Q9H0P0; Q6ICB0: DESI1; NbExp=5; IntAct=EBI-3918356, EBI-2806959;
CC Q9H0P0; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-3918356, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2;
CC IsoId=Q9H0P0-4; Sequence=Displayed;
CC Name=1; Synonyms=P5N-I;
CC IsoId=Q9H0P0-1; Sequence=VSP_021565;
CC Name=3; Synonyms=p36;
CC IsoId=Q9H0P0-2; Sequence=VSP_015623;
CC Name=4; Synonyms=P5N-R;
CC IsoId=Q9H0P0-3; Sequence=VSP_015624;
CC -!- TISSUE SPECIFICITY: Isoforms 1, 3 and 4 are expressed in reticulocytes.
CC Isoform 4 is hardly detectable in bone marrow and fetal liver.
CC {ECO:0000269|PubMed:11369620, ECO:0000269|PubMed:15238149}.
CC -!- INDUCTION: Isoform 2 is induced by interferon alpha in Raji cells in
CC association with lupus inclusions. {ECO:0000269|PubMed:8557639}.
CC -!- DISEASE: P5N deficiency (P5ND) [MIM:266120]: Autosomal recessive
CC condition causing hemolytic anemia characterized by marked basophilic
CC stippling and the accumulation of high concentrations of pyrimidine
CC nucleotides within the erythrocyte. It is implicated in the anemia of
CC lead poisoning and is possibly associated with learning difficulties.
CC {ECO:0000269|PubMed:11369620, ECO:0000269|PubMed:12930399,
CC ECO:0000269|PubMed:15238149, ECO:0000269|PubMed:15604219,
CC ECO:0000269|PubMed:15968458, ECO:0000269|PubMed:16461318,
CC ECO:0000269|PubMed:18499901, ECO:0000269|PubMed:25153905}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the pyrimidine 5'-nucleotidase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF36153.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAG33630.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF312735; AAG33630.1; ALT_SEQ; mRNA.
DR EMBL; AL136716; CAB66650.1; -; mRNA.
DR EMBL; AK290118; BAF82807.1; -; mRNA.
DR EMBL; AK314109; BAG36802.1; -; mRNA.
DR EMBL; CR533518; CAG38549.1; -; mRNA.
DR EMBL; AC074338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC083863; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471073; EAW94007.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW94008.1; -; Genomic_DNA.
DR EMBL; BC013292; AAH13292.2; -; mRNA.
DR EMBL; BC015856; AAH15856.2; -; mRNA.
DR EMBL; BC066914; AAH66914.1; -; mRNA.
DR EMBL; BC071652; AAH71652.2; -; mRNA.
DR EMBL; AF151067; AAF36153.1; ALT_INIT; mRNA.
DR CCDS; CCDS34617.1; -. [Q9H0P0-1]
DR CCDS; CCDS55101.1; -. [Q9H0P0-3]
DR RefSeq; NP_001002009.1; NM_001002009.2. [Q9H0P0-1]
DR RefSeq; NP_001002010.1; NM_001002010.2.
DR RefSeq; NP_001159590.1; NM_001166118.2. [Q9H0P0-3]
DR RefSeq; NP_057573.2; NM_016489.12. [Q9H0P0-1]
DR RefSeq; XP_011513711.1; XM_011515409.2.
DR PDB; 2CN1; X-ray; 2.67 A; A=64-336.
DR PDB; 2JGA; X-ray; 3.01 A; A=64-336.
DR PDB; 2VKQ; X-ray; 2.50 A; A=64-336.
DR PDBsum; 2CN1; -.
DR PDBsum; 2JGA; -.
DR PDBsum; 2VKQ; -.
DR AlphaFoldDB; Q9H0P0; -.
DR SMR; Q9H0P0; -.
DR BioGRID; 119408; 101.
DR IntAct; Q9H0P0; 57.
DR MINT; Q9H0P0; -.
DR STRING; 9606.ENSP00000484415; -.
DR DEPOD; NT5C3A; -.
DR GlyGen; Q9H0P0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H0P0; -.
DR MetOSite; Q9H0P0; -.
DR PhosphoSitePlus; Q9H0P0; -.
DR SwissPalm; Q9H0P0; -.
DR BioMuta; NT5C3A; -.
DR DMDM; 117949804; -.
DR EPD; Q9H0P0; -.
DR jPOST; Q9H0P0; -.
DR MassIVE; Q9H0P0; -.
DR MaxQB; Q9H0P0; -.
DR PaxDb; Q9H0P0; -.
DR PeptideAtlas; Q9H0P0; -.
DR PRIDE; Q9H0P0; -.
DR ProteomicsDB; 80305; -. [Q9H0P0-4]
DR ProteomicsDB; 80306; -. [Q9H0P0-1]
DR ProteomicsDB; 80307; -. [Q9H0P0-2]
DR ProteomicsDB; 80308; -. [Q9H0P0-3]
DR Antibodypedia; 26385; 187 antibodies from 27 providers.
DR DNASU; 51251; -.
DR Ensembl; ENST00000409467.6; ENSP00000387166.1; ENSG00000122643.23. [Q9H0P0-3]
DR Ensembl; ENST00000643244.1; ENSP00000496364.1; ENSG00000122643.23. [Q9H0P0-1]
DR GeneID; 51251; -.
DR KEGG; hsa:51251; -.
DR UCSC; uc003tdi.5; human. [Q9H0P0-4]
DR CTD; 51251; -.
DR DisGeNET; 51251; -.
DR GeneCards; NT5C3A; -.
DR HGNC; HGNC:17820; NT5C3A.
DR HPA; ENSG00000122643; Tissue enhanced (skeletal).
DR MalaCards; NT5C3A; -.
DR MIM; 266120; phenotype.
DR MIM; 606224; gene.
DR neXtProt; NX_Q9H0P0; -.
DR OpenTargets; ENSG00000122643; -.
DR Orphanet; 35120; Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency.
DR PharmGKB; PA31802; -.
DR VEuPathDB; HostDB:ENSG00000122643; -.
DR eggNOG; KOG3128; Eukaryota.
DR GeneTree; ENSGT00390000012959; -.
DR HOGENOM; CLU_048584_0_2_1; -.
DR OrthoDB; 1171042at2759; -.
DR PhylomeDB; Q9H0P0; -.
DR TreeFam; TF314663; -.
DR BRENDA; 3.1.3.91; 2681.
DR PathwayCommons; Q9H0P0; -.
DR Reactome; R-HSA-73621; Pyrimidine catabolism. [Q9H0P0-4]
DR SABIO-RK; Q9H0P0; -.
DR SignaLink; Q9H0P0; -.
DR BioGRID-ORCS; 51251; 55 hits in 1040 CRISPR screens.
DR ChiTaRS; NT5C3A; human.
DR EvolutionaryTrace; Q9H0P0; -.
DR GeneWiki; NT5C3; -.
DR GenomeRNAi; 51251; -.
DR Pharos; Q9H0P0; Tbio.
DR PRO; PR:Q9H0P0; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9H0P0; protein.
DR Bgee; ENSG00000122643; Expressed in quadriceps femoris and 103 other tissues.
DR ExpressionAtlas; Q9H0P0; baseline and differential.
DR Genevisible; Q9H0P0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0008253; F:5'-nucleotidase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; NAS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0000215; F:tRNA 2'-phosphotransferase activity; TAS:UniProtKB.
DR GO; GO:0106411; F:XMP 5'-nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006213; P:pyrimidine nucleoside metabolic process; NAS:UniProtKB.
DR CDD; cd07504; HAD_5NT; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006434; Pyrimidine_nucleotidase_eu.
DR Pfam; PF05822; UMPH-1; 1.
DR SFLD; SFLDG01128; C1.4:_5'-Nucleotidase_Like; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01544; HAD-SF-IE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Disease variant; Endoplasmic reticulum; Hydrolase; Magnesium;
KW Metal-binding; Nucleotide metabolism; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..336
FT /note="Cytosolic 5'-nucleotidase 3A"
FT /id="PRO_0000064387"
FT ACT_SITE 88
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:17405878"
FT ACT_SITE 90
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:17405878"
FT BINDING 88
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17405878"
FT BINDING 90
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17405878"
FT BINDING 135
FT /ligand="CMP"
FT /ligand_id="ChEBI:CHEBI:60377"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 135
FT /ligand="N(7)-methyl-GMP"
FT /ligand_id="ChEBI:CHEBI:58285"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 156
FT /ligand="N(7)-methyl-GMP"
FT /ligand_id="ChEBI:CHEBI:58285"
FT /evidence="ECO:0000250|UniProtKB:Q9W197"
FT BINDING 203..204
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17405878"
FT BINDING 252
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9D020"
FT BINDING 277
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17405878"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D020"
FT VAR_SEQ 1..51
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15238149"
FT /id="VSP_015624"
FT VAR_SEQ 1..50
FT /note="MRAPSMDRAAVARVGAVASASVCALVAGVVLAQYIFTLKRKTGRKTKIIE
FT -> MTNQESAVHVK (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:11369620,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021565"
FT VAR_SEQ 1..50
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11369620,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_015623"
FT VARIANT 95
FT /note="R -> G (in P5ND; dbSNP:rs766577643)"
FT /evidence="ECO:0000269|PubMed:25153905"
FT /id="VAR_073160"
FT VARIANT 113
FT /note="C -> R (in P5ND; reduced catalytic activity
FT especially towards UMP)"
FT /evidence="ECO:0000269|PubMed:18499901"
FT /id="VAR_073161"
FT VARIANT 137
FT /note="D -> V (in P5ND; reduced catalytic activity;
FT dbSNP:rs104894025)"
FT /evidence="ECO:0000269|PubMed:11369620,
FT ECO:0000269|PubMed:15604219"
FT /id="VAR_023511"
FT VARIANT 181
FT /note="L -> P (in P5ND; reduced catalytic activity in
FT vitro; reduced protein stability in vivo, probably through
FT increased proteasomal degradation)"
FT /evidence="ECO:0000269|PubMed:15238149,
FT ECO:0000269|PubMed:15604219, ECO:0000269|PubMed:16461318"
FT /id="VAR_023512"
FT VARIANT 207
FT /note="G -> R (in P5ND; reduced catalytic activity
FT especially towards UMP)"
FT /evidence="ECO:0000269|PubMed:16461318,
FT ECO:0000269|PubMed:18499901"
FT /id="VAR_073162"
FT VARIANT 229
FT /note="N -> S (in P5ND; almost complete loss of catalytic
FT activity; dbSNP:rs104894028)"
FT /evidence="ECO:0000269|PubMed:12930399,
FT ECO:0000269|PubMed:15604219, ECO:0000269|PubMed:15968458"
FT /id="VAR_023513"
FT VARIANT 280
FT /note="G -> R (in P5ND; greatly reduced catalytic activity;
FT dbSNP:rs104894029)"
FT /evidence="ECO:0000269|PubMed:15238149,
FT ECO:0000269|PubMed:15604219, ECO:0000269|PubMed:15968458"
FT /id="VAR_023514"
FT VARIANT 297
FT /note="I -> T (in P5ND)"
FT /evidence="ECO:0000269|PubMed:16461318,
FT ECO:0000269|PubMed:18499901"
FT /id="VAR_073163"
FT MUTAGEN 88
FT /note="D->N: Loss of nucleotidase and phosphotransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT MUTAGEN 89
FT /note="F->A: Almost complete loss of nucleotidase and
FT phosphotransferase activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT MUTAGEN 90
FT /note="D->N: Loss of nucleotidase and phosphotransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT MUTAGEN 135
FT /note="E->D: No effect on nucleotidase activity. Almost
FT complete loss of phosphotransferase activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT MUTAGEN 232
FT /note="D->N: No effect on nucleotidase and
FT phosphotransferase activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT MUTAGEN 233
FT /note="F->A: Almost complete loss of nucleotidase and
FT phosphotransferase activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT MUTAGEN 234
FT /note="D->N: No effect on nucleotidase and
FT phosphotransferase activity."
FT /evidence="ECO:0000269|PubMed:15968458"
FT CONFLICT 95
FT /note="R -> K (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="E -> Q (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="N -> R (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 65..78
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:2VKQ"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 106..111
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 118..135
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 142..163
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 170..175
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 185..194
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 199..206
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 207..216
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 224..229
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 252..258
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 260..264
FT /evidence="ECO:0007829|PDB:2VKQ"
FT TURN 265..268
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 271..279
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 280..283
FT /evidence="ECO:0007829|PDB:2VKQ"
FT TURN 284..287
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 292..300
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 304..312
FT /evidence="ECO:0007829|PDB:2VKQ"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:2VKQ"
FT HELIX 326..335
FT /evidence="ECO:0007829|PDB:2VKQ"
SQ SEQUENCE 336 AA; 37948 MW; C5D75CCF1BB61021 CRC64;
MRAPSMDRAA VARVGAVASA SVCALVAGVV LAQYIFTLKR KTGRKTKIIE MMPEFQKSSV
RIKNPTRVEE IICGLIKGGA AKLQIITDFD MTLSRFSYKG KRCPTCHNII DNCKLVTDEC
RKKLLQLKEK YYAIEVDPVL TVEEKYPYMV EWYTKSHGLL VQQALPKAKL KEIVAESDVM
LKEGYENFFD KLQQHSIPVF IFSAGIGDVL EEVIRQAGVY HPNVKVVSNF MDFDETGVLK
GFKGELIHVF NKHDGALRNT EYFNQLKDNS NIILLGDSQG DLRMADGVAN VEHILKIGYL
NDRVDELLEK YMDSYDIVLV QDESLEVANS ILQKIL
