Full text data of NT5C3A
NT5C3A
(NT5C3, P5N1, UMPH1)
[Confidence: low (only semi-automatic identification from reviews)]
Cytosolic 5'-nucleotidase 3A; 3.1.3.5 (Cytosolic 5'-nucleotidase 3; Cytosolic 5'-nucleotidase III; cN-III; Pyrimidine 5'-nucleotidase 1; P5'N-1; P5N-1; PN-I; Uridine 5'-monophosphate hydrolase 1; p36)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Cytosolic 5'-nucleotidase 3A; 3.1.3.5 (Cytosolic 5'-nucleotidase 3; Cytosolic 5'-nucleotidase III; cN-III; Pyrimidine 5'-nucleotidase 1; P5'N-1; P5N-1; PN-I; Uridine 5'-monophosphate hydrolase 1; p36)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9H0P0
ID 5NT3A_HUMAN Reviewed; 336 AA.
AC Q9H0P0; A8K253; B2RAA5; B8ZZC4; Q6IPZ1; Q6NXS6; Q7L3G6; Q9P0P5;
read moreAC Q9UC42; Q9UC43; Q9UC44; Q9UC45;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 3.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Cytosolic 5'-nucleotidase 3A;
DE EC=3.1.3.5;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Placenta;
RX PubMed=10942414;
RA Amici A., Emanuelli M., Raffaelli N., Ruggieri S., Saccucci F.,
RA Magni G.;
RT "Human erythrocyte pyrimidine 5'-nucleotidase, PN-I, is identical to
RT p36, a protein associated to lupus inclusion formation in response to
RT alpha-interferon.";
RL Blood 96:1596-1598(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND
RP VARIANT P5N DEFICIENCY 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.,
RA Thein S.L., Rees D.C.;
RT "Genetic basis of hemolytic anemia caused by pyrimidine 5'
RT nucleotidase deficiency.";
RL Blood 97:3327-3332(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, VARIANTS
RP P5N DEFICIENCY PRO-181 AND ARG-280, AND CHARACTERIZATION OF VARIANTS
RP P5N DEFICIENCY 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 [4]
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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
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 [7]
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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
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
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [11]
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 [12]
RP PROTEIN SEQUENCE OF 1-11, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES,
RP CHARACTERIZATION OF VARIANTS P5N DEFICIENCY VAL-137; PRO-181; SER-229
RP AND ARG-280, AND MUTAGENESIS OF ASP-88; PHE-89; ASP-90; GLU-135 AND
RP PHE-233.
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.,
RA Buerckstuemmer T., 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.67 ANGSTROMS) OF 64-336 IN COMPLEX WITH
RP PHOSPHATE AND MAGNESIUM IONS.
RX PubMed=17405878; DOI=10.1074/jbc.M700917200;
RA Wallden K., Stenmark P., Nyman T., Flodin S., Graeslund S.,
RA Loppnau P., Bianchi V., Nordlund P.;
RT "Crystal structure of human cytosolic 5'-nucleotidase II: insights
RT into allosteric regulation and substrate recognition.";
RL J. Biol. Chem. 282:17828-17836(2007).
RN [16]
RP VARIANT P5N DEFICIENCY 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.,
RA Ferraro F., Guzzo I., Rotoli B., Zanella A.;
RT "Molecular characterization of six unrelated Italian patients affected
RT by pyrimidine 5'-nucleotidase deficiency.";
RL Br. J. Haematol. 122:847-851(2003).
CC -!- FUNCTION: Can act both as nucleotidase and as phosphotransferase.
CC -!- CATALYTIC ACTIVITY: A 5'-ribonucleotide + H(2)O = a ribonucleoside
CC + phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=66 uM for CMP;
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
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;
CC IsoId=Q9H0P0-1; Sequence=VSP_021565;
CC Name=3;
CC IsoId=Q9H0P0-2; Sequence=VSP_015623;
CC Name=4; Synonyms=P5N-R;
CC IsoId=Q9H0P0-3; Sequence=VSP_015624;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are expressed in
CC reticulocytes and lymphocytes. Isoform 4 is expressed only in
CC reticulocytes.
CC -!- INDUCTION: Isoform 2 is induced by interferon alpha in Raji cells
CC in association with lupus inclusions.
CC -!- DISEASE: P5N deficiency (P5ND) [MIM:266120]: Autosomal recessive
CC condition causing hemolytic anemia characterized by marked
CC basophilic stippling and the accumulation of high concentrations
CC of pyrimidine nucleotides within the erythrocyte. It is implicated
CC in the anemia of lead poisoning and is possibly associated with
CC learning difficulties. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the pyrimidine 5'-nucleotidase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF36153.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAG33630.1; Type=Frameshift; Positions=Several;
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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 RefSeq; NP_001002009.1; NM_001002009.2.
DR RefSeq; NP_001002010.1; NM_001002010.2.
DR RefSeq; NP_001159590.1; NM_001166118.2.
DR RefSeq; NP_057573.2; NM_016489.12.
DR UniGene; Hs.487933; -.
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 ProteinModelPortal; Q9H0P0; -.
DR SMR; Q9H0P0; 64-336.
DR IntAct; Q9H0P0; 3.
DR MINT; MINT-3065844; -.
DR PhosphoSite; Q9H0P0; -.
DR DMDM; 117949804; -.
DR PaxDb; Q9H0P0; -.
DR PRIDE; Q9H0P0; -.
DR DNASU; 51251; -.
DR Ensembl; ENST00000242210; ENSP00000242210; ENSG00000122643.
DR Ensembl; ENST00000381626; ENSP00000371039; ENSG00000122643.
DR Ensembl; ENST00000396152; ENSP00000379456; ENSG00000122643.
DR Ensembl; ENST00000405342; ENSP00000385261; ENSG00000122643.
DR Ensembl; ENST00000409467; ENSP00000387166; ENSG00000122643.
DR GeneID; 51251; -.
DR KEGG; hsa:51251; -.
DR UCSC; uc003tdk.4; human.
DR CTD; 51251; -.
DR GeneCards; GC07M033056; -.
DR HGNC; HGNC:17820; NT5C3A.
DR HPA; HPA029058; -.
DR MIM; 266120; phenotype.
DR MIM; 606224; gene.
DR neXtProt; NX_Q9H0P0; -.
DR Orphanet; 35120; Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency.
DR PharmGKB; PA31802; -.
DR eggNOG; NOG266578; -.
DR HOVERGEN; HBG059750; -.
DR InParanoid; Q9H0P0; -.
DR KO; K01081; -.
DR OMA; NTEYFKQ; -.
DR PhylomeDB; Q9H0P0; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q9H0P0; -.
DR EvolutionaryTrace; Q9H0P0; -.
DR GeneWiki; NT5C3; -.
DR GenomeRNAi; 51251; -.
DR NextBio; 54391; -.
DR PRO; PR:Q9H0P0; -.
DR ArrayExpress; Q9H0P0; -.
DR Bgee; Q9H0P0; -.
DR Genevestigator; Q9H0P0; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0008665; F:2'-phosphotransferase activity; NAS:UniProtKB.
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:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; TAS:Reactome.
DR GO; GO:0046135; P:pyrimidine nucleoside catabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.1000; -; 2.
DR InterPro; IPR023214; HAD-like_dom.
DR InterPro; IPR006434; Pyrimidine_nucleotidase_eu.
DR PANTHER; PTHR13045; PTHR13045; 1.
DR Pfam; PF05822; UMPH-1; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01544; HAD-SF-IE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disease mutation; Endoplasmic reticulum;
KW Hydrolase; Magnesium; Metal-binding; Nucleotide metabolism;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1 336 Cytosolic 5'-nucleotidase 3A.
FT /FTId=PRO_0000064387.
FT REGION 203 204 Substrate binding.
FT ACT_SITE 88 88 Nucleophile.
FT ACT_SITE 90 90 Proton donor.
FT METAL 88 88 Magnesium.
FT METAL 90 90 Magnesium; via carbonyl oxygen.
FT METAL 277 277 Magnesium.
FT BINDING 252 252 Substrate.
FT VAR_SEQ 1 51 Missing (in isoform 4).
FT /FTId=VSP_015624.
FT VAR_SEQ 1 50 MRAPSMDRAAVARVGAVASASVCALVAGVVLAQYIFTLKRK
FT TGRKTKIIE -> MTNQESAVHVK (in isoform 1).
FT /FTId=VSP_021565.
FT VAR_SEQ 1 50 Missing (in isoform 3).
FT /FTId=VSP_015623.
FT VARIANT 137 137 D -> V (in P5N deficiency; may alter
FT protein structure).
FT /FTId=VAR_023511.
FT VARIANT 181 181 L -> P (in P5N deficiency; may alter
FT protein structure and markedly decreases
FT activity).
FT /FTId=VAR_023512.
FT VARIANT 229 229 N -> S (in P5N deficiency; markedly
FT decreases activity).
FT /FTId=VAR_023513.
FT VARIANT 280 280 G -> R (in P5N deficiency; markedly
FT decreases activity).
FT /FTId=VAR_023514.
FT MUTAGEN 88 88 D->N: Loss of nucleotidase and
FT phosphotransferase activity.
FT MUTAGEN 89 89 F->A: Increases Km for CMP 45-fold.
FT Reduces nucleotidase and
FT phosphotransferase activity by 99%.
FT MUTAGEN 90 90 D->N: Loss of nucleotidase and
FT phosphotransferase activity.
FT MUTAGEN 135 135 E->D: No effect on nucleotidase activity.
FT Reduces phosphotransferase activity by
FT 99%.
FT MUTAGEN 233 233 F->A: Reduces nucleotidase and
FT phosphotransferase activity by 97%.
FT CONFLICT 95 95 R -> K (in Ref. 11; AA sequence).
FT CONFLICT 144 144 E -> Q (in Ref. 11; AA sequence).
FT CONFLICT 329 329 N -> R (in Ref. 11; AA sequence).
FT HELIX 65 78
FT HELIX 80 82
FT STRAND 83 87
FT TURN 90 92
FT STRAND 96 98
FT HELIX 106 111
FT HELIX 118 135
FT STRAND 138 140
FT HELIX 142 163
FT HELIX 167 169
FT HELIX 170 175
FT HELIX 185 194
FT STRAND 199 206
FT HELIX 207 216
FT STRAND 224 229
FT STRAND 231 233
FT STRAND 237 242
FT HELIX 252 258
FT HELIX 260 264
FT TURN 265 268
FT STRAND 271 279
FT HELIX 280 283
FT TURN 284 287
FT STRAND 292 300
FT HELIX 304 312
FT STRAND 315 320
FT HELIX 326 335
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
//
ID 5NT3A_HUMAN Reviewed; 336 AA.
AC Q9H0P0; A8K253; B2RAA5; B8ZZC4; Q6IPZ1; Q6NXS6; Q7L3G6; Q9P0P5;
read moreAC Q9UC42; Q9UC43; Q9UC44; Q9UC45;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 3.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Cytosolic 5'-nucleotidase 3A;
DE EC=3.1.3.5;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Placenta;
RX PubMed=10942414;
RA Amici A., Emanuelli M., Raffaelli N., Ruggieri S., Saccucci F.,
RA Magni G.;
RT "Human erythrocyte pyrimidine 5'-nucleotidase, PN-I, is identical to
RT p36, a protein associated to lupus inclusion formation in response to
RT alpha-interferon.";
RL Blood 96:1596-1598(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND
RP VARIANT P5N DEFICIENCY 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.,
RA Thein S.L., Rees D.C.;
RT "Genetic basis of hemolytic anemia caused by pyrimidine 5'
RT nucleotidase deficiency.";
RL Blood 97:3327-3332(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, VARIANTS
RP P5N DEFICIENCY PRO-181 AND ARG-280, AND CHARACTERIZATION OF VARIANTS
RP P5N DEFICIENCY 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 [4]
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.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
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 [7]
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.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA 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.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
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
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [11]
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 [12]
RP PROTEIN SEQUENCE OF 1-11, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES,
RP CHARACTERIZATION OF VARIANTS P5N DEFICIENCY VAL-137; PRO-181; SER-229
RP AND ARG-280, AND MUTAGENESIS OF ASP-88; PHE-89; ASP-90; GLU-135 AND
RP PHE-233.
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.,
RA Buerckstuemmer T., 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.67 ANGSTROMS) OF 64-336 IN COMPLEX WITH
RP PHOSPHATE AND MAGNESIUM IONS.
RX PubMed=17405878; DOI=10.1074/jbc.M700917200;
RA Wallden K., Stenmark P., Nyman T., Flodin S., Graeslund S.,
RA Loppnau P., Bianchi V., Nordlund P.;
RT "Crystal structure of human cytosolic 5'-nucleotidase II: insights
RT into allosteric regulation and substrate recognition.";
RL J. Biol. Chem. 282:17828-17836(2007).
RN [16]
RP VARIANT P5N DEFICIENCY 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.,
RA Ferraro F., Guzzo I., Rotoli B., Zanella A.;
RT "Molecular characterization of six unrelated Italian patients affected
RT by pyrimidine 5'-nucleotidase deficiency.";
RL Br. J. Haematol. 122:847-851(2003).
CC -!- FUNCTION: Can act both as nucleotidase and as phosphotransferase.
CC -!- CATALYTIC ACTIVITY: A 5'-ribonucleotide + H(2)O = a ribonucleoside
CC + phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=66 uM for CMP;
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (Potential).
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;
CC IsoId=Q9H0P0-1; Sequence=VSP_021565;
CC Name=3;
CC IsoId=Q9H0P0-2; Sequence=VSP_015623;
CC Name=4; Synonyms=P5N-R;
CC IsoId=Q9H0P0-3; Sequence=VSP_015624;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are expressed in
CC reticulocytes and lymphocytes. Isoform 4 is expressed only in
CC reticulocytes.
CC -!- INDUCTION: Isoform 2 is induced by interferon alpha in Raji cells
CC in association with lupus inclusions.
CC -!- DISEASE: P5N deficiency (P5ND) [MIM:266120]: Autosomal recessive
CC condition causing hemolytic anemia characterized by marked
CC basophilic stippling and the accumulation of high concentrations
CC of pyrimidine nucleotides within the erythrocyte. It is implicated
CC in the anemia of lead poisoning and is possibly associated with
CC learning difficulties. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the pyrimidine 5'-nucleotidase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF36153.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAG33630.1; Type=Frameshift; Positions=Several;
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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 RefSeq; NP_001002009.1; NM_001002009.2.
DR RefSeq; NP_001002010.1; NM_001002010.2.
DR RefSeq; NP_001159590.1; NM_001166118.2.
DR RefSeq; NP_057573.2; NM_016489.12.
DR UniGene; Hs.487933; -.
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 ProteinModelPortal; Q9H0P0; -.
DR SMR; Q9H0P0; 64-336.
DR IntAct; Q9H0P0; 3.
DR MINT; MINT-3065844; -.
DR PhosphoSite; Q9H0P0; -.
DR DMDM; 117949804; -.
DR PaxDb; Q9H0P0; -.
DR PRIDE; Q9H0P0; -.
DR DNASU; 51251; -.
DR Ensembl; ENST00000242210; ENSP00000242210; ENSG00000122643.
DR Ensembl; ENST00000381626; ENSP00000371039; ENSG00000122643.
DR Ensembl; ENST00000396152; ENSP00000379456; ENSG00000122643.
DR Ensembl; ENST00000405342; ENSP00000385261; ENSG00000122643.
DR Ensembl; ENST00000409467; ENSP00000387166; ENSG00000122643.
DR GeneID; 51251; -.
DR KEGG; hsa:51251; -.
DR UCSC; uc003tdk.4; human.
DR CTD; 51251; -.
DR GeneCards; GC07M033056; -.
DR HGNC; HGNC:17820; NT5C3A.
DR HPA; HPA029058; -.
DR MIM; 266120; phenotype.
DR MIM; 606224; gene.
DR neXtProt; NX_Q9H0P0; -.
DR Orphanet; 35120; Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency.
DR PharmGKB; PA31802; -.
DR eggNOG; NOG266578; -.
DR HOVERGEN; HBG059750; -.
DR InParanoid; Q9H0P0; -.
DR KO; K01081; -.
DR OMA; NTEYFKQ; -.
DR PhylomeDB; Q9H0P0; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; Q9H0P0; -.
DR EvolutionaryTrace; Q9H0P0; -.
DR GeneWiki; NT5C3; -.
DR GenomeRNAi; 51251; -.
DR NextBio; 54391; -.
DR PRO; PR:Q9H0P0; -.
DR ArrayExpress; Q9H0P0; -.
DR Bgee; Q9H0P0; -.
DR Genevestigator; Q9H0P0; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0008665; F:2'-phosphotransferase activity; NAS:UniProtKB.
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:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; TAS:Reactome.
DR GO; GO:0046135; P:pyrimidine nucleoside catabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.1000; -; 2.
DR InterPro; IPR023214; HAD-like_dom.
DR InterPro; IPR006434; Pyrimidine_nucleotidase_eu.
DR PANTHER; PTHR13045; PTHR13045; 1.
DR Pfam; PF05822; UMPH-1; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR01544; HAD-SF-IE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disease mutation; Endoplasmic reticulum;
KW Hydrolase; Magnesium; Metal-binding; Nucleotide metabolism;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1 336 Cytosolic 5'-nucleotidase 3A.
FT /FTId=PRO_0000064387.
FT REGION 203 204 Substrate binding.
FT ACT_SITE 88 88 Nucleophile.
FT ACT_SITE 90 90 Proton donor.
FT METAL 88 88 Magnesium.
FT METAL 90 90 Magnesium; via carbonyl oxygen.
FT METAL 277 277 Magnesium.
FT BINDING 252 252 Substrate.
FT VAR_SEQ 1 51 Missing (in isoform 4).
FT /FTId=VSP_015624.
FT VAR_SEQ 1 50 MRAPSMDRAAVARVGAVASASVCALVAGVVLAQYIFTLKRK
FT TGRKTKIIE -> MTNQESAVHVK (in isoform 1).
FT /FTId=VSP_021565.
FT VAR_SEQ 1 50 Missing (in isoform 3).
FT /FTId=VSP_015623.
FT VARIANT 137 137 D -> V (in P5N deficiency; may alter
FT protein structure).
FT /FTId=VAR_023511.
FT VARIANT 181 181 L -> P (in P5N deficiency; may alter
FT protein structure and markedly decreases
FT activity).
FT /FTId=VAR_023512.
FT VARIANT 229 229 N -> S (in P5N deficiency; markedly
FT decreases activity).
FT /FTId=VAR_023513.
FT VARIANT 280 280 G -> R (in P5N deficiency; markedly
FT decreases activity).
FT /FTId=VAR_023514.
FT MUTAGEN 88 88 D->N: Loss of nucleotidase and
FT phosphotransferase activity.
FT MUTAGEN 89 89 F->A: Increases Km for CMP 45-fold.
FT Reduces nucleotidase and
FT phosphotransferase activity by 99%.
FT MUTAGEN 90 90 D->N: Loss of nucleotidase and
FT phosphotransferase activity.
FT MUTAGEN 135 135 E->D: No effect on nucleotidase activity.
FT Reduces phosphotransferase activity by
FT 99%.
FT MUTAGEN 233 233 F->A: Reduces nucleotidase and
FT phosphotransferase activity by 97%.
FT CONFLICT 95 95 R -> K (in Ref. 11; AA sequence).
FT CONFLICT 144 144 E -> Q (in Ref. 11; AA sequence).
FT CONFLICT 329 329 N -> R (in Ref. 11; AA sequence).
FT HELIX 65 78
FT HELIX 80 82
FT STRAND 83 87
FT TURN 90 92
FT STRAND 96 98
FT HELIX 106 111
FT HELIX 118 135
FT STRAND 138 140
FT HELIX 142 163
FT HELIX 167 169
FT HELIX 170 175
FT HELIX 185 194
FT STRAND 199 206
FT HELIX 207 216
FT STRAND 224 229
FT STRAND 231 233
FT STRAND 237 242
FT HELIX 252 258
FT HELIX 260 264
FT TURN 265 268
FT STRAND 271 279
FT HELIX 280 283
FT TURN 284 287
FT STRAND 292 300
FT HELIX 304 312
FT STRAND 315 320
FT HELIX 326 335
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
//
MIM
266120
*RECORD*
*FIELD* NO
266120
*FIELD* TI
#266120 URIDINE 5-PRIME MONOPHOSPHATE HYDROLASE DEFICIENCY, HEMOLYTIC ANEMIA
DUE TO
read more;;HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY;;
PYRIMIDINE 5-PRIME NUCLEOTIDASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO;;
HEMOLYTIC ANEMIA DUE TO P5N DEFICIENCY;;
P5N DEFICIENCY;;
UMPH1 DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because hemolytic anemia due
to uridine 5-prime monophosphate hydrolase deficiency is caused by
homozygous or compound heterozygous mutation in the NT5C3A gene (606224)
on chromosome 7p14.
DESCRIPTION
Deficiency of pyrimidine 5-prime nucleotidase, also called uridine
5-prime monophosphate hydrolase, causes an autosomal recessive hemolytic
anemia characterized by marked basophilic stippling and the accumulation
of high concentrations of pyrimidine nucleotides within the erythrocyte.
The enzyme is implicated in the anemia of lead poisoning and is possibly
associated with learning difficulties. Hirono et al. (1988) suggested
that this deficiency is the third most common RBC enzymopathy--after
G6PD (300908) and pyruvate kinase (see 266200) deficiencies--causing
hemolysis (summary by Marinaki et al., 2001).
CLINICAL FEATURES
Valentine et al. (1974) showed deficiency of this enzyme in 4 subjects
with hereditary hemolytic anemia. Ribosephosphate pyrophosphokinase was
severely reduced, probably as an epiphenomenon resulting from inhibition
of its synthesis by high concentrations of pyrimidine.
Hansen et al. (1983) reported 2 affected Norwegian sibs, the first cases
in Scandinavia. The parents were distantly related. The 2 children
showed intravascular hemolysis with hemoglobinuria and loss of iron in
the urine necessitating iron medication.
Ericson et al. (1983) reported 2 affected Norwegian children, a brother
and sister, and noted that one of the first families of Valentine et al.
(1974) was of Norwegian origin. The disease has, however, been described
in many parts of the world. Disturbed synthesis of red cell membrane
phospholipids was suggested as being partly responsible for
intravascular hemolysis. Energy production was thought to be adequate.
Although not separable electrophoretically, 2 P5N isozymes with
different substrate specificities are demonstrable by the fact that
UMPH1 is lacking in patients with hemolytic anemia, whereas normal UMPH2
activity is retained in these patients; see 191720 (Swallow et al.,
1983; Paglia et al., 1984). Hirono et al. (1987) separated the 2
isozymes of P5N chromatographically and studied their biochemical
properties from 5 patients with P5N deficiency. They found that P5N-II
had normal activity and other normal enzymologic properties, whereas
P5N-I from these patients had abnormal properties including reduced
activity. They suggested that the main cause of P5N deficiency may be an
abnormality of P5N-I, probably arising from a structural gene mutation.
De Korte et al. (1989) concluded that analysis of ribonucleotide
patterns, in combination with determination of P5N activity, improves
the accuracy of diagnosis of heterozygosity. David et al. (1991)
demonstrated inhibition of the hexose monophosphate shunt in young
erythrocytes by pyrimidine nucleotides.
MOLECULAR GENETICS
In patients with hemolytic anemia due to deficiency of P5N, Marinaki et
al. (2001) identified mutations in the UMPH1 gene
(606224.0001-606224.0003).
In Turkish patients with pyrimidine 5-prime nucleotidase deficiency
(266120), Balta et al. (2003) identified homozygous mutations in the
UMPH1 gene (606224.0004-606224.0005).
*FIELD* SA
Anderson et al. (1975); Ben-Bassat et al. (1976); Beutler et al. (1980);
Harley et al. (1978); Hirono et al. (1983); Oda et al. (1984); Ozsoylu
and Gurgey (1981); Paglia et al. (1980); Paglia and Valentine (1980);
Paglia et al. (1983); Torrance et al. (1977); Vives-Corrons et al.
(1976)
*FIELD* RF
1. Anderson, J. A.; Teng, Y.-S.; Giblett, E. R.: Stains for six enzymes
potentially applicable to chromosomal assignment by cell hybridization. Cytogenet.
Cell Genet. 14: 295-299, 1975.
2. Balta, G.; Gumruk, F.; Akarsu, N.; Gurgey, A.; Altay, C.: Molecular
characterization of Turkish patients with pyrimidine 5-prime nucleotidase-I
deficiency. Blood 102: 1900-1903, 2003.
3. Ben-Bassat, I.; Brok-Simoni, F.; Kende, G.; Holtzmann, F.; Ramot,
B.: A family with red cell pyrimidine 5-prime-nucleotidase deficiency. Blood 47:
919-922, 1976.
4. Beutler, E.; Baranko, P. V.; Feagler, J.; Matsumoto, F.; Miro-Quesdada,
M.; Selby, G.; Singh, P.: Hemolytic anemia due to pyrimidine-5-prime-nucleotidase
deficiency: report of eight cases in six families. Blood 56: 251-255,
1980.
5. David, O.; Ramenghi, U.; Camaschella, C.; Vota, M. G.; Comino,
L.; Pescarmona, G. P.; Nicola, P.: Inhibition of hexose monophosphate
shunt in young erythrocytes by pyrimidine nucleotides in hereditary
pyrimidine 5-prime nucleotidase deficiency. Europ. J. Haemat. 47:
48-54, 1991.
6. de Korte, D.; Sijstermans, J. M.; Seip, M.; van Doorn, C. C. H.;
van Gennip, A. H.; Roos, D.: Pyrimidine 5-prime-nucleotidase deficiency:
improved detection of carriers. Clin. Chim. Acta 184: 175-180, 1989.
7. Ericson, A.; de Verdier, C.-H.; Hansen, T. W. R.; Seip, M.: Erythrocyte
nucleotide pattern in two children in a Norwegian family with pyrimidine
5-prime-nucleotidase deficiency. Clin. Chim. Acta 134: 25-33, 1983.
8. Hansen, T. W. R.; Seip, M.; de Verdier, C.-H.; Ericson, A.: Erythrocyte
pyrimidine 5-prime-nucleotidase deficiency: report of 2 new cases,
with a review of the literature. Scand. J. Haemat. 31: 122-128,
1983.
9. Harley, E. H.; Heaton, A.; Wicomb, W.: Pyrimidine metabolism in
hereditary erythrocyte pyrimidine 5-prime-nucleotidase deficiency. Metabolism 27:
1743-1754, 1978.
10. Hirono, A.; Forman, L.; Beutler, E.: Enzymatic diagnosis in non-spherocytic
hemolytic anemia. Medicine 67: 110-117, 1988.
11. Hirono, A.; Fujii, H.; Miyajima, H.; Kawakatsu, T.; Hiyoshi, Y.;
Miwa, S.: Three families with hereditary hemolytic anemia and pyrimidine
5-prime-nucleotidase deficiency: electrophoretic and kinetic studies. Clin.
Chim. Acta 130: 189-197, 1983.
12. Hirono, A.; Fujii, H.; Natori, H.; Kurokawa, I.; Miwa, S.: Chromatographic
analysis of human erythrocyte pyrimidine 5-prime-nucleotidase from
five patients with pyrimidine 5-prime-nucleotidase deficiency. Brit.
J. Haemat. 65: 35-41, 1987.
13. Marinaki, A. M.; Escuredo, E.; Duley, J. A.; Simmonds, H. A.;
Amici, A.; Naponelli, V.; Magni, G.; Seip, M.; Ben-Bassat, I.; Harley,
E. H.; Thein, S. L.; Rees, D. C.: Genetic basis of hemolytic anemia
caused by pyrimidine 5-prime-nucleotidase deficiency. Blood 97:
3327-3332, 2001.
14. Oda, E.; Oda, S.; Tomoda, A.; Lachant, N. A.; Tanaka, K. R.:
Hemolytic anemia in hereditary pyrimidine 5-prime-nucleotidase deficiency.
II. Effect of pyrimidine nucleotides and their derivatives on glycolytic
and pentose phosphate shunt enzyme activity. Clin. Chim. Acta 141:
93-100, 1984.
15. Ozsoylu, S.; Gurgey, A.: A case of hemolytic anemia due to erythrocyte
pyrimidine 5-prime-nucleotidase deficiency. Acta Haemat. 66: 56-58,
1981.
16. Paglia, D. E.; Fink, K.; Valentine, W. N.: Additional data from
two kindreds with genetically induced deficiencies of erythrocyte
pyrimidine nucleotidase. Acta Haemat. 63: 262-267, 1980.
17. Paglia, D. E.; Valentine, W. N.: Hereditary and acquired defects
in the pyrimidine nucleotidase of human erythrocytes. Curr. Top.
Hemat. 3: 75-109, 1980.
18. Paglia, D. E.; Valentine, W. N.; Brockway, R. A.: Identification
of thymidine nucleotidase and deoxyribonucleotidase activities among
normal isozymes of 5-prime-nucleotidase in human erythrocytes. Proc.
Nat. Acad. Sci. 81: 588-592, 1984.
19. Paglia, D. E.; Valentine, W. N.; Keitt, A. S.; Brockway, R. A.;
Nakatani, M.: Pyrimidine nucleotidase deficiency with active dephosphorylation
of dTMP: evidence for existence of thymidine nucleotidase in human
erythrocytes. Blood 62: 1147-1149, 1983.
20. Swallow, D. M.; Turner, V. S.; Hopkinson, D. A.: Isozymes of
rodent 5-prime-nucleotidase: evidence for two independent structural
loci UMPH-1 and UMPH-2. Ann. Hum. Genet. 47: 9-17, 1983.
21. Torrance, J. D.; Karabus, C. D.; Shnier, M.; Meltzer, M.; Katz,
J.; Jenkins, T.: Haemolytic anaemia due to erythrocyte pyrimidine
5-prime-nucleotidase deficiency: report of the first South African
family. S. Afr. Med. J. 52: 671-672, 1977.
22. Valentine, W. N.; Fink, K.; Paglia, D. E.; Harris, S. R.; Adams,
W. S.: Hereditary hemolytic anemia with human erythrocyte pyrimidine
5-prime-nucleotidase deficiency. J. Clin. Invest. 54: 866-879, 1974.
23. Vives-Corrons, J. L.; Montserrat-Costa, E.; Rozman, C.: Hereditary
hemolytic anemia with erythrocyte pyrimidine 5-prime-nucleotidase
deficiency in Spain. Clinical, biological and familial studies. Hum.
Genet. 34: 285-292, 1976.
*FIELD* CS
Heme:
Hemolytic anemia
Lab:
Intravascular hemolysis;
Hemoglobinuria;
Pyrimidine 5-prime-nucleotidase (P5N-I) deficiency;
Normal P5N-II;
Ribosephosphate pyrophosphokinase reduced
Inheritance:
Autosomal recessive;
probable heterogeneity
*FIELD* CN
Victor A. McKusick - updated: 8/28/2001
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/12/2013
carol: 10/24/2013
carol: 11/18/2005
carol: 8/28/2001
mimadm: 3/12/1994
carol: 3/31/1992
supermim: 3/17/1992
carol: 10/3/1991
carol: 3/29/1991
carol: 12/10/1990
*RECORD*
*FIELD* NO
266120
*FIELD* TI
#266120 URIDINE 5-PRIME MONOPHOSPHATE HYDROLASE DEFICIENCY, HEMOLYTIC ANEMIA
DUE TO
read more;;HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY;;
PYRIMIDINE 5-PRIME NUCLEOTIDASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO;;
HEMOLYTIC ANEMIA DUE TO P5N DEFICIENCY;;
P5N DEFICIENCY;;
UMPH1 DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because hemolytic anemia due
to uridine 5-prime monophosphate hydrolase deficiency is caused by
homozygous or compound heterozygous mutation in the NT5C3A gene (606224)
on chromosome 7p14.
DESCRIPTION
Deficiency of pyrimidine 5-prime nucleotidase, also called uridine
5-prime monophosphate hydrolase, causes an autosomal recessive hemolytic
anemia characterized by marked basophilic stippling and the accumulation
of high concentrations of pyrimidine nucleotides within the erythrocyte.
The enzyme is implicated in the anemia of lead poisoning and is possibly
associated with learning difficulties. Hirono et al. (1988) suggested
that this deficiency is the third most common RBC enzymopathy--after
G6PD (300908) and pyruvate kinase (see 266200) deficiencies--causing
hemolysis (summary by Marinaki et al., 2001).
CLINICAL FEATURES
Valentine et al. (1974) showed deficiency of this enzyme in 4 subjects
with hereditary hemolytic anemia. Ribosephosphate pyrophosphokinase was
severely reduced, probably as an epiphenomenon resulting from inhibition
of its synthesis by high concentrations of pyrimidine.
Hansen et al. (1983) reported 2 affected Norwegian sibs, the first cases
in Scandinavia. The parents were distantly related. The 2 children
showed intravascular hemolysis with hemoglobinuria and loss of iron in
the urine necessitating iron medication.
Ericson et al. (1983) reported 2 affected Norwegian children, a brother
and sister, and noted that one of the first families of Valentine et al.
(1974) was of Norwegian origin. The disease has, however, been described
in many parts of the world. Disturbed synthesis of red cell membrane
phospholipids was suggested as being partly responsible for
intravascular hemolysis. Energy production was thought to be adequate.
Although not separable electrophoretically, 2 P5N isozymes with
different substrate specificities are demonstrable by the fact that
UMPH1 is lacking in patients with hemolytic anemia, whereas normal UMPH2
activity is retained in these patients; see 191720 (Swallow et al.,
1983; Paglia et al., 1984). Hirono et al. (1987) separated the 2
isozymes of P5N chromatographically and studied their biochemical
properties from 5 patients with P5N deficiency. They found that P5N-II
had normal activity and other normal enzymologic properties, whereas
P5N-I from these patients had abnormal properties including reduced
activity. They suggested that the main cause of P5N deficiency may be an
abnormality of P5N-I, probably arising from a structural gene mutation.
De Korte et al. (1989) concluded that analysis of ribonucleotide
patterns, in combination with determination of P5N activity, improves
the accuracy of diagnosis of heterozygosity. David et al. (1991)
demonstrated inhibition of the hexose monophosphate shunt in young
erythrocytes by pyrimidine nucleotides.
MOLECULAR GENETICS
In patients with hemolytic anemia due to deficiency of P5N, Marinaki et
al. (2001) identified mutations in the UMPH1 gene
(606224.0001-606224.0003).
In Turkish patients with pyrimidine 5-prime nucleotidase deficiency
(266120), Balta et al. (2003) identified homozygous mutations in the
UMPH1 gene (606224.0004-606224.0005).
*FIELD* SA
Anderson et al. (1975); Ben-Bassat et al. (1976); Beutler et al. (1980);
Harley et al. (1978); Hirono et al. (1983); Oda et al. (1984); Ozsoylu
and Gurgey (1981); Paglia et al. (1980); Paglia and Valentine (1980);
Paglia et al. (1983); Torrance et al. (1977); Vives-Corrons et al.
(1976)
*FIELD* RF
1. Anderson, J. A.; Teng, Y.-S.; Giblett, E. R.: Stains for six enzymes
potentially applicable to chromosomal assignment by cell hybridization. Cytogenet.
Cell Genet. 14: 295-299, 1975.
2. Balta, G.; Gumruk, F.; Akarsu, N.; Gurgey, A.; Altay, C.: Molecular
characterization of Turkish patients with pyrimidine 5-prime nucleotidase-I
deficiency. Blood 102: 1900-1903, 2003.
3. Ben-Bassat, I.; Brok-Simoni, F.; Kende, G.; Holtzmann, F.; Ramot,
B.: A family with red cell pyrimidine 5-prime-nucleotidase deficiency. Blood 47:
919-922, 1976.
4. Beutler, E.; Baranko, P. V.; Feagler, J.; Matsumoto, F.; Miro-Quesdada,
M.; Selby, G.; Singh, P.: Hemolytic anemia due to pyrimidine-5-prime-nucleotidase
deficiency: report of eight cases in six families. Blood 56: 251-255,
1980.
5. David, O.; Ramenghi, U.; Camaschella, C.; Vota, M. G.; Comino,
L.; Pescarmona, G. P.; Nicola, P.: Inhibition of hexose monophosphate
shunt in young erythrocytes by pyrimidine nucleotides in hereditary
pyrimidine 5-prime nucleotidase deficiency. Europ. J. Haemat. 47:
48-54, 1991.
6. de Korte, D.; Sijstermans, J. M.; Seip, M.; van Doorn, C. C. H.;
van Gennip, A. H.; Roos, D.: Pyrimidine 5-prime-nucleotidase deficiency:
improved detection of carriers. Clin. Chim. Acta 184: 175-180, 1989.
7. Ericson, A.; de Verdier, C.-H.; Hansen, T. W. R.; Seip, M.: Erythrocyte
nucleotide pattern in two children in a Norwegian family with pyrimidine
5-prime-nucleotidase deficiency. Clin. Chim. Acta 134: 25-33, 1983.
8. Hansen, T. W. R.; Seip, M.; de Verdier, C.-H.; Ericson, A.: Erythrocyte
pyrimidine 5-prime-nucleotidase deficiency: report of 2 new cases,
with a review of the literature. Scand. J. Haemat. 31: 122-128,
1983.
9. Harley, E. H.; Heaton, A.; Wicomb, W.: Pyrimidine metabolism in
hereditary erythrocyte pyrimidine 5-prime-nucleotidase deficiency. Metabolism 27:
1743-1754, 1978.
10. Hirono, A.; Forman, L.; Beutler, E.: Enzymatic diagnosis in non-spherocytic
hemolytic anemia. Medicine 67: 110-117, 1988.
11. Hirono, A.; Fujii, H.; Miyajima, H.; Kawakatsu, T.; Hiyoshi, Y.;
Miwa, S.: Three families with hereditary hemolytic anemia and pyrimidine
5-prime-nucleotidase deficiency: electrophoretic and kinetic studies. Clin.
Chim. Acta 130: 189-197, 1983.
12. Hirono, A.; Fujii, H.; Natori, H.; Kurokawa, I.; Miwa, S.: Chromatographic
analysis of human erythrocyte pyrimidine 5-prime-nucleotidase from
five patients with pyrimidine 5-prime-nucleotidase deficiency. Brit.
J. Haemat. 65: 35-41, 1987.
13. Marinaki, A. M.; Escuredo, E.; Duley, J. A.; Simmonds, H. A.;
Amici, A.; Naponelli, V.; Magni, G.; Seip, M.; Ben-Bassat, I.; Harley,
E. H.; Thein, S. L.; Rees, D. C.: Genetic basis of hemolytic anemia
caused by pyrimidine 5-prime-nucleotidase deficiency. Blood 97:
3327-3332, 2001.
14. Oda, E.; Oda, S.; Tomoda, A.; Lachant, N. A.; Tanaka, K. R.:
Hemolytic anemia in hereditary pyrimidine 5-prime-nucleotidase deficiency.
II. Effect of pyrimidine nucleotides and their derivatives on glycolytic
and pentose phosphate shunt enzyme activity. Clin. Chim. Acta 141:
93-100, 1984.
15. Ozsoylu, S.; Gurgey, A.: A case of hemolytic anemia due to erythrocyte
pyrimidine 5-prime-nucleotidase deficiency. Acta Haemat. 66: 56-58,
1981.
16. Paglia, D. E.; Fink, K.; Valentine, W. N.: Additional data from
two kindreds with genetically induced deficiencies of erythrocyte
pyrimidine nucleotidase. Acta Haemat. 63: 262-267, 1980.
17. Paglia, D. E.; Valentine, W. N.: Hereditary and acquired defects
in the pyrimidine nucleotidase of human erythrocytes. Curr. Top.
Hemat. 3: 75-109, 1980.
18. Paglia, D. E.; Valentine, W. N.; Brockway, R. A.: Identification
of thymidine nucleotidase and deoxyribonucleotidase activities among
normal isozymes of 5-prime-nucleotidase in human erythrocytes. Proc.
Nat. Acad. Sci. 81: 588-592, 1984.
19. Paglia, D. E.; Valentine, W. N.; Keitt, A. S.; Brockway, R. A.;
Nakatani, M.: Pyrimidine nucleotidase deficiency with active dephosphorylation
of dTMP: evidence for existence of thymidine nucleotidase in human
erythrocytes. Blood 62: 1147-1149, 1983.
20. Swallow, D. M.; Turner, V. S.; Hopkinson, D. A.: Isozymes of
rodent 5-prime-nucleotidase: evidence for two independent structural
loci UMPH-1 and UMPH-2. Ann. Hum. Genet. 47: 9-17, 1983.
21. Torrance, J. D.; Karabus, C. D.; Shnier, M.; Meltzer, M.; Katz,
J.; Jenkins, T.: Haemolytic anaemia due to erythrocyte pyrimidine
5-prime-nucleotidase deficiency: report of the first South African
family. S. Afr. Med. J. 52: 671-672, 1977.
22. Valentine, W. N.; Fink, K.; Paglia, D. E.; Harris, S. R.; Adams,
W. S.: Hereditary hemolytic anemia with human erythrocyte pyrimidine
5-prime-nucleotidase deficiency. J. Clin. Invest. 54: 866-879, 1974.
23. Vives-Corrons, J. L.; Montserrat-Costa, E.; Rozman, C.: Hereditary
hemolytic anemia with erythrocyte pyrimidine 5-prime-nucleotidase
deficiency in Spain. Clinical, biological and familial studies. Hum.
Genet. 34: 285-292, 1976.
*FIELD* CS
Heme:
Hemolytic anemia
Lab:
Intravascular hemolysis;
Hemoglobinuria;
Pyrimidine 5-prime-nucleotidase (P5N-I) deficiency;
Normal P5N-II;
Ribosephosphate pyrophosphokinase reduced
Inheritance:
Autosomal recessive;
probable heterogeneity
*FIELD* CN
Victor A. McKusick - updated: 8/28/2001
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 11/12/2013
carol: 10/24/2013
carol: 11/18/2005
carol: 8/28/2001
mimadm: 3/12/1994
carol: 3/31/1992
supermim: 3/17/1992
carol: 10/3/1991
carol: 3/29/1991
carol: 12/10/1990
MIM
606224
*RECORD*
*FIELD* NO
606224
*FIELD* TI
*606224 5-PRIME-@NUCLEOTIDASE, CYTOSOLIC IIIA; NT5C3A
;;NUCLEOTIDASE, 5-PRIME, CYTOSOLIC III; NT5C3;;
read moreURIDINE 5-PRIME MONOPHOSPHATE HYDROLASE 1; UMPH1;;
PYRIMIDINE 5-PRIME-NUCLEOTIDASE 1; P5N1
*FIELD* TX
DESCRIPTION
Pyrimidine 5-prime-nucleotidase (P5N; EC 3.1.3.5), also called uridine
5-prime monophosphate hydrolase (UMPH), catalyzes the dephosphorylation
of the pyrimidine 5-prime monophosphates UMP and CMP to the
corresponding nucleosides. There are 2 isozymes of pyrimidine 5-prime
nucleotidase in red blood cells, referred to as type I (UMPH1) and type
II (UMPH2; 191720). The 2 enzymes are not separable by electrophoresis
in humans but have distinct kinetic properties, and the proteins show no
homology.
CLONING
Cloning of UMPH1 and expression in E. coli demonstrated that the protein
consists of 286 amino acids and is identical to a previously identified
lupus inclusion protein, p36 (Amici et al., 1994, 2000). Marinaki et al.
(2001) determined that alternative splicing of exon 2 results in a
297-amino acid form of the protein. Both forms of the protein are
expressed in reticulocytes and lymphocytes.
Kanno et al. (2004) identified a third alternatively spliced form of the
NT4C3 gene in reticulocytes, which included an additional 87-bp
sequence. The sequence is located 6.2 kb downstream of the exon 2
sequence and 2.7 kb upstream of the exon 3 sequence; consequently, the
gene contains 11 exons, which span approximately 48 kb.
GENE STRUCTURE
Using the putative cDNA sequence for UMPH1, Marinaki et al. (2001)
generated the genomic DNA sequence. The gene contains 10 exons with
alternative splicing of exon 2.
MAPPING
By sequence analysis, Marinaki et al. (2001) mapped the UMPH1 gene to
chromosome 7p15-p14. They identified UMPH1 pseudogenes on chromosomes 4
and 7.
MOLECULAR GENETICS
Pyrimidine 5-prime nucleotidase deficiency (266120) causes an autosomal
recessive hemolytic anemia characterized by marked basophilic stippling
and the accumulation of high concentrations of pyrimidine nucleotides
within the erythrocyte. The enzyme is implicated in the anemia of lead
poisoning and is possibly associated with learning difficulties. Type I
UMPH is deficient in cases of hemolytic anemia; the activity of type II
UMPH2 is normal in these cases. In patients with hemolytic anemia due to
deficiency of UMPH1, Marinaki et al. (2001) identified causative
homozygous mutations in the UMPH1 gene (606224.0001-606224.0003).
Rees et al. (2003) reviewed pyrimidine 5-prime nucleotidase deficiency.
They tabulated 7 mutations that had been identified in the UMPH1 gene.
They noted that following the discovery of pyrimidine 5-prime
nucleotidase deficiency, it was realized that the only other condition
that could cause such marked basophilic stippling was lead poisoning,
which is also a cause of hemolysis. The enzyme was known to be very
sensitive to inhibition by heavy metal ions. Most of the hematologic
features of lead poisoning can be explained by inhibition of this
enzyme, although the neurologic and other features are presumably due to
separate mechanisms.
Balta et al. (2003) characterized the molecular pathology of pyrimidine
5-prime nucleotidase deficiency in 6 Turkish patients from 4 unrelated
consanguineous families. They identified 3 different mutations in the
UMPH1 gene in these patients (606224.0004-606224.0006). In all families,
the parents were heterozygous for the relevant mutations.
Bianchi et al. (2003) studied the hematologic and molecular
characteristics of 6 unrelated patients with pyrimidine 5-prime
nucleotidase deficiency (1 from northern and 5 from southern Italy).
They identified 4 different mutations in the UMPH1 gene in these
patients (606224.0007-606224.0009), 5 of whom were homozygotes and 1 a
compound heterozygote. Parental consanguinity could be confirmed in only
1 case. Two patients carried the 743insGG mutation (604224.0004)
previously identified by Balta et al. (2003).
Kanno et al. (2004) identified 5 novel homozygous mutations in 9
Japanese families with pyrimidine 5-prime nucleotidase deficiency: 2
missense mutations (see 606224.0010), a splice mutation, a 1-bp
insertion, and a 9-bp deletion.
*FIELD* AV
.0001
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, ASP98VAL
In a Norwegian brother and sister with hemolytic anemia and basophilic
stippling (266120) reported by Hansen et al. (1983), Marinaki et al.
(2001) identified an asp98-to-val mutation of the UMPH1 gene. The sibs
were unusual in having intravascular hemolysis, urinary iron loss, iron
deposition in the kidneys, and iron deficiency. This had not been noted
in other published reports of UMPH1 deficiency. The parents, who were
heterozygous for the mutation, had a common ancestor 5 generations
earlier. At the time of the report, the sibs were in their late twenties
and maintained hemoglobin levels of approximately 10g/dL with no
significant complications from their chronic hemolysis.
.0002
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, GLN177TER
In an adopted South African girl who had typical hemolytic anemia with
basophilic stippling due to deficiency of pyrimidine 5-prime
nucleotidase (266120), Marinaki et al. (2001) found homozygosity for a
gln177-to-ter mutation in the UMPH1 gene.
.0003
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, IVS9AS, G-T, -1
In a 55-year-old white South African farmer with hemolytic anemia
associated with low levels of pyrimidine 5-prime nucleotidase and
intraerythrocytic accumulation of pyrimidine nucleotides (266120),
Marinaki et al. (2001) identified a splice site mutation in the UMPH1
gene, resulting in the loss of exon 9 (201 bp) from the cDNA. The same
nucleotide is involved in another splicing mutation (606224.0007).
.0004
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, 2-BP INS, 743GG
In 4 Turkish patients from 2 families with pyrimidine 5-prime
nucleotidase deficiency (266120), Balta et al. (2003) identified a
homozygous 2-bp insertion (743insGG) in exon 9 of the UMPH1 gene,
resulting in premature termination of translation 23 bp downstream.
In 2 Italian patients with 5-prime nucleotidase deficiency, Bianchi et
al. (2003) identified the 743insGG mutation, in homozygous state in 1
and in compound heterozygous state with an IVS9-1G-C mutation
(606224.0007) in the other.
.0005
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, TYR181TER
In affected members of a Turkish family with pyrimidine 5-prime
nucleotidase deficiency (266120), Balta et al. (2003) identified
homozygosity for a 543T-G transition in exon 8 of the UMPH1 gene,
resulting in a tyr181-to-ter (Y181X) mutation.
In 2 unrelated Italian patients with pyrimidine 5-prime nucleotidase
deficiency, Bianchi et al. (2003) identified the Y181X mutation.
.0006
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, 1-BP INS, 384A
In affected members of a Turkish family with pyrimidine 5-prime
nucleotidase deficiency (266120), Balta et al. (2003) identified
homozygosity for a 1-bp insertion (384insA) in exon 7 of the UMPH1 gene,
creating a stop signal at the codon nearby.
.0007
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, IVS9AS, G-C, -1
In an Italian patient with pyrimidine 5-prime nucleotidase deficiency
(266120), Bianchi et al. (2003) identified compound heterozygosity for 2
mutations in the UMPH1 gene: an IVS9-1G-C splicing mutation and a 2-bp
insertion (743insGG; 606224.0004). The same nucleotide is involved in
another splicing mutation (606224.0003).
.0008
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, ASN190SER
In affected members of an Italian family with pyrimidine 5-prime
nucleotidase deficiency (266120), Bianchi et al. (2003) identified an
AAT (asn)-to-AGT (ser) mutation at codon 190 (N190S) of the UMPH1 gene.
.0009
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, 1-BP DEL, 576G
In 3 patients originating from southern Italy with pyrimidine 5-prime
nucleotidase deficiency (266120), Bianchi et al. (2003) identified a
1-bp deletion (576delG) in the UMPH1 gene.
.0010
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, GLY241ARG
In affected members of 5 of 9 Japanese families with pyrimidine 5-prime
nucleotidase deficiency (266120), Kanno et al. (2004) identified
homozygosity for a G-to-C transversion in the UMPH1 gene, changing codon
241 from GGA (gly) to CGA (arg) (G241R). The 5 families with the G241R
mutation originated from the western coastal area of the Kyushu district
and shared a common haplotype, suggesting that G241R is a founder
mutation.
*FIELD* RF
1. Amici, A.; Emanuelli, M.; Ferretti, E.; Raffaelli, N.; Ruggieri,
S.; Magni, G.: Homogeneous pyrimidine nucleotidase from human erythrocytes:
enzymic and molecular properties. Biochem. J. 304: 987-992, 1994.
2. Amici, A.; Emanuelli, M.; Raffaelli, N.; Ruggieri, S.; Saccucci,
F.; Magni, G.: Human erythrocyte pyrimidine 5-prime-nucleotidase,
PN-I, is identical to p36, a protein associated to lupus inclusion
formation in response to alpha-interferon. Blood 96: 1596-1598,
2000.
3. Balta, G.; Gumruk, F.; Akarsu, N.; Gurgey, A.; Altay, C.: Molecular
characterization of Turkish patients with pyrimidine 5-prime nucleotidase-I
deficiency. Blood 102: 1900-1903, 2003.
4. Bianchi, P.; Fermo, E.; Alfinito, F.; Vercellati, C.; Baserga,
M.; Ferraro, F.; Guzzo, I.; Rotoli, B.; Zanella, A.: Molecular characterization
of six unrelated Italian patients affected by pyrimidine 5-prime-nucleotidase
deficiency. Brit. J. Haemat. 122: 847-851, 2003.
5. Hansen, T. W. R.; Seip, M.; de Verdier, C.-H.; Ericson, A.: Erythrocyte
pyrimidine 5-prime-nucleotidase deficiency: report of 2 new cases,
with a review of the literature. Scand. J. Haemat. 31: 122-128,
1983.
6. Kanno, H.; Takizawa, T.; Miwa, S.; Fujii, H.: Molecular basis
of Japanese variants of pyrimidine 5-prime-nucleotidase deficiency. Brit.
J. Haemat. 126: 265-271, 2004.
7. Marinaki, A. M.; Escuredo, E.; Duley, J. A.; Simmonds, H. A.; Amici,
A.; Naponelli, V.; Magni, G.; Seip, M.; Ben-Bassat, I.; Harley, E.
H.; Thein, S. L.; Rees, D. C.: Genetic basis of hemolytic anemia
caused by pyrimidine 5-prime nucleotidase deficiency. Blood 97:
3327-3332, 2001.
8. Rees, D. C.; Duley, J. A.; Marinaki, A. M.: Pyrimidine 5-prime-nucelotidase
deficiency. Brit. J. Haemat. 120: 375-383, 2003.
*FIELD* CN
Victor A. McKusick - updated: 10/4/2004
Victor A. McKusick - updated: 11/26/2003
Victor A. McKusick - updated: 4/17/2003
*FIELD* CD
Victor A. McKusick: 8/27/2001
*FIELD* ED
carol: 11/12/2013
carol: 10/12/2004
carol: 10/11/2004
tkritzer: 10/8/2004
terry: 10/4/2004
tkritzer: 12/8/2003
tkritzer: 12/4/2003
terry: 11/26/2003
tkritzer: 4/30/2003
terry: 4/17/2003
carol: 4/19/2002
mcapotos: 12/19/2001
carol: 8/28/2001
*RECORD*
*FIELD* NO
606224
*FIELD* TI
*606224 5-PRIME-@NUCLEOTIDASE, CYTOSOLIC IIIA; NT5C3A
;;NUCLEOTIDASE, 5-PRIME, CYTOSOLIC III; NT5C3;;
read moreURIDINE 5-PRIME MONOPHOSPHATE HYDROLASE 1; UMPH1;;
PYRIMIDINE 5-PRIME-NUCLEOTIDASE 1; P5N1
*FIELD* TX
DESCRIPTION
Pyrimidine 5-prime-nucleotidase (P5N; EC 3.1.3.5), also called uridine
5-prime monophosphate hydrolase (UMPH), catalyzes the dephosphorylation
of the pyrimidine 5-prime monophosphates UMP and CMP to the
corresponding nucleosides. There are 2 isozymes of pyrimidine 5-prime
nucleotidase in red blood cells, referred to as type I (UMPH1) and type
II (UMPH2; 191720). The 2 enzymes are not separable by electrophoresis
in humans but have distinct kinetic properties, and the proteins show no
homology.
CLONING
Cloning of UMPH1 and expression in E. coli demonstrated that the protein
consists of 286 amino acids and is identical to a previously identified
lupus inclusion protein, p36 (Amici et al., 1994, 2000). Marinaki et al.
(2001) determined that alternative splicing of exon 2 results in a
297-amino acid form of the protein. Both forms of the protein are
expressed in reticulocytes and lymphocytes.
Kanno et al. (2004) identified a third alternatively spliced form of the
NT4C3 gene in reticulocytes, which included an additional 87-bp
sequence. The sequence is located 6.2 kb downstream of the exon 2
sequence and 2.7 kb upstream of the exon 3 sequence; consequently, the
gene contains 11 exons, which span approximately 48 kb.
GENE STRUCTURE
Using the putative cDNA sequence for UMPH1, Marinaki et al. (2001)
generated the genomic DNA sequence. The gene contains 10 exons with
alternative splicing of exon 2.
MAPPING
By sequence analysis, Marinaki et al. (2001) mapped the UMPH1 gene to
chromosome 7p15-p14. They identified UMPH1 pseudogenes on chromosomes 4
and 7.
MOLECULAR GENETICS
Pyrimidine 5-prime nucleotidase deficiency (266120) causes an autosomal
recessive hemolytic anemia characterized by marked basophilic stippling
and the accumulation of high concentrations of pyrimidine nucleotides
within the erythrocyte. The enzyme is implicated in the anemia of lead
poisoning and is possibly associated with learning difficulties. Type I
UMPH is deficient in cases of hemolytic anemia; the activity of type II
UMPH2 is normal in these cases. In patients with hemolytic anemia due to
deficiency of UMPH1, Marinaki et al. (2001) identified causative
homozygous mutations in the UMPH1 gene (606224.0001-606224.0003).
Rees et al. (2003) reviewed pyrimidine 5-prime nucleotidase deficiency.
They tabulated 7 mutations that had been identified in the UMPH1 gene.
They noted that following the discovery of pyrimidine 5-prime
nucleotidase deficiency, it was realized that the only other condition
that could cause such marked basophilic stippling was lead poisoning,
which is also a cause of hemolysis. The enzyme was known to be very
sensitive to inhibition by heavy metal ions. Most of the hematologic
features of lead poisoning can be explained by inhibition of this
enzyme, although the neurologic and other features are presumably due to
separate mechanisms.
Balta et al. (2003) characterized the molecular pathology of pyrimidine
5-prime nucleotidase deficiency in 6 Turkish patients from 4 unrelated
consanguineous families. They identified 3 different mutations in the
UMPH1 gene in these patients (606224.0004-606224.0006). In all families,
the parents were heterozygous for the relevant mutations.
Bianchi et al. (2003) studied the hematologic and molecular
characteristics of 6 unrelated patients with pyrimidine 5-prime
nucleotidase deficiency (1 from northern and 5 from southern Italy).
They identified 4 different mutations in the UMPH1 gene in these
patients (606224.0007-606224.0009), 5 of whom were homozygotes and 1 a
compound heterozygote. Parental consanguinity could be confirmed in only
1 case. Two patients carried the 743insGG mutation (604224.0004)
previously identified by Balta et al. (2003).
Kanno et al. (2004) identified 5 novel homozygous mutations in 9
Japanese families with pyrimidine 5-prime nucleotidase deficiency: 2
missense mutations (see 606224.0010), a splice mutation, a 1-bp
insertion, and a 9-bp deletion.
*FIELD* AV
.0001
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, ASP98VAL
In a Norwegian brother and sister with hemolytic anemia and basophilic
stippling (266120) reported by Hansen et al. (1983), Marinaki et al.
(2001) identified an asp98-to-val mutation of the UMPH1 gene. The sibs
were unusual in having intravascular hemolysis, urinary iron loss, iron
deposition in the kidneys, and iron deficiency. This had not been noted
in other published reports of UMPH1 deficiency. The parents, who were
heterozygous for the mutation, had a common ancestor 5 generations
earlier. At the time of the report, the sibs were in their late twenties
and maintained hemoglobin levels of approximately 10g/dL with no
significant complications from their chronic hemolysis.
.0002
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, GLN177TER
In an adopted South African girl who had typical hemolytic anemia with
basophilic stippling due to deficiency of pyrimidine 5-prime
nucleotidase (266120), Marinaki et al. (2001) found homozygosity for a
gln177-to-ter mutation in the UMPH1 gene.
.0003
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, IVS9AS, G-T, -1
In a 55-year-old white South African farmer with hemolytic anemia
associated with low levels of pyrimidine 5-prime nucleotidase and
intraerythrocytic accumulation of pyrimidine nucleotides (266120),
Marinaki et al. (2001) identified a splice site mutation in the UMPH1
gene, resulting in the loss of exon 9 (201 bp) from the cDNA. The same
nucleotide is involved in another splicing mutation (606224.0007).
.0004
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, 2-BP INS, 743GG
In 4 Turkish patients from 2 families with pyrimidine 5-prime
nucleotidase deficiency (266120), Balta et al. (2003) identified a
homozygous 2-bp insertion (743insGG) in exon 9 of the UMPH1 gene,
resulting in premature termination of translation 23 bp downstream.
In 2 Italian patients with 5-prime nucleotidase deficiency, Bianchi et
al. (2003) identified the 743insGG mutation, in homozygous state in 1
and in compound heterozygous state with an IVS9-1G-C mutation
(606224.0007) in the other.
.0005
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, TYR181TER
In affected members of a Turkish family with pyrimidine 5-prime
nucleotidase deficiency (266120), Balta et al. (2003) identified
homozygosity for a 543T-G transition in exon 8 of the UMPH1 gene,
resulting in a tyr181-to-ter (Y181X) mutation.
In 2 unrelated Italian patients with pyrimidine 5-prime nucleotidase
deficiency, Bianchi et al. (2003) identified the Y181X mutation.
.0006
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, 1-BP INS, 384A
In affected members of a Turkish family with pyrimidine 5-prime
nucleotidase deficiency (266120), Balta et al. (2003) identified
homozygosity for a 1-bp insertion (384insA) in exon 7 of the UMPH1 gene,
creating a stop signal at the codon nearby.
.0007
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, IVS9AS, G-C, -1
In an Italian patient with pyrimidine 5-prime nucleotidase deficiency
(266120), Bianchi et al. (2003) identified compound heterozygosity for 2
mutations in the UMPH1 gene: an IVS9-1G-C splicing mutation and a 2-bp
insertion (743insGG; 606224.0004). The same nucleotide is involved in
another splicing mutation (606224.0003).
.0008
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, ASN190SER
In affected members of an Italian family with pyrimidine 5-prime
nucleotidase deficiency (266120), Bianchi et al. (2003) identified an
AAT (asn)-to-AGT (ser) mutation at codon 190 (N190S) of the UMPH1 gene.
.0009
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, 1-BP DEL, 576G
In 3 patients originating from southern Italy with pyrimidine 5-prime
nucleotidase deficiency (266120), Bianchi et al. (2003) identified a
1-bp deletion (576delG) in the UMPH1 gene.
.0010
HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY
NT5C3A, GLY241ARG
In affected members of 5 of 9 Japanese families with pyrimidine 5-prime
nucleotidase deficiency (266120), Kanno et al. (2004) identified
homozygosity for a G-to-C transversion in the UMPH1 gene, changing codon
241 from GGA (gly) to CGA (arg) (G241R). The 5 families with the G241R
mutation originated from the western coastal area of the Kyushu district
and shared a common haplotype, suggesting that G241R is a founder
mutation.
*FIELD* RF
1. Amici, A.; Emanuelli, M.; Ferretti, E.; Raffaelli, N.; Ruggieri,
S.; Magni, G.: Homogeneous pyrimidine nucleotidase from human erythrocytes:
enzymic and molecular properties. Biochem. J. 304: 987-992, 1994.
2. Amici, A.; Emanuelli, M.; Raffaelli, N.; Ruggieri, S.; Saccucci,
F.; Magni, G.: Human erythrocyte pyrimidine 5-prime-nucleotidase,
PN-I, is identical to p36, a protein associated to lupus inclusion
formation in response to alpha-interferon. Blood 96: 1596-1598,
2000.
3. Balta, G.; Gumruk, F.; Akarsu, N.; Gurgey, A.; Altay, C.: Molecular
characterization of Turkish patients with pyrimidine 5-prime nucleotidase-I
deficiency. Blood 102: 1900-1903, 2003.
4. Bianchi, P.; Fermo, E.; Alfinito, F.; Vercellati, C.; Baserga,
M.; Ferraro, F.; Guzzo, I.; Rotoli, B.; Zanella, A.: Molecular characterization
of six unrelated Italian patients affected by pyrimidine 5-prime-nucleotidase
deficiency. Brit. J. Haemat. 122: 847-851, 2003.
5. Hansen, T. W. R.; Seip, M.; de Verdier, C.-H.; Ericson, A.: Erythrocyte
pyrimidine 5-prime-nucleotidase deficiency: report of 2 new cases,
with a review of the literature. Scand. J. Haemat. 31: 122-128,
1983.
6. Kanno, H.; Takizawa, T.; Miwa, S.; Fujii, H.: Molecular basis
of Japanese variants of pyrimidine 5-prime-nucleotidase deficiency. Brit.
J. Haemat. 126: 265-271, 2004.
7. Marinaki, A. M.; Escuredo, E.; Duley, J. A.; Simmonds, H. A.; Amici,
A.; Naponelli, V.; Magni, G.; Seip, M.; Ben-Bassat, I.; Harley, E.
H.; Thein, S. L.; Rees, D. C.: Genetic basis of hemolytic anemia
caused by pyrimidine 5-prime nucleotidase deficiency. Blood 97:
3327-3332, 2001.
8. Rees, D. C.; Duley, J. A.; Marinaki, A. M.: Pyrimidine 5-prime-nucelotidase
deficiency. Brit. J. Haemat. 120: 375-383, 2003.
*FIELD* CN
Victor A. McKusick - updated: 10/4/2004
Victor A. McKusick - updated: 11/26/2003
Victor A. McKusick - updated: 4/17/2003
*FIELD* CD
Victor A. McKusick: 8/27/2001
*FIELD* ED
carol: 11/12/2013
carol: 10/12/2004
carol: 10/11/2004
tkritzer: 10/8/2004
terry: 10/4/2004
tkritzer: 12/8/2003
tkritzer: 12/4/2003
terry: 11/26/2003
tkritzer: 4/30/2003
terry: 4/17/2003
carol: 4/19/2002
mcapotos: 12/19/2001
carol: 8/28/2001