UMPS_HUMAN
ID UMPS_HUMAN Reviewed; 480 AA.
AC P11172; B5LY68; B5LY72; O00758; O00759; O00760; Q16862; Q9H3Q2; Q9UG49;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Uridine 5'-monophosphate synthase {ECO:0000305};
DE Short=UMP synthase;
DE Includes:
DE RecName: Full=Orotate phosphoribosyltransferase {ECO:0000305};
DE Short=OPRT {ECO:0000303|PubMed:9042911};
DE Short=OPRTase;
DE EC=2.4.2.10 {ECO:0000269|PubMed:9042911};
DE Includes:
DE RecName: Full=Orotidine 5'-phosphate decarboxylase {ECO:0000305};
DE Short=ODC {ECO:0000303|PubMed:9042911};
DE Short=OMPD {ECO:0000303|PubMed:18184586};
DE EC=4.1.1.23 {ECO:0000269|PubMed:18184586, ECO:0000269|PubMed:9042911};
DE AltName: Full=OMPdecase;
GN Name=UMPS {ECO:0000312|HGNC:HGNC:12563}; ORFNames=OK/SW-cl.21;
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 1).
RX PubMed=3279416; DOI=10.1073/pnas.85.6.1754;
RA Suttle D.P., Bugg B.Y., Winkler J.K., Kanalas J.J.;
RT "Molecular cloning and nucleotide sequence for the complete coding region
RT of human UMP synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:1754-1758(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2624233; DOI=10.1007/978-1-4684-5673-8_83;
RA Suchi M., Harada N., Tsuboi T., Asai K., Okajima K., Wada Y., Takagi Y.;
RT "Molecular cloning of human UMP synthase.";
RL Adv. Exp. Med. Biol. 253A:511-518(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ORAC1 GLY-96; GLY-109 AND
RP ARG-429, VARIANT ALA-213, CATALYTIC ACTIVITY, FUNCTION, AND
RP CHARACTERIZATION OF VARIANTS ORAC1 GLY-96; GLY-109 AND ARG-429.
RC TISSUE=Leukocyte;
RX PubMed=9042911;
RA Suchi M., Mizuno H., Kawai Y., Tsuboi T., Sumi S., Okajima K.,
RA Hodgson M.E., Ogawa H., Wada Y.;
RT "Molecular cloning of the human UMP synthase gene and characterization of
RT point mutations in two hereditary orotic aciduria families.";
RL Am. J. Hum. Genet. 60:525-539(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RA Griffith M., Pugh T.J., Tang M.J., Asano J.K., Ally A., Chan S.Y.,
RA Taylor G., Morin G.B., Tai I.T., Marra M.A.;
RT "Genomic analysis of UMPS expression and sequence reveals novel isoforms
RT and sequence polymorphisms associated with 5-FU resistance.";
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-reactive
RT CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-30; ALA-213 AND
RP VAL-446.
RG NIEHS SNPs program;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-480 (ISOFORM 1).
RA Suchi M.;
RT "Molecular genetic studies on hereditary orotic aciduria: I. Purification
RT of human orotidine 5'-monophosphate decarboxylase and cloning of its
RT cDNA.";
RL Nagoya Med. J. 32:207-220(1988).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-37 AND SER-214, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19] {ECO:0007744|PDB:2QCC, ECO:0007744|PDB:2QCD, ECO:0007744|PDB:2QCE, ECO:0007744|PDB:2QCF, ECO:0007744|PDB:2QCG, ECO:0007744|PDB:2QCH, ECO:0007744|PDB:2QCL, ECO:0007744|PDB:2QCM, ECO:0007744|PDB:2QCN}
RP X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 224-480 IN COMPLEX WITH
RP SUBSTRATE, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF ASP-312, FUNCTION,
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18184586; DOI=10.1016/j.str.2007.10.020;
RA Wittmann J.G., Heinrich D., Gasow K., Frey A., Diederichsen U.,
RA Rudolph M.G.;
RT "Structures of the human orotidine-5'-monophosphate decarboxylase support a
RT covalent mechanism and provide a framework for drug design.";
RL Structure 16:82-92(2008).
CC -!- FUNCTION: Bifunctional enzyme catalyzing the last two steps of de novo
CC pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT),
CC which converts orotate to orotidine-5'-monophosphate (OMP), and
CC orotidine-5'-monophosphate decarboxylase (ODC), the terminal enzymatic
CC reaction that decarboxylates OMP to uridine monophosphate (UMP).
CC {ECO:0000269|PubMed:18184586, ECO:0000269|PubMed:9042911}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + orotidine 5'-phosphate = 5-phospho-alpha-D-
CC ribose 1-diphosphate + orotate; Xref=Rhea:RHEA:10380,
CC ChEBI:CHEBI:30839, ChEBI:CHEBI:33019, ChEBI:CHEBI:57538,
CC ChEBI:CHEBI:58017; EC=2.4.2.10;
CC Evidence={ECO:0000269|PubMed:9042911};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10382;
CC Evidence={ECO:0000269|PubMed:9042911};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + orotidine 5'-phosphate = CO2 + UMP;
CC Xref=Rhea:RHEA:11596, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57538, ChEBI:CHEBI:57865; EC=4.1.1.23;
CC Evidence={ECO:0000269|PubMed:18184586, ECO:0000269|PubMed:9042911};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11597;
CC Evidence={ECO:0000269|PubMed:18184586, ECO:0000269|PubMed:9042911};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16.6 uM for orotidine 5'-phosphate {ECO:0000269|PubMed:18184586};
CC Note=kcat is 0.75 sec(-1) with orotidine 5'-phosphate as substrate.
CC {ECO:0000269|PubMed:18184586};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC UMP from orotate: step 1/2. {ECO:0000269|PubMed:9042911}.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC UMP from orotate: step 2/2. {ECO:0000269|PubMed:9042911}.
CC -!- SUBUNIT: Homodimer; dimerization is required for enzymatic activity.
CC {ECO:0000269|PubMed:18184586}.
CC -!- INTERACTION:
CC P11172-1; P11172-1: UMPS; NbExp=2; IntAct=EBI-15679357, EBI-15679357;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P11172-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11172-2; Sequence=VSP_009273;
CC Name=3;
CC IsoId=P11172-3; Sequence=VSP_047611;
CC Name=4;
CC IsoId=P11172-4; Sequence=VSP_009273, VSP_047612;
CC -!- DISEASE: Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of
CC pyrimidine metabolism resulting in megaloblastic anemia and orotic acid
CC crystalluria that is frequently associated with some degree of physical
CC and intellectual disability. A minority of cases have additional
CC features, particularly congenital malformations and immune
CC deficiencies. {ECO:0000269|PubMed:9042911}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: In the N-terminal section; belongs to the purine/pyrimidine
CC phosphoribosyltransferase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the OMP decarboxylase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB45710.3; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/umps/";
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DR EMBL; J03626; AAA61255.1; -; mRNA.
DR EMBL; D86227; BAA19920.1; -; mRNA.
DR EMBL; D86228; BAA19921.1; -; mRNA.
DR EMBL; D86230; BAA19923.1; -; mRNA.
DR EMBL; AB041359; BAB20663.1; -; Genomic_DNA.
DR EMBL; EU921891; ACH48229.1; -; mRNA.
DR EMBL; EU921895; ACH48233.1; -; mRNA.
DR EMBL; AB062285; BAB93468.1; -; mRNA.
DR EMBL; CR456787; CAG33068.1; -; mRNA.
DR EMBL; AL080099; CAB45710.3; ALT_SEQ; mRNA.
DR EMBL; AY691629; AAT85801.1; -; Genomic_DNA.
DR EMBL; AC022336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000364; AAH00364.1; -; mRNA.
DR EMBL; BC007511; AAH07511.1; -; mRNA.
DR EMBL; M36661; AAA61256.1; -; mRNA.
DR CCDS; CCDS3029.1; -. [P11172-1]
DR PIR; A30148; A30148.
DR RefSeq; NP_000364.1; NM_000373.3. [P11172-1]
DR PDB; 2EAW; X-ray; 2.88 A; A/B=190-480.
DR PDB; 2JGY; X-ray; 1.95 A; A/B=224-479.
DR PDB; 2P1F; X-ray; 1.76 A; A=190-480.
DR PDB; 2QCC; X-ray; 1.85 A; A/B=224-480.
DR PDB; 2QCD; X-ray; 2.03 A; A/B=224-480.
DR PDB; 2QCE; X-ray; 1.43 A; A=224-480.
DR PDB; 2QCF; X-ray; 1.22 A; A=224-480.
DR PDB; 2QCG; X-ray; 1.75 A; A/B=224-480.
DR PDB; 2QCH; X-ray; 1.95 A; A/B=224-480.
DR PDB; 2QCL; X-ray; 1.85 A; A/B=224-480.
DR PDB; 2QCM; X-ray; 1.67 A; A=224-480.
DR PDB; 2QCN; X-ray; 1.85 A; A/B=224-480.
DR PDB; 2V30; X-ray; 2.00 A; A/B=224-479.
DR PDB; 2WNS; X-ray; 1.90 A; A/B=7-203.
DR PDB; 3BGG; X-ray; 1.93 A; A=190-480.
DR PDB; 3BGJ; X-ray; 2.00 A; A/B=190-480.
DR PDB; 3BK0; X-ray; 1.60 A; A/B=223-480.
DR PDB; 3BVJ; X-ray; 1.80 A; A/B=190-480.
DR PDB; 3DBP; X-ray; 1.50 A; A/B=223-480.
DR PDB; 3EWU; X-ray; 1.60 A; A/B=224-480.
DR PDB; 3EWW; X-ray; 1.10 A; A/B=224-480.
DR PDB; 3EWX; X-ray; 1.40 A; A=224-480.
DR PDB; 3EWY; X-ray; 1.10 A; A=224-480.
DR PDB; 3EWZ; X-ray; 1.40 A; A/B/C/D=224-480.
DR PDB; 3EX1; X-ray; 1.40 A; A/B=224-480.
DR PDB; 3EX2; X-ray; 1.55 A; A/B=224-480.
DR PDB; 3EX3; X-ray; 1.45 A; A/B=224-480.
DR PDB; 3EX4; X-ray; 1.24 A; A=224-480.
DR PDB; 3EX6; X-ray; 1.30 A; A/B=224-480.
DR PDB; 3G3D; X-ray; 1.70 A; A/B=190-480.
DR PDB; 3G3M; X-ray; 1.40 A; A=223-480.
DR PDB; 3L0K; X-ray; 1.34 A; A/B=224-480.
DR PDB; 3L0N; X-ray; 1.74 A; A/B=224-480.
DR PDB; 3MI2; X-ray; 1.20 A; A/B=223-480.
DR PDB; 3MO7; X-ray; 1.35 A; A=223-480.
DR PDB; 3MW7; X-ray; 2.32 A; A/B=190-480.
DR PDB; 4HIB; X-ray; 1.80 A; A/B=190-480.
DR PDB; 4HKP; X-ray; 1.75 A; A/B=190-480.
DR PDB; 6YVK; X-ray; 1.25 A; A=224-480.
DR PDB; 6YVL; X-ray; 1.25 A; A=224-480.
DR PDB; 6YVM; X-ray; 1.25 A; A=224-480.
DR PDB; 6YVN; X-ray; 1.25 A; A=224-480.
DR PDB; 6YVO; X-ray; 1.25 A; A=224-480.
DR PDB; 6YWT; X-ray; 1.05 A; A=224-480.
DR PDB; 6YWU; X-ray; 1.10 A; A=224-480.
DR PDB; 6ZWY; X-ray; 1.00 A; A=224-480.
DR PDB; 6ZWZ; X-ray; 1.20 A; A=224-480.
DR PDB; 6ZX0; X-ray; 1.25 A; A=224-480.
DR PDB; 6ZX1; X-ray; 1.00 A; A=224-480.
DR PDB; 6ZX2; X-ray; 1.20 A; A=224-480.
DR PDB; 6ZX3; X-ray; 1.15 A; A=224-480.
DR PDB; 7AM9; X-ray; 0.99 A; A=224-480.
DR PDB; 7ASQ; X-ray; 0.95 A; A=224-480.
DR PDB; 7OQF; X-ray; 1.05 A; A/B=224-480.
DR PDB; 7OQI; X-ray; 1.15 A; A/B=224-480.
DR PDB; 7OQK; X-ray; 1.10 A; A/B=224-480.
DR PDB; 7OQM; X-ray; 1.05 A; A/B=224-480.
DR PDB; 7OQN; X-ray; 1.10 A; A/B=224-480.
DR PDBsum; 2EAW; -.
DR PDBsum; 2JGY; -.
DR PDBsum; 2P1F; -.
DR PDBsum; 2QCC; -.
DR PDBsum; 2QCD; -.
DR PDBsum; 2QCE; -.
DR PDBsum; 2QCF; -.
DR PDBsum; 2QCG; -.
DR PDBsum; 2QCH; -.
DR PDBsum; 2QCL; -.
DR PDBsum; 2QCM; -.
DR PDBsum; 2QCN; -.
DR PDBsum; 2V30; -.
DR PDBsum; 2WNS; -.
DR PDBsum; 3BGG; -.
DR PDBsum; 3BGJ; -.
DR PDBsum; 3BK0; -.
DR PDBsum; 3BVJ; -.
DR PDBsum; 3DBP; -.
DR PDBsum; 3EWU; -.
DR PDBsum; 3EWW; -.
DR PDBsum; 3EWX; -.
DR PDBsum; 3EWY; -.
DR PDBsum; 3EWZ; -.
DR PDBsum; 3EX1; -.
DR PDBsum; 3EX2; -.
DR PDBsum; 3EX3; -.
DR PDBsum; 3EX4; -.
DR PDBsum; 3EX6; -.
DR PDBsum; 3G3D; -.
DR PDBsum; 3G3M; -.
DR PDBsum; 3L0K; -.
DR PDBsum; 3L0N; -.
DR PDBsum; 3MI2; -.
DR PDBsum; 3MO7; -.
DR PDBsum; 3MW7; -.
DR PDBsum; 4HIB; -.
DR PDBsum; 4HKP; -.
DR PDBsum; 6YVK; -.
DR PDBsum; 6YVL; -.
DR PDBsum; 6YVM; -.
DR PDBsum; 6YVN; -.
DR PDBsum; 6YVO; -.
DR PDBsum; 6YWT; -.
DR PDBsum; 6YWU; -.
DR PDBsum; 6ZWY; -.
DR PDBsum; 6ZWZ; -.
DR PDBsum; 6ZX0; -.
DR PDBsum; 6ZX1; -.
DR PDBsum; 6ZX2; -.
DR PDBsum; 6ZX3; -.
DR PDBsum; 7AM9; -.
DR PDBsum; 7ASQ; -.
DR PDBsum; 7OQF; -.
DR PDBsum; 7OQI; -.
DR PDBsum; 7OQK; -.
DR PDBsum; 7OQM; -.
DR PDBsum; 7OQN; -.
DR AlphaFoldDB; P11172; -.
DR SMR; P11172; -.
DR BioGRID; 113218; 107.
DR DIP; DIP-29595N; -.
DR IntAct; P11172; 35.
DR MINT; P11172; -.
DR STRING; 9606.ENSP00000232607; -.
DR BindingDB; P11172; -.
DR ChEMBL; CHEMBL5216; -.
DR DrugBank; DB02890; 6-hydroxyuridine-5'-phosphate.
DR DrugBank; DB00544; Fluorouracil.
DR DrugCentral; P11172; -.
DR GlyGen; P11172; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P11172; -.
DR MetOSite; P11172; -.
DR PhosphoSitePlus; P11172; -.
DR BioMuta; UMPS; -.
DR EPD; P11172; -.
DR jPOST; P11172; -.
DR MassIVE; P11172; -.
DR MaxQB; P11172; -.
DR PaxDb; P11172; -.
DR PeptideAtlas; P11172; -.
DR PRIDE; P11172; -.
DR ProteomicsDB; 52713; -. [P11172-1]
DR ProteomicsDB; 52714; -. [P11172-2]
DR ProteomicsDB; 5937; -.
DR ProteomicsDB; 5938; -.
DR Antibodypedia; 32990; 223 antibodies from 32 providers.
DR DNASU; 7372; -.
DR Ensembl; ENST00000232607.7; ENSP00000232607.2; ENSG00000114491.14. [P11172-1]
DR GeneID; 7372; -.
DR KEGG; hsa:7372; -.
DR MANE-Select; ENST00000232607.7; ENSP00000232607.2; NM_000373.4; NP_000364.1.
DR UCSC; uc003ehl.5; human. [P11172-1]
DR CTD; 7372; -.
DR DisGeNET; 7372; -.
DR GeneCards; UMPS; -.
DR HGNC; HGNC:12563; UMPS.
DR HPA; ENSG00000114491; Low tissue specificity.
DR MalaCards; UMPS; -.
DR MIM; 258900; phenotype.
DR MIM; 613891; gene.
DR neXtProt; NX_P11172; -.
DR OpenTargets; ENSG00000114491; -.
DR Orphanet; 30; Hereditary orotic aciduria.
DR PharmGKB; PA363; -.
DR VEuPathDB; HostDB:ENSG00000114491; -.
DR eggNOG; KOG1377; Eukaryota.
DR GeneTree; ENSGT00390000001856; -.
DR HOGENOM; CLU_049275_1_0_1; -.
DR OMA; DHLGQQY; -.
DR PhylomeDB; P11172; -.
DR TreeFam; TF314694; -.
DR BRENDA; 4.1.1.23; 2681.
DR PathwayCommons; P11172; -.
DR Reactome; R-HSA-500753; Pyrimidine biosynthesis.
DR SignaLink; P11172; -.
DR SIGNOR; P11172; -.
DR UniPathway; UPA00070; UER00119.
DR UniPathway; UPA00070; UER00120.
DR BioGRID-ORCS; 7372; 246 hits in 1085 CRISPR screens.
DR ChiTaRS; UMPS; human.
DR EvolutionaryTrace; P11172; -.
DR GeneWiki; Uridine_monophosphate_synthetase; -.
DR GenomeRNAi; 7372; -.
DR Pharos; P11172; Tclin.
DR PRO; PR:P11172; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P11172; protein.
DR Bgee; ENSG00000114491; Expressed in adrenal tissue and 190 other tissues.
DR ExpressionAtlas; P11172; baseline and differential.
DR Genevisible; P11172; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004588; F:orotate phosphoribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004590; F:orotidine-5'-phosphate decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IEA:InterPro.
DR GO; GO:0044205; P:'de novo' UMP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IBA:GO_Central.
DR GO; GO:0006225; P:UDP biosynthetic process; IEA:Ensembl.
DR GO; GO:0006222; P:UMP biosynthetic process; IDA:UniProtKB.
DR CDD; cd06223; PRTases_typeI; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.40.50.2020; -; 1.
DR HAMAP; MF_01208; PyrE; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR014732; OMPdecase.
DR InterPro; IPR018089; OMPdecase_AS.
DR InterPro; IPR001754; OMPdeCOase_dom.
DR InterPro; IPR023031; OPRT.
DR InterPro; IPR004467; Or_phspho_trans_dom.
DR InterPro; IPR000836; PRibTrfase_dom.
DR InterPro; IPR029057; PRTase-like.
DR InterPro; IPR011060; RibuloseP-bd_barrel.
DR Pfam; PF00215; OMPdecase; 1.
DR Pfam; PF00156; Pribosyltran; 1.
DR SMART; SM00934; OMPdecase; 1.
DR SUPFAM; SSF51366; SSF51366; 1.
DR SUPFAM; SSF53271; SSF53271; 1.
DR TIGRFAMs; TIGR00336; pyrE; 1.
DR TIGRFAMs; TIGR01740; pyrF; 1.
DR PROSITE; PS00156; OMPDECASE; 1.
DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Decarboxylase;
KW Disease variant; Glycosyltransferase; Lyase; Multifunctional enzyme;
KW Phosphoprotein; Pyrimidine biosynthesis; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..480
FT /note="Uridine 5'-monophosphate synthase"
FT /id="PRO_0000139649"
FT REGION 2..214
FT /note="OPRTase"
FT REGION 215..220
FT /note="Domain linker"
FT REGION 221..480
FT /note="OMPdecase"
FT ACT_SITE 312
FT /note="For OMPdecase activity"
FT /evidence="ECO:0000269|PubMed:18184586"
FT ACT_SITE 314
FT /note="For OMPdecase activity"
FT /evidence="ECO:0000269|PubMed:18184586"
FT ACT_SITE 317
FT /note="For OMPdecase activity"
FT /evidence="ECO:0000269|PubMed:18184586"
FT BINDING 257
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 257
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD"
FT BINDING 259
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD, ECO:0007744|PDB:2QCH"
FT BINDING 281..283
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD, ECO:0007744|PDB:2QCH"
FT BINDING 281
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 314
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 317
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 317
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD"
FT BINDING 321
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 321
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD"
FT BINDING 372
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 372
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD, ECO:0007744|PDB:2QCH"
FT BINDING 430..432
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 430..432
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD, ECO:0007744|PDB:2QCH"
FT BINDING 450..451
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCL"
FT BINDING 450..451
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000269|PubMed:18184586,
FT ECO:0007744|PDB:2QCD, ECO:0007744|PDB:2QCH"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 37
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..178
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:17974005, ECO:0000303|Ref.4"
FT /id="VSP_009273"
FT VAR_SEQ 1..92
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047611"
FT VAR_SEQ 328..424
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047612"
FT VARIANT 30
FT /note="S -> G (in dbSNP:rs17843776)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_020614"
FT VARIANT 96
FT /note="R -> G (in ORAC1; reduced OPRT activity; no effect
FT on ODC activity; reduced OPRT and ODC activities when
FT associated with R-429; dbSNP:rs121917890)"
FT /evidence="ECO:0000269|PubMed:9042911"
FT /id="VAR_006807"
FT VARIANT 109
FT /note="V -> G (in ORAC1; reduced OPRT activity; reduced ODC
FT activity; dbSNP:rs121917892)"
FT /evidence="ECO:0000269|PubMed:9042911"
FT /id="VAR_006808"
FT VARIANT 213
FT /note="G -> A (in dbSNP:rs1801019)"
FT /evidence="ECO:0000269|PubMed:9042911, ECO:0000269|Ref.8"
FT /id="VAR_006809"
FT VARIANT 429
FT /note="G -> R (in ORAC1; increased OPRT activity; reduced
FT ODC activity; reduced OPRT and ODC activities when
FT associated with G-96; dbSNP:rs121917891)"
FT /evidence="ECO:0000269|PubMed:9042911"
FT /id="VAR_006810"
FT VARIANT 446
FT /note="I -> V (in dbSNP:rs3772809)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_020615"
FT MUTAGEN 312
FT /note="D->N: Loss of OMPdecase activity."
FT /evidence="ECO:0000269|PubMed:18184586"
FT CONFLICT 13
FT /note="T -> G (in Ref. 11; AAA61256)"
FT /evidence="ECO:0000305"
FT CONFLICT 377
FT /note="L -> Q (in Ref. 11; AAA61256)"
FT /evidence="ECO:0000305"
FT HELIX 8..16
FT /evidence="ECO:0007829|PDB:2WNS"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 47..63
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:2WNS"
FT TURN 75..78
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 79..89
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:2WNS"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 118..129
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 130..141
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 148..154
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 159..164
FT /evidence="ECO:0007829|PDB:2WNS"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:2WNS"
FT STRAND 169..175
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 191..202
FT /evidence="ECO:0007829|PDB:2WNS"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 238..250
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 292..305
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 308..315
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 319..327
FT /evidence="ECO:0007829|PDB:7ASQ"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 333..336
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 338..344
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 349..358
FT /evidence="ECO:0007829|PDB:7ASQ"
FT TURN 359..362
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 364..368
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 380..391
FT /evidence="ECO:0007829|PDB:7ASQ"
FT TURN 394..396
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 397..401
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 412..416
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:7AM9"
FT HELIX 435..439
FT /evidence="ECO:0007829|PDB:7ASQ"
FT TURN 440..442
FT /evidence="ECO:0007829|PDB:3MI2"
FT STRAND 445..450
FT /evidence="ECO:0007829|PDB:7ASQ"
FT HELIX 451..454
FT /evidence="ECO:0007829|PDB:7ASQ"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:6YVM"
FT HELIX 459..477
FT /evidence="ECO:0007829|PDB:7ASQ"
SQ SEQUENCE 480 AA; 52222 MW; D985CD566B72F5CA CRC64;
MAVARAALGP LVTGLYDVQA FKFGDFVLKS GLSSPIYIDL RGIVSRPRLL SQVADILFQT
AQNAGISFDT VCGVPYTALP LATVICSTNQ IPMLIRRKET KDYGTKRLVE GTINPGETCL
IIEDVVTSGS SVLETVEVLQ KEGLKVTDAI VLLDREQGGK DKLQAHGIRL HSVCTLSKML
EILEQQKKVD AETVGRVKRF IQENVFVAAN HNGSPLSIKE APKELSFGAR AELPRIHPVA
SKLLRLMQKK ETNLCLSADV SLARELLQLA DALGPSICML KTHVDILNDF TLDVMKELIT
LAKCHEFLIF EDRKFADIGN TVKKQYEGGI FKIASWADLV NAHVVPGSGV VKGLQEVGLP
LHRGCLLIAE MSSTGSLATG DYTRAAVRMA EEHSEFVVGF ISGSRVSMKP EFLHLTPGVQ
LEAGGDNLGQ QYNSPQEVIG KRGSDIIIVG RGIISAADRL EAAEMYRKAA WEAYLSRLGV
