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 02-SEP-2026, entry version 248. 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=orotidine 5'-phosphate + diphosphate = orotate + 5-phospho- CC alpha-D-ribose 1-diphosphate; 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=orotidine 5'-phosphate + H(+) = UMP + CO2; 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; P54764: EPHA4; NbExp=2; IntAct=EBI-723452, EBI-5773557; 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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_000373.4. [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 PDB; 7OTU; X-ray; 0.95 A; A=224-480. DR PDB; 7OUZ; X-ray; 0.90 A; A=224-479. DR PDB; 7OV0; X-ray; 0.95 A; A=224-480. DR PDB; 7Q1H; X-ray; 1.31 A; A=224-480. DR PDB; 9HDS; X-ray; 0.86 A; A=224-480. DR PDB; 9HDT; X-ray; 1.30 A; A=224-480. DR PDB; 9HDU; X-ray; 1.00 A; A=224-480. DR PDB; 9HDV; X-ray; 1.50 A; A=224-480. DR PDB; 9HDW; X-ray; 0.83 A; A=224-480. DR PDB; 9HDX; X-ray; 1.05 A; A/B=224-480. DR PDB; 9HDY; X-ray; 1.60 A; A=224-480. DR PDB; 9HDZ; X-ray; 1.79 A; A/B=224-480. DR PDB; 9HIL; X-ray; 1.60 A; A/B=224-479. DR PDB; 9HY0; X-ray; 0.95 A; A=224-480. DR AlphaFoldDB; P11172; -. DR MDposit; P11172; -. DR MDRepo; P11172; -. DR SMR; P11172; -. DR BioGRID; 113218; 164. DR CORUM; P11172; -. DR DIP; DIP-29595N; -. DR FunCoup; P11172; 4207. DR IntAct; P11172; 65. DR MINT; P11172; -. DR NDEx; IQUERY-CP-UMPS; 5 NDEx IQuery Curated Pathways. 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 SwissPalm; P11172; -. DR BioMuta; UMPS; -. DR jPOST; P11172; -. DR MassIVE; P11172; -. DR PaxDb; 9606-ENSP00000232607; -. DR PeptideAtlas; P11172; -. DR ProteomicsDB; 52713; -. [P11172-1] DR ProteomicsDB; 52714; -. [P11172-2] DR ProteomicsDB; 5937; -. DR ProteomicsDB; 5938; -. DR Pumba; P11172; -. DR Antibodypedia; 32990; 226 antibodies from 33 providers. DR DNASU; 7372; -. DR Ensembl; ENST00000232607.7; ENSP00000232607.2; ENSG00000114491.15. [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 AGR; HGNC:12563; -. DR ClinPGx; PA363; -. 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 OpenTargets; ENSG00000114491; -. DR Orphanet; 30; Hereditary orotic aciduria. DR VEuPathDB; HostDB:ENSG00000114491; -. DR eggNOG; KOG1377; Eukaryota. DR GeneTree; ENSGT00390000001856; -. DR HOGENOM; CLU_049275_1_0_1; -. DR InParanoid; P11172; -. DR OMA; SAKHVCG; -. DR OrthoDB; 10263753at2759; -. DR PAN-GO; P11172; 4 GO annotations based on evolutionary models. DR PhylomeDB; P11172; -. DR BRENDA; 2.4.2.10; 2681. 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 Agora; ENSG00000114491; -. DR BioGRID-ORCS; 7372; 274 hits in 1169 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 192 other cell types or tissues. DR ExpressionAtlas; P11172; baseline and differential. 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:0044210; P:'de novo' CTP biosynthetic process; IEA:Ensembl. 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: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; cd04725; OMP_decarboxylase_like; 1. DR CDD; cd06223; PRTases_typeI; 1. DR FunFam; 3.20.20.70:FF:000092; Uridine monophosphate synthetase; 1. DR FunFam; 3.40.50.2020:FF:000025; Uridine monophosphate synthetase; 1. DR Gene3D; 3.40.50.2020; -; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 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; IPR029057; PRTase-like. DR InterPro; IPR000836; PRTase_dom. DR InterPro; IPR011060; RibuloseP-bd_barrel. DR NCBIfam; TIGR00336; pyrE; 1. DR NCBIfam; TIGR01740; pyrF; 1. DR PANTHER; PTHR19278; OROTATE PHOSPHORIBOSYLTRANSFERASE; 1. DR PANTHER; PTHR19278:SF9; URIDINE 5'-MONOPHOSPHATE SYNTHASE; 1. DR Pfam; PF00215; OMPdecase; 1. DR Pfam; PF00156; Pribosyltran; 1. DR SMART; SM00934; OMPdecase; 1. DR SUPFAM; SSF53271; PRTase-like; 1. DR SUPFAM; SSF51366; Ribulose-phoshate binding barrel; 1. DR PROSITE; PS00156; OMPDECASE; 1. DR PROSITE; PS00103; PUR_PYR_PR_TRANSFER; 1. 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 PDBsum; 7OTU; -. DR PDBsum; 7OUZ; -. DR PDBsum; 7OV0; -. DR PDBsum; 7Q1H; -. DR PDBsum; 9HDS; -. DR PDBsum; 9HDT; -. DR PDBsum; 9HDU; -. DR PDBsum; 9HDV; -. DR PDBsum; 9HDW; -. DR PDBsum; 9HDX; -. DR PDBsum; 9HDY; -. DR PDBsum; 9HDZ; -. DR PDBsum; 9HIL; -. DR PDBsum; 9HY0; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Decarboxylase; KW Disease variant; Glycosyltransferase; Lyase; Multifunctional enzyme; KW Phosphoprotein; Proteomics identification; Pyrimidine biosynthesis; KW 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 224..226 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 227..230 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 238..250 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 254..257 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 263..273 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 274..276 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 278..282 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 284..286 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 292..305 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 308..315 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 319..327 FT /evidence="ECO:0007829|PDB:7OUZ" FT TURN 329..331 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 333..336 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 338..344 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 349..358 FT /evidence="ECO:0007829|PDB:7OUZ" FT TURN 359..362 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 364..368 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 381..392 FT /evidence="ECO:0007829|PDB:7OUZ" FT TURN 393..396 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 397..401 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 412..416 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 421..425 FT /evidence="ECO:0007829|PDB:7OUZ" FT TURN 427..429 FT /evidence="ECO:0007829|PDB:6ZWZ" FT STRAND 431..433 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 436..441 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 445..450 FT /evidence="ECO:0007829|PDB:7OUZ" FT HELIX 451..454 FT /evidence="ECO:0007829|PDB:7OUZ" FT STRAND 456..458 FT /evidence="ECO:0007829|PDB:7OQM" FT HELIX 459..478 FT /evidence="ECO:0007829|PDB:7OUZ" 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 //