UMPS_CAEEL
ID UMPS_CAEEL Reviewed; 497 AA.
AC G5EDZ2;
DT 18-JAN-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Uridine 5'-monophosphate synthase {ECO:0000250|UniProtKB:P11172};
DE Short=UMP synthase {ECO:0000250|UniProtKB:P11172};
DE Includes:
DE RecName: Full=Orotate phosphoribosyltransferase {ECO:0000303|PubMed:19645718};
DE Short=OPRT {ECO:0000303|PubMed:19645718};
DE Short=OPRTase {ECO:0000303|PubMed:19645718};
DE EC=2.4.2.10 {ECO:0000269|PubMed:19645718};
DE Includes:
DE RecName: Full=Orotidine 5'-phosphate decarboxylase {ECO:0000303|PubMed:19645718};
DE Short=ODC {ECO:0000303|PubMed:19645718};
DE Short=ODCase {ECO:0000303|PubMed:24262006};
DE EC=4.1.1.23 {ECO:0000269|PubMed:19645718};
GN Name=umps-1 {ECO:0000312|WormBase:T07C4.1};
GN Synonyms=rad-6 {ECO:0000303|PubMed:24262006};
GN ORFNames=T07C4.1 {ECO:0000312|WormBase:T07C4.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19645718; DOI=10.1111/j.1742-4658.2009.07168.x;
RA Kim S., Park D.H., Kim T.H., Hwang M., Shim J.;
RT "Functional analysis of pyrimidine biosynthesis enzymes using the
RT anticancer drug 5-fluorouracil in Caenorhabditis elegans.";
RL FEBS J. 276:4715-4726(2009).
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=20148972; DOI=10.1111/j.1742-4658.2010.07573.x;
RA Levitte S., Salesky R., King B., Coe Smith S., Depper M., Cole M.,
RA Hermann G.J.;
RT "A Caenorhabditis elegans model of orotic aciduria reveals enlarged
RT lysosome-related organelles in embryos lacking umps-1 function.";
RL FEBS J. 277:1420-1439(2010).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24262006; DOI=10.1042/bj20131085;
RA Merry A., Qiao M., Hasler M., Kuwabara P.E.;
RT "RAD-6: pyrimidine synthesis and radiation sensitivity in Caenorhabditis
RT elegans.";
RL Biochem. J. 458:343-353(2014).
CC -!- FUNCTION: Bifunctional enzyme which catalyzes the formation of UMP from
CC orotate in the de novo pathway of pyrimidine biosynthesis
CC (PubMed:19645718). May also form UMP from uracil (PubMed:19645718).
CC Regulates the size of gut granules during embryonic development
CC (PubMed:20148972). Involved in resistance to DNA damaging agents
CC including UV-C and X-ray radiation (PubMed:24262006).
CC {ECO:0000269|PubMed:19645718, ECO:0000269|PubMed:20148972,
CC ECO:0000269|PubMed:24262006}.
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:19645718};
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:19645718};
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC UMP from orotate: step 1/2. {ECO:0000269|PubMed:19645718}.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo pathway;
CC UMP from orotate: step 2/2. {ECO:0000269|PubMed:19645718}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20148972}.
CC Note=Localizes near the apical surface of the embryonic intestine.
CC Appears not to localize to gut granules. {ECO:0000269|PubMed:20148972}.
CC -!- TISSUE SPECIFICITY: Expressed in intestine and in neurons near the
CC nerve ring and rectum. {ECO:0000269|PubMed:19645718,
CC ECO:0000269|PubMed:20148972}.
CC -!- DEVELOPMENTAL STAGE: Expression starts at the early embryonic pretzel-
CC stage in the intestine and in a few cells in the head and the tail, and
CC continues throughout larval stages and adulthood.
CC {ECO:0000269|PubMed:20148972}.
CC -!- DISRUPTION PHENOTYPE: 56 percent of embryos fail to hatch and are
CC arrested at various stages between the bean stage and the four-fold
CC stage (PubMed:20148972). 30 percent of L1 larvae fail to reach
CC adulthood (PubMed:20148972). Embryos from the bean stage through to
CC hatching have abnormally enlarged gut granules which fail to acidify
CC (PubMed:20148972). Their size and number decreases at the L1 larval
CC stage (PubMed:20148972). Normal gut granules in L2 larvae and adults
CC (PubMed:20148972). Lysosomes in intestinal cells are mislocalized. 7
CC percent of embryos lack attachment of the anterior pharynx to the
CC buccal cavity (PubMed:20148972). Exposure to hypertonic conditions
CC reduces the number of vacuoles in mutant larvae (PubMed:20148972).
CC Resistance to 5-fluorouracil (5-FU)-mediated toxicity (PubMed:19645718,
CC PubMed:24262006). {ECO:0000269|PubMed:19645718,
CC ECO:0000269|PubMed:20148972, ECO:0000269|PubMed:24262006}.
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}.
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DR EMBL; BX284603; CAA82579.1; -; Genomic_DNA.
DR PIR; S41014; S41014.
DR RefSeq; NP_499291.1; NM_066890.4.
DR AlphaFoldDB; G5EDZ2; -.
DR SMR; G5EDZ2; -.
DR IntAct; G5EDZ2; 13.
DR MINT; G5EDZ2; -.
DR STRING; 6239.T07C4.1.1; -.
DR EPD; G5EDZ2; -.
DR PaxDb; G5EDZ2; -.
DR PeptideAtlas; G5EDZ2; -.
DR EnsemblMetazoa; T07C4.1.1; T07C4.1.1; WBGene00011559.
DR GeneID; 176453; -.
DR KEGG; cel:CELE_T07C4.1; -.
DR CTD; 176453; -.
DR WormBase; T07C4.1; CE00638; WBGene00011559; umps-1.
DR eggNOG; KOG1377; Eukaryota.
DR GeneTree; ENSGT00390000001856; -.
DR HOGENOM; CLU_049275_1_0_1; -.
DR InParanoid; G5EDZ2; -.
DR OMA; DHLGQQY; -.
DR OrthoDB; 1303452at2759; -.
DR PhylomeDB; G5EDZ2; -.
DR Reactome; R-CEL-500753; Pyrimidine biosynthesis.
DR UniPathway; UPA00070; UER00119.
DR UniPathway; UPA00070; UER00120.
DR PRO; PR:G5EDZ2; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00011559; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0004588; F:orotate phosphoribosyltransferase activity; IDA:WormBase.
DR GO; GO:0004590; F:orotidine-5'-phosphate decarboxylase activity; IDA:WormBase.
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:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:UniProtKB.
DR GO; GO:0019856; P:pyrimidine nucleobase biosynthetic process; IDA:WormBase.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR GO; GO:0010332; P:response to gamma radiation; IMP:UniProtKB.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:UniProtKB.
DR GO; GO:0009411; P:response to UV; IMP:WormBase.
DR GO; GO:0010225; P:response to UV-C; IMP:UniProtKB.
DR GO; GO:0010165; P:response to X-ray; IMP:UniProtKB.
DR GO; GO:0006222; P:UMP biosynthetic process; IMP:WormBase.
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; 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 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; PS00103; PUR_PYR_PR_TRANSFER; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Decarboxylase; Glycosyltransferase; Lyase;
KW Multifunctional enzyme; Pyrimidine biosynthesis; Reference proteome;
KW Transferase.
FT CHAIN 1..497
FT /note="Uridine 5'-monophosphate synthase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438772"
FT REGION 8..226
FT /note="OPRTase"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT REGION 227..232
FT /note="Domain linker"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT REGION 233..496
FT /note="OMPdecase"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT ACT_SITE 324
FT /note="For OMPdecase activity"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT ACT_SITE 326
FT /note="For OMPdecase activity"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT ACT_SITE 329
FT /note="For OMPdecase activity"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 271
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 293..295
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 293
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 326
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 329
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 329
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 333
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 333
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 387
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 387
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 446..448
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 446..448
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 466..467
FT /ligand="orotidine 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:57538"
FT /evidence="ECO:0000250|UniProtKB:P11172"
FT BINDING 466..467
FT /ligand="UMP"
FT /ligand_id="ChEBI:CHEBI:57865"
FT /evidence="ECO:0000250|UniProtKB:P11172"
SQ SEQUENCE 497 AA; 54805 MW; 789AE78A9DE50233 CRC64;
MSSLTDKTRN GALKRNLLRQ MLKASVFKFG EFQLKSGQIS PIYIDLRECF GHPGLLMLIS
EAISKQVEIS EVQYAGVLGI PYAALPYASV AAGNYLKKPL LIVRKEAKSY GTKKLIEGLY
QPNDRLILIE DVVTTGGSIL DVVKVLHTEN LVASDVFCIL DREQGGRQKL QDAGVTLHSL
LDMQTVLTFL YSTGAIGDEQ WHGIVQALNL PYTSPTKLEI NSELENLSSL PYVENVRTPL
AERESLTESA LIKKILGIMR RKKSNLCLAV DYTTVEQCLQ MIELAGPFVL AIKLHADAIT
DFNEEFTRKL TTMANDMDFI IFEDRKFGDT GNTNLLQLTG AQKIANWADV VTVHAVQGSD
SIAGVFRKLA KDPTYRLSGV LLIAQLSTKG SLTALEGYTE TAVKIANENR DVISGFITQT
RVSACSDLLN WTPGVNLDAK SDSAGQQWRG VDEAIEVQQN DIIIVGRGVT SSSEPVQQLK
RYRQIAWDAL TRSDDSI
