ID UMPS_HUMAN Reviewed; 480 AA.
AC P11172; O00758; O00759; O00760; Q16862; Q9H3Q2; Q9UG49;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 01-MAY-2013, entry version 158.
DE RecName: Full=Uridine 5'-monophosphate synthase;
DE Short=UMP synthase;
DE Includes:
DE RecName: Full=Orotate phosphoribosyltransferase;
DE Short=OPRT;
DE Short=OPRTase;
DE EC=2.4.2.10;
DE Includes:
DE RecName: Full=Orotidine 5'-phosphate decarboxylase;
DE Short=ODC;
DE EC=4.1.1.23;
DE AltName: Full=OMPdecase;
GN Name=UMPS; ORFNames=OK/SW-cl.21;
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 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
RT region 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;
RA Suchi M., Harada N., Tsuboi T., Asai K., Okajima K., Wada Y.,
RA 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, AND VARIANT ALA-213.
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
RT of point mutations in two hereditary orotic aciduria families.";
RL Am. J. Hum. Genet. 60:525-539(1997).
RN [4]
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-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
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 [8]
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-480 (ISOFORM 1).
RA Suchi M.;
RT "Molecular genetic studies on hereditary orotic aciduria: I.
RT Purification of human orotidine 5'-monophosphate decarboxylase and
RT cloning of its cDNA.";
RL Nagoya Med. J. 32:207-220(1988).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, AND MASS
RP SPECTROMETRY.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
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 [13]
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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 224-480 IN COMPLEX WITH
RP SUBSTRATE, SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF ASP-312.
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
RT support a covalent mechanism and provide a framework for drug
RT design.";
RL Structure 16:82-92(2008).
CC -!- CATALYTIC ACTIVITY: Orotidine 5'-phosphate + diphosphate = orotate
CC + 5-phospho-alpha-D-ribose 1-diphosphate.
CC -!- CATALYTIC ACTIVITY: Orotidine 5'-phosphate = UMP + CO(2).
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo
CC pathway; UMP from orotate: step 1/2.
CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via de novo
CC pathway; UMP from orotate: step 2/2.
CC -!- SUBUNIT: Homodimer.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11172-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11172-2; Sequence=VSP_009273;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Orotic aciduria 1 (ORAC1) [MIM:258900]: A disorder of
CC pyrimidine metabolism resulting in megaloblastic anemia and orotic
CC acid crystalluria that is frequently associated with some degree
CC of physical and mental retardation. A minority of cases have
CC additional features, particularly congenital malformations and
CC immune deficiencies. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC purine/pyrimidine phosphoribosyltransferase family.
CC -!- SIMILARITY: In the C-terminal section; belongs to the OMP
CC decarboxylase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB45710.3; Type=Erroneous termination; Positions=430; Note=Translated as Gln;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/UMPS";
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; 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; BC000364; AAH00364.1; -; mRNA.
DR EMBL; BC007511; AAH07511.1; -; mRNA.
DR EMBL; M36661; AAA61256.1; -; mRNA.
DR IPI; IPI00003923; -.
DR IPI; IPI00398067; -.
DR PIR; A30148; A30148.
DR RefSeq; NP_000364.1; NM_000373.3.
DR UniGene; Hs.2057; -.
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 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 ProteinModelPortal; P11172; -.
DR DIP; DIP-29595N; -.
DR IntAct; P11172; 11.
DR MINT; MINT-1397000; -.
DR STRING; 9606.ENSP00000232607; -.
DR PhosphoSite; P11172; -.
DR DMDM; 131708; -.
DR PaxDb; P11172; -.
DR PeptideAtlas; P11172; -.
DR PRIDE; P11172; -.
DR DNASU; 7372; -.
DR Ensembl; ENST00000232607; ENSP00000232607; ENSG00000114491.
DR Ensembl; ENST00000538242; ENSP00000444988; ENSG00000114491.
DR GeneID; 7372; -.
DR KEGG; hsa:7372; -.
DR UCSC; uc003ehl.4; human.
DR CTD; 7372; -.
DR GeneCards; GC03P124449; -.
DR HGNC; HGNC:12563; UMPS.
DR HPA; HPA036178; -.
DR HPA; HPA036179; -.
DR MIM; 258900; phenotype.
DR MIM; 613891; gene.
DR neXtProt; NX_P11172; -.
DR Orphanet; 30; Hereditary orotic aciduria.
DR PharmGKB; PA363; -.
DR eggNOG; COG0284; -.
DR HOVERGEN; HBG000870; -.
DR InParanoid; P11172; -.
DR KO; K13421; -.
DR OMA; MYRKAAW; -.
DR OrthoDB; EOG4TXBRR; -.
DR PhylomeDB; P11172; -.
DR BRENDA; 4.1.1.23; 2681.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00070; UER00119.
DR UniPathway; UPA00070; UER00120.
DR BindingDB; P11172; -.
DR ChEMBL; CHEMBL5216; -.
DR EvolutionaryTrace; P11172; -.
DR GenomeRNAi; 7372; -.
DR NextBio; 28866; -.
DR ArrayExpress; P11172; -.
DR Bgee; P11172; -.
DR CleanEx; HS_UMPS; -.
DR Genevestigator; P11172; -.
DR GermOnline; ENSG00000114491; Homo sapiens.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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:0035690; P:cellular response to drug; IEA:Compara.
DR GO; GO:0007565; P:female pregnancy; IEA:Compara.
DR GO; GO:0007595; P:lactation; IEA:Compara.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; TAS:Reactome.
DR GO; GO:0006222; P:UMP biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.20.20.70; -; 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; IPR011060; RibuloseP-bd_barrel.
DR Pfam; PF00215; OMPdecase; 1.
DR Pfam; PF00156; Pribosyltran; 1.
DR SMART; SM00934; OMPdecase; 1.
DR SUPFAM; SSF51366; RibP_bind_barrel; 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; Alternative splicing; Complete proteome; Decarboxylase;
KW Disease mutation; Glycosyltransferase; Lyase; Multifunctional enzyme;
KW Phosphoprotein; Polymorphism; Pyrimidine biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 480 Uridine 5'-monophosphate synthase.
FT /FTId=PRO_0000139649.
FT REGION 1 214 OPRTase.
FT REGION 215 220 Domain linker.
FT REGION 221 480 OMPdecase.
FT ACT_SITE 312 312 For OMPdecase activity.
FT ACT_SITE 314 314 For OMPdecase activity.
FT ACT_SITE 317 317 For OMPdecase activity.
FT MOD_RES 214 214 Phosphoserine.
FT VAR_SEQ 1 178 Missing (in isoform 2).
FT /FTId=VSP_009273.
FT VARIANT 30 30 S -> G (in dbSNP:rs17843776).
FT /FTId=VAR_020614.
FT VARIANT 96 96 R -> G (in ORAC1).
FT /FTId=VAR_006807.
FT VARIANT 109 109 V -> G (in ORAC1).
FT /FTId=VAR_006808.
FT VARIANT 213 213 G -> A (in dbSNP:rs1801019).
FT /FTId=VAR_006809.
FT VARIANT 429 429 G -> R (in ORAC1).
FT /FTId=VAR_006810.
FT VARIANT 446 446 I -> V (in dbSNP:rs3772809).
FT /FTId=VAR_020615.
FT MUTAGEN 312 312 D->N: Loss of OMPdecase activity.
FT CONFLICT 13 13 T -> G (in Ref. 9; AAA61256).
FT CONFLICT 377 377 L -> Q (in Ref. 9; AAA61256).
FT HELIX 8 16
FT TURN 17 19
FT STRAND 21 27
FT STRAND 33 38
FT HELIX 40 45
FT HELIX 47 63
FT STRAND 69 73
FT TURN 75 78
FT HELIX 79 89
FT STRAND 93 96
FT TURN 99 102
FT STRAND 103 105
FT STRAND 108 111
FT STRAND 118 129
FT HELIX 130 141
FT STRAND 148 154
FT HELIX 159 164
FT TURN 165 167
FT STRAND 169 175
FT HELIX 176 185
FT HELIX 191 202
FT HELIX 227 230
FT HELIX 238 250
FT STRAND 254 257
FT HELIX 263 273
FT HELIX 274 276
FT STRAND 278 282
FT HELIX 284 286
FT HELIX 292 305
FT STRAND 308 315
FT HELIX 319 327
FT TURN 329 331
FT HELIX 333 335
FT STRAND 338 344
FT HELIX 349 358
FT TURN 359 362
FT STRAND 364 368
FT HELIX 381 392
FT TURN 393 396
FT STRAND 397 401
FT STRAND 412 416
FT STRAND 421 425
FT STRAND 427 429
FT STRAND 431 433
FT HELIX 435 439
FT TURN 440 442
FT STRAND 445 450
FT HELIX 451 454
FT STRAND 456 458
FT HELIX 459 478
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
//
