ID   UPP1_HUMAN              Reviewed;         310 AA.
AC   Q16831; D3DVM4; Q15362;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   27-MAR-2024, entry version 183.
DE   RecName: Full=Uridine phosphorylase 1 {ECO:0000303|PubMed:19291308};
DE            Short=UPase 1;
DE            Short=UrdPase 1;
DE            EC=2.4.2.3 {ECO:0000269|PubMed:7488099};
GN   Name=UPP1 {ECO:0000312|HGNC:HGNC:12576}; Synonyms=UP;
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] (ISOFORMS 1 AND 2), FUNCTION, AND CATALYTIC
RP   ACTIVITY.
RC   TISSUE=Colon;
RX   PubMed=7488099; DOI=10.1006/bbrc.1995.2619;
RA   Watanabe S., Uchida T.;
RT   "Cloning and expression of human uridine phosphorylase.";
RL   Biochem. Biophys. Res. Commun. 216:265-272(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Ovary, Placenta, and Skin;
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   [5]
RP   IDENTIFICATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=13737038; DOI=10.1016/0006-3002(61)91024-1;
RA   Pontis H., Degerstedt G., Reichard P.;
RT   "Uridine and deoxyuridine phosphorylases from Ehrlich ascites tumor.";
RL   Biochim. Biophys. Acta 51:138-147(1961).
RN   [6]
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   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) ALONE AND IN COMPLEX WITH INHIBITOR
RP   BAU AND PHOSPHATE, AND SUBUNIT.
RX   PubMed=19291308; DOI=10.1186/1472-6807-9-14;
RA   Roosild T.P., Castronovo S., Fabbiani M., Pizzorno G.;
RT   "Implications of the structure of human uridine phosphorylase 1 on the
RT   development of novel inhibitors for improving the therapeutic window of
RT   fluoropyrimidine chemotherapy.";
RL   BMC Struct. Biol. 9:14-14(2009).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH 5-FLUOROURACIL, AND
RP   SUBUNIT.
RX   PubMed=20856879; DOI=10.1371/journal.pone.0012741;
RA   Roosild T.P., Castronovo S.;
RT   "Active site conformational dynamics in human uridine phosphorylase 1.";
RL   PLoS ONE 5:E12741-E12741(2010).
CC   -!- FUNCTION: Catalyzes the reversible phosphorylytic cleavage of uridine
CC       to uracil and ribose-1-phosphate which can then be utilized as carbon
CC       and energy sources or in the rescue of pyrimidine bases for nucleotide
CC       synthesis (PubMed:7488099). Shows broad substrate specificity and can
CC       also accept deoxyuridine and other analogous compounds (Probable).
CC       {ECO:0000269|PubMed:7488099, ECO:0000305|PubMed:13737038}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=phosphate + uridine = alpha-D-ribose 1-phosphate + uracil;
CC         Xref=Rhea:RHEA:24388, ChEBI:CHEBI:16704, ChEBI:CHEBI:17568,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:57720; EC=2.4.2.3;
CC         Evidence={ECO:0000269|PubMed:7488099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24389;
CC         Evidence={ECO:0000305|PubMed:7488099};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2'-deoxyuridine + phosphate = 2-deoxy-alpha-D-ribose 1-
CC         phosphate + uracil; Xref=Rhea:RHEA:22824, ChEBI:CHEBI:16450,
CC         ChEBI:CHEBI:17568, ChEBI:CHEBI:43474, ChEBI:CHEBI:57259;
CC         Evidence={ECO:0000305|PubMed:13737038};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22825;
CC         Evidence={ECO:0000305|PubMed:13737038};
CC   -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via salvage pathway;
CC       uracil from uridine (phosphorylase route): step 1/1.
CC       {ECO:0000305|PubMed:7488099}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19291308,
CC       ECO:0000269|PubMed:20856879}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q16831-1; Sequence=Displayed;
CC       Name=2; Synonyms=Truncated;
CC         IsoId=Q16831-2; Sequence=VSP_001279, VSP_001280;
CC   -!- INDUCTION: By vitamin D3 and a mixture of inflammatory cytokines: TNF,
CC       IL1/interleukin-1 and IFNG/IFN-gamma. {ECO:0000269|PubMed:7488099}.
CC   -!- MISCELLANEOUS: [Isoform 2]: Inactive. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the PNP/UDP phosphorylase family. {ECO:0000305}.
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DR   EMBL; X90858; CAA62369.1; -; mRNA.
DR   EMBL; X90858; CAA62370.1; -; mRNA.
DR   EMBL; BT006699; AAP35345.1; -; mRNA.
DR   EMBL; CH471128; EAW60994.1; -; Genomic_DNA.
DR   EMBL; CH471128; EAW60995.1; -; Genomic_DNA.
DR   EMBL; BC001405; AAH01405.1; -; mRNA.
DR   EMBL; BC007348; AAH07348.1; -; mRNA.
DR   EMBL; BC053592; AAH53592.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS5507.1; -. [Q16831-1]
DR   PIR; JC4343; JC4343.
DR   RefSeq; NP_001274355.1; NM_001287426.1. [Q16831-1]
DR   RefSeq; NP_001274357.1; NM_001287428.1.
DR   RefSeq; NP_001274358.1; NM_001287429.1.
DR   RefSeq; NP_001274359.1; NM_001287430.1.
DR   RefSeq; NP_003355.1; NM_003364.3. [Q16831-1]
DR   RefSeq; XP_011513814.1; XM_011515512.2. [Q16831-1]
DR   PDB; 3EUE; X-ray; 2.30 A; A=1-310.
DR   PDB; 3EUF; X-ray; 1.90 A; A/B/C/D=1-310.
DR   PDB; 3NBQ; X-ray; 2.30 A; A/B/C/D=1-310.
DR   PDBsum; 3EUE; -.
DR   PDBsum; 3EUF; -.
DR   PDBsum; 3NBQ; -.
DR   AlphaFoldDB; Q16831; -.
DR   SMR; Q16831; -.
DR   BioGRID; 113224; 105.
DR   IntAct; Q16831; 20.
DR   MINT; Q16831; -.
DR   STRING; 9606.ENSP00000330032; -.
DR   BindingDB; Q16831; -.
DR   ChEMBL; CHEMBL4811; -.
DR   DrugBank; DB07437; 5-Benzylacyclouridine.
DR   DrugBank; DB00544; Fluorouracil.
DR   GlyGen; Q16831; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q16831; -.
DR   PhosphoSitePlus; Q16831; -.
DR   BioMuta; UPP1; -.
DR   DMDM; 2494059; -.
DR   EPD; Q16831; -.
DR   jPOST; Q16831; -.
DR   MassIVE; Q16831; -.
DR   MaxQB; Q16831; -.
DR   PaxDb; 9606-ENSP00000330032; -.
DR   PeptideAtlas; Q16831; -.
DR   ProteomicsDB; 61093; -. [Q16831-1]
DR   ProteomicsDB; 61094; -. [Q16831-2]
DR   Pumba; Q16831; -.
DR   Antibodypedia; 27594; 204 antibodies from 25 providers.
DR   DNASU; 7378; -.
DR   Ensembl; ENST00000331803.8; ENSP00000330032.4; ENSG00000183696.14. [Q16831-1]
DR   Ensembl; ENST00000395560.7; ENSP00000378927.3; ENSG00000183696.14. [Q16831-2]
DR   Ensembl; ENST00000395564.9; ENSP00000378931.4; ENSG00000183696.14. [Q16831-1]
DR   Ensembl; ENST00000417464.6; ENSP00000413611.2; ENSG00000183696.14. [Q16831-2]
DR   Ensembl; ENST00000457596.5; ENSP00000408899.1; ENSG00000183696.14. [Q16831-2]
DR   GeneID; 7378; -.
DR   KEGG; hsa:7378; -.
DR   MANE-Select; ENST00000395564.9; ENSP00000378931.4; NM_003364.4; NP_003355.1.
DR   UCSC; uc003tok.5; human. [Q16831-1]
DR   AGR; HGNC:12576; -.
DR   CTD; 7378; -.
DR   DisGeNET; 7378; -.
DR   GeneCards; UPP1; -.
DR   HGNC; HGNC:12576; UPP1.
DR   HPA; ENSG00000183696; Tissue enhanced (esophagus).
DR   MIM; 191730; gene.
DR   neXtProt; NX_Q16831; -.
DR   OpenTargets; ENSG00000183696; -.
DR   PharmGKB; PA365; -.
DR   VEuPathDB; HostDB:ENSG00000183696; -.
DR   eggNOG; KOG3728; Eukaryota.
DR   GeneTree; ENSGT00940000157781; -.
DR   HOGENOM; CLU_054104_0_0_1; -.
DR   InParanoid; Q16831; -.
DR   OMA; VQLCNPH; -.
DR   OrthoDB; 22073at2759; -.
DR   PhylomeDB; Q16831; -.
DR   TreeFam; TF314310; -.
DR   BioCyc; MetaCyc:HS00053-MONOMER; -.
DR   BRENDA; 2.4.2.3; 2681.
DR   PathwayCommons; Q16831; -.
DR   Reactome; R-HSA-73614; Pyrimidine salvage.
DR   Reactome; R-HSA-73621; Pyrimidine catabolism.
DR   SABIO-RK; Q16831; -.
DR   SignaLink; Q16831; -.
DR   UniPathway; UPA00574; UER00633.
DR   BioGRID-ORCS; 7378; 17 hits in 1151 CRISPR screens.
DR   ChiTaRS; UPP1; human.
DR   EvolutionaryTrace; Q16831; -.
DR   GeneWiki; UPP1; -.
DR   GenomeRNAi; 7378; -.
DR   Pharos; Q16831; Tchem.
DR   PRO; PR:Q16831; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q16831; Protein.
DR   Bgee; ENSG00000183696; Expressed in lower esophagus mucosa and 155 other cell types or tissues.
DR   ExpressionAtlas; Q16831; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0047847; F:deoxyuridine phosphorylase activity; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR   GO; GO:0009032; F:thymidine phosphorylase activity; IEA:Ensembl.
DR   GO; GO:0004850; F:uridine phosphorylase activity; IDA:UniProtKB.
DR   GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl.
DR   GO; GO:0006248; P:CMP catabolic process; IEA:Ensembl.
DR   GO; GO:0006249; P:dCMP catabolic process; IEA:Ensembl.
DR   GO; GO:0046074; P:dTMP catabolic process; IEA:Ensembl.
DR   GO; GO:0046079; P:dUMP catabolic process; IEA:Ensembl.
DR   GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR   GO; GO:0046050; P:UMP catabolic process; IEA:Ensembl.
DR   GO; GO:0044206; P:UMP salvage; IEA:UniProtKB-UniPathway.
DR   GO; GO:0006218; P:uridine catabolic process; IDA:UniProtKB.
DR   CDD; cd17763; UP_hUPP-like; 1.
DR   Gene3D; 3.40.50.1580; Nucleoside phosphorylase domain; 1.
DR   InterPro; IPR018016; Nucleoside_phosphorylase_CS.
DR   InterPro; IPR000845; Nucleoside_phosphorylase_d.
DR   InterPro; IPR035994; Nucleoside_phosphorylase_sf.
DR   InterPro; IPR010059; Uridine_phosphorylase_euk.
DR   NCBIfam; TIGR01719; euk_UDPppase; 1.
DR   PANTHER; PTHR43691; URIDINE PHOSPHORYLASE; 1.
DR   PANTHER; PTHR43691:SF10; URIDINE PHOSPHORYLASE 1; 1.
DR   Pfam; PF01048; PNP_UDP_1; 1.
DR   SUPFAM; SSF53167; Purine and uridine phosphorylases; 1.
DR   PROSITE; PS01232; PNP_UDP_1; 1.
DR   Genevisible; Q16831; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Glycosyltransferase;
KW   Reference proteome; Transferase.
FT   CHAIN           1..310
FT                   /note="Uridine phosphorylase 1"
FT                   /id="PRO_0000063191"
FT   BINDING         60
FT                   /ligand="phosphate"
FT                   /ligand_id="ChEBI:CHEBI:43474"
FT                   /evidence="ECO:0000269|PubMed:19291308,
FT                   ECO:0007744|PDB:3EUF"
FT   BINDING         94
FT                   /ligand="phosphate"
FT                   /ligand_id="ChEBI:CHEBI:43474"
FT                   /evidence="ECO:0000269|PubMed:19291308,
FT                   ECO:0007744|PDB:3EUF"
FT   BINDING         138..141
FT                   /ligand="phosphate"
FT                   /ligand_id="ChEBI:CHEBI:43474"
FT                   /evidence="ECO:0000269|PubMed:19291308,
FT                   ECO:0007744|PDB:3EUF"
FT   BINDING         142..143
FT                   /ligand="uridine"
FT                   /ligand_id="ChEBI:CHEBI:16704"
FT                   /evidence="ECO:0000305|PubMed:20856879,
FT                   ECO:0007744|PDB:3EUF, ECO:0007744|PDB:3NBQ"
FT   BINDING         217..219
FT                   /ligand="uridine"
FT                   /ligand_id="ChEBI:CHEBI:16704"
FT                   /evidence="ECO:0000305|PubMed:19291308,
FT                   ECO:0000305|PubMed:20856879, ECO:0007744|PDB:3EUF,
FT                   ECO:0007744|PDB:3NBQ"
FT   VAR_SEQ         15..36
FT                   /note="NDCPVRLLNPNIAKMKEDILYH -> KSGARHCGHNRAGSGYLLQGRV (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7488099"
FT                   /id="VSP_001279"
FT   VAR_SEQ         37..310
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7488099"
FT                   /id="VSP_001280"
FT   HELIX           26..28
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   TURN            35..38
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   TURN            41..43
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           46..50
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          55..60
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           62..76
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          81..83
FT                   /evidence="ECO:0007829|PDB:3EUE"
FT   TURN            88..91
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          97..100
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          103..107
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           112..128
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          135..147
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          152..159
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          165..171
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          174..179
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           184..197
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          202..209
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           215..217
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          222..224
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           229..241
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          244..250
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           251..260
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   STRAND          264..274
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           275..277
FT                   /evidence="ECO:0007829|PDB:3EUE"
FT   HELIX           285..292
FT                   /evidence="ECO:0007829|PDB:3EUF"
FT   HELIX           294..306
FT                   /evidence="ECO:0007829|PDB:3EUF"
SQ   SEQUENCE   310 AA;  33934 MW;  110CF678561E53F3 CRC64;
     MAATGANAEK AESHNDCPVR LLNPNIAKMK EDILYHFNLT TSRHNFPALF GDVKFVCVGG
     SPSRMKAFIR CVGAELGLDC PGRDYPNICA GTDRYAMYKV GPVLSVSHGM GIPSISIMLH
     ELIKLLYYAR CSNVTIIRIG TSGGIGLEPG TVVITEQAVD TCFKAEFEQI VLGKRVIRKT
     DLNKKLVQEL LLCSAELSEF TTVVGNTMCT LDFYEGQGRL DGALCSYTEK DKQAYLEAAY
     AAGVRNIEME SSVFAAMCSA CGLQAAVVCV TLLNRLEGDQ ISSPRNVLSE YQQRPQRLVS
     YFIKKKLSKA
//