UPP1_HUMAN
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 03-AUG-2022, entry version 174.
DE RecName: Full=Uridine phosphorylase 1;
DE Short=UPase 1;
DE Short=UrdPase 1;
DE EC=2.4.2.3 {ECO:0000269|PubMed:7488099};
GN Name=UPP1; 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 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 [6]
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 [7]
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 and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate
CC (PubMed:7488099). The produced molecules are then utilized as carbon
CC and energy sources or in the rescue of pyrimidine bases for nucleotide
CC synthesis. {ECO:0000269|PubMed:7488099, ECO:0000305}.
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 -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via salvage pathway;
CC uracil from uridine (phosphorylase route): step 1/1. {ECO:0000305}.
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; 99.
DR IntAct; Q16831; 18.
DR MINT; Q16831; -.
DR STRING; 9606.ENSP00000330032; -.
DR BindingDB; Q16831; -.
DR ChEMBL; CHEMBL4811; -.
DR DrugBank; DB07437; 5-Benzylacyclouridine.
DR DrugBank; DB00544; Fluorouracil.
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; Q16831; -.
DR PeptideAtlas; Q16831; -.
DR PRIDE; Q16831; -.
DR ProteomicsDB; 61093; -. [Q16831-1]
DR ProteomicsDB; 61094; -. [Q16831-2]
DR Antibodypedia; 27594; 166 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 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; FIHLCNP; -.
DR OrthoDB; 1423938at2759; -.
DR PhylomeDB; Q16831; -.
DR TreeFam; TF314310; -.
DR BioCyc; MetaCyc:HS00053-MON; -.
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 1071 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 153 other tissues.
DR ExpressionAtlas; Q16831; baseline and differential.
DR Genevisible; Q16831; HS.
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; -; 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 Pfam; PF01048; PNP_UDP_1; 1.
DR SUPFAM; SSF53167; SSF53167; 1.
DR TIGRFAMs; TIGR01719; euk_UDPppase; 1.
DR PROSITE; PS01232; PNP_UDP_1; 1.
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
