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Protein

Uridine phosphorylase 2

Gene

UPP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. Shows substrate specificity and accept uridine, deoxyuridine, and thymidine as well as the two pyrimidine nucleoside analogs 5-fluorouridine and 5-fluoro-2(')-deoxyuridine as substrates.

Catalytic activityi

Uridine + phosphate = uracil + alpha-D-ribose 1-phosphate.

Enzyme regulationi

A conditional disulfide bridge can form within the protein that dislocates a critical phosphate-coordinating arginine Arg-100 away from the active site, disabling the enzyme.1 Publication

Pathwayi: UMP biosynthesis via salvage pathway

This protein is involved in step 1 of the subpathway that synthesizes uracil from uridine (phosphorylase route).
Proteins known to be involved in this subpathway in this organism are:
  1. Uridine phosphorylase 1 (UPP1), Uridine phosphorylase (UPP2), Uridine phosphorylase (UPP2), Uridine phosphorylase 2 (UPP2)
This subpathway is part of the pathway UMP biosynthesis via salvage pathway, which is itself part of Pyrimidine metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes uracil from uridine (phosphorylase route), the pathway UMP biosynthesis via salvage pathway and in Pyrimidine metabolism.

GO - Molecular functioni

  • uridine phosphorylase activity Source: UniProtKB

GO - Biological processi

  • nucleoside metabolic process Source: UniProtKB
  • nucleotide catabolic process Source: InterPro
  • pyrimidine nucleoside catabolic process Source: Reactome
  • pyrimidine nucleoside salvage Source: Reactome
  • UMP salvage Source: UniProtKB-UniPathway
  • uridine metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BioCyciZFISH:HS00200-MONOMER.
BRENDAi2.4.2.3. 2681.
ReactomeiR-HSA-73614. Pyrimidine salvage reactions.
R-HSA-73621. Pyrimidine catabolism.
SABIO-RKO95045.
SignaLinkiO95045.
UniPathwayiUPA00574; UER00633.

Names & Taxonomyi

Protein namesi
Recommended name:
Uridine phosphorylase 2 (EC:2.4.2.3)
Short name:
UPase 2
Short name:
UrdPase 2
Gene namesi
Name:UPP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:23061. UPP2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • type III intermediate filament Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi151531.
OpenTargetsiENSG00000007001.
PharmGKBiPA134866434.

Chemistry databases

DrugBankiDB00544. Fluorouracil.

Polymorphism and mutation databases

BioMutaiUPP2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000631931 – 317Uridine phosphorylase 2Add BLAST317

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi95 ↔ 102Redox-active1 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiO95045.
PRIDEiO95045.

PTM databases

iPTMnetiO95045.
PhosphoSitePlusiO95045.

Expressioni

Tissue specificityi

Predominantly expressed in kidney.1 Publication

Gene expression databases

BgeeiENSG00000007001.
CleanExiHS_UPP2.
ExpressionAtlasiO95045. baseline and differential.
GenevisibleiO95045. HS.

Organism-specific databases

HPAiHPA035225.
HPA035226.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
SIAH1Q8IUQ43EBI-10191025,EBI-747107

Protein-protein interaction databases

BioGridi127387. 3 interactors.
IntActiO95045. 1 interactor.
STRINGi9606.ENSP00000387230.

Structurei

Secondary structure

1317
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 34Combined sources3
Helixi41 – 43Combined sources3
Turni47 – 49Combined sources3
Helixi52 – 56Combined sources5
Beta strandi61 – 66Combined sources6
Helixi68 – 82Combined sources15
Helixi88 – 90Combined sources3
Turni94 – 97Combined sources4
Beta strandi98 – 100Combined sources3
Beta strandi103 – 106Combined sources4
Beta strandi109 – 113Combined sources5
Helixi118 – 134Combined sources17
Beta strandi141 – 153Combined sources13
Beta strandi158 – 165Combined sources8
Beta strandi171 – 177Combined sources7
Beta strandi180 – 185Combined sources6
Helixi190 – 201Combined sources12
Beta strandi208 – 215Combined sources8
Helixi221 – 223Combined sources3
Beta strandi226 – 229Combined sources4
Helixi235 – 248Combined sources14
Beta strandi250 – 256Combined sources7
Helixi257 – 266Combined sources10
Beta strandi270 – 280Combined sources11
Turni281 – 283Combined sources3
Helixi291 – 298Combined sources8
Helixi300 – 313Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XRFX-ray2.30A/B/C23-317[»]
3P0EX-ray2.00A/B/C/D/E/F21-314[»]
3P0FX-ray1.54A21-314[»]
ProteinModelPortaliO95045.
SMRiO95045.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95045.

Family & Domainsi

Sequence similaritiesi

Belongs to the PNP/UDP phosphorylase family.Curated

Keywords - Domaini

Redox-active center

Phylogenomic databases

eggNOGiKOG3728. Eukaryota.
COG2820. LUCA.
GeneTreeiENSGT00390000004400.
HOGENOMiHOG000231747.
HOVERGENiHBG047725.
InParanoidiO95045.
KOiK00757.
OMAiFHIVERM.
OrthoDBiEOG091G0EIO.
PhylomeDBiO95045.
TreeFamiTF314310.

Family and domain databases

Gene3Di3.40.50.1580. 1 hit.
InterProiIPR018017. Nucleoside_phosphorylase.
IPR018016. Nucleoside_phosphorylase_CS.
IPR000845. Nucleoside_phosphorylase_d.
IPR010059. Uridine_phosphorylase_euk.
[Graphical view]
PANTHERiPTHR21234. PTHR21234. 1 hit.
PfamiPF01048. PNP_UDP_1. 1 hit.
[Graphical view]
SUPFAMiSSF53167. SSF53167. 1 hit.
TIGRFAMsiTIGR01719. euk_UDPppase. 1 hit.
PROSITEiPS01232. PNP_UDP_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95045-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASVIPASNR SMRSDRNTYV GKRFVHVKNP YLDLMDEDIL YHLDLGTKTH
60 70 80 90 100
NLPAMFGDVK FVCVGGSPNR MKAFALFMHK ELGFEEAEED IKDICAGTDR
110 120 130 140 150
YCMYKTGPVL AISHGMGIPS ISIMLHELIK LLHHARCCDV TIIRIGTSGG
160 170 180 190 200
IGIAPGTVVI TDIAVDSFFK PRFEQVILDN IVTRSTELDK ELSEELFNCS
210 220 230 240 250
KEIPNFPTLV GHTMCTYDFY EGQGRLDGAL CSFSREKKLD YLKRAFKAGV
260 270 280 290 300
RNIEMESTVF AAMCGLCGLK AAVVCVTLLD RLDCDQINLP HDVLVEYQQR
310
PQLLISNFIR RRLGLCD
Length:317
Mass (Da):35,527
Last modified:May 1, 1999 - v1
Checksum:i69F6BA1DC44977A3
GO
Isoform 2 (identifier: O95045-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLAPGCELDPDQEVVRTRPEDVPASPSTSTMIVSVLRPPSHASCTACGTVTFHIVERM

Note: No experimental confirmation available.
Show »
Length:374
Mass (Da):41,602
Checksum:iF1FF70496CD41D8F
GO

Sequence cautioni

The sequence AAH33529 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti153I → M in AAO61681 (PubMed:12849978).Curated1
Sequence conflicti157T → R in AAO61681 (PubMed:12849978).Curated1
Sequence conflicti256 – 262ESTVFAA → GIYSVCS in AAO61681 (PubMed:12849978).Curated7

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02443110R → S.Corresponds to variant rs6710480dbSNPEnsembl.1
Natural variantiVAR_03458078M → L.Corresponds to variant rs7561584dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0437561M → MLAPGCELDPDQEVVRTRPE DVPASPSTSTMIVSVLRPPS HASCTACGTVTFHIVERM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY225131 mRNA. Translation: AAO61681.1.
AK122743 mRNA. Translation: BAG53699.1.
AC005539 Genomic DNA. Translation: AAD12227.1.
BC033529 mRNA. Translation: AAH33529.1. Different initiation.
CCDSiCCDS2207.1. [O95045-1]
CCDS46435.1. [O95045-2]
RefSeqiNP_001128570.1. NM_001135098.1. [O95045-2]
NP_775491.1. NM_173355.3. [O95045-1]
UniGeneiHs.128427.

Genome annotation databases

EnsembliENST00000005756; ENSP00000005756; ENSG00000007001. [O95045-1]
ENST00000605860; ENSP00000474090; ENSG00000007001. [O95045-2]
GeneIDi151531.
KEGGihsa:151531.
UCSCiuc002tzp.4. human. [O95045-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY225131 mRNA. Translation: AAO61681.1.
AK122743 mRNA. Translation: BAG53699.1.
AC005539 Genomic DNA. Translation: AAD12227.1.
BC033529 mRNA. Translation: AAH33529.1. Different initiation.
CCDSiCCDS2207.1. [O95045-1]
CCDS46435.1. [O95045-2]
RefSeqiNP_001128570.1. NM_001135098.1. [O95045-2]
NP_775491.1. NM_173355.3. [O95045-1]
UniGeneiHs.128427.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XRFX-ray2.30A/B/C23-317[»]
3P0EX-ray2.00A/B/C/D/E/F21-314[»]
3P0FX-ray1.54A21-314[»]
ProteinModelPortaliO95045.
SMRiO95045.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127387. 3 interactors.
IntActiO95045. 1 interactor.
STRINGi9606.ENSP00000387230.

Chemistry databases

DrugBankiDB00544. Fluorouracil.

PTM databases

iPTMnetiO95045.
PhosphoSitePlusiO95045.

Polymorphism and mutation databases

BioMutaiUPP2.

Proteomic databases

PaxDbiO95045.
PRIDEiO95045.

Protocols and materials databases

DNASUi151531.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000005756; ENSP00000005756; ENSG00000007001. [O95045-1]
ENST00000605860; ENSP00000474090; ENSG00000007001. [O95045-2]
GeneIDi151531.
KEGGihsa:151531.
UCSCiuc002tzp.4. human. [O95045-1]

Organism-specific databases

CTDi151531.
DisGeNETi151531.
GeneCardsiUPP2.
HGNCiHGNC:23061. UPP2.
HPAiHPA035225.
HPA035226.
neXtProtiNX_O95045.
OpenTargetsiENSG00000007001.
PharmGKBiPA134866434.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3728. Eukaryota.
COG2820. LUCA.
GeneTreeiENSGT00390000004400.
HOGENOMiHOG000231747.
HOVERGENiHBG047725.
InParanoidiO95045.
KOiK00757.
OMAiFHIVERM.
OrthoDBiEOG091G0EIO.
PhylomeDBiO95045.
TreeFamiTF314310.

Enzyme and pathway databases

UniPathwayiUPA00574; UER00633.
BioCyciZFISH:HS00200-MONOMER.
BRENDAi2.4.2.3. 2681.
ReactomeiR-HSA-73614. Pyrimidine salvage reactions.
R-HSA-73621. Pyrimidine catabolism.
SABIO-RKO95045.
SignaLinkiO95045.

Miscellaneous databases

EvolutionaryTraceiO95045.
GenomeRNAii151531.
PROiO95045.

Gene expression databases

BgeeiENSG00000007001.
CleanExiHS_UPP2.
ExpressionAtlasiO95045. baseline and differential.
GenevisibleiO95045. HS.

Family and domain databases

Gene3Di3.40.50.1580. 1 hit.
InterProiIPR018017. Nucleoside_phosphorylase.
IPR018016. Nucleoside_phosphorylase_CS.
IPR000845. Nucleoside_phosphorylase_d.
IPR010059. Uridine_phosphorylase_euk.
[Graphical view]
PANTHERiPTHR21234. PTHR21234. 1 hit.
PfamiPF01048. PNP_UDP_1. 1 hit.
[Graphical view]
SUPFAMiSSF53167. SSF53167. 1 hit.
TIGRFAMsiTIGR01719. euk_UDPppase. 1 hit.
PROSITEiPS01232. PNP_UDP_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUPP2_HUMAN
AccessioniPrimary (citable) accession number: O95045
Secondary accession number(s): B3KV87
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.