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Protein

Uridine phosphorylase 2

Gene

UPP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • identical protein binding Source: IntAct
  • 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

Keywordsi

Molecular functionGlycosyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.4.2.3 2681
ReactomeiR-HSA-73614 Pyrimidine salvage
R-HSA-73621 Pyrimidine catabolism
SABIO-RKiO95045
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

EuPathDBiHostDB:ENSG00000007001.12
HGNCiHGNC:23061 UPP2
MIMi617340 gene
neXtProtiNX_O95045

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi151531
OpenTargetsiENSG00000007001
PharmGKBiPA134866434

Chemistry databases

DrugBankiDB00544 Fluorouracil
DB05041 RP101

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
PeptideAtlasiO95045
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

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi127387, 3 interactors
IntActiO95045, 4 interactors
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
OMAiLDCDQIN
OrthoDBiEOG091G0EIO
PhylomeDBiO95045
TreeFamiTF314310

Family and domain databases

InterProiView protein in InterPro
IPR018016 Nucleoside_phosphorylase_CS
IPR000845 Nucleoside_phosphorylase_d
IPR035994 Nucleoside_phosphorylase_sf
IPR010059 Uridine_phosphorylase_euk
PfamiView protein in Pfam
PF01048 PNP_UDP_1, 1 hit
SUPFAMiSSF53167 SSF53167, 1 hit
TIGRFAMsiTIGR01719 euk_UDPppase, 1 hit
PROSITEiView protein in PROSITE
PS01232 PNP_UDP_1, 1 hit

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 dbSNP:rs6710480Ensembl.1
Natural variantiVAR_03458078M → L. Corresponds to variant dbSNP:rs7561584Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiUPP2_HUMAN
AccessioniPrimary (citable) accession number: O95045
Secondary accession number(s): B3KV87
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: May 1, 1999
Last modified: May 23, 2018
This is version 143 of the entry and version 1 of the sequence. See 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health