UPP2

Summary

UPP2 (uridine phosphorylase 2, HGNC:23061) is a protein-coding gene on chromosome 2q24.1, encoding Uridine phosphorylase 2 (O95045). Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.

Enables deoxyuridine phosphorylase activity; identical protein binding activity; and uridine phosphorylase activity. Involved in dCMP catabolic process and uridine catabolic process. Located in type III intermediate filament.

Source: NCBI Gene 151531 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_173355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23061
Approved symbol	UPP2
Name	uridine phosphorylase 2
Location	2q24.1
Locus type	gene with protein product
Status	Approved
Aliases	UPASE2, UP2, UDRPASE2
Ensembl gene	ENSG00000007001
Ensembl biotype	protein_coding
OMIM	617340
Entrez	151531

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000005756, ENST00000439185, ENST00000460456, ENST00000489438, ENST00000605860, ENST00000715224, ENST00000890004, ENST00000890005

RefSeq mRNA: 2 — MANE Select: NM_173355 NM_001135098, NM_173355

CCDS: CCDS2207, CCDS46435

Canonical transcript exons

ENST00000005756 — 7 exons

Exon	Start	End
ENSE00000778634	158115101	158115259
ENSE00000778636	158117824	158117938
ENSE00000778638	158121409	158121618
ENSE00001371573	158101876	158102125
ENSE00003597020	158123749	158123895
ENSE00003643227	158106099	158106216
ENSE00003902502	158134748	158136154

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 93.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2706 / max 6.5249, expressed in 143 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23206	0.2706	143

Top tissues by expression

203 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	93.47	silver quality
adult mammalian kidney	UBERON:0000082	82.83	gold quality
kidney	UBERON:0002113	77.25	gold quality
pancreatic ductal cell	CL:0002079	76.96	silver quality
anterior cingulate cortex	UBERON:0009835	69.49	gold quality
cortical plate	UBERON:0005343	68.98	gold quality
prefrontal cortex	UBERON:0000451	68.49	gold quality
nucleus accumbens	UBERON:0001882	68.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.95	gold quality
right frontal lobe	UBERON:0002810	67.70	gold quality
amygdala	UBERON:0001876	67.31	gold quality
right lobe of liver	UBERON:0001114	66.24	gold quality
liver	UBERON:0002107	66.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	64.84	gold quality
cortex of kidney	UBERON:0001225	64.67	gold quality
neocortex	UBERON:0001950	64.18	gold quality
frontal cortex	UBERON:0001870	63.41	gold quality
ileal mucosa	UBERON:0000331	62.29	silver quality
cerebellar hemisphere	UBERON:0002245	62.15	gold quality
ganglionic eminence	UBERON:0004023	62.13	gold quality
cerebellar cortex	UBERON:0002129	62.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.11	gold quality
caudate nucleus	UBERON:0001873	61.89	gold quality
cerebral cortex	UBERON:0000956	61.86	gold quality
putamen	UBERON:0001874	61.12	gold quality
metanephros cortex	UBERON:0010533	60.77	gold quality
Ammon’s horn	UBERON:0001954	60.73	gold quality
cerebellum	UBERON:0002037	60.55	gold quality
forebrain	UBERON:0001890	60.04	gold quality
brain	UBERON:0000955	59.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting UPP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4743-3P	99.62	68.12	2095

Literature-anchored findings (GeneRIF, showing 3)

• identification of the novel human uridine phosphorylase, UDPase 2, with broad substrate specificity; UPase-2 gene was mapped to chromosome 2q24.1 and the 2.2-kb mRNA was predominantly expressed in kidney (PMID:12849978)
• This study demonistrated that use joint test to identified that UPP2 association to Autism Spectrum Disorder. (PMID:21151189)
• A novel structural mechanism for redox regulation of uridine phosphorylase 2 activity (PMID:21855639)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	upp2	ENSDARG00000036833
mus_musculus	Upp2	ENSMUSG00000026839
rattus_norvegicus	Upp2	ENSRNOG00000005341
drosophila_melanogaster	CG12065	FBGN0030052
caenorhabditis_elegans		WBGENE00019199

Paralogs (1): UPP1 (ENSG00000183696)

Protein

Protein identifiers

Uridine phosphorylase 2 — O95045 (reviewed: O95045)

All UniProt accessions (4): O95045, A0A0S2Z634, A0A0S2Z698, A0AAQ5BIC7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis. Shows broad substrate specificity and can also accept deoxyuridine and other analogous compounds.

Subunit / interactions. Homodimer.

Tissue specificity. Predominantly expressed in kidney.

Activity regulation. 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.

Pathway. Pyrimidine metabolism; UMP biosynthesis via salvage pathway; uracil from uridine (phosphorylase route): step 1/1.

Similarity. Belongs to the PNP/UDP phosphorylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95045-1	1	yes
O95045-2	2

RefSeq proteins (2): NP_001128570, NP_775491* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000845	Nucleoside_phosphorylase_d	Domain
IPR010059	Uridine_phosphorylase_euk	Family
IPR018016	Nucleoside_phosphorylase_CS	Conserved_site
IPR035994	Nucleoside_phosphorylase_sf	Homologous_superfamily

Pfam: PF01048

Enzyme classification (BRENDA):

• EC 2.4.2.3 — uridine phosphorylase (BRENDA: 34 organisms, 120 substrates, 109 inhibitors, 84 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
URIDINE	0.016–7.55	24
PHOSPHATE	0.076–16.1	16
URACIL	0.06–0.485	7
ALPHA-D-RIBOSE-1-PHOSPHATE	0.02–0.087	5
RIBOSE 1-PHOSPHATE	0.017–0.14	5
THYMIDINE	0.0489–0.215	5
5-METHYLURIDINE	0.065–4	4
5-FLUOROURACIL	0.036–0.06	3
2’-DEOXYURIDINE	0.121–0.13	2
DEOXYURIDINE	0.3–0.71	2
5’-DEOXY-5-FLUOROURIDINE	0.756	1
5-BROMODEOXYURIDINE	0.1	1
5-BROMOURIDINE	0.03	1
5-FLUORO-2’-DEOXYURIDINE	0.427	1
5-FLUOROURIDINE	0.024	1

Catalyzed reactions (Rhea), 2 shown:

• 2’-deoxyuridine + phosphate = 2-deoxy-alpha-D-ribose 1-phosphate + uracil (RHEA:22824)
• uridine + phosphate = alpha-D-ribose 1-phosphate + uracil (RHEA:24388)

UniProt features (40 total): helix 12, strand 12, binding site 5, sequence conflict 3, turn 3, sequence variant 2, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3P0F	X-RAY DIFFRACTION	1.54
3P0E	X-RAY DIFFRACTION	2
2XRF	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95045-F1	92.74	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 66; 100; 144–147; 148–149; 223–225

Disulfide bonds (1): 95–102

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-73614	Pyrimidine salvage
R-HSA-73621	Pyrimidine catabolism

MSigDB gene sets: 140 (showing top): TAATAAT_MIR126, REACTOME_PYRIMIDINE_CATABOLISM, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, UEDA_PERIFERAL_CLOCK, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, chr2q24

GO Biological Process (11): uridine catabolic process (GO:0006218), CMP catabolic process (GO:0006248), dCMP catabolic process (GO:0006249), nucleoside metabolic process (GO:0009116), xenobiotic catabolic process (GO:0042178), UMP salvage (GO:0044206), UMP catabolic process (GO:0046050), dTMP catabolic process (GO:0046074), dUMP catabolic process (GO:0046079), uridine metabolic process (GO:0046108), nucleotide catabolic process (GO:0009166)

GO Molecular Function (10): uridine phosphorylase activity (GO:0004850), thymidine phosphorylase activity (GO:0009032), pyrimidine-nucleoside phosphorylase activity (GO:0016154), identical protein binding (GO:0042802), deoxyuridine phosphorylase activity (GO:0047847), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757), pentosyltransferase activity (GO:0016763)

GO Cellular Component (3): cytosol (GO:0005829), type III intermediate filament (GO:0045098), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nucleotide salvage	1
Nucleotide catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine deoxyribonucleoside monophosphate catabolic process	3
pyrimidine deoxyribonucleotide catabolic process	3
pyrimidine-nucleoside phosphorylase activity	3
pyrimidine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleotide catabolic process	2
cellular anatomical structure	2
uridine metabolic process	1
pyrimidine ribonucleoside catabolic process	1
CMP metabolic process	1
dCMP metabolic process	1
nucleobase-containing small molecule metabolic process	1
carbohydrate derivative metabolic process	1
xenobiotic metabolic process	1
catabolic process	1
UMP biosynthetic process	1
pyrimidine ribonucleotide salvage	1
UMP metabolic process	1
dTMP metabolic process	1
dUMP metabolic process	1
pyrimidine ribonucleoside metabolic process	1
nucleotide metabolic process	1
nucleoside phosphate catabolic process	1
pentosyltransferase activity	1
protein binding	1
molecular_function	1
binding	1
catalytic activity	1
transferase activity	1
glycosyltransferase activity	1
cytoplasm	1
intermediate filament	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UPP2	PNP	P00491	925
UPP2	PGM2L1	Q6PCE3	900
UPP2	TYMP	P19971	851
UPP2	UMPS	P11172	845
UPP2	PGM2	Q96G03	841
UPP2	UCK1	Q9HA47	834
UPP2	UCKL1	Q9NWZ5	829
UPP2	UCK2	Q9BZX2	763
UPP2	DPYD	Q12882	727
UPP2	UPRT	Q96BW1	670
UPP2	CDA	P32320	665
UPP2	TYMS	P04818	641
UPP2	UPB1	Q9UBR1	597
UPP2	TK2	O00142	545
UPP2	DTYMK	P23919	533

IntAct

8 interactions, top by confidence:

A	B	Type	Score
UPP2	UPP2	psi-mi:“MI:0915”(physical association)	0.670
UPP2	SIAH1	psi-mi:“MI:0915”(physical association)	0.560
UPP2	CCZ1B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (13): UPP2 (Two-hybrid), UPP2 (Two-hybrid), UPP2 (Two-hybrid), MEOX2 (Two-hybrid), SIAH1 (Two-hybrid), UPP2 (Two-hybrid), UPP2 (Two-hybrid), UPP2 (Two-hybrid), LNX1 (Two-hybrid), MRPL28 (Two-hybrid), CCZ1 (Affinity Capture-MS), VIM (Affinity Capture-MS), VIM (Co-purification)

ESM2 similar proteins: A4FUD3, A4FV84, F4JGR5, G1TUB8, O08810, O80526, O95045, P11497, P21343, P42932, P50990, P62913, P62914, Q13085, Q15029, Q28559, Q29205, Q2QNG7, Q2QZ86, Q2YDN6, Q3T087, Q3ZCI9, Q4R5J0, Q5F3X4, Q5M939, Q5R6E0, Q5R8Q7, Q5R8T5, Q5RAP1, Q5RC11, Q5RCW2, Q5SWU9, Q5XGS8, Q5XK67, Q5ZID6, Q5ZJ08, Q6EE31, Q6QMZ8, Q80YV4, Q80Z29

Diamond homologs: G4VGH9, G4VGI0, O95045, P52624, Q16831, Q23588, Q8CGR7, P12758, P43770, A1S477, A3D7J1, A4IN93, A5VHR2, A6WRB5, A7GN01, A8LJI8, B2G592, B3W8N4, B8E6P7, B9LS20, O08444, O32810, O83990, P0A1F6, P0A1F7, P50389, P52671, Q02ZT0, Q03CD2, Q169T2, Q1J733, Q28U96, Q5JJC1, Q5KZM1, Q8R973, Q9CH10, A0AJW1, A0RBS0, A1SYK4, A3QGT0

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
UPP2	“down-regulates quantity”	uracil	“chemical modification”
UPP2	“down-regulates quantity”	“alpha-D-ribose 1-phosphate(2-)”	“chemical modification”
UPP2	“up-regulates quantity”	uridine	“chemical modification”
UPP2	“down-regulates quantity”	“2-deoxy-D-ribofuranose 1-phosphate(2-)”	“chemical modification”
UPP2	“up-regulates quantity”	2’-deoxyuridine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

60 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1078 predictions. Top by Δscore:

Variant	Effect	Δscore
2:158121615:GAAG:G	donor_gain	1.0000
2:158121617:AGG:A	donor_loss	1.0000
2:158121619:G:A	donor_loss	1.0000
2:158121620:T:A	donor_loss	1.0000
2:158123747:A:AG	acceptor_gain	1.0000
2:158123748:G:GG	acceptor_gain	1.0000
2:158123891:AAAAG:A	donor_loss	1.0000
2:158123893:AAGGT:A	donor_loss	1.0000
2:158123894:AGGT:A	donor_loss	1.0000
2:158123897:T:A	donor_loss	1.0000
2:158106095:CCA:C	acceptor_loss	0.9900
2:158106097:A:AC	acceptor_loss	0.9900
2:158106097:A:AG	acceptor_gain	0.9900
2:158106098:G:GG	acceptor_gain	0.9900
2:158106212:TAAAG:T	donor_loss	0.9900
2:158106213:AAAG:A	donor_loss	0.9900
2:158106214:AAG:A	donor_gain	0.9900
2:158106214:AAGGT:A	donor_loss	0.9900
2:158106215:AGGTA:A	donor_loss	0.9900
2:158106216:GGT:G	donor_loss	0.9900
2:158106217:GTA:G	donor_loss	0.9900
2:158106218:T:G	donor_loss	0.9900
2:158115099:A:AG	acceptor_gain	0.9900
2:158115100:G:GG	acceptor_gain	0.9900
2:158115100:GTTT:G	acceptor_gain	0.9900
2:158115258:GT:G	donor_gain	0.9900
2:158115260:G:GG	donor_gain	0.9900
2:158121400:A:AG	acceptor_gain	0.9900
2:158121401:C:G	acceptor_gain	0.9900
2:158121402:A:AG	acceptor_gain	0.9900

AlphaMissense

2103 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:158117833:G:C	G117R	0.999
2:158121609:T:C	F219L	0.999
2:158121611:T:A	F219L	0.999
2:158121611:T:G	F219L	0.999
2:158123849:G:A	M255I	0.999
2:158123849:G:C	M255I	0.999
2:158123849:G:T	M255I	0.999
2:158106160:C:G	H42D	0.998
2:158117915:G:C	R144T	0.998
2:158123840:T:A	N252K	0.998
2:158123840:T:G	N252K	0.998
2:158123851:A:T	E256V	0.998
2:158115105:T:A	V62D	0.997
2:158117864:A:T	E127V	0.997
2:158117916:A:C	R144S	0.997
2:158117916:A:T	R144S	0.997
2:158123845:A:T	E254V	0.997
2:158123848:T:C	M255T	0.997
2:158123850:G:A	E256K	0.997
2:158134761:T:G	C275W	0.997
2:158106162:C:A	H42Q	0.996
2:158106162:C:G	H42Q	0.996
2:158117833:G:T	G117C	0.996
2:158117834:G:A	G117D	0.996
2:158117834:G:T	G117V	0.996
2:158121427:T:A	V158D	0.996
2:158121599:T:G	C215W	0.996
2:158121610:T:C	F219S	0.996
2:158121610:T:G	F219C	0.996
2:158123758:G:C	R225P	0.996

dbSNP variants (sampled 300 via entrez): RS1000018541 (2:158082930 A>C), RS1000022848 (2:158078948 C>T), RS1000049488 (2:158036909 T>C,G), RS1000086166 (2:158077214 T>C), RS1000124547 (2:158061812 C>T), RS1000135225 (2:158032847 C>T), RS1000147128 (2:158048234 G>A), RS1000170610 (2:158015334 A>G), RS1000204959 (2:158013013 T>TTA), RS1000272608 (2:158054933 TC>T), RS1000275111 (2:158095837 T>A), RS1000278486 (2:158012567 T>G), RS1000313572 (2:158099120 T>C), RS1000328526 (2:158121839 A>G), RS1000329224 (2:158096129 G>A)

Disease associations

OMIM: gene MIM:617340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000825_3	Cerebrospinal P-tau181p levels	1.000000e-07
GCST002711_4	Sleep duration	6.000000e-06
GCST004198_4	Severe gingival inflammation	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004763	p-tau measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs35806662	UPP2		0.00	0

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Aflatoxin B1	decreases expression, decreases methylation	2
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
obeticholic acid	increases expression	1
ortho-topolin riboside	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Folic Acid	decreases expression	1
Melatonin	affects cotreatment, increases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.