UBR2

Summary

UBR2 (ubiquitin protein ligase E3 component n-recognin 2, HGNC:21289) is a protein-coding gene on chromosome 6p21.1, encoding E3 ubiquitin-protein ligase UBR2 (Q8IWV8). E3 ubiquitin-protein ligase which is a component of the N-end rule pathway.

Enables L-leucine binding activity and ubiquitin protein ligase activity. Involved in several processes, including cellular response to L-leucine; protein K63-linked ubiquitination; and regulation of signal transduction. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm.

Source: NCBI Gene 23304 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 261 total
• Druggable target: yes
• MANE Select transcript: NM_001363705

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21289
Approved symbol	UBR2
Name	ubiquitin protein ligase E3 component n-recognin 2
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	bA49A4.1, dJ392M17.3, KIAA0349
Ensembl gene	ENSG00000024048
Ensembl biotype	protein_coding
OMIM	609134
Entrez	23304

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000372899, ENST00000372901, ENST00000372903, ENST00000910623, ENST00000910624, ENST00000910625, ENST00000910626, ENST00000918155, ENST00000964716

RefSeq mRNA: 3 — MANE Select: NM_001363705 NM_001184801, NM_001363705, NM_015255

CCDS: CCDS4870, CCDS55001, CCDS87404

Canonical transcript exons

ENST00000372901 — 47 exons

Exon	Start	End
ENSE00000751374	42635418	42635546
ENSE00000751375	42637011	42637194
ENSE00000751376	42640209	42640270
ENSE00000751377	42641582	42641692
ENSE00000751378	42642416	42642481
ENSE00000751379	42644214	42644336
ENSE00000751380	42644473	42644536
ENSE00000751381	42645466	42645590
ENSE00000751382	42648118	42648170
ENSE00000751384	42650284	42650386
ENSE00000751385	42652023	42652071
ENSE00000751389	42658024	42658133
ENSE00000751390	42658240	42658320
ENSE00000751391	42658646	42658824
ENSE00000751402	42676056	42676191
ENSE00000849978	42652491	42652645
ENSE00000849979	42655621	42655723
ENSE00001458942	42691032	42693505
ENSE00002222659	42605721	42605859
ENSE00002225699	42616002	42616090
ENSE00002233361	42615071	42615178
ENSE00002247311	42594191	42594304
ENSE00002260289	42573734	42573993
ENSE00002269138	42612171	42612291
ENSE00002270923	42606589	42606651
ENSE00002291580	42603588	42603718
ENSE00002301987	42592151	42592229
ENSE00003460771	42632805	42632904
ENSE00003464441	42684794	42684871
ENSE00003482448	42663258	42663419
ENSE00003493839	42683055	42683111
ENSE00003496925	42659656	42659855
ENSE00003499291	42689569	42689670
ENSE00003508302	42666167	42666245
ENSE00003510399	42670092	42670240
ENSE00003558273	42679724	42679832
ENSE00003558783	42676783	42676873
ENSE00003572572	42678539	42678669
ENSE00003577038	42674126	42674193
ENSE00003591623	42665409	42665512
ENSE00003622522	42670660	42670715
ENSE00003628663	42617409	42617507
ENSE00003640751	42662184	42662277
ENSE00003654726	42688216	42688386
ENSE00003666499	42673791	42673887
ENSE00003693496	42632552	42632715
ENSE00003907413	42564029	42564397

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.2988 / max 488.4779, expressed in 1818 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67801	22.3107	1809
67800	2.3679	1115
67804	1.7576	881
67803	1.5250	896
67805	0.7834	361
67802	0.6179	355
203993	0.5367	281
67799	0.3846	170
67806	0.0150	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.64	gold quality
endothelial cell	CL:0000115	95.12	gold quality
biceps brachii	UBERON:0001507	94.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.44	gold quality
vastus lateralis	UBERON:0001379	94.12	gold quality
skin of hip	UBERON:0001554	93.85	gold quality
hair follicle	UBERON:0002073	93.75	gold quality
oocyte	CL:0000023	93.63	gold quality
quadriceps femoris	UBERON:0001377	93.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.22	gold quality
deltoid	UBERON:0001476	92.96	gold quality
jejunum	UBERON:0002115	92.65	gold quality
jejunal mucosa	UBERON:0000399	92.52	gold quality
tibialis anterior	UBERON:0001385	92.41	gold quality
skeletal muscle tissue	UBERON:0001134	92.31	gold quality
ileal mucosa	UBERON:0000331	92.29	gold quality
germinal epithelium of ovary	UBERON:0001304	92.21	gold quality
choroid plexus epithelium	UBERON:0003911	92.15	gold quality
upper leg skin	UBERON:0004262	92.00	gold quality
trabecular bone tissue	UBERON:0002483	91.91	gold quality
blood	UBERON:0000178	91.73	gold quality
metanephric glomerulus	UBERON:0004736	91.45	gold quality
muscle tissue	UBERON:0002385	91.27	gold quality
renal glomerulus	UBERON:0000074	91.00	gold quality
pancreatic ductal cell	CL:0002079	90.49	gold quality
myocardium	UBERON:0002349	90.32	gold quality
left ventricle myocardium	UBERON:0006566	90.07	gold quality
mammary duct	UBERON:0001765	89.99	gold quality
colonic mucosa	UBERON:0000317	89.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.31
E-MTAB-7606	no	518.93
E-CURD-89	no	378.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG

miRNA regulators (miRDB)

96 targeting UBR2, 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-4668-3P	100.00	68.74	2635
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 6)

• Study provides functional data for the mouse ubiquitin protein ligase E3 component n-recognin 2 protein. (PMID:14585983)
• The c.1,066A>T variant in the UBR2 gene is associated with increased susceptibility to azoospermia caused by meiotic arrest. (PMID:21573678)
• There was a significant difference between the oligospermia men (oligospermia group) and the fertile men (control group) observed in this research that could indicate that the combined AT-TC-CC genotype in the UBR2 gene (rs16895863, rs373341, rs3749897 respectively) is a possible risk of idiopathic oligospermia for men in Sichuan, China. (PMID:26940145)
• The E3 ligase UBR2 regulates cell death under caspase deficiency via Erk/MAPK pathway. (PMID:33288741)
• Burden of rare coding variants in an Italian cohort of familial multiple sclerosis. (PMID:34922125)
• The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling. (PMID:38225265)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubr2	ENSDARG00000070164
mus_musculus	Ubr2	ENSMUSG00000023977
rattus_norvegicus	Ubr2	ENSRNOG00000015813
drosophila_melanogaster	Ubr1	FBGN0030809
caenorhabditis_elegans	ubr-1	WBGENE00016326

Paralogs (2): UBR3 (ENSG00000144357), UBR1 (ENSG00000159459)

Protein

Protein identifiers

E3 ubiquitin-protein ligase UBR2 — Q8IWV8 (reviewed: Q8IWV8)

Alternative names: N-recognin-2, Ubiquitin-protein ligase E3-alpha-2, Ubiquitin-protein ligase E3-alpha-II

All UniProt accessions (1): Q8IWV8

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues (N-degrons) that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively. Does not ubiquitinate proteins that are acetylated at the N-terminus. In contrast, it strongly binds methylated N-degrons. Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth. Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis. Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization. Catalyzes ubiquitination and degradation of the N-terminal part of NLRP1 following NLRP1 activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of NLRP1, which polymerizes and forms the NLRP1 inflammasome followed by host cell pyroptosis. Plays a role in T-cell receptor signaling by inducing ‘Lys-63’-linked ubiquitination of lymphocyte cell-specific kinase LCK. This activity is regulated by DUSP22, which induces ‘Lys-48’-linked ubiquitination of UBR2, leading to its proteasomal degradation by SCF E3 ubiquitin-protein ligase complex.

Subunit / interactions. Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2. Interacts with RECQL4. Interacts with TEX19; does not lead to TEX19 degradation and stabilizes it. Interacts with CASP8. Interacts with ATXN3. Interacts with UBE2O.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Broadly expressed, with highest levels in skeletal muscle, kidney and pancreas. Present in acinar cells of the pancreas (at protein level).

Post-translational modifications. Dephosphorylated by DUSP22 at Ser-1694 and Tyr-1697, leading to subsequent ubiquitination and proteasomal degradation. ‘Lys-48’-linked ubiquitinated at Lys-94, Lys-779 and Lys-1599 following DUSP22-mediated dephosphorylation of Ser-1694 and Tyr-1697 which promotes UBR2 interaction with the SCF(FBW1A) E3 ubiquitin-protein ligase complex.

Domain organisation. The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif. The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for arginine in the first position, and a lower preference for lysine and histidine. It binds N-degrons with a methylated arginine or lysine in the first position.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the E3 ubiquitin-protein ligase UBR1-like family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8IWV8-1	1	yes
Q8IWV8-2	2
Q8IWV8-3	3
Q8IWV8-4	4

RefSeq proteins (3): NP_001171730, NP_001350634, NP_056070 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003126	Znf_UBR	Domain
IPR003769	ClpS_core	Domain
IPR014719	Ribosomal_bL12_C/ClpS-like	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR039164	UBR1-like	Family
IPR042065	E3_ELL-like	Homologous_superfamily
IPR044046	E3_ligase_UBR-like_C	Domain
IPR047508	UBR-box_UBR2	Domain
IPR055194	UBR1-like_WH	Domain

Pfam: PF02207, PF02617, PF18995, PF22960

UniProt features (79 total): binding site 23, cross-link 13, mutagenesis site 9, splice variant 7, modified residue 4, sequence variant 4, strand 4, turn 3, zinc finger region 2, region of interest 2, compositionally biased region 2, helix 2, initiator methionine 1, chain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5TDA	X-RAY DIFFRACTION	0.79
5TDB	X-RAY DIFFRACTION	1.1
9PG4	X-RAY DIFFRACTION	1.18
5UM3	X-RAY DIFFRACTION	1.2
9DNP	X-RAY DIFFRACTION	1.22
9DNQ	X-RAY DIFFRACTION	1.22
9DNR	X-RAY DIFFRACTION	1.22
9PG9	X-RAY DIFFRACTION	1.22
5TDD	X-RAY DIFFRACTION	1.55
3NY3	X-RAY DIFFRACTION	1.6
3NY2	X-RAY DIFFRACTION	2.61

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWV8-F1	84.86	0.50

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 (23): 112; 115; 124; 127; 127; 133; 136; 148; 149; 150; 151; 153 …

Post-translational modifications (17): 2, 476, 1694, 1697, 94, 158, 165, 248, 255, 470, 488, 568, 779, 789, 1496, 1599, 1689

Mutagenesis-validated functional residues (9):

Position	Phenotype
94	blocks dusp22-mediated degradation.
122	36-fold decrease in affinity for n-degron peptide rlfs.
476	no effect on dusp22-mediated degradation.
779	blocks dusp22-mediated degradation.
1599	blocks dusp22-mediated degradation.
1694	enhances interaction with btrc and undergoes dusp22-mediated degradation; when associated with f-1697.
1694	blocks dusp22-mediated degradation. impairs interaction with btrc, abolishes dusp22-mediated ubiquitination and degradat
1697	blocks dusp22-mediated degradation. impairs interaction with btrc, abolishes dusp22-mediated ubiquitination and degradat
1697	enhances interaction with btrc and undergoes dusp22-mediated degradation; when associated with a-1694.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 214 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, MORF_ATRX, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (16): reciprocal meiotic recombination (GO:0007131), male meiotic nuclear division (GO:0007140), male meiosis I (GO:0007141), spermatogenesis (GO:0007283), transposable element silencing (GO:0010526), protein ubiquitination (GO:0016567), heterochromatin formation (GO:0031507), negative regulation of TOR signaling (GO:0032007), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of T cell receptor signaling pathway (GO:0050862), protein K63-linked ubiquitination (GO:0070534), cellular response to L-leucine (GO:0071233), ubiquitin-dependent protein catabolic process via the N-end rule pathway (GO:0071596), ubiquitin-dependent protein catabolic process (GO:0006511), protein catabolic process (GO:0030163), T cell receptor signaling pathway (GO:0050852)

GO Molecular Function (7): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), L-leucine binding (GO:0070728), histone H2A ubiquitin ligase activity (GO:0141053), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): ubiquitin ligase complex (GO:0000151), chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
male gamete generation	3
cellular anatomical structure	3
meiosis I	2
meiotic cell cycle	2
cation binding	2
reciprocal homologous recombination	1
meiotic cell cycle process	1
meiotic nuclear division	1
male meiotic nuclear division	1
developmental process involved in reproduction	1
negative regulation of gene expression	1
retrotransposition	1
protein modification by small protein conjugation	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
TOR signaling	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
protein polyubiquitination	1
response to L-leucine	1
cellular response to amino acid stimulus	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
macromolecule catabolic process	1
protein metabolic process	1
antigen receptor-mediated signaling pathway	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
amino acid binding	1

Protein interactions and networks

STRING

2138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBR2	RECQL4	O94761	917
UBR2	UBR4	Q5T4S7	871
UBR2	UBE2A	P49459	817
UBR2	UBE2B	P23567	793
UBR2	UBR1	Q8IWV7	793
UBR2	ATE1	O95260	725
UBR2	NTAQ1	Q96HA8	717
UBR2	CASP8	Q14790	673
UBR2	UBR5	O95071	673
UBR2	POLB	P06746	648
UBR2	UBR7	Q8N806	645
UBR2	NTAN1	Q96AB6	636
UBR2	XRCC1	P18887	632
UBR2	WRN	Q14191	556
UBR2	MARCHF6	O60337	551

IntAct

119 interactions, top by confidence:

A	B	Type	Score
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
TIRAP	TLR4	psi-mi:“MI:0914”(association)	0.810
NRP1	CSNK2A2	psi-mi:“MI:0914”(association)	0.790
RBM7	PPP2R1A	psi-mi:“MI:0914”(association)	0.730
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
GCFC2	SNRNP200	psi-mi:“MI:0914”(association)	0.640
UBR2		psi-mi:“MI:0407”(direct interaction)	0.620
UBR2	vif	psi-mi:“MI:0915”(physical association)	0.560
FAF2	PJA2	psi-mi:“MI:0914”(association)	0.530
IGFBP4	MYCBP2	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
NUDT6	DENR	psi-mi:“MI:0914”(association)	0.530
SPINK2	STRN	psi-mi:“MI:0914”(association)	0.530
UBR2	PAM	psi-mi:“MI:0914”(association)	0.530
YJU2B	RCCD1	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530
DKK4	LRP5	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
GH2	METAP1	psi-mi:“MI:0914”(association)	0.530
CLCC1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
POGLUT1	CLGN	psi-mi:“MI:0914”(association)	0.530
vif	UBL4A	psi-mi:“MI:0914”(association)	0.500
vif	BAG6	psi-mi:“MI:0914”(association)	0.460
SOD2	UBR2	psi-mi:“MI:0915”(physical association)	0.400
UBR2	PCNA	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (185): UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), PAM (Affinity Capture-MS), PLXDC2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), METTL15 (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1TB62, A4VCH4, G3V7Q0, O14795, O35841, O43237, O70585, P23116, P48553, Q0P5J8, Q14152, Q15542, Q1JU68, Q3TLI0, Q3UHE1, Q4R5P6, Q5R660, Q5R7S4, Q5R7U7, Q5RE09, Q5RE70, Q5VSL9, Q5XI83, Q658Y4, Q68E01, Q6IQ26, Q6PAL8, Q6PDL0, Q6TEP1, Q6WKZ8, Q7SYD9, Q7TPD0, Q8BIK4, Q8BWQ6, Q8C079, Q8C092, Q8C9H6, Q8CBY8, Q8IWV8, Q8K400

Diamond homologs: O60014, P19812, Q8IWV8, O70481, Q6WKZ8, Q8IWV7, Q9VX91

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
UBR2	up-regulates	RECQL4	binding
UBR2	“down-regulates quantity”	DSN1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	179
Likely benign	19
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

6737 predictions. Top by Δscore:

Variant	Effect	Δscore
6:42564394:GGGG:G	donor_gain	1.0000
6:42564395:GGGG:G	donor_gain	1.0000
6:42573731:A:G	acceptor_gain	1.0000
6:42573732:A:AG	acceptor_gain	1.0000
6:42573733:G:GG	acceptor_gain	1.0000
6:42573733:GAA:G	acceptor_gain	1.0000
6:42573733:GAAAT:G	acceptor_gain	1.0000
6:42592141:A:AG	acceptor_gain	1.0000
6:42592149:A:AG	acceptor_gain	1.0000
6:42592150:G:GG	acceptor_gain	1.0000
6:42592150:GA:G	acceptor_gain	1.0000
6:42592201:G:GT	donor_gain	1.0000
6:42592201:G:T	donor_gain	1.0000
6:42592228:GG:G	donor_gain	1.0000
6:42592229:GG:G	donor_gain	1.0000
6:42594188:A:AG	acceptor_gain	1.0000
6:42594188:AAGAT:A	acceptor_gain	1.0000
6:42594189:A:G	acceptor_gain	1.0000
6:42594190:G:GG	acceptor_gain	1.0000
6:42594190:GAT:G	acceptor_gain	1.0000
6:42594296:G:GT	donor_gain	1.0000
6:42594300:AAGAG:A	donor_loss	1.0000
6:42594301:AGAG:A	donor_loss	1.0000
6:42594302:GAGGT:G	donor_loss	1.0000
6:42594303:AGGT:A	donor_loss	1.0000
6:42594304:GGT:G	donor_loss	1.0000
6:42594305:G:GA	donor_loss	1.0000
6:42594306:T:A	donor_loss	1.0000
6:42603573:T:TA	acceptor_gain	1.0000
6:42603576:T:A	acceptor_gain	1.0000

AlphaMissense

11638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:42573963:T:C	F103S	1.000
6:42573983:T:G	Y110D	1.000
6:42573989:T:A	C112S	1.000
6:42573989:T:C	C112R	1.000
6:42573990:G:A	C112Y	1.000
6:42573990:G:C	C112S	1.000
6:42573991:C:G	C112W	1.000
6:42592174:G:A	C121Y	1.000
6:42592175:T:G	C121W	1.000
6:42592182:T:C	C124R	1.000
6:42592191:T:C	C127R	1.000
6:42592194:T:C	F128L	1.000
6:42592195:T:C	F128S	1.000
6:42592196:T:A	F128L	1.000
6:42592196:T:G	F128L	1.000
6:42592224:T:G	Y138D	1.000
6:42594192:T:C	M140T	1.000
6:42594218:T:A	C149S	1.000
6:42594218:T:C	C149R	1.000
6:42594219:G:A	C149Y	1.000
6:42594219:G:C	C149S	1.000
6:42594219:G:T	C149F	1.000
6:42594220:T:G	C149W	1.000
6:42594222:A:T	D150V	1.000
6:42594224:T:C	C151R	1.000
6:42594226:T:G	C151W	1.000
6:42594242:T:A	W157R	1.000
6:42594242:T:C	W157R	1.000
6:42594243:G:C	W157S	1.000
6:42594244:G:C	W157C	1.000

dbSNP variants (sampled 300 via entrez): RS1000068275 (6:42684238 T>C), RS1000102259 (6:42581443 G>A,T), RS1000150268 (6:42591449 A>G), RS1000188310 (6:42608286 C>T), RS1000188941 (6:42634702 G>A,T), RS1000227177 (6:42663542 A>G), RS1000246857 (6:42659532 C>G,T), RS1000268112 (6:42568362 T>C), RS1000316654 (6:42653848 G>A), RS1000319949 (6:42686756 C>A,G,T), RS1000332504 (6:42660920 T>C), RS1000363837 (6:42641063 A>G), RS1000470466 (6:42648325 T>C,G), RS1000471056 (6:42679354 C>T), RS1000474868 (6:42693140 T>A)

Disease associations

OMIM: gene MIM:609134 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001762_120	Obesity-related traits	3.000000e-06
GCST004747_23	Lung cancer in never smokers	3.000000e-06
GCST005989_16	Serum total protein levels	4.000000e-09
GCST011743_74	HDL cholesterol levels in HIV infection	9.000000e-07
GCST011743_75	HDL cholesterol levels in HIV infection	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL6066414 (SINGLE PROTEIN), CHEMBL6193816 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193829 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193830 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects binding, increases reaction, increases abundance	3
cobaltous chloride	increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases expression	1
Caffeine	decreases phosphorylation	1
Demecolcine	increases expression	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silver	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

32 unique, capped per target: 32 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5518725	Binding	Binding affinity to UBR2 (unknown origin) expressed in HEK293T cells incubated for 3 hrs by pull-down assay	Degradation of Polo-like Kinase 1 by the Novel Poly-Arginine N-Degron Pathway PROTAC Regulates Tumor Growth in Nonsmall Cell Lung Cancer. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7HR	Ubigene HEK293T UBR2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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