USPL1

Summary

USPL1 (ubiquitin specific peptidase like 1, HGNC:20294) is a protein-coding gene on chromosome 13q12.3, encoding SUMO-specific isopeptidase USPL1 (Q5W0Q7). SUMO-specific isopeptidase involved in protein desumoylation. It is a common-essential gene (DepMap: required in 98.3% of cancer cell lines).

Enables SUMO binding activity and deSUMOylase activity. Involved in several processes, including Cajal body organization; protein desumoylation; and snRNA transcription. Located in Cajal body.

Source: NCBI Gene 10208 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 179 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 98.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_005800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20294
Approved symbol	USPL1
Name	ubiquitin specific peptidase like 1
Location	13q12.3
Locus type	gene with protein product
Status	Approved
Aliases	bA121O19.1, D13S106E
Ensembl gene	ENSG00000132952
Ensembl biotype	protein_coding
OMIM	617470
Entrez	10208

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000255304, ENST00000465952, ENST00000614860, ENST00000898133, ENST00000898134, ENST00000898135, ENST00000898136, ENST00000898137, ENST00000898138, ENST00000898139

RefSeq mRNA: 4 — MANE Select: NM_005800 NM_001321532, NM_001321533, NM_001321534, NM_005800

CCDS: CCDS81760, CCDS9336

Canonical transcript exons

ENST00000255304 — 9 exons

Exon	Start	End
ENSE00000906658	30621073	30621239
ENSE00000906661	30637744	30637857
ENSE00000906662	30642628	30642757
ENSE00000906663	30646932	30647057
ENSE00000906664	30653148	30653305
ENSE00000906665	30657474	30660766
ENSE00001872347	30617920	30618056
ENSE00003495195	30621764	30621892
ENSE00003559186	30630835	30631474

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2034 / max 216.9864, expressed in 1750 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134618	5.1496	1573
134619	4.1426	1544
134620	0.7992	385
134616	0.6482	168
134617	0.4306	165
134622	0.0214	4
134623	0.0087	3
134624	0.0031	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.52	gold quality
male germ cell	CL:0000015	96.52	gold quality
diaphragm	UBERON:0001103	92.36	silver quality
calcaneal tendon	UBERON:0003701	90.54	gold quality
left ventricle myocardium	UBERON:0006566	88.93	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.02	gold quality
cortical plate	UBERON:0005343	87.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.76	gold quality
superficial temporal artery	UBERON:0001614	86.59	gold quality
cauda epididymis	UBERON:0004360	86.58	gold quality
myocardium	UBERON:0002349	86.40	gold quality
granulocyte	CL:0000094	85.83	gold quality
biceps brachii	UBERON:0001507	85.78	gold quality
ventricular zone	UBERON:0003053	85.72	gold quality
adrenal tissue	UBERON:0018303	85.27	gold quality
embryo	UBERON:0000922	85.23	gold quality
tibia	UBERON:0000979	84.96	gold quality
heart right ventricle	UBERON:0002080	84.93	gold quality
lymph node	UBERON:0000029	84.91	gold quality
vastus lateralis	UBERON:0001379	84.91	silver quality
epithelium of nasopharynx	UBERON:0001951	84.91	gold quality
nasopharynx	UBERON:0001728	84.89	gold quality
skeletal muscle tissue	UBERON:0001134	84.75	gold quality
muscle tissue	UBERON:0002385	84.64	gold quality
mononuclear cell	CL:0000842	84.58	gold quality
visceral pleura	UBERON:0002401	84.57	gold quality
leukocyte	CL:0000738	84.51	gold quality
monocyte	CL:0000576	84.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	173.15
E-ANND-3	no	3.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting USPL1, 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-656-3P	100.00	72.15	2788
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-3200-3P	95.41	64.23	396

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• genetic variability in USPL1 may have a role in breast cancer, especially in rs7984952 (PMID:23338788)
• USPL1 plays a key role in RNAPII-mediated snRNA transcription. (PMID:24413172)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	uspl1	ENSDARG00000034825
mus_musculus	Uspl1	ENSMUSG00000041264
rattus_norvegicus	Uspl1	ENSRNOG00000000909

Protein

Protein identifiers

SUMO-specific isopeptidase USPL1 — Q5W0Q7 (reviewed: Q5W0Q7)

Alternative names: Ubiquitin-specific peptidase-like protein 1

All UniProt accessions (1): Q5W0Q7

UniProt curated annotations — full annotation on UniProt →

Function. SUMO-specific isopeptidase involved in protein desumoylation. Specifically binds SUMO proteins with a higher affinity for SUMO2 and SUMO3 which it cleaves more efficiently. Also able to process full-length SUMO proteins to their mature forms. Plays a key role in RNA polymerase-II-mediated snRNA transcription in the Cajal bodies. Is a component of complexes that can bind to U snRNA genes.

Subunit / interactions. Interacts with ELL.

Subcellular location. Nucleus. Cajal body.

Similarity. Belongs to the peptidase C19 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5W0Q7-1	1	yes
Q5W0Q7-2	2

RefSeq proteins (4): NP_001308461, NP_001308462, NP_001308463, NP_005791* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028889	USP	Domain
IPR028890	Peptidase_C98	Domain
IPR029388	DUF4650	Domain
IPR033505	USPL1	Family
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF15499, PF15509

Enzyme classification (BRENDA):

• EC 3.4.22.B70 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (59 total): strand 12, helix 10, sequence variant 9, region of interest 6, mutagenesis site 6, compositionally biased region 5, turn 5, active site 2, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7P99	X-RAY DIFFRACTION	1.8
7ZJU	X-RAY DIFFRACTION	2.17
7ZJV	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W0Q7-F1	54.42	0.23

Functional residue map

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

Catalytic / active sites (2): 236 (nucleophile); 456 (proton acceptor)

Post-translational modifications (1): 909

Mutagenesis-validated functional residues (6):

Position	Phenotype
229	altered sumo-binding and sumo-specific isopeptidase activity.
236	abolishes the sumo-specific isopeptidase activity.
237	altered sumo-binding and sumo-specific isopeptidase activity.
340–341	altered sumo-binding and sumo-specific isopeptidase activity.
421	altered sumo-binding and sumo-specific isopeptidase activity.
494–495	loss of sumo-binding and catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, AACYNNNNTTCCS_UNKNOWN, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_PEPTIDYL_LYSINE_MODIFICATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_NUCLEUS_ORGANIZATION, BILD_E2F3_ONCOGENIC_SIGNATURE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, SCHLOSSER_SERUM_RESPONSE_DN, DANG_BOUND_BY_MYC, PITX2_Q2, WANG_PROSTATE_CANCER_ANDROGEN_INDEPENDENT, TTCNRGNNNNTTC_HSF_Q6

GO Biological Process (5): proteolysis (GO:0006508), cell population proliferation (GO:0008283), snRNA transcription (GO:0009301), protein desumoylation (GO:0016926), Cajal body organization (GO:0030576)

GO Molecular Function (6): deSUMOylase activity (GO:0016929), SUMO binding (GO:0032183), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), Cajal body (GO:0015030), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
cellular process	1
DNA-templated transcription	1
snRNA metabolic process	1
peptidyl-lysine modification	1
protein modification by small protein removal	1
nuclear body organization	1
cysteine-type peptidase activity	1
ubiquitin-like protein peptidase activity	1
ubiquitin-like protein binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USPL1	DESI1	Q6ICB0	832
USPL1	DESI2	Q9BSY9	772
USPL1	SENP5	Q96HI0	693
USPL1	SENP1	Q9P0U3	635
USPL1	SENP3	Q9H4L4	609
USPL1	SENP7	Q9BQF6	604
USPL1	ICE2	Q659A1	591
USPL1	SENP6	Q9GZR1	587
USPL1	USP50	Q70EL3	581
USPL1	COIL	P38432	569
USPL1	PAN2	Q504Q3	568
USPL1	SUMO1	P55856	561
USPL1	SUMO2	P55855	533
USPL1	SAE1	Q9UBE0	524
USPL1	USP33	Q8TEY7	508

IntAct

37 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
USPL1	SUMO3	psi-mi:“MI:0915”(physical association)	0.780
USPL1	SUMO3	psi-mi:“MI:0407”(direct interaction)	0.780
SUMO3	USPL1	psi-mi:“MI:0407”(direct interaction)	0.780
SUMO3	USPL1	psi-mi:“MI:0194”(cleavage reaction)	0.780
USPL1	SUMO3	psi-mi:“MI:0194”(cleavage reaction)	0.780
USPL1	SUMO1	psi-mi:“MI:0915”(physical association)	0.610
USPL1	SUMO1	psi-mi:“MI:0407”(direct interaction)	0.610
SUMO1	USPL1	psi-mi:“MI:0194”(cleavage reaction)	0.610
USPL1	SUMO1	psi-mi:“MI:0194”(cleavage reaction)	0.610
SUMO2	USPL1	psi-mi:“MI:0915”(physical association)	0.570
USPL1	SUMO2	psi-mi:“MI:0915”(physical association)	0.570
USPL1	TPMT	psi-mi:“MI:0915”(physical association)	0.400
USPL1	TSC2	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
GP	IPO5	psi-mi:“MI:0914”(association)	0.350
USPL1	ANXA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (57): SUMO1 (Biochemical Activity), SUMO2 (Biochemical Activity), SUMO3 (Biochemical Activity), SP100 (Biochemical Activity), USPL1 (Two-hybrid), USPL1 (Affinity Capture-RNA), USPL1 (Affinity Capture-RNA), USPL1 (Affinity Capture-RNA), USPL1 (Affinity Capture-Western), ELL (Affinity Capture-Western), USPL1 (Co-localization), COIL (Co-localization), ICE1 (Co-localization), POLR2A (Co-localization), USPL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: Q3ULM6, Q5W0Q7, Q6DRC5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	151
Likely benign	19
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
441765	GRCh37/hg19 13q11-34(chr13:19436287-115107733)	Pathogenic

SpliceAI

1798 predictions. Top by Δscore:

Variant	Effect	Δscore
13:30618041:G:T	donor_gain	1.0000
13:30618052:GGCAG:G	donor_gain	1.0000
13:30618053:GCAG:G	donor_gain	1.0000
13:30618053:GCAGG:G	donor_gain	1.0000
13:30618054:C:T	donor_gain	1.0000
13:30618055:AGGTA:A	donor_loss	1.0000
13:30618057:G:GG	donor_gain	1.0000
13:30621191:G:T	donor_gain	1.0000
13:30621202:GGA:G	donor_gain	1.0000
13:30621203:G:T	donor_gain	1.0000
13:30621240:G:GG	donor_gain	1.0000
13:30621762:A:AG	acceptor_gain	1.0000
13:30621763:G:GG	acceptor_gain	1.0000
13:30621763:GA:G	acceptor_gain	1.0000
13:30621763:GAAT:G	acceptor_gain	1.0000
13:30621888:TGCAG:T	donor_loss	1.0000
13:30621890:CAGGT:C	donor_loss	1.0000
13:30621891:AGGTA:A	donor_loss	1.0000
13:30621892:GG:G	donor_loss	1.0000
13:30621893:GTA:G	donor_loss	1.0000
13:30621894:T:G	donor_loss	1.0000
13:30647053:GAAAA:G	donor_gain	1.0000
13:30647058:G:GG	donor_gain	1.0000
13:30653146:A:AG	acceptor_gain	1.0000
13:30653147:G:GG	acceptor_gain	1.0000
13:30653147:GA:G	acceptor_gain	1.0000
13:30653147:GAGT:G	acceptor_gain	1.0000
13:30617914:G:GT	donor_gain	0.9900
13:30618041:G:GT	donor_gain	0.9900
13:30621190:G:GT	donor_gain	0.9900

AlphaMissense

7176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:30646975:T:A	W386R	0.997
13:30646975:T:C	W386R	0.997
13:30621878:T:C	C72R	0.996
13:30630835:T:C	C77R	0.996
13:30631291:T:A	W229R	0.996
13:30631291:T:C	W229R	0.996
13:30631315:T:A	W237R	0.996
13:30631315:T:C	W237R	0.996
13:30621800:T:C	C46R	0.995
13:30631293:G:C	W229C	0.994
13:30631293:G:T	W229C	0.994
13:30621809:T:C	C49R	0.993
13:30621880:T:G	C72W	0.993
13:30621879:G:A	C72Y	0.992
13:30630835:T:A	C77S	0.992
13:30630836:G:C	C77S	0.992
13:30647008:T:C	C397R	0.992
13:30657566:T:A	W497R	0.992
13:30657566:T:C	W497R	0.992
13:30621878:T:A	C72S	0.991
13:30621879:G:C	C72S	0.991
13:30642726:T:C	C361R	0.991
13:30653278:T:C	F457L	0.991
13:30653280:T:A	F457L	0.991
13:30653280:T:G	F457L	0.991
13:30631317:G:C	W237C	0.990
13:30631317:G:T	W237C	0.990
13:30621802:C:G	C46W	0.989
13:30621809:T:A	C49S	0.989
13:30621810:G:C	C49S	0.989

dbSNP variants (sampled 300 via entrez): RS1000078493 (13:30630086 C>T), RS1000094358 (13:30649823 G>A), RS1000143927 (13:30656831 T>C), RS1000374556 (13:30636463 G>A), RS1000446514 (13:30650119 A>G), RS1000478216 (13:30617173 G>C), RS1000574989 (13:30631363 A>C), RS1000676764 (13:30657126 T>A,G), RS1000757080 (13:30625627 G>A), RS1000784876 (13:30638526 G>A), RS1000818404 (13:30618186 G>A,C), RS1000907034 (13:30618573 T>G), RS1000915868 (13:30650045 A>G), RS1000917318 (13:30657326 A>G), RS1000960302 (13:30618964 A>G)

Disease associations

OMIM: gene MIM:617470 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_438	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010385	phosphatidylcholine 38:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
Arsenic	decreases expression, affects cotreatment, increases abundance, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
elesclomol	increases expression, decreases reaction	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases activity, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acetylcysteine	decreases reaction, increases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Disulfiram	decreases expression, affects binding	1
Doxorubicin	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1

Clinical trials (associated diseases)

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