USP17L1

Summary

USP17L1 (ubiquitin specific peptidase 17 like family member 1, HGNC:37182) is a protein-coding gene on chromosome 8p23.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 1 (Q7RTZ2). Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes that may include cell proliferation, progression through the cell cycle, apoptosis, cell migration, and the cellular response to viral infection.

Predicted to enable cysteine-type deubiquitinase activity. Predicted to be involved in regulation of apoptotic process and regulation of protein stability. Predicted to be located in endoplasmic reticulum. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 401447 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001256873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37182
Approved symbol	USP17L1
Name	ubiquitin specific peptidase 17 like family member 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000230549
Ensembl biotype	protein_coding
Entrez	401447

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000529559

RefSeq mRNA: 1 — MANE Select: NM_001256873 NM_001256873

CCDS: CCDS78298

Canonical transcript exons

ENST00000529559 — 1 exons

Exon	Start	End
ENSE00002164335	7332387	7333979

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 47.73.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	47.73	gold quality
cortical plate	UBERON:0005343	46.11	gold quality
ganglionic eminence	UBERON:0004023	44.07	silver quality
sural nerve	UBERON:0015488	37.52	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
superior frontal gyrus	UBERON:0002661	35.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	35.10	silver quality
skeletal muscle tissue	UBERON:0001134	34.84	gold quality
right frontal lobe	UBERON:0002810	34.69	silver quality
urinary bladder	UBERON:0001255	33.84	gold quality
hypothalamus	UBERON:0001898	33.37	silver quality
cerebral cortex	UBERON:0000956	32.59	silver quality
substantia nigra	UBERON:0002038	32.47	silver quality
brain	UBERON:0000955	32.42	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.13	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
tonsil	UBERON:0002372	30.20	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
skin of abdomen	UBERON:0001416	29.36	gold quality
placenta	UBERON:0001987	29.18	gold quality
zone of skin	UBERON:0000014	28.88	gold quality
liver	UBERON:0002107	28.71	gold quality
islet of Langerhans	UBERON:0000006	28.31	gold quality
skin of leg	UBERON:0001511	28.26	gold quality
duodenum	UBERON:0002114	28.14	gold quality
adrenal tissue	UBERON:0018303	27.84	gold quality
ovary	UBERON:0000992	27.79	silver quality
muscle of leg	UBERON:0001383	27.58	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.33

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 17-like protein 1 — Q7RTZ2 (reviewed: Q7RTZ2)

Alternative names: Deubiquitinating enzyme 17-like protein 1, Ubiquitin thioesterase 17-like protein 1, Ubiquitin-specific-processing protease 17-like protein 1

All UniProt accessions (1): Q7RTZ2

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes that may include cell proliferation, progression through the cell cycle, apoptosis, cell migration, and the cellular response to viral infection.

Subcellular location. Nucleus. Endoplasmic reticulum.

Similarity. Belongs to the peptidase C19 family. USP17 subfamily.

RefSeq proteins (1): NP_001243802* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443

UniProt features (7 total): compositionally biased region 2, active site 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTZ2-F1	67.65	0.44

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): 89 (nucleophile); 334 (proton acceptor)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 14 (showing top): GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_PEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_DEUBIQUITINATION, REACTOME_UB_SPECIFIC_PROCESSING_PROTEASES, GOBP_REGULATION_OF_PROGRAMMED_CELL_DEATH, GOBP_PROTEIN_MODIFICATION_PROCESS, GOMF_DEUBIQUITINASE_ACTIVITY, chr8p23

GO Biological Process (5): proteolysis (GO:0006508), apoptotic process (GO:0006915), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), regulation of apoptotic process (GO:0042981)

GO Molecular Function (4): cysteine-type deubiquitinase activity (GO:0004843), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cytoplasm	2
protein metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
apoptotic process	1
regulation of programmed cell death	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L1	FAM90A10	A6NDY2	661
USP17L1	PRAMEF25	A6NGN4	519
USP17L1	DEFB107A	Q8IZN7	479
USP17L1	XKR5	Q6UX68	447
USP17L1	ZSCAN4	Q8NAM6	430
USP17L1	DEFB108B	Q8NET1	400
USP17L1	ZNF735	P0CB33	393
USP17L1	TMEM92	Q6UXU6	380
USP17L1	PRR23B	Q6ZRT6	371
USP17L1	PRR23A	A6NEV1	370
USP17L1	PRR23D1	E9PI22	370
USP17L1	DEFB105A	Q8NG35	339
USP17L1	Q3LFD5	Q3LFD5	336
USP17L1	DEFB106A	Q8N104	332
USP17L1	USP54	Q70EL1	325

IntAct

2 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (6): USP17L1 (Affinity Capture-MS), USP17L1 (Affinity Capture-MS), ATP5I (Cross-Linking-MS (XL-MS)), USP17L1 (Cross-Linking-MS (XL-MS)), USP17L1 (Affinity Capture-MS), USP17L1 (Affinity Capture-MS)

ESM2 similar proteins: A2A5N8, A6NCW0, A6NCW7, A8MUK1, B1AQJ2, B2RQC2, C9J2P7, C9JJH3, C9JLJ4, C9JPN9, C9JVI0, D3ZWK4, D6R901, D6R9N7, D6RA61, D6RBM5, D6RBQ6, D6RCP7, D6RJB6, E9Q9U0, G5E8G2, G5E8I7, O94966, P0C7H9, P0C7I0, P35125, P51784, Q0E2F9, Q0WX57, Q2TAC6, Q3UJD6, Q4KLL9, Q5R7G8, Q5TKR9, Q61068, Q66HE5, Q6J1Y9, Q6PFD6, Q6QN14, Q6R6M4

Diamond homologs: A1L1K8, A6NCW0, A6NCW7, A8MUK1, C9J2P7, C9JJH3, C9JLJ4, C9JPN9, C9JVI0, D6R901, D6R9N7, D6RA61, D6RBQ6, D6RCP7, D6RJB6, G1SW77, P0C7H9, P0C7I0, Q0WX57, Q5JVS0, Q5XJA5, Q6AXS5, Q6NRY1, Q6PB22, Q6R6M4, Q7RTZ2, Q8NC51, Q9CY58, Q9I9R0, Q9JKS5, A1CIL1, A1CW53, A2Q9N1, A4FUN7, A5D9H7, A5PJS6, A5WWB0, A6QR55, B0Y4P5, B2GUZ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

81 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7333678:A:T	donor_gain	0.5600
8:7333413:G:GT	donor_gain	0.5500
8:7333423:G:GA	donor_gain	0.5400
8:7333677:G:GT	donor_gain	0.5300
8:7333485:GCC:G	donor_gain	0.4700
8:7333660:TGGA:T	donor_gain	0.4600
8:7333604:A:T	donor_gain	0.4500
8:7333751:CGAAG:C	donor_loss	0.4400
8:7333752:GAAG:G	donor_loss	0.4400
8:7333753:AAG:A	donor_loss	0.4400
8:7333754:AG:A	donor_loss	0.4400
8:7333755:GGTAC:G	donor_loss	0.4400
8:7333756:G:C	donor_loss	0.4400
8:7333757:T:A	donor_loss	0.4400
8:7332501:G:GC	acceptor_gain	0.3900
8:7333503:A:AG	acceptor_gain	0.3900
8:7333504:T:G	acceptor_gain	0.3900
8:7333750:TCGAA:T	donor_loss	0.3900
8:7333507:A:AG	acceptor_gain	0.3800
8:7333508:G:GG	acceptor_gain	0.3800
8:7333750:TCGA:T	donor_gain	0.3800
8:7333508:GAAGA:G	acceptor_gain	0.3700
8:7333368:TG:T	donor_gain	0.3600
8:7333369:GG:G	donor_gain	0.3600
8:7333508:GAA:G	acceptor_gain	0.3500
8:7333130:A:T	donor_gain	0.3400
8:7333758:A:C	donor_loss	0.3400
8:7332594:C:CG	donor_gain	0.3300
8:7332594:C:G	donor_gain	0.3200
8:7333422:T:TA	donor_gain	0.3200

AlphaMissense

3499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7332876:T:C	F164L	0.880
8:7332878:T:A	F164L	0.880
8:7332878:T:G	F164L	0.880
8:7332843:T:C	F153L	0.857
8:7332845:C:A	F153L	0.857
8:7332845:C:G	F153L	0.857
8:7333233:T:C	F283L	0.850
8:7333235:C:A	F283L	0.850
8:7333235:C:G	F283L	0.850
8:7333497:T:C	F371L	0.834
8:7333499:T:A	F371L	0.834
8:7333499:T:G	F371L	0.834
8:7332885:T:C	F167L	0.832
8:7332887:C:A	F167L	0.832
8:7332887:C:G	F167L	0.832
8:7332975:T:C	F197L	0.824
8:7332977:T:A	F197L	0.824
8:7332977:T:G	F197L	0.824
8:7333422:T:A	W346R	0.741
8:7333422:T:C	W346R	0.741
8:7333035:T:C	F217L	0.679
8:7333037:T:A	F217L	0.679
8:7333037:T:G	F217L	0.679
8:7332902:G:A	M172I	0.658
8:7332902:G:C	M172I	0.658
8:7332902:G:T	M172I	0.658
8:7333424:G:C	W346C	0.631
8:7333424:G:T	W346C	0.631
8:7333406:A:C	K340N	0.618
8:7333406:A:T	K340N	0.618

dbSNP variants (sampled 300 via entrez): RS1000492919 (8:7331782 A>T), RS1002166917 (8:7330892 A>G), RS1002302661 (8:7331064 C>G,T), RS1004085959 (8:7331474 C>G), RS1004117089 (8:7331346 C>A,G,T), RS1005438278 (8:7332751 G>A), RS1005739483 (8:7330564 T>G), RS1007975189 (8:7331736 G>A), RS1008422439 (8:7331521 T>C), RS1009010791 (8:7334060 AACACAC>A,AAC,AACAC,AACACACAC,AACACACACAC), RS1009684550 (8:7330614 C>A,T), RS1010064603 (8:7330857 G>A,C,T), RS1012495089 (8:7332674 G>A), RS1013552631 (8:7331243 G>C), RS1014583421 (8:7331117 T>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyltin	decreases expression	1
tributyltinisothiocyanate	decreases expression	1
Benzo(a)pyrene	increases expression	1

Clinical trials (associated diseases)

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