USP17L15

Summary

USP17L15 (ubiquitin specific peptidase 17 like family member 15, HGNC:44443) is a protein-coding gene on chromosome 4p16.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 15 (C9J2P7). 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 100288520 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001256894

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44443
Approved symbol	USP17L15
Name	ubiquitin specific peptidase 17 like family member 15
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000223569
Ensembl biotype	protein_coding
Entrez	100288520

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000456464

RefSeq mRNA: 1 — MANE Select: NM_001256894 NM_001256894

CCDS: CCDS77901

Canonical transcript exons

ENST00000456464 — 1 exons

Exon	Start	End
ENSE00001705928	9234385	9236046

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 78.61.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	78.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.54	gold quality
monocyte	CL:0000576	50.54	gold quality
right uterine tube	UBERON:0001302	49.99	gold quality
leukocyte	CL:0000738	49.07	gold quality
adrenal tissue	UBERON:0018303	45.93	gold quality
primary visual cortex	UBERON:0002436	44.94	gold quality
mucosa of transverse colon	UBERON:0004991	43.63	silver quality
tonsil	UBERON:0002372	43.15	gold quality
nucleus accumbens	UBERON:0001882	42.71	gold quality
putamen	UBERON:0001874	42.27	gold quality
caudate nucleus	UBERON:0001873	42.00	gold quality
amygdala	UBERON:0001876	41.68	gold quality
temporal lobe	UBERON:0001871	41.52	gold quality
right frontal lobe	UBERON:0002810	41.44	gold quality
colonic epithelium	UBERON:0000397	41.42	gold quality
fallopian tube	UBERON:0003889	41.37	silver quality
pituitary gland	UBERON:0000007	41.34	gold quality
anterior cingulate cortex	UBERON:0009835	41.01	gold quality
urinary bladder	UBERON:0001255	40.96	silver quality
Ammon’s horn	UBERON:0001954	40.84	gold quality
bone marrow cell	CL:0002092	40.48	gold quality
mucosa of stomach	UBERON:0001199	40.32	silver quality
ventricular zone	UBERON:0003053	40.20	gold quality
left uterine tube	UBERON:0001303	39.88	silver quality
skeletal muscle tissue	UBERON:0001134	39.47	gold quality
stromal cell of endometrium	CL:0002255	39.36	gold quality
adenohypophysis	UBERON:0002196	39.21	silver quality
muscle tissue	UBERON:0002385	39.08	gold quality
hypothalamus	UBERON:0001898	38.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

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 15 — C9J2P7 (reviewed: C9J2P7)

All UniProt accessions (1): C9J2P7

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_001243823* (*=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 (10 total): compositionally biased region 4, region of interest 2, active site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9J2P7-F1	66.37	0.43

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, chr4p16, 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

GO Biological Process (4): proteolysis (GO:0006508), 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
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

108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L15	OR1J1	Q8NGS3	590
USP17L15	FAM98B	Q52LJ0	506
USP17L15	METTL15	A6NJ78	480
USP17L15	TASOR	Q9UK61	448
USP17L15	MRPS27	Q92552	447
USP17L15	OR9Q1	Q8NGQ5	432
USP17L15	OR1L8	Q8NGR8	432
USP17L15	HEMGN	Q9BXL5	419
USP17L15	OR2T10	Q8NGZ9	419
USP17L15	OR10V1	Q8NGI7	398
USP17L15	SLC30A6	Q6NXT4	391
USP17L15	OR2T11	Q8NH01	370
USP17L15	OR52B6	Q8NGF0	368
USP17L15	UPF3B	Q9BZI7	348
USP17L15	OR2A42	Q8NGT9	322

IntAct

2 interactions, top by confidence:

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

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, A0JM59, A5PMR2, A5PN09, A6H8I0, A6NNY8, A6QNM7, A7Z056, B1AY13, B1WBD7, D3ZJ96

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

44 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9235676:A:T	donor_gain	0.4600
4:9235675:G:GT	donor_gain	0.4200
4:9234499:G:GC	acceptor_gain	0.4000
4:9235749:CGAAG:C	donor_loss	0.3900
4:9235750:GAAG:G	donor_loss	0.3900
4:9235751:AAGGT:A	donor_loss	0.3900
4:9235752:AGG:A	donor_loss	0.3900
4:9235753:G:GT	donor_loss	0.3900
4:9235754:G:GA	donor_loss	0.3900
4:9235755:T:A	donor_loss	0.3900
4:9235756:A:C	donor_loss	0.3700
4:9235658:TGGA:T	donor_gain	0.3500
4:9234592:C:CG	donor_gain	0.3400
4:9235602:A:T	donor_gain	0.3300
4:9234592:C:G	donor_gain	0.3200
4:9234652:T:TA	acceptor_gain	0.3200
4:9234653:A:AA	acceptor_gain	0.3200
4:9235748:TCGA:T	donor_gain	0.2900
4:9235483:GCC:G	donor_gain	0.2800
4:9235989:G:GG	donor_gain	0.2800
4:9234579:G:GT	donor_gain	0.2700
4:9235161:G:C	acceptor_gain	0.2700
4:9235780:A:AG	donor_gain	0.2700
4:9235923:G:GT	donor_gain	0.2700
4:9235877:A:T	donor_gain	0.2500
4:9235986:G:GT	donor_gain	0.2500
4:9235988:A:AG	donor_gain	0.2500
4:9235502:T:G	acceptor_gain	0.2400
4:9235588:C:T	donor_gain	0.2400
4:9235893:C:T	donor_gain	0.2400

AlphaMissense

3488 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1157273565 (4:9234828 A>T), RS1157314212 (4:9235625 G>T), RS1158294351 (4:9236060 C>G,T), RS1158567322 (4:9233632 A>G), RS1158911495 (4:9234149 C>A,T), RS1160891183 (4:9235560 A>T), RS1160983619 (4:9234568 C>G), RS1162769640 (4:9235914 G>A,C), RS1164013166 (4:9235242 C>G), RS1164574455 (4:9233977 C>A,G), RS1164675223 (4:9236368 G>C), RS1167359459 (4:9235377 C>T), RS1168131900 (4:9236099 C>T), RS1168472935 (4:9234282 C>A,T), RS1170149506 (4:9235531 G>A)

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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
2-palmitoylglycerol	increases expression	1
Arsenic Trioxide	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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