USP17L17

Summary

USP17L17 (ubiquitin specific peptidase 17 like family member 17, HGNC:44445) is a protein-coding gene on chromosome 4p16.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 17 (D6RBQ6). 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 100287327 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total — 1 pathogenic
• MANE Select transcript: NM_001256857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44445
Approved symbol	USP17L17
Name	ubiquitin specific peptidase 17 like family member 17
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000249104
Ensembl biotype	protein_coding
Entrez	100287327

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000511568

RefSeq mRNA: 1 — MANE Select: NM_001256857 NM_001256857

CCDS: CCDS59458

Canonical transcript exons

ENST00000511568 — 1 exons

Exon	Start	End
ENSE00002040555	9243879	9245471

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 39.87.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	39.87	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.12	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.79	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.13	gold quality
right uterine tube	UBERON:0001302	31.91	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.63	silver quality
urinary bladder	UBERON:0001255	29.12	gold quality
lymph node	UBERON:0000029	28.67	gold quality
liver	UBERON:0002107	28.50	gold quality
duodenum	UBERON:0002114	28.14	gold quality
smooth muscle tissue	UBERON:0001135	27.27	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.88	gold quality
superior frontal gyrus	UBERON:0002661	26.73	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.21	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
kidney	UBERON:0002113	25.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
endometrium	UBERON:0001295	25.85	gold quality
placenta	UBERON:0001987	25.81	gold quality
leukocyte	CL:0000738	25.47	gold quality
muscle of leg	UBERON:0001383	25.46	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 17 — D6RBQ6 (reviewed: D6RBQ6)

All UniProt accessions (1): D6RBQ6

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_001243786* (*=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-D6RBQ6-F1	68.02	0.47

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

100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L17	OR4N4	Q8N0Y3	543
USP17L17	ZDBF2	Q9HCK1	390
USP17L17	CHRNE	Q04844	348
USP17L17	GOLGA8O	A6NCC3	339
USP17L17	MBD3L5	A6NJ08	310
USP17L17	VSIG10L	Q86VR7	310
USP17L17	VN1R1	Q9GZP7	305
USP17L17	ZNF480	Q8WV37	297
USP17L17	AMOTL2	Q9Y2J4	277
USP17L17	AMOTL1	Q8IY63	270
USP17L17	KCTD14	Q9BQ13	259
USP17L17	UBB	P02248	258
USP17L17	GPATCH4	Q5T3I0	249
USP17L17	AMOT	Q4VCS5	224
USP17L17	DEFB126	Q9BYW3	224

IntAct

2 interactions, top by confidence:

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

BioGRID (8): USP17L17 (Positive Genetic), USP17L17 (Affinity Capture-MS), USP17L17 (Affinity Capture-MS), USP17L17 (Affinity Capture-MS), USP17L17 (Affinity Capture-MS), USP17L17 (Affinity Capture-MS), USP17L17 (Co-fractionation), USP17L17 (Co-fractionation)

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
146353	GRCh38/hg38 4p16.3-15.32(chr4:72555-17278013)x1	Pathogenic

SpliceAI

67 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9245169:G:GT	donor_gain	0.5500
4:9245170:A:T	donor_gain	0.5200
4:9245152:TGGA:T	donor_gain	0.4900
4:9245243:CGAAG:C	donor_loss	0.4600
4:9245244:GAAGG:G	donor_loss	0.4600
4:9245245:AAGGT:A	donor_loss	0.4600
4:9245246:AGGT:A	donor_loss	0.4600
4:9245247:GG:G	donor_loss	0.4600
4:9245248:GTA:G	donor_loss	0.4500
4:9245249:T:A	donor_loss	0.4500
4:9243993:G:GC	acceptor_gain	0.4300
4:9245242:TCGAA:T	donor_loss	0.4200
4:9245250:A:C	donor_loss	0.4100
4:9244977:GCC:G	donor_gain	0.4000
4:9245096:A:T	donor_gain	0.3800
4:9245242:TCGA:T	donor_gain	0.3800
4:9244146:T:TA	acceptor_gain	0.3600
4:9244147:A:AA	acceptor_gain	0.3600
4:9244086:C:CG	donor_gain	0.3500
4:9244996:T:G	acceptor_gain	0.3500
4:9244086:C:G	donor_gain	0.3400
4:9245082:C:T	donor_gain	0.3400
4:9244073:G:GT	donor_gain	0.3200
4:9245153:GGAA:G	donor_gain	0.3200
4:9245216:G:GT	donor_gain	0.3200
4:9245000:GAAGA:G	acceptor_gain	0.3000
4:9245023:G:GG	donor_gain	0.3000
4:9245155:A:T	donor_gain	0.3000
4:9244655:G:C	acceptor_gain	0.2900
4:9245022:A:AG	donor_gain	0.2900

AlphaMissense

3496 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:9244725:T:C	F283L	0.998
4:9244727:C:A	F283L	0.998
4:9244727:C:G	F283L	0.998
4:9244930:A:T	D351V	0.996
4:9244931:T:A	D351E	0.996
4:9244931:T:G	D351E	0.996
4:9244130:T:A	N84K	0.994
4:9244130:T:G	N84K	0.994
4:9244368:T:C	F164L	0.994
4:9244370:T:A	F164L	0.994
4:9244370:T:G	F164L	0.994
4:9244880:T:A	H334Q	0.994
4:9244880:T:G	H334Q	0.994
4:9244914:T:A	W346R	0.994
4:9244914:T:C	W346R	0.994
4:9244358:T:A	D160E	0.993
4:9244358:T:G	D160E	0.993
4:9244929:G:C	D351H	0.992
4:9244930:A:C	D351A	0.992
4:9244497:T:C	C207R	0.991
4:9244878:C:G	H334D	0.991
4:9244335:T:C	F153L	0.990
4:9244337:C:A	F153L	0.990
4:9244337:C:G	F153L	0.990
4:9244369:T:C	F164S	0.990
4:9244666:C:A	A263D	0.990
4:9244717:T:C	L280S	0.990
4:9244876:G:A	G333E	0.989
4:9244143:T:C	C89R	0.988
4:9244154:C:A	N92K	0.988

dbSNP variants (sampled 300 via entrez): RS1156578251 (4:9243427 C>CA), RS1158144764 (4:9243454 T>A), RS1160027461 (4:9244012 G>A,C), RS1160252499 (4:9243204 G>C,T), RS1160935840 (4:9243470 A>C,G,T), RS1161034504 (4:9244770 C>A), RS1161451468 (4:9242926 A>C), RS1162256421 (4:9243380 C>A,T), RS1162920258 (4:9243628 T>A), RS1163212918 (4:9243948 C>A,T), RS1163607635 (4:9243423 G>A,C,T), RS1165104033 (4:9244507 G>A), RS1165173980 (4:9244249 T>A), RS1167153456 (4:9242951 C>T), RS1167240797 (4:9243316 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
2-palmitoylglycerol	increases expression	1
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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