USP17L3

Summary

USP17L3 (ubiquitin specific peptidase 17 like family member 3, HGNC:37175) is a protein-coding gene on chromosome 8p23.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 3 (A6NCW0). 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 645836 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001256871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37175
Approved symbol	USP17L3
Name	ubiquitin specific peptidase 17 like family member 3
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	USP17B, USP17F
Ensembl gene	ENSG00000225327
Ensembl biotype	protein_coding
Entrez	645836

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000530484

RefSeq mRNA: 1 — MANE Select: NM_001256871 NM_001256871

CCDS: CCDS78301

Canonical transcript exons

ENST00000530484 — 1 exons

Exon	Start	End
ENSE00002159688	7976393	7977985

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 43.08.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	43.08	gold quality
ganglionic eminence	UBERON:0004023	42.38	gold quality
cortical plate	UBERON:0005343	39.75	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.22	gold quality
sural nerve	UBERON:0015488	34.94	gold quality
skeletal muscle tissue	UBERON:0001134	34.88	gold quality
tonsil	UBERON:0002372	34.12	gold quality
muscle tissue	UBERON:0002385	32.16	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.83	gold quality
superior frontal gyrus	UBERON:0002661	29.48	gold quality
gall bladder	UBERON:0002110	28.33	gold quality
liver	UBERON:0002107	28.27	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.60	gold quality
leukocyte	CL:0000738	27.60	gold quality
islet of Langerhans	UBERON:0000006	27.58	gold quality
lymph node	UBERON:0000029	27.57	gold quality
placenta	UBERON:0001987	27.30	gold quality
primary visual cortex	UBERON:0002436	27.28	gold quality
urinary bladder	UBERON:0001255	26.61	gold quality
blood	UBERON:0000178	26.42	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
muscle of leg	UBERON:0001383	26.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
gastrocnemius	UBERON:0001388	25.18	gold quality
frontal cortex	UBERON:0001870	25.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.21

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 3 — A6NCW0 (reviewed: A6NCW0)

Alternative names: Deubiquitinating enzyme 17-like protein 3, Ubiquitin thioesterase 17-like protein 3, Ubiquitin-specific-processing protease 17-like protein 3

All UniProt accessions (1): A6NCW0

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_001243800* (*=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-A6NCW0-F1	67.87	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

84 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L3	GOLGA6B	A6NDN3	576
USP17L3	A6NGT6	A6NGT6	570
USP17L3	DEFB108B	Q8NET1	474
USP17L3	DEFB107A	Q8IZN7	448
USP17L3	DEFB105A	Q8NG35	404
USP17L3	A0A0G2JN59	A0A0G2JN59	400
USP17L3	DEFB106A	Q8N104	396
USP17L3	PRR20A	P86496	365
USP17L3	DEFB104A	Q8WTQ1	320
USP17L3	JOSD1	Q15040	318
USP17L3	NBPF20	P0DPF2	284
USP17L3	ZUP1	Q96AP4	264
USP17L3	DEFA1	P11479	251
USP17L3	RCE1	Q9Y256	211
USP17L3	DEFB103A	P81534	201

IntAct

2 interactions, top by confidence:

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

BioGRID (6): USP17L3 (Affinity Capture-MS), ATP5I (Cross-Linking-MS (XL-MS)), USP17L3 (Affinity Capture-MS), USP17L3 (Affinity Capture-MS), USP17L3 (Affinity Capture-MS), USP17L3 (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

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

84 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7976694:T:A	donor_gain	0.5900
8:7976768:T:A	donor_gain	0.4900
8:7976611:GGGTA:G	donor_loss	0.4700
8:7976612:GGTAC:G	donor_loss	0.4700
8:7976613:GTA:G	donor_loss	0.4700
8:7976614:TACC:T	donor_loss	0.4700
8:7976615:A:C	donor_loss	0.4700
8:7976616:CCT:C	donor_loss	0.4700
8:7976708:TTCC:T	donor_gain	0.4700
8:7976884:AGG:A	donor_gain	0.4700
8:7976617:CTTCG:C	donor_loss	0.4300
8:7976948:C:CT	donor_gain	0.4300
8:7976618:TTCG:T	donor_gain	0.4100
8:7976864:C:CC	acceptor_gain	0.4000
8:7976868:A:C	acceptor_gain	0.4000
8:7976859:CTCTT:C	acceptor_gain	0.3900
8:7976868:A:AC	acceptor_gain	0.3900
8:7977001:TC:T	donor_gain	0.3800
8:7977002:CC:C	donor_gain	0.3800
8:7976861:CTT:C	acceptor_gain	0.3700
8:7976610:AGGGT:A	donor_loss	0.3600
8:7976954:G:A	donor_gain	0.3600
8:7977777:A:AC	donor_gain	0.3500
8:7977778:G:C	donor_gain	0.3500
8:7977870:T:TG	acceptor_gain	0.3500
8:7976619:TCG:T	donor_gain	0.3400
8:7977242:T:A	donor_gain	0.3400
8:7976782:G:A	donor_gain	0.3200
8:7977122:G:A	donor_gain	0.3200
8:7976568:CA:C	donor_gain	0.3100

AlphaMissense

3498 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7977494:A:C	F164L	0.882
8:7977494:A:T	F164L	0.882
8:7977496:A:G	F164L	0.882
8:7977527:G:C	F153L	0.874
8:7977527:G:T	F153L	0.874
8:7977529:A:G	F153L	0.874
8:7977395:A:C	F197L	0.869
8:7977395:A:T	F197L	0.869
8:7977397:A:G	F197L	0.869
8:7977137:G:C	F283L	0.858
8:7977137:G:T	F283L	0.858
8:7977139:A:G	F283L	0.858
8:7977485:G:C	F167L	0.838
8:7977485:G:T	F167L	0.838
8:7977487:A:G	F167L	0.838
8:7976873:A:C	F371L	0.832
8:7976873:A:T	F371L	0.832
8:7976875:A:G	F371L	0.832
8:7976950:A:G	W346R	0.813
8:7976950:A:T	W346R	0.813
8:7976966:T:A	K340N	0.710
8:7976966:T:G	K340N	0.710
8:7976948:C:A	W346C	0.707
8:7976948:C:G	W346C	0.707
8:7976933:A:C	D351E	0.681
8:7976933:A:T	D351E	0.681
8:7977335:A:C	F217L	0.680
8:7977335:A:T	F217L	0.680
8:7977337:A:G	F217L	0.680
8:7977470:C:A	M172I	0.670

dbSNP variants (sampled 300 via entrez): RS1029028542 (8:7979218 C>T), RS1030799718 (8:7979697 T>C), RS1036510049 (8:7977853 A>ATGAGAG), RS1046703154 (8:7976781 C>G,T), RS111485122 (8:7976598 G>A), RS112255439 (8:7976375 T>C), RS112257485 (8:7978050 T>C), RS1156575817 (8:7977350 C>G), RS1157959806 (8:7979709 C>A), RS1159398429 (8:7978669 A>C,G), RS1159569472 (8:7976508 G>A,T), RS1160533492 (8:7978680 G>A,T), RS1161109277 (8:7977844 G>A,T), RS1161194829 (8:7979739 A>G), RS1161259564 (8:7976266 G>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)

Clinical trials (associated diseases)

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