PRSS50

Summary

PRSS50 (serine protease 50, HGNC:17910) is a protein-coding gene on chromosome 3p21.31, encoding Probable threonine protease PRSS50 (Q9UI38). May be involved in proteolysis through its threonine endopeptidase activity.

Enables threonine-type endopeptidase activity. Involved in proteolysis. Located in endoplasmic reticulum.

Source: NCBI Gene 29122 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_013270

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17910
Approved symbol	PRSS50
Name	serine protease 50
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	TSP50, CT20
Ensembl gene	ENSG00000283706
Ensembl biotype	protein_coding
OMIM	607950
Entrez	29122

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000315170

RefSeq mRNA: 1 — MANE Select: NM_013270 NM_013270

CCDS: CCDS2745

Canonical transcript exons

ENST00000315170 — 6 exons

Exon	Start	End
ENSE00001291985	46717719	46717869
ENSE00001628208	46712117	46712482
ENSE00003810391	46712901	46713067
ENSE00003810676	46714218	46714501
ENSE00003811228	46717437	46717637
ENSE00003811374	46715535	46715697

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 94.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0761 / max 41.9509, expressed in 25 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42000	0.0320	11
42001	0.0278	8
42002	0.0163	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.18	gold quality
left testis	UBERON:0004533	93.06	gold quality
testis	UBERON:0000473	92.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.30	gold quality
pituitary gland	UBERON:0000007	83.58	gold quality
adenohypophysis	UBERON:0002196	82.57	gold quality
left lobe of thyroid gland	UBERON:0001120	81.92	gold quality
thyroid gland	UBERON:0002046	81.15	gold quality
right lobe of thyroid gland	UBERON:0001119	79.72	gold quality
endocervix	UBERON:0000458	68.15	gold quality
ventricular zone	UBERON:0003053	67.94	gold quality
right lobe of liver	UBERON:0001114	66.20	gold quality
body of pancreas	UBERON:0001150	66.11	gold quality
mucosa of stomach	UBERON:0001199	65.89	gold quality
metanephros cortex	UBERON:0010533	65.57	gold quality
prostate gland	UBERON:0002367	65.22	gold quality
left uterine tube	UBERON:0001303	64.39	gold quality
cortical plate	UBERON:0005343	63.91	gold quality
body of uterus	UBERON:0009853	63.86	gold quality
adult mammalian kidney	UBERON:0000082	63.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.91	gold quality
left ovary	UBERON:0002119	62.40	gold quality
lower esophagus mucosa	UBERON:0035834	62.08	gold quality
hypothalamus	UBERON:0001898	61.88	gold quality
vagina	UBERON:0000996	61.82	gold quality
fundus of stomach	UBERON:0001160	61.50	gold quality
popliteal artery	UBERON:0002250	61.43	gold quality
tibial artery	UBERON:0007610	61.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.21	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

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, NKX3-1, SP1, TP53

miRNA regulators (miRDB)

5 targeting PRSS50, 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-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-939-3P	98.97	65.07	2347

Literature-anchored findings (GeneRIF, showing 21)

• TSP50, a possible protease in human testes, is activated in breast cancer epithelial cells. (PMID:11782390)
• TSP50 was largely downregulated in all testicular germ cell tumors. It may function in mammalian spermatogenesis. Its linear catalytic structure is similar to many serine proteases, except for a Thr-for-Ser residual catalytic site substitution. (PMID:15491742)
• Overexpression of Sp1 and C/EBPbeta transcriptional factors upregulated the activities of the TSP50 promoter. (PMID:18462069)
• These findings suggested that DNA methylation might regulate the TSP50 and mTSP50 gene expressions in different types of tissues and spermatic cells. (PMID:18662669)
• Results strongly suggest that bFGF mediates TSP50 downregulation by ERK1/2 activation, leading to the phosphorylation of Sp1 in this process. (PMID:20506264)
• TSP50 is a potential effective indicator of poor survival for colorectal carcinoma patients, especially for those with early-stage tumors. (PMID:21765952)
• the importance of threonine 310, the most critical protease catalytic site in TSP50, to TSP50-induced cell proliferation and tumor formation (PMID:22574111)
• The mutations in the catalytic triad of TSP50 could significantly depressed TSP50-mediated cell proliferation and tumor formation. (PMID:25049081)
• High TSP50 expression is associated with laryngocarcinoma. (PMID:25077921)
• TSP50’s threonine protease activity is crucial for its effects on tumor formation. (PMID:25312478)
• Results show that TSP50 is up-regulated in laryngocarcinoma tumour tissues and its down-regulation inhibits cell proliferation, reduces cell migration and induces cell apoptosis of laryngocarcinoma in NF-KB mediated pathway. (PMID:25399078)
• we found that some breast cancer diagnosis-associated features such as tumor size, tumor grade, estrogen receptors (ER) and progesterone receptors (PR) levels, were correlated well with TSP50/p65 and TSP50/MMP9 expression status (PMID:25811800)
• Results suggest that 7P3A, which consists of 70 % 25-methoxyl-dammarane-3beta, 12beta, 20-triol and 30 % artemisinin, exhibits anti-cancer effects, in part, through downregulation of testes-specific protease 50 (TSP50) expression. (PMID:27039397)
• TSP50 plays a significant role in NSCLC cell proliferation and may act as a novel oncogene in the development and progression of NSCLC. (PMID:27109614)
• In patients with Colon cancer, the expression of TSP50 gene was associated with a poor prognosis. (PMID:28631709)
• human epidermal growth factor receptor 2 (HER-2) levels, were correlated well with TSP50/p-Samd2/3 and TSP50/p27 expression status. Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer (PMID:28650473)
• TSP50 promotes the proliferation, migration and invasion of gastric cancer cells involving NF-kappaB dependent EMT activation. Targeting TSP50 may provide a novel therapeutic strategy for the management of gastric cancer (PMID:29361914)
• TSP50 promotes hepatocyte proliferation and tumour formation by activating glucose-6-phosphate dehydrogenase (G6PD). (PMID:33630390)
• miR-4709-3p Inhibits Cell Proliferation by Downregulating TSP50 Expression in Breast Cancer Cells. (PMID:33956530)
• TSP50 promotes the Warburg effect and hepatocyte proliferation via regulating PKM2 acetylation. (PMID:34016961)
• Expression of TSP50, SERCA2 and IL-8 in Colorectal Adenoma and Carcinoma: Correlation to Clinicopathological Factors. (PMID:34744521)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss50	ENSMUSG00000048752
rattus_norvegicus	Prss50	ENSRNOG00000037175

Paralogs (14): PRSS33 (ENSG00000103355), PLAT (ENSG00000104368), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022)

Protein

Protein identifiers

Probable threonine protease PRSS50 — Q9UI38 (reviewed: Q9UI38)

Alternative names: Cancer/testis antigen 20, Serine protease 50, Testis-specific protease-like protein 50

All UniProt accessions (2): A0A140VJY3, Q9UI38

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in proteolysis through its threonine endopeptidase activity.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Testis specific. Differentially expressed in some breast cancer tissues.

Miscellaneous. DNA hypomethylation is accompanied by the expression of the gene in the testis.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_037402* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR043504

Pfam: PF00089

UniProt features (15 total): disulfide bond 4, active site 3, sequence variant 2, glycosylation site 2, signal peptide 1, chain 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UI38-F1	75.38	0.54

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 (3): 153 (charge relay system); 206 (charge relay system); 310 (charge relay system)

Disulfide bonds (4): 273–296, 306–334, 138–154, 240–316

Glycosylation sites (2): 133, 279

Mutagenesis-validated functional residues (1):

Position	Phenotype
310	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): LFA1_Q6, GOBP_PROTEIN_MATURATION, WEBER_METHYLATED_HCP_IN_SPERM_UP, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_THREONINE_TYPE_PEPTIDASE_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, HATADA_METHYLATED_IN_LUNG_CANCER_UP, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_PROTEIN_PROCESSING, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), threonine-type endopeptidase activity (GO:0004298), serine-type peptidase activity (GO:0008236), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endopeptidase activity	2
protein metabolic process	1
serine-type peptidase activity	1
threonine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS50	PAGE5	Q96GU1	841
PRSS50	SAGE1	Q9NXZ1	771
PRSS50	LIPI	Q6XZB0	696
PRSS50	SPA17	Q15506	661
PRSS50	ADAM2	P78326	646
PRSS50	MAGEC2	Q9UBF1	625
PRSS50	ACRBP	Q8NEB7	580
PRSS50	PER2	O15055	571
PRSS50	BMAL1	O00327	523
PRSS50	NR1D1	P20393	436
PRSS50	CLOCK	O15516	435
PRSS50	CRY1	Q16526	432
PRSS50	MYOZ3	Q8TDC0	425
PRSS50	ADAM30	Q9UKF2	425
PRSS50	APP	P05067	423

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CASP8	PRSS50	psi-mi:“MI:0915”(physical association)	0.370
ESR2	PRSS50	psi-mi:“MI:0915”(physical association)	0.370
HRAS	PRSS50	psi-mi:“MI:0915”(physical association)	0.370
STK11	PRSS50	psi-mi:“MI:0915”(physical association)	0.370
TGFB1	PRSS50	psi-mi:“MI:0915”(physical association)	0.370
PRSS50	TSG101	psi-mi:“MI:0915”(physical association)	0.370
PRSS50		psi-mi:“MI:0914”(association)	0.350
PRSS50	PRSS46P	psi-mi:“MI:0914”(association)	0.350
PRSS50	TUBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): TUBB1 (Affinity Capture-MS), PRSS46 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), PIGT (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), PIGS (Affinity Capture-MS), SPCS2 (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), FOXF1 (Affinity Capture-MS), ADAMTS1 (Affinity Capture-MS), CBWD3 (Affinity Capture-MS), PIGK (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), GNL3L (Affinity Capture-MS), TOR3A (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A4D1T9, A6H6T1, A8MTI9, A8QL53, A8QL57, B5U6Y3, E5RG02, O35453, O70169, P00745, P04070, P08709, P0CG03, P0DJE9, P22891, Q14BX2, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3V0Q7, Q402U7, Q4R7Y7, Q5FBW1, Q5M8S2, Q6AXZ6, Q6AY28, Q6IE62, Q6IE63, Q6PEW0, Q6UWB4, Q76HL1, Q7M756, Q7M761, Q7RTY5, Q7RTY7, Q7Z5A4

Diamond homologs: A0A182C2Z2, A1L453, A2VE36, A6H6T1, A6NIE9, O15393, O60235, O70169, P00747, P03951, P03952, P06868, P08519, P12545, P14272, P14417, P15944, P17538, P19236, P20231, P20918, P21845, P26262, P27435, P40313, P50342, P50343, P57727, P69525, P69526, P80009, P80010, P80646, P81286, P83748, P86091, P98072, P98073, P98074, Q01177

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

864 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46712895:GCTCA:G	donor_loss	1.0000
3:46712896:CTCA:C	donor_loss	1.0000
3:46712897:TCACA:T	donor_loss	1.0000
3:46712898:CA:C	donor_loss	1.0000
3:46712899:A:AC	donor_gain	1.0000
3:46712899:A:C	donor_loss	1.0000
3:46712900:C:CC	donor_gain	1.0000
3:46712900:CATAG:C	donor_gain	1.0000
3:46712904:G:C	donor_gain	1.0000
3:46712912:T:TA	donor_gain	1.0000
3:46712915:C:CA	donor_gain	1.0000
3:46713063:CATGC:C	acceptor_gain	1.0000
3:46713065:TGC:T	acceptor_gain	1.0000
3:46713066:GC:G	acceptor_gain	1.0000
3:46713067:CC:C	acceptor_gain	1.0000
3:46713068:C:CC	acceptor_gain	1.0000
3:46714213:CTCA:C	donor_loss	1.0000
3:46714214:TCACC:T	donor_loss	1.0000
3:46714215:CACC:C	donor_loss	1.0000
3:46714216:A:AC	donor_gain	1.0000
3:46714216:A:T	donor_loss	1.0000
3:46714217:C:CA	donor_loss	1.0000
3:46714217:C:CC	donor_gain	1.0000
3:46714499:CGC:C	acceptor_gain	1.0000
3:46715530:CTCA:C	donor_loss	1.0000
3:46715531:TCA:T	donor_loss	1.0000
3:46715532:CACCA:C	donor_loss	1.0000
3:46715533:A:AC	donor_gain	1.0000
3:46715534:C:CC	donor_gain	1.0000
3:46715534:CCAG:C	donor_gain	1.0000

AlphaMissense

2489 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:46714237:C:A	W245C	0.986
3:46714237:C:G	W245C	0.986
3:46715618:G:C	S129R	0.977
3:46715618:G:T	S129R	0.977
3:46715620:T:G	S129R	0.977
3:46714346:A:G	L209P	0.975
3:46715629:A:G	W126R	0.975
3:46715629:A:T	W126R	0.975
3:46715627:C:A	W126C	0.974
3:46715627:C:G	W126C	0.974
3:46714253:C:G	C240S	0.971
3:46714254:A:T	C240S	0.971
3:46714343:A:G	L210P	0.969
3:46712348:C:A	W352C	0.967
3:46712348:C:G	W352C	0.967
3:46714239:A:G	W245R	0.966
3:46714239:A:T	W245R	0.966
3:46713004:C:G	C273S	0.965
3:46713005:A:T	C273S	0.965
3:46714254:A:G	C240R	0.964
3:46714468:A:C	S168R	0.960
3:46714468:A:T	S168R	0.960
3:46714470:T:G	S168R	0.960
3:46715566:A:G	W147R	0.958
3:46715566:A:T	W147R	0.958
3:46714337:A:T	L212H	0.956
3:46712935:C:G	C296S	0.954
3:46712936:A:T	C296S	0.954
3:46714343:A:T	L210H	0.954
3:46715559:A:G	L149P	0.953

dbSNP variants (sampled 300 via entrez): RS1000042625 (3:46718830 G>A), RS1000431829 (3:46719036 T>C), RS1000451833 (3:46714611 A>G), RS1001794690 (3:46714628 C>T), RS1002495038 (3:46716995 G>A), RS1003471999 (3:46713330 C>T), RS1003652041 (3:46712535 A>G), RS1004056581 (3:46717966 C>G,T), RS1004664165 (3:46713906 G>A), RS1004738552 (3:46714230 A>G), RS1004965789 (3:46719758 C>G,T), RS1005668157 (3:46714955 A>G), RS1005741677 (3:46715202 A>C), RS1006672803 (3:46716253 C>G), RS1006733343 (3:46716600 C>G)

Disease associations

OMIM: gene MIM:607950 | 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
GCST006630_55	Diastolic blood pressure	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure

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
alantolactone	decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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