PRSS33

Summary

PRSS33 (serine protease 33, HGNC:30405) is a protein-coding gene on chromosome 16p13.3, encoding Serine protease 33 (Q8NF86). Serine protease that has amidolytic activity, cleaving its substrates before Arg residues.

Predicted to enable serine-type endopeptidase activity. Involved in proteolysis. Located in cytoplasm.

Source: NCBI Gene 260429 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_152891

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30405
Approved symbol	PRSS33
Name	serine protease 33
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	EOS
Ensembl gene	ENSG00000103355
Ensembl biotype	protein_coding
OMIM	613797
Entrez	260429

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000293851, ENST00000570702, ENST00000571674, ENST00000576886, ENST00000682474, ENST00000955838, ENST00000955839

RefSeq mRNA: 4 — MANE Select: NM_152891 NM_001385462, NM_001385463, NM_001385464, NM_152891

CCDS: CCDS42110

Canonical transcript exons

ENST00000682474 — 7 exons

Exon	Start	End
ENSE00001061783	2785375	2785646
ENSE00001158468	2785799	2785961
ENSE00001158481	2786089	2786121
ENSE00001214054	2785002	2785171
ENSE00001402260	2783953	2784802
ENSE00002673130	2786502	2786604
ENSE00003918753	2787533	2787560

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 90.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4646 / max 78.3642, expressed in 83 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155950	0.2425	62
155952	0.1393	23
155951	0.0828	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	90.04	gold quality
oviduct epithelium	UBERON:0004804	81.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.29	silver quality
trabecular bone tissue	UBERON:0002483	79.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	72.97	gold quality
epithelium of nasopharynx	UBERON:0001951	71.86	silver quality
oocyte	CL:0000023	70.90	gold quality
blood	UBERON:0000178	70.88	gold quality
myocardium	UBERON:0002349	70.87	gold quality
buccal mucosa cell	CL:0002336	70.32	gold quality
cartilage tissue	UBERON:0002418	68.62	gold quality
sperm	CL:0000019	68.58	gold quality
germinal epithelium of ovary	UBERON:0001304	66.09	gold quality
nasal cavity epithelium	UBERON:0005384	66.05	gold quality
mammary duct	UBERON:0001765	65.70	gold quality
heart right ventricle	UBERON:0002080	65.61	gold quality
fallopian tube	UBERON:0003889	65.48	gold quality
vena cava	UBERON:0004087	64.35	silver quality
tendon of biceps brachii	UBERON:0008188	64.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.12	gold quality
bone marrow	UBERON:0002371	62.94	gold quality
quadriceps femoris	UBERON:0001377	62.81	gold quality
vastus lateralis	UBERON:0001379	62.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.94	gold quality
cardia of stomach	UBERON:0001162	61.78	gold quality
right uterine tube	UBERON:0001302	60.86	gold quality
substantia nigra pars reticulata	UBERON:0001966	59.87	gold quality
lateral nuclear group of thalamus	UBERON:0002736	59.47	gold quality
superficial temporal artery	UBERON:0001614	59.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting PRSS33, 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-3925-3P	100.00	69.95	1237
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934

Literature-anchored findings (GeneRIF, showing 2)

• highly expressed in spleen and moderately expressed in intestine, colon, lung and brain (PMID:12795636)
• activated eosinophils may induce fibroblast extracellular matrix protein synthesis through cell-surface expression of PRSS33, which would at least partly explain eosinophils’ role(s) in airway remodeling. (PMID:28216055)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:100868	ENSDARG00000004748
danio_rerio	zgc:123217	ENSDARG00000059026
danio_rerio	si:dkeyp-93a5.3	ENSDARG00000096975
danio_rerio	si:ch73-182e20.3	ENSDARG00000100953
danio_rerio	si:ch73-182e20.4	ENSDARG00000102727
mus_musculus	Prss33	ENSMUSG00000049620
rattus_norvegicus	Prss33	ENSRNOG00000029279

Paralogs (14): 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), PRSS50 (ENSG00000283706)

Protein

Protein identifiers

Serine protease 33 — Q8NF86 (reviewed: Q8NF86)

Alternative names: Serine protease EOS

All UniProt accessions (3): Q8NF86, I3L1S0, I3L3D7

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that has amidolytic activity, cleaving its substrates before Arg residues.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in macrophages. Present in the spleen, small and large intestine, lung and brain (at protein level). Highly expressed in peripheral leukocytes, ovary, retina, spleen and stomach. Moderately expressed in thymus, uterus and platelets, as well as some brain tissues, such as thalamus and fetal brain.

Induction. Up-regulated by phorbol myristate acetate (PMA).

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (4): NP_001372391, NP_001372392, NP_001372393, NP_690851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

UniProt features (11 total): disulfide bond 4, active site 3, signal peptide 1, chain 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NF86-F1	86.12	0.65

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): 77 (charge relay system); 126 (charge relay system); 231 (charge relay system)

Disulfide bonds (4): 62–78, 160–237, 193–216, 227–255

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, PEREZ_TP63_TARGETS, PITX2_Q2, GOBP_PROTEOLYSIS, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_PEPTIDASE_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, E2F3_UP.V1_DN, MYC_UP.V1_DN, SRC_UP.V1_DN, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNG_KO_DN, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, ZFP91_TARGET_GENES

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

GO Molecular Function (4): serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

618 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS33	GGT5	P36269	483
PRSS33	SEC14L5	O43304	467
PRSS33	IL5RA	Q01344	452
PRSS33	SIGLEC8	Q9NYZ4	435
PRSS33	FLYWCH1	Q4VC44	418
PRSS33	FLYWCH2	Q96CP2	383
PRSS33	SLFN14	P0C7P3	379
PRSS33	PURG	Q9UJV8	369
PRSS33	TMEM235	A6NFC5	368
PRSS33	SRRM2	Q9UQ35	362
PRSS33	BICDL2	A1A5D9	358
PRSS33	ALOX15	P16050	356
PRSS33	HCFC1R1	Q9NWW0	353
PRSS33	ZNF792	Q3KQV3	340
PRSS33	PAQR4	Q8N4S7	339

IntAct

8 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PRSS33	SAC3D1	psi-mi:“MI:0914”(association)	0.350
FAM187B	DCTN3	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): CACNA2D1 (Affinity Capture-MS), SAC3D1 (Affinity Capture-MS), CD109 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), POMC (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), SAC3D1 (Affinity Capture-MS), CD109 (Affinity Capture-MS), SP3 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), PRSS33 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A6NIE9, O35164, O43240, P00746, P00770, P03953, P05981, P06870, P07288, P09582, P12323, P15944, P20151, P20160, P20231, P21845, P22457, P32038, P35034, P49862, P50343, P51124, P51779, P69526, P80015, Q00356, Q03238, Q05511, Q07276, Q14B24, Q15661, Q28773, Q3T0A3, Q3UP87, Q571E5, Q5R5E8, Q6GPI1, Q6IE59, Q7JIG6, Q80WM7

Diamond homologs: A0A1B0GVH4, A1L453, A2VE36, E5RG02, F2YMG0, O35205, O35453, O60235, O97370, P03952, P05981, P06868, P08001, P08709, P10323, P14272, P19236, P20231, P22457, P23578, P26262, P29293, P29786, P35035, P35036, P35038, P35039, P35040, P35041, P39675, P49275, P49864, P50342, P69526, P70375, P83748, P98139, Q05511, Q14B25, Q14BX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

707 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2785172:C:CC	acceptor_gain	1.0000
16:2785167:GGGCA:G	acceptor_gain	0.9900
16:2785168:GGCA:G	acceptor_gain	0.9900
16:2785169:GCA:G	acceptor_gain	0.9900
16:2785169:GCAC:G	acceptor_loss	0.9900
16:2785170:CA:C	acceptor_gain	0.9900
16:2785170:CAC:C	acceptor_gain	0.9900
16:2785171:AC:A	acceptor_loss	0.9900
16:2785173:T:C	acceptor_loss	0.9900
16:2785369:CCTTA:C	donor_loss	0.9900
16:2785370:CTTA:C	donor_loss	0.9900
16:2785371:TTAC:T	donor_loss	0.9900
16:2785372:TA:T	donor_loss	0.9900
16:2785373:ACCT:A	donor_gain	0.9900
16:2785374:C:CA	donor_loss	0.9900
16:2785374:CCTC:C	donor_gain	0.9900
16:2785376:T:TA	donor_gain	0.9900
16:2785642:CCCTC:C	acceptor_gain	0.9900
16:2785643:CCTCC:C	acceptor_gain	0.9900
16:2786497:CTCA:C	donor_loss	0.9900
16:2786498:TCAC:T	donor_loss	0.9900
16:2786499:CA:C	donor_loss	0.9900
16:2786500:AC:A	donor_gain	0.9900
16:2786501:C:CA	donor_loss	0.9900
16:2786501:CC:C	donor_gain	0.9900
16:2786501:CCCAG:C	donor_gain	0.9900
16:2784286:A:T	acceptor_gain	0.9800
16:2785012:T:TA	donor_gain	0.9800
16:2785374:CCT:C	donor_gain	0.9800
16:2785644:CTC:C	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1001326837 (16:2787729 A>G), RS1001534880 (16:2787877 A>G), RS1001997820 (16:2787350 A>C,T), RS1002051679 (16:2787129 A>C,T), RS1002206715 (16:2788204 A>G), RS1002321823 (16:2789390 T>A), RS1002552344 (16:2783879 T>C), RS1002571609 (16:2789383 G>A), RS1002584921 (16:2783584 G>A), RS1002611688 (16:2783735 G>A), RS1002841100 (16:2788097 G>C), RS1004109828 (16:2787521 G>A), RS1004140841 (16:2786669 G>A,C), RS1005715347 (16:2788128 G>C), RS1005869632 (16:2783919 T>C)

Disease associations

OMIM: gene MIM:613797 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004600_19	Eosinophil percentage of white cells	7.000000e-15
GCST004606_87	Eosinophil count	3.000000e-15
GCST004617_110	Eosinophil percentage of granulocytes	8.000000e-14
GCST004623_74	Neutrophil percentage of granulocytes	9.000000e-11
GCST90002381_635	Eosinophil count	2.000000e-40
GCST90002382_427	Eosinophil percentage of white cells	2.000000e-41

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	decreases expression	1
entinostat	increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Ozone	increases abundance, affects expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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