PRSS36

Summary

PRSS36 (serine protease 36, HGNC:26906) is a protein-coding gene on chromosome 16p11.2, encoding Polyserase-2 (Q5K4E3). Serine protease.

Enables serine-type endopeptidase activity. Predicted to be involved in proteolysis. Located in cytoplasm.

Source: NCBI Gene 146547 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 134 total
• MANE Select transcript: NM_173502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26906
Approved symbol	PRSS36
Name	serine protease 36
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90661
Ensembl gene	ENSG00000178226
Ensembl biotype	protein_coding
OMIM	610560
Entrez	146547

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 retained_intron, 4 protein_coding, 1 nonsense_mediated_decay

ENST00000268281, ENST00000418068, ENST00000561897, ENST00000562368, ENST00000562390, ENST00000563693, ENST00000569305, ENST00000569614, ENST00000571878, ENST00000955222

RefSeq mRNA: 3 — MANE Select: NM_173502 NM_001258290, NM_001258291, NM_173502

CCDS: CCDS32436, CCDS58452, CCDS58453

Canonical transcript exons

ENST00000268281 — 15 exons

Exon	Start	End
ENSE00001255589	31149696	31149731
ENSE00001294887	31148395	31148675
ENSE00002262104	31149999	31150066
ENSE00002598067	31138926	31139416
ENSE00003459453	31145789	31145955
ENSE00003469170	31141723	31141960
ENSE00003495234	31142737	31142993
ENSE00003522825	31140492	31140757
ENSE00003538367	31143342	31143471
ENSE00003648261	31149463	31149498
ENSE00003653300	31149073	31149235
ENSE00003656968	31142481	31142644
ENSE00003661520	31141469	31141610
ENSE00003672151	31143588	31143837
ENSE00003682985	31140294	31140415

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 79.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0808 / max 31.2870, expressed in 26 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157142	0.0539	20
207842	0.0269	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.43	gold quality
right adrenal gland cortex	UBERON:0035827	75.74	gold quality
mucosa of transverse colon	UBERON:0004991	75.06	gold quality
right adrenal gland	UBERON:0001233	74.53	gold quality
pituitary gland	UBERON:0000007	74.39	gold quality
left adrenal gland	UBERON:0001234	73.98	gold quality
right coronary artery	UBERON:0001625	73.95	gold quality
left adrenal gland cortex	UBERON:0035825	73.90	gold quality
omental fat pad	UBERON:0010414	73.37	gold quality
peritoneum	UBERON:0002358	73.32	gold quality
apex of heart	UBERON:0002098	73.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.86	gold quality
adrenal cortex	UBERON:0001235	72.79	gold quality
transverse colon	UBERON:0001157	72.75	gold quality
granulocyte	CL:0000094	72.20	gold quality
adenohypophysis	UBERON:0002196	71.88	gold quality
adipose tissue of abdominal region	UBERON:0007808	71.63	gold quality
skin of leg	UBERON:0001511	70.88	gold quality
small intestine	UBERON:0002108	70.87	gold quality
skin of abdomen	UBERON:0001416	70.16	gold quality
leukocyte	CL:0000738	70.05	gold quality
descending thoracic aorta	UBERON:0002345	69.97	gold quality
monocyte	CL:0000576	69.90	gold quality
left coronary artery	UBERON:0001626	69.64	gold quality
coronary artery	UBERON:0001621	69.37	gold quality
minor salivary gland	UBERON:0001830	69.35	gold quality
blood	UBERON:0000178	69.12	gold quality
rectum	UBERON:0001052	69.02	gold quality
lower esophagus	UBERON:0013473	68.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting PRSS36, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6742-3P	97.95	64.50	1490

Literature-anchored findings (GeneRIF, showing 1)

• analysis of post-translational processing mechanisms of polyserase-2 revealed that this novel polyprotein is a secreted enzyme whose three protease domains remain as an integral part of a single polypeptide chain (PMID:15536082)

Cross-species orthologs

31 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prss36	ENSMUSG00000070371
rattus_norvegicus	Prss36	ENSRNOG00000033343
drosophila_melanogaster	alphaTry	FBGN0003863
drosophila_melanogaster	betaTry	FBGN0010357
drosophila_melanogaster	deltaTry	FBGN0010358
drosophila_melanogaster	gammaTry	FBGN0010359
drosophila_melanogaster	epsilonTry	FBGN0010425
drosophila_melanogaster	thetaTry	FBGN0011555
drosophila_melanogaster	zetaTry	FBGN0011556
drosophila_melanogaster	Ser12	FBGN0011832
drosophila_melanogaster	iotaTry	FBGN0015001
drosophila_melanogaster	Try29F	FBGN0015316
drosophila_melanogaster	Ser8	FBGN0019928
drosophila_melanogaster	Send1	FBGN0031406
drosophila_melanogaster	CG8299	FBGN0034052
drosophila_melanogaster	CG11192	FBGN0034507
drosophila_melanogaster	CG13430	FBGN0034518
drosophila_melanogaster	CG10405	FBGN0038431
drosophila_melanogaster	CG7829	FBGN0039703
drosophila_melanogaster	CG17239	FBGN0042186
drosophila_melanogaster	CG17234	FBGN0042187
drosophila_melanogaster	lambdaTry	FBGN0043470
drosophila_melanogaster	kappaTry	FBGN0043471
drosophila_melanogaster	CG30025	FBGN0050025
drosophila_melanogaster	CG30031	FBGN0050031
drosophila_melanogaster	CG31265	FBGN0051265
drosophila_melanogaster	CG31681	FBGN0051681
drosophila_melanogaster	CG31954	FBGN0051954
drosophila_melanogaster	CG32374	FBGN0052374
drosophila_melanogaster	CG34458	FBGN0085487
drosophila_melanogaster	CG17571	FBGN0259998

Paralogs (1): PRSS53 (ENSG00000151006)

Protein

Protein identifiers

Polyserase-2 — Q5K4E3 (reviewed: Q5K4E3)

Alternative names: Polyserine protease 2, Serine protease 36

All UniProt accessions (2): Q5K4E3, I3L3A6

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease. Hydrolyzes the peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln-Gly-Arg-AMC and, to a lesser extent, N-t-Boc-Ala-Phe-Lys-AMC and N-t-Boc-Val-Leu-Lys-AMC. Has a preference for substrates with an Arg instead of a Lys residue in position P1.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in fetal kidney, skeletal muscle, liver, placenta and heart. Also expressed in tumor cell lines derived from lung and colon adenocarcinomas.

Post-translational modifications. The 3 protease domains are not proteolytically cleaved. N-glycosylated.

Activity regulation. Inhibited by serine proteinase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not with EDTA or E-64.

Domain organisation. The first serine protease domain is catalytically active, whereas the second domain lacks the essential His residue of the catalytic triad at position 363, and the third domain lacks the essential Asp residue of the catalytic triad at position 679. The second and third domains are therefore predicted to be inactive.

Similarity. Belongs to the peptidase S1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5K4E3-1	1	yes
Q5K4E3-2	2
Q5K4E3-3	3

RefSeq proteins (3): NP_001245219, NP_001245220, NP_775773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR017326	Pept_S1A_polyserase-2	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

UniProt features (34 total): disulfide bond 10, glycosylation site 9, active site 3, domain 3, splice variant 2, sequence conflict 2, signal peptide 1, propeptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5K4E3-F1	78.91	0.38

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): 243 (charge relay system); 87 (charge relay system); 139 (charge relay system)

Disulfide bonds (10): 72–88, 173–249, 206–228, 239–267, 348–364, 444–516, 506–534, 615–631, 711–772, 739–751

Glycosylation sites (9): 92, 130, 217, 317, 369, 402, 407, 421, 508

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): LFA1_Q6, GGGTGGRR_PAX4_03, NF1_Q6_01, chr16p11, BACH2_01, TGANTCA_AP1_C, TGGNNNNNNKCCAR_UNKNOWN, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MIKKELSEN_IPS_ICP_WITH_H3K4ME3_AND_H327ME3, MIKKELSEN_ES_ICP_WITH_H3K4ME3_AND_H3K27ME3, CACBINDINGPROTEIN_Q6, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, CCTNTMAGA_UNKNOWN

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 (2): 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

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRSS36	CFAP119	A1A4V9	571
PRSS36	CEACAM19	Q7Z692	567
PRSS36	HOXD13	P35453	542
PRSS36	CPD	O75976	535
PRSS36	DEF8	Q6ZN54	534
PRSS36	CPB1	P15086	497
PRSS36	ZNF668	Q96K58	477
PRSS36	ABI3	Q9P2A4	461
PRSS36	SAMSN1	Q9NSI8	456
PRSS36	TREML2	Q5T2D2	455
PRSS36	INPP5D	Q92835	442
PRSS36	PPP1R37	O75864	410
PRSS36	A0A087WVV2	A0A087WVV2	410
PRSS36	FAM241A	Q8N8J7	407
PRSS36	KAT8	Q9H7Z6	400

IntAct

0 interactions, top by confidence:

BioGRID (1): PRSS36 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A2VE36, A6NIE9, A8MTI9, E5RG02, O35453, O43240, O70169, O97507, P00748, P83748, P98140, Q04962, Q14B25, Q14BX2, Q16651, Q2L4Q9, Q2UVH8, Q3UKY7, Q3V0Q7, Q402U7, Q571E5, Q5K2P8, Q5K2P9, Q5K4E3, Q5M8S2, Q6BEA2, Q6IE62, Q6IE63, Q6UWB4, Q76HL1, Q7RTY3, Q7RTY5, Q7Z5A4, Q8BJR6, Q8BLH5, Q8IU80, Q8K4I7, Q8VIF2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2305 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31148391:TCA:T	donor_loss	1.0000
16:31148392:CA:C	donor_loss	1.0000
16:31149507:C:CT	acceptor_gain	1.0000
16:31142497:T:TA	donor_gain	0.9900
16:31148393:A:AC	donor_gain	0.9900
16:31148393:ACCTG:A	donor_gain	0.9900
16:31148394:C:CC	donor_gain	0.9900
16:31148394:CCTG:C	donor_gain	0.9900
16:31148394:CCTGC:C	donor_gain	0.9900
16:31148397:G:A	donor_gain	0.9900
16:31149507:C:T	acceptor_gain	0.9900
16:31149508:A:T	acceptor_gain	0.9900
16:31149865:T:TA	donor_gain	0.9900
16:31149963:AGGC:A	donor_gain	0.9900
16:31140753:CTGGC:C	acceptor_gain	0.9800
16:31141607:CAGG:C	acceptor_gain	0.9800
16:31141713:T:TA	donor_gain	0.9800
16:31141760:AGTCT:A	donor_gain	0.9800
16:31142480:CCCAG:C	donor_gain	0.9800
16:31142500:T:TA	donor_gain	0.9800
16:31142506:T:A	donor_gain	0.9800
16:31143340:A:AC	donor_gain	0.9800
16:31143340:ACT:A	donor_gain	0.9800
16:31143341:C:CC	donor_gain	0.9800
16:31143341:CTC:C	donor_gain	0.9800
16:31149692:TTA:T	donor_loss	0.9800
16:31149694:A:AG	donor_loss	0.9800
16:31149695:CCTG:C	donor_loss	0.9800
16:31140416:C:CC	acceptor_gain	0.9700
16:31141795:G:C	donor_gain	0.9700

AlphaMissense

5433 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31148414:C:A	W178C	0.997
16:31148414:C:G	W178C	0.997
16:31143772:G:C	S262R	0.994
16:31143772:G:T	S262R	0.994
16:31143774:T:G	S262R	0.994
16:31145826:C:G	C228S	0.994
16:31145827:A:T	C228S	0.994
16:31143769:A:C	F263L	0.993
16:31143769:A:T	F263L	0.993
16:31143771:A:G	F263L	0.993
16:31149165:C:A	W60C	0.993
16:31149165:C:G	W60C	0.993
16:31143818:A:G	L247P	0.992
16:31143730:G:C	F276L	0.991
16:31143730:G:T	F276L	0.991
16:31143731:A:C	F276C	0.991
16:31143732:A:G	F276L	0.991
16:31143758:C:G	C267S	0.991
16:31143759:A:T	C267S	0.991
16:31143833:T:A	D242V	0.990
16:31145793:C:G	C239S	0.990
16:31145794:A:T	C239S	0.990
16:31145826:C:T	C228Y	0.990
16:31148416:A:G	W178R	0.990
16:31148416:A:T	W178R	0.990
16:31149081:A:C	C88W	0.990
16:31149130:C:T	C72Y	0.990
16:31145827:A:G	C228R	0.989
16:31148645:C:A	W101C	0.989
16:31148645:C:G	W101C	0.989

dbSNP variants (sampled 300 via entrez): RS1000046435 (16:31144093 G>C), RS1000077537 (16:31143761 C>A,T), RS1000197605 (16:31145144 T>G), RS1000267707 (16:31149912 C>A,T), RS1000700085 (16:31150236 C>A,T), RS1000923687 (16:31145069 A>G), RS1000959864 (16:31139471 C>A,T), RS1001328466 (16:31139751 A>G), RS1001520241 (16:31150630 C>A,T), RS1001747331 (16:31142542 C>A,G,T), RS1002313328 (16:31139619 C>T), RS1002345122 (16:31148274 C>A,T), RS1002607652 (16:31145657 A>G), RS1002644044 (16:31141171 C>T), RS1003419731 (16:31141357 T>C,G)

Disease associations

OMIM: gene MIM:610560 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_175	Bipolar disorder	8.000000e-06
GCST008115_45	Bipolar I disorder	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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