TMPRSS13

Summary

TMPRSS13 (transmembrane serine protease 13, HGNC:29808) is a protein-coding gene on chromosome 11q23.3, encoding Transmembrane protease serine 13 (Q9BYE2). Serine protease.

This gene encodes a member of the type II transmembrane serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Transmembrane serine proteases are regulated by protease inhibitors and known to function in development, homeostasis, infection, and tumorigenesis. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins.

Source: NCBI Gene 84000 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_001077263

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29808
Approved symbol	TMPRSS13
Name	transmembrane serine protease 13
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MSPL, MSPS
Ensembl gene	ENSG00000137747
Ensembl biotype	protein_coding
OMIM	610050
Entrez	84000

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000430170, ENST00000445164, ENST00000524993, ENST00000525794, ENST00000526090, ENST00000528135, ENST00000528626, ENST00000966153

RefSeq mRNA: 4 — MANE Select: NM_001077263 NM_001077263, NM_001206789, NM_001206790, NM_001244995

CCDS: CCDS41721, CCDS55788, CCDS55789, CCDS58185

Canonical transcript exons

ENST00000524993 — 13 exons

Exon	Start	End
ENSE00000930746	117911768	117911860
ENSE00000930747	117910707	117910750
ENSE00000991437	117917170	117917274
ENSE00000991442	117905638	117905736
ENSE00001053164	117903959	117904101
ENSE00001209120	117903655	117903807
ENSE00002142359	117929287	117929402
ENSE00002179716	117900641	117902265
ENSE00003515382	117918409	117918838
ENSE00003570318	117914392	117914514
ENSE00003685985	117913777	117913906
ENSE00003988831	117908612	117908784
ENSE00003988841	117909806	117909968

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 91.73.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4986 / max 48.5061, expressed in 313 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122544	1.4986	313

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	91.73	gold quality
skin of leg	UBERON:0001511	89.86	gold quality
skin of abdomen	UBERON:0001416	87.93	gold quality
zone of skin	UBERON:0000014	87.39	gold quality
lower esophagus mucosa	UBERON:0035834	85.26	gold quality
esophagus mucosa	UBERON:0002469	82.61	gold quality
nasal cavity epithelium	UBERON:0005384	82.21	gold quality
gingival epithelium	UBERON:0001949	80.67	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	80.61	gold quality
minor salivary gland	UBERON:0001830	79.95	gold quality
saliva-secreting gland	UBERON:0001044	79.54	gold quality
heart right ventricle	UBERON:0002080	79.28	gold quality
mouth mucosa	UBERON:0003729	79.28	gold quality
cortical plate	UBERON:0005343	79.14	gold quality
sperm	CL:0000019	78.99	gold quality
gingiva	UBERON:0001828	78.60	gold quality
amniotic fluid	UBERON:0000173	77.83	gold quality
right lobe of thyroid gland	UBERON:0001119	77.64	gold quality
left lobe of thyroid gland	UBERON:0001120	76.53	gold quality
vena cava	UBERON:0004087	76.45	gold quality
cerebellar vermis	UBERON:0004720	76.37	gold quality
upper leg skin	UBERON:0004262	76.14	gold quality
endothelial cell	CL:0000115	76.13	gold quality
thyroid gland	UBERON:0002046	75.62	gold quality
vastus lateralis	UBERON:0001379	74.28	gold quality
superficial temporal artery	UBERON:0001614	74.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.02	gold quality
palpebral conjunctiva	UBERON:0001812	73.51	gold quality
buccal mucosa cell	CL:0002336	73.23	silver quality
quadriceps femoris	UBERON:0001377	72.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	10.38
E-ANND-3	yes	5.42

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 11)

• cloning of MSPL/TMPRSS13, which may play roles in the proteolytic processing of prohormones, precursors of growth factors, and also play roles in the pathogenicity of many viruses and bacteria in vivo (PMID:17981585)
• The authors report that serine proteases, MSPL and its splice variant TMPRSS13, are novel candidates for proteases processing HA proteins of highly pathogenic avian influenza (HPAI) viruses. (PMID:20219906)
• results suggest that TMPRSS13 functions as an HGF-converting protease, the activity of which may be regulated by HAI-1 (PMID:20977675)
• study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, because of their expression in human lung tissue, might promote viral spread in the infected host (PMID:25122802)
• The data provide novel insight into the cellular properties of TMPRSS13 and highlight phosphorylation of TMPRSS13 as a novel post-translational modification of this TTSP family member and potentially other members of this family of proteases. (PMID:28710277)
• TMPRSS13 promotes cell survival, invasion, and resistance to drug-induced apoptosis in colorectal cancer. (PMID:32807808)
• The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy. (PMID:32868877)
• TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein. (PMID:33671076)
• Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza. (PMID:33820827)
• Posttranslational modifications of serine protease TMPRSS13 regulate zymogen activation, proteolytic activity, and cell surface localization. (PMID:34562451)
• IL4I1 binds to TMPRSS13 and competes with SARS-CoV-2 spike. (PMID:36131918)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmprss13b	ENSDARG00000077573
mus_musculus	Tmprss13	ENSMUSG00000037129
rattus_norvegicus	Tmprss13	ENSRNOG00000016397
drosophila_melanogaster	Sb	FBGN0003319
drosophila_melanogaster	CG17242	FBGN0250841

Paralogs (17): PRSS22 (ENSG00000005001), PRSS21 (ENSG00000007038), TMPRSS11E (ENSG00000087128), HPN (ENSG00000105707), ST14 (ENSG00000149418), TMPRSS11D (ENSG00000153802), TMPRSS15 (ENSG00000154646), TMPRSS3 (ENSG00000160183), TMPRSS5 (ENSG00000166682), TMPRSS7 (ENSG00000176040), TMPRSS9 (ENSG00000178297), TMPRSS2 (ENSG00000184012), TMPRSS11B (ENSG00000185873), TMPRSS6 (ENSG00000187045), TMPRSS11A (ENSG00000187054), TMPRSS11F (ENSG00000198092), PRSS41 (ENSG00000215148)

Protein

Protein identifiers

Transmembrane protease serine 13 — Q9BYE2 (reviewed: Q9BYE2)

Alternative names: Membrane-type mosaic serine protease

All UniProt accessions (2): Q9BYE2, E9PR79

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease. Cleaves the proform of PRSS8/prostasin to form the active protein. Cleaves the proform of HGF to form the active protein which promotes MAPK signaling. Promotes the formation of the stratum corneum and subsequently the epidermal barrier in embryos.

Subunit / interactions. Interacts with SPINT1/HAI-1; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13. Interacts with SPINT2/HAI-2; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13.

Subcellular location. Cell membrane. Secreted. Cytoplasm.

Tissue specificity. Expressed in placenta. Predominantly expressed in lung, placenta, pancreas, and prostate. Expressed in lung, placenta, pancreas, and prostate. Weakly expressed in testis and peripheral blood lymphocytes.

Post-translational modifications. The inactive zymogen is post-translationally modified and then trafficked to the cell surface, whereby it undergoes autocatalytic cleavage resulting in an activated form that is released extracellularly. Phosphorylation is required for localization at the cell surface. Phosphorylation increases following inhibition of protease activity by SPINT2/HAI-2. N-glycosylation of Asn-405 and Asn-445 is required for exit from the endoplasmic reticulum and trafficking to the cell surface. Also required for autocleavage of the zymogen, activation and secretion of the mature protein.

Activity regulation. Cleavage of HGF is inhibited by SPINT1/HAI-1 via the BPTI/Kunitz inhibitor 1 domain.

Polymorphism. The repeat A-S-P-A-[GLQR] is polymorphic and the number of copies varies between 12 to 14.

Similarity. Belongs to the peptidase S1 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BYE2-1	1, MSPL	yes
Q9BYE2-2	2
Q9BYE2-3	3, MSPS
Q9BYE2-4	4
Q9BYE2-6	6

RefSeq proteins (4): NP_001070731, NP_001193718, NP_001193719, NP_001231924 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR017327	Peptidase_S1A_TMPRSS13	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR043504

Pfam: PF00089, PF15494

UniProt features (71 total): repeat 16, mutagenesis site 10, disulfide bond 6, splice variant 6, region of interest 5, compositionally biased region 5, sequence conflict 5, glycosylation site 4, domain 3, active site 3, topological domain 2, site 2, sequence variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6KD5	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYE2-F1	75.14	0.51

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 (5): 366 (charge relay system); 414 (charge relay system); 511 (charge relay system); 228–229 (cleavage; by autolysis; required for cell surface localization and secretion); 325 (required for autocleavage and prss8 cleavage)

Disulfide bonds (6): 250–314, 263–317, 351–367, 448–517, 480–496, 507–535

Glycosylation sites (4): 255, 292, 405, 445

Mutagenesis-validated functional residues (10):

Position	Phenotype
196	no effect on autocleavage.
201	no effect on autocleavage.
210	no effect on autocleavage.
228	significantly reduces autocleavage and cleavage of substrates. abolishes phosphorylation when inhibited by spint2/hai-2,
255	no effect on autocleavage. no effect on prss8 cleavage and activation.
292	no effect on autocleavage. no effect on prss8 cleavage and activation.
325	abolishes autocleavage. abolishes prss8 cleavage and activation. increases localization to the cell surface. no effect o
405	loss of localization to the cell surface even in the presence of the inhibitor spint2. reduces prss8 cleavage and activa
445	reduces autocleavage. loss of localization to the cell surface even in the presence of the inhibitor spint2. reduces prs
511	abolishes autocleavage. abolishes serine protease activity including prss8 cleavage and activation. increases localizati

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_PROTEIN_MATURATION, GOCC_BLOOD_MICROPARTICLE, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, MIKKELSEN_MCV6_LCP_WITH_H3K27ME3, GOBP_PROTEIN_PROCESSING, LIM_MAMMARY_STEM_CELL_DN, GSE13522_WT_VS_IFNAR_KO_SKING_T_CRUZI_Y_STRAIN_INF_UP, GLI1_TARGET_GENES, GREB1_TARGET_GENES, ZNF768_TARGET_GENES, MIR8485, MIR4795_3P

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

GO Molecular Function (5): serine-type endopeptidase activity (GO:0004252), serine-type peptidase activity (GO:0008236), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (5): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), blood microparticle (GO:0072562), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein metabolic process	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
extracellular region	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMPRSS13	SPINT1	O43278	647
TMPRSS13	ERV3-1	Q14264	642
TMPRSS13	ERVFRD-1	P60508	641
TMPRSS13	ERVW-1	Q9UQF0	555
TMPRSS13	KRTAP4-5	Q9BYR2	543
TMPRSS13	FURIN	P09958	516
TMPRSS13	SPINT2	O43291	493
TMPRSS13	GOLGA8B	A8MQT2	420
TMPRSS13	ACE2	Q9BYF1	419
TMPRSS13	DEPDC4	Q8N2C3	410
TMPRSS13	LMLN	Q96KR4	397
TMPRSS13	SLC13A2	Q13183	384
TMPRSS13	SLC46A2	Q9BY10	373
TMPRSS13	CTSL	P07711	370
TMPRSS13	ZNF200	P98182	367

IntAct

13 interactions, top by confidence:

A	B	Type	Score
LRRK2		psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SMIM26	METTL15	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	PROS1	psi-mi:“MI:0914”(association)	0.350

BioGRID (107): TMPRSS13 (Affinity Capture-MS), TMPRSS13 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), ADAM9 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), PTPRK (Affinity Capture-MS), UFL1 (Affinity Capture-MS), SEZ6L2 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), OAF (Affinity Capture-MS), MAN1A1 (Affinity Capture-MS), MANEAL (Affinity Capture-MS), POGLUT1 (Affinity Capture-MS), INHBE (Affinity Capture-MS), CTSV (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, B8V7S0, O08762, O60235, P00747, P00760, P00762, P00765, P00766, P00767, P00774, P03951, P03952, P04070, P04813, P05981, P06867, P06871, P06872, P07146, P07338, P07477, P08217, P08426, P08519, P12545, P14272, P15944, P17538, P19799, P20231, P20918, P26262, P27435, P29786, P35033, P40313, P47796, P50342, P56677

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2030 predictions. Top by Δscore:

Variant	Effect	Δscore
11:117903652:TA:T	donor_loss	1.0000
11:117903653:A:C	donor_loss	1.0000
11:117903654:C:A	donor_loss	1.0000
11:117903954:CTCA:C	donor_loss	1.0000
11:117903955:TCAC:T	donor_loss	1.0000
11:117903956:CAC:C	donor_loss	1.0000
11:117903958:CCTG:C	donor_loss	1.0000
11:117904107:G:GC	acceptor_gain	1.0000
11:117904112:G:C	acceptor_gain	1.0000
11:117904112:G:GC	acceptor_gain	1.0000
11:117904117:G:C	acceptor_gain	1.0000
11:117904117:G:GC	acceptor_gain	1.0000
11:117909805:CA:C	donor_gain	1.0000
11:117910664:C:CA	donor_gain	1.0000
11:117910705:A:AC	donor_gain	1.0000
11:117910706:C:CC	donor_gain	1.0000
11:117911780:T:A	donor_gain	1.0000
11:117911856:GAGCA:G	acceptor_gain	1.0000
11:117911857:AGCA:A	acceptor_gain	1.0000
11:117911858:GCA:G	acceptor_gain	1.0000
11:117911859:CA:C	acceptor_gain	1.0000
11:117911859:CAC:C	acceptor_gain	1.0000
11:117911860:ACT:A	acceptor_loss	1.0000
11:117911861:C:A	acceptor_loss	1.0000
11:117911861:C:CC	acceptor_gain	1.0000
11:117911864:C:CT	acceptor_gain	1.0000
11:117911865:A:T	acceptor_gain	1.0000
11:117914386:CCTTA:C	donor_loss	1.0000
11:117914387:CTTA:C	donor_loss	1.0000
11:117914388:TTACC:T	donor_loss	1.0000

AlphaMissense

3664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:117903728:C:G	C535S	1.000
11:117903728:C:T	C535Y	1.000
11:117903729:A:T	C535S	1.000
11:117903739:C:A	W531C	1.000
11:117903739:C:G	W531C	1.000
11:117903798:C:A	G512W	1.000
11:117903963:C:G	C507S	1.000
11:117903963:C:T	C507Y	1.000
11:117903964:A:T	C507S	1.000
11:117903995:A:C	C496W	1.000
11:117903996:C:G	C496S	1.000
11:117903997:A:G	C496R	1.000
11:117903997:A:T	C496S	1.000
11:117904044:C:G	C480S	1.000
11:117904045:A:T	C480S	1.000
11:117908653:T:A	D414V	1.000
11:117909814:G:C	C367W	1.000
11:117903673:C:A	W553C	0.999
11:117903673:C:G	W553C	0.999
11:117903702:A:C	Y544D	0.999
11:117903727:A:C	C535W	0.999
11:117903728:C:A	C535F	0.999
11:117903729:A:G	C535R	0.999
11:117903738:C:A	G532C	0.999
11:117903738:C:G	G532R	0.999
11:117903741:A:G	W531R	0.999
11:117903741:A:T	W531R	0.999
11:117903742:G:C	S530R	0.999
11:117903742:G:T	S530R	0.999
11:117903744:T:G	S530R	0.999

dbSNP variants (sampled 300 via entrez): RS1000011196 (11:117906119 A>G), RS1000074568 (11:117927208 A>G), RS1000201177 (11:117915408 G>A), RS1000337372 (11:117905649 C>A,T), RS1000382200 (11:117909271 A>G), RS1000400842 (11:117903271 T>A,C), RS1000425043 (11:117929474 A>G), RS1000565898 (11:117911890 G>T), RS1000674762 (11:117904278 G>A,C), RS1000859581 (11:117927557 C>A), RS1001048517 (11:117919347 A>G), RS1001102513 (11:117913668 G>A,C), RS1001122580 (11:117907736 G>C), RS1001209073 (11:117924655 A>G), RS1001302518 (11:117921852 C>T)

Disease associations

OMIM: gene MIM:610050 | 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	3
mercuric bromide	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Estradiol	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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