ST14

This article is about the gene and protein. For the Star Trek 14 film, see Star Trek Beyond § Sequel. For the ST14 postcode, see ST postcode area.

Suppressor of tumorigenicity 14 protein, also known as matriptase, is a protein that in humans is encoded by the ST14 gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.

ST14
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1EAW, 1EAX, 2GV6, 2GV7, 3BN9, 3NCL, 3P8F, 3P8G, 3SO3, 4IS5, 4ISL, 4ISN, 4ISO, 4JYT, 4JZ1, 4JZI, 4O97, 4O9V, 4R0I
Identifiers
Aliases	ST14, ARCI11, HAI, MT-SP1, MTSP1, PRSS14, SNC19, TADG15, TMPRSS14, suppression of tumorigenicity 14, ST14 transmembrane serine protease matriptase, CAP3
External IDs	OMIM: 606797; MGI: 1338881; HomoloGene: 7906; GeneCards: ST14; OMA:ST14 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q24.3 Start 130,159,782 bp End 130,210,362 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 A4|9 16.61 cM Start 31,000,698 bp End 31,043,149 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon nasal epithelium duodenum mucosa of ileum mucosa of pharynx jejunal mucosa olfactory zone of nasal mucosa rectum gingival epithelium mucosa of sigmoid colon Top expressed in hair follicle intestinal villus crypt of lieberkuhn of small intestine gastric mucosa mucous cell of stomach large intestine colon epithelium of stomach lip Eustachian tube More reference expression data BioGPS n/a
Gene ontology Molecular function peptidase activity serine-type peptidase activity hydrolase activity endopeptidase activity serine-type endopeptidase activity Cellular component integral component of membrane extracellular region plasma membrane basolateral plasma membrane integral component of plasma membrane extrinsic component of plasma membrane membrane extracellular space Biological process neural tube closure epithelial cell morphogenesis involved in placental branching proteolysis keratinocyte differentiation cornification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6768 19143 Ensembl ENSG00000149418 ENSMUSG00000031995 UniProt Q9Y5Y6 P56677 RefSeq (mRNA) NM_021978 NM_011176 RefSeq (protein) NP_068813 NP_035306 Location (UCSC) Chr 11: 130.16 – 130.21 Mb Chr 9: 31 – 31.04 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

Matriptase is an epithelial-derived, integral membrane serine protease. This protease forms a complex with the Kunitz-type serine protease inhibitor, HAI-1, and is found to be activated by sphingosine-1-phosphate. This protease has been shown to cleave and activate hepatocyte growth factor/scatter factor, and urokinase plasminogen activator, which suggest the function of this protease as an epithelial membrane activator for other proteases and latent growth factors.

Matriptase is a type II transmembrane serine protease expressed in most human epithelia, where it is coexpressed with its cognate transmembrane inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. Activation of the matriptase zymogen requires sequential N-terminal cleavage, activation site autocleavage, and transient association with HAI-1. Matriptase has an essential physiological role in profilaggrin processing, corneocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the epidermis, and is also critical for hair follicle growth. Matriptase is an 80- to 90-kDa cell surface glycoprotein with a complex modular structure that is common to all matriptases.

Clinical significance

The expression of this protease has been associated with breast, colon, prostate, and ovarian tumors, which implicates its role in cancer invasion, and metastasis.

Matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression that is unopposed by HAI-1 potently promotes carcinogenesis and metastatic dissemination in animal models.

Further reading

• Uhland K (2007). "Matriptase and its putative role in cancer". Cell. Mol. Life Sci. 63 (24): 2968–78. doi:10.1007/s00018-006-6298-x. PMC 11136049. PMID 17131055. S2CID 20643074.
• Zhang Y, Cai X, Schlegelberger B, Zheng S (1999). "Assignment1 of human putative tumor suppressor genes ST13 (alias SNC6) and ST14 (alias SNC19) to human chromosome bands 22q13 and 11q24→q25 by in situ hybridization". Cytogenet. Cell Genet. 83 (1–2): 56–7. doi:10.1159/000015125. PMID 9925927. S2CID 37163219.
• Lin CY, Anders J, Johnson M, et al. (1999). "Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity". J. Biol. Chem. 274 (26): 18231–6. doi:10.1074/jbc.274.26.18231. PMID 10373424.
• Lin CY, Anders J, Johnson M, Dickson RB (1999). "Purification and characterization of a complex containing matriptase and a Kunitz-type serine protease inhibitor from human milk". J. Biol. Chem. 274 (26): 18237–42. doi:10.1074/jbc.274.26.18237. PMID 10373425.
• Takeuchi T, Shuman MA, Craik CS (1999). "Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11054–61. Bibcode:1999PNAS...9611054T. doi:10.1073/pnas.96.20.11054. PMC 34240. PMID 10500122.
• Takeuchi T, Harris JL, Huang W, et al. (2000). "Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates". J. Biol. Chem. 275 (34): 26333–42. doi:10.1074/jbc.M002941200. PMID 10831593.
• Lee SL, Dickson RB, Lin CY (2001). "Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease". J. Biol. Chem. 275 (47): 36720–5. doi:10.1074/jbc.M007802200. PMID 10962009.
• Tanimoto H, Underwood LJ, Wang Y, et al. (2001). "Ovarian tumor cells express a transmembrane serine protease: a potential candidate for early diagnosis and therapeutic intervention". Tumour Biol. 22 (2): 104–14. doi:10.1159/000050604. PMID 11125283. S2CID 46846436.
• Oberst M, Anders J, Xie B, et al. (2001). "Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo". Am. J. Pathol. 158 (4): 1301–11. doi:10.1016/S0002-9440(10)64081-3. PMC 1891898. PMID 11290548.
• Benaud C, Oberst M, Hobson JP, et al. (2002). "Sphingosine 1-phosphate, present in serum-derived lipoproteins, activates matriptase". J. Biol. Chem. 277 (12): 10539–46. doi:10.1074/jbc.M109064200. PMID 11792696.
• Ihara S, Miyoshi E, Ko JH, et al. (2002). "Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching". J. Biol. Chem. 277 (19): 16960–7. doi:10.1074/jbc.M200673200. PMID 11864986.
• Peek M, Moran P, Mendoza N, et al. (2003). "Unusual proteolytic activation of pro-hepatocyte growth factor by plasma kallikrein and coagulation factor XIa". J. Biol. Chem. 277 (49): 47804–9. doi:10.1074/jbc.M209778200. PMID 12372819.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Benaud CM, Oberst M, Dickson RB, Lin CY (2003). "Deregulated activation of matriptase in breast cancer cells". Clin. Exp. Metastasis. 19 (7): 639–49. doi:10.1023/A:1020985632550. PMID 12498394. S2CID 25387216.
• Oberst MD, Williams CA, Dickson RB, et al. (2003). "The activation of matriptase requires its noncatalytic domains, serine protease domain, and its cognate inhibitor". J. Biol. Chem. 278 (29): 26773–9. doi:10.1074/jbc.M304282200. PMID 12738778.
• Santin AD, Cane' S, Bellone S, et al. (2003). "The novel serine protease tumor-associated differentially expressed gene-15 (matriptase/MT-SP1) is highly overexpressed in cervical carcinoma". Cancer. 98 (9): 1898–904. doi:10.1002/cncr.11753. PMID 14584072. S2CID 29921089.
• Suzuki M, Kobayashi H, Kanayama N, et al. (2004). "Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase". J. Biol. Chem. 279 (15): 14899–908. doi:10.1074/jbc.M313130200. PMID 14747469.
• Hung RJ, Hsu IaW, Dreiling JL, et al. (2004). "Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts". Am. J. Physiol., Cell Physiol. 286 (5): C1159–69. doi:10.1152/ajpcell.00400.2003. PMID 15075215.
• Sun LF, Zheng S, Shi Y, et al. (2004). "[SNC19/ST14 gene transfection and expression influence the biological behavior of colorectal cancer cells]". Zhonghua Yi Xue Za Zhi. 84 (10): 843–8. PMID 15200890.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.