SPINT2

Kunitz-type protease inhibitor 2 is an enzyme inhibitor that in humans is encoded by the SPINT2 gene. SPINT2 is a transmembrane protein with two extracellular Kunitz domains to inhibit serine proteases. This gene is a presumed tumor suppressor by inhibiting HGF activator which prevents the formation of active hepatocyte growth factor. Mutations in SPINT2 could result in congenital sodium diarrhea (CSD).

SPINT2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4U32
Identifiers
Aliases	SPINT2, DIAR3, HAI-2, HAI2, Kop, PB, serine peptidase inhibitor, Kunitz type, 2, serine peptidase inhibitor, Kunitz type 2
External IDs	OMIM: 605124 MGI: 1338031 HomoloGene: 7955 GeneCards: SPINT2
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.2 Start 38,244,035 bp End 38,292,615 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 B1 Start 28,955,748 bp End 28,981,337 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parotid gland pituitary gland anterior pituitary left lobe of thyroid gland right lobe of thyroid gland right uterine tube palpebral conjunctiva ascending aorta rectum trachea Top expressed in left colon submandibular gland intestinal villus crypt of lieberkuhn of small intestine pyloric antrum duodenum parotid gland ileum lacrimal gland jejunum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity endopeptidase inhibitor activity serine-type endopeptidase inhibitor activity protein binding Cellular component cytoplasm integral component of membrane extracellular region membrane plasma membrane Biological process negative regulation of cell motility negative regulation of peptidase activity negative regulation of cell-cell adhesion establishment or maintenance of cell polarity negative regulation of neural precursor cell proliferation neural tube closure negative regulation of endopeptidase activity epithelial cell morphogenesis involved in placental branching cellular response to BMP stimulus basement membrane organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10653 20733 Ensembl ENSG00000167642 ENSMUSG00000074227 UniProt O43291 Q9WU03 RefSeq (mRNA) NM_021102 NM_001166103 NM_001082548 NM_011464 RefSeq (protein) NP_001159575 NP_066925 NP_001076017 NP_035594 Location (UCSC) Chr 19: 38.24 – 38.29 Mb Chr 7: 28.96 – 28.98 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Further reading

• Morelle W, Capon C, Balduyck M, Sautiere P, Kouach M, Michalski C, Fournet B, Mizon J (Apr 1994). "Chondroitin sulphate covalently cross-links the three polypeptide chains of inter-alpha-trypsin inhibitor". European Journal of Biochemistry. 221 (2): 881–8. doi:10.1111/j.1432-1033.1994.tb18803.x. PMID 7513643.
• Mizon C, Balduyck M, Albani D, Michalski C, Burnouf T, Mizon J (Mar 1996). "Development of an enzyme-linked immunosorbent assay for human plasma inter-alpha-trypsin inhibitor (ITI) using specific antibodies against each of the H1 and H2 heavy chains". Journal of Immunological Methods. 190 (1): 61–70. doi:10.1016/0022-1759(95)00257-X. PMID 8601712.
• Gress TM, Müller-Pillasch F, Geng M, Zimmerhackl F, Zehetner G, Friess H, Büchler M, Adler G, Lehrach H (Oct 1996). "A pancreatic cancer-specific expression profile". Oncogene. 13 (8): 1819–30. PMID 8895530.
• Shimomura T, Denda K, Kitamura A, Kawaguchi T, Kito M, Kondo J, Kagaya S, Qin L, Takata H, Miyazawa K, Kitamura N (Mar 1997). "Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor". The Journal of Biological Chemistry. 272 (10): 6370–6. doi:10.1074/jbc.272.10.6370. PMID 9045658.
• Blom AM, Thuveson M, Fries E (Nov 1997). "Intracellular coupling of bikunin and the heavy chain of rat pre-alpha-inhibitor in COS-1 cells". The Biochemical Journal. 328 ( Pt 1) (Pt 1): 185–91. doi:10.1042/bj3280185. PMC 1218904. PMID 9359851.
• Müller-Pillasch F, Wallrapp C, Bartels K, Varga G, Friess H, Büchler M, Adler G, Gress TM (Jan 1998). "Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1395 (1): 88–95. doi:10.1016/s0167-4781(97)00129-2. PMID 9434156.
• Kataoka H, Shimomura T, Kawaguchi T, Hamasuna R, Itoh H, Kitamura N, Miyazawa K, Koono M (Dec 2000). "Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA activity in the pericellular microenvironment". The Journal of Biological Chemistry. 275 (51): 40453–62. doi:10.1074/jbc.M006412200. PMID 11013244.
• Itoh H, Kataoka H, Yamauchi M, Naganuma S, Akiyama Y, Nuki Y, Shimomura T, Miyazawa K, Kitamura N, Koono M (Oct 2001). "Identification of hepatocyte growth factor activator inhibitor type 2 (HAI-2)-related small peptide (H2RSP): its nuclear localization and generation of chimeric mRNA transcribed from both HAI-2 and H2RSP genes". Biochemical and Biophysical Research Communications. 288 (2): 390–9. doi:10.1006/bbrc.2001.5767. PMID 11606055.
• Suzuki M, Kobayashi H, Fujie M, Nishida T, Takigawa M, Kanayama N, Terao T (Mar 2002). "Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells". The Journal of Biological Chemistry. 277 (10): 8022–32. doi:10.1074/jbc.M108545200. PMID 11777908.
• Kobayashi H, Suzuki M, Kanayama N, Nishida T, Takigawa M, Terao T (Aug 2002). "Suppression of urokinase receptor expression by bikunin is associated with inhibition of upstream targets of extracellular signal-regulated kinase-dependent cascade". European Journal of Biochemistry. 269 (16): 3945–57. doi:10.1046/j.1432-1033.2002.03068.x. PMID 12180971.
• Mizon C, Piva F, Queyrel V, Balduyck M, Hachulla E, Mizon J (Jun 2002). "Urinary bikunin determination provides insight into proteinase/proteinase inhibitor imbalance in patients with inflammatory diseases". Clinical Chemistry and Laboratory Medicine. 40 (6): 579–86. doi:10.1515/CCLM.2002.100. PMID 12211652. S2CID 22630736.
• Isogai R, Matsukura A, Aragane Y, Maeda A, Matsukura M, Yudate T, Sugihara K, Takahashi M, Aisu K, Tezuka T (Dec 2002). "Quantitative analysis of bikunin-laden mast cells in follicular eruptions and chronic skin lesions of atopic dermatitis". Archives of Dermatological Research. 294 (9): 387–92. doi:10.1007/s00403-002-0336-9. PMID 12522575. S2CID 9514861.
• Yamauchi M, Itoh H, Naganuma S, Koono M, Hasui Y, Osada Y, Kataoka H (Dec 2002). "Expression of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in human testis: identification of a distinct transcription start site for the HAI-2 gene in testis". Biological Chemistry. 383 (12): 1953–7. doi:10.1515/BC.2002.220. PMID 12553733. S2CID 19734313.
• Suzuki M, Kobayashi H, Tanaka Y, Hirashima Y, Kanayama N, Takei Y, Saga Y, Suzuki M, Itoh H, Terao T (Apr 2003). "Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cell line by overexpression of bikunin". International Journal of Cancer. 104 (3): 289–302. doi:10.1002/ijc.10950. hdl:10271/1250. PMID 12569552. S2CID 84583247.
• Suzuki M, Kobayashi H, Tanaka Y, Hirashima Y, Kanayama N, Takei Y, Saga Y, Suzuki M, Itoh H, Terao T (Apr 2003). "Bikunin target genes in ovarian cancer cells identified by microarray analysis". The Journal of Biological Chemistry. 278 (17): 14640–6. doi:10.1074/jbc.M300239200. PMID 12571229.
• Schuster JM, Longo M, Nelson PS (Sep 2003). "Differential expression of bikunin (HAI-2/PB), a proposed mediator of glioma invasion, by demethylation treatment". Journal of Neuro-Oncology. 64 (3): 219–25. doi:10.1023/A:1025674227750. PMID 14558597. S2CID 22607445.
• Fukai K, Yokosuka O, Chiba T, Hirasawa Y, Tada M, Imazeki F, Kataoka H, Saisho H (Dec 2003). "Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma". Cancer Research. 63 (24): 8674–9. PMID 14695180.

External links

• Overview of all the structural information available in the PDB for UniProt: O43291 (Kunitz-type protease inhibitor 2) at the PDBe-KB.