SPINT2

Kunitz-type protease inhibitor 2 is an enzyme inhibitor that in humans is encoded by the SPINT2 gene.[5][6][7] 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)[1] Band 19q13.2 Start 38,244,035 bp[1] End 38,292,615 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 B1 Start 29,256,323 bp[2] End 29,281,912 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • peptidase inhibitor activity • endopeptidase inhibitor activity • serine-type endopeptidase inhibitor activity • GO:0001948 protein binding Cellular component • cytoplasm • integral component of membrane • extracellular region • membrane • cell 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: 29.26 – 29.28 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

References

1. GRCh38: Ensembl release 89: ENSG00000167642 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000074227 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Marlor CW, Delaria KA, Davis G, Muller DK, Greve JM, Tamburini PP (May 1997). "Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains". The Journal of Biological Chemistry. 272 (18): 12202–8. doi:10.1074/jbc.272.18.12202. PMID 9115294.
6. Kawaguchi T, Qin L, Shimomura T, Kondo J, Matsumoto K, Denda K, Kitamura N (Oct 1997). "Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor". The Journal of Biological Chemistry. 272 (44): 27558–64. doi:10.1074/jbc.272.44.27558. PMID 9346890.
7. "Entrez Gene: SPINT2 serine peptidase inhibitor, Kunitz type, 2".

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 / FEBS. 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 / FEBS. 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.
• 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.
• 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.
• 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.
• 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.
• 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.