SPINK gene family

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 10.05.2021

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DefinitionThis section has been translated automatically.

SPINK is the acronym for "Serine Peptidase Inhibitor Kazal" and comprises a gene family placed on different chromosomes. The members of this gene family code for specific proteases, the SPINK protease inhibitor Kazal-type (SPINK) family. These are serine peptidase inhibitors. They contain at least one inhibitory Kazal domain. This domain binds to their targets, the serine proteases, and inhibits their proteolytic functions. This regulatory inhibitory function and its fine-tuning is fundamental for many epithelia.

SPINK family members 1, 2, and 4 have comparable size and structure, encoded by 4 exons with a single Kazal-type serine protease inhibitor domain. SPINK5, on the other hand, contains 33 exons encoding 15 inhibitory domains. These SPINK protease inhibitors are thought to be involved in protection against proteolytic degradation of epithelial and mucosal tissues, although their respective major sites of expression may differ.

Some SPINK protease inhibitors (e.g., SPINK7, also known as esophageal cancer-related gene 2) has a role as a tumor suppressor through its ability to inhibit urokinase plasminogen-type activator (uPA) binding to the uPA receptor (uPAR) and cleavage of uPAR, which suppresses cell migration/invasion and signaling pathways including increased cytosolic calcium.

General informationThis section has been translated automatically.

SPINK family members 1, 2, and 4 have comparable size and structure, encoded by 4 exons with a single Kazal-type serine protease inhibitory domain. SPINK5, on the other hand, contains 33 exons encoding 15 inhibitory domains. These SPINK protease inhibitors are thought to be involved in protection against proteolytic degradation of epithelial and mucosal tissues, although their respective major sites of expression may differ.

Some SPINK protease inhibitors (e.g., SPINK7, also known as esophageal cancer-related gene 2) has a role as a tumor suppressor through its ability to inhibit urokinase plasminogen-type activator (uPA) binding to the uPA receptor (uPAR) and cleavage of uPAR, which suppresses cell migration/invasion and signaling pathways including increased cytosolic calcium.

LiteratureThis section has been translated automatically.

  1. Averbukh LD et al.(2019) SPINK-1 polymorphism as a pancreatitis risk factor. Cureus. 11(1):e3852.
  2. Bitoun E et al. (2002) Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. J Invest Dermatol 118:352-361.
  3. Redelfs L et al (2016) The serine protease inhibitor of Kazal-type 9 (SPINK9) is expressed in lichen simplex chronicus, actinic keratosis and squamous cell carcinomas. Archives of Dermatological Research 308: 133-137
  4. Rockett JC, Patrizio P, Schmid JE et al (2004) Gene expression patterns associated with infertility in humans and rodent models. Mutat Res 549:225-240
  5. Weber C et al (2017) The serine protease inhibitor of Kazal-type 7 (SPINK7) is expressed in human skin. Arch Dermatol Res 309:767-771.
  6. Xue C et al (2019) Elevated SPINK2 gene expression is a predictor of poor prognosis in acute myeloid leukemia. Oncol Lett 18:2877-2884.
  7. Wapenaar MC et al (2007) The SPINK-gene family. Immunogenetics 59: 349-357

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Last updated on: 10.05.2021