Keratin, type I cytoskeletal 19 also known as cytokeratin-19 (CK-19) or keratin-19 (K19) is a 40 kDa
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''KRT19''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Keratin 19 is a
type I keratin Type I keratins (or Type I cytokeratins) are cytokeratins that constitute the Type I intermediate filaments (IFs) of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells. Most of the type I keratins consist of acid ...
.
Function
Keratin 19 is a member of the
keratin
Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ...
family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins.
Keratin 19 is a
type I keratin Type I keratins (or Type I cytokeratins) are cytokeratins that constitute the Type I intermediate filaments (IFs) of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells. Most of the type I keratins consist of acid ...
. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. Unlike its related family members, this smallest known acidic
cytokeratin
Cytokeratins are keratin proteins found in the intracytoplasmic cytoskeleton of epithelial tissue. They are an important component of intermediate filaments, which help cells resist mechanical stress. Expression of these cytokeratins within epi ...
is not paired with a basic cytokeratin in
epithelial cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
s. It is specifically found in the
periderm
Bark is the outermost layers of stems and roots of woody plants. Plants with bark include trees, woody vines, and shrubs. Bark refers to all the tissues outside the vascular cambium and is a nontechnical term. It overlays the wood and consis ...
, the transiently superficial layer that envelops the developing
epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the ...
. The type I cytokeratins are clustered in a region of chromosome 17q12-q21.
Use as biomarker
KRT19 is also known as Cyfra 21-1.
Due to its high sensitivity, KRT19 is the most used marker for the
RT-PCR
Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase chai ...
-mediated detection of tumor cells disseminated in
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inc ...
s,
peripheral blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...
, and
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoieti ...
of
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
patients. Depending on the assays, KRT19 has been shown to be both a specific and a non-specific marker. False positivity in such KRT19 RT-PCR studies include: illegitimate transcription (expression of small amounts of KRT19 mRNA by tissues in which it has no real physiological role), haematological disorders (KRT19 induction in peripheral blood cells by
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
s and
growth factor
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for r ...
s, which circulate at higher concentrations in inflammatory conditions and neutropenia), the presence of
pseudogene
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are ...
s (two KRT19 pseudogenes, KRT19a and KRT19b, have been identified, which have significant sequence homology to KRT19 mRNA. Subsequently, attempts to detect the expression of the authentic KRT19 may result in the detection of either or both of these pseudogenes), sample contamination (introduction of contaminating epithelial cells during peripheral blood sampling for subsequent RT-PCR analysis).
Moreover, Ck-19 is widely applied as post-operative diagnostic marker of papillary thyroid carcinoma.
Keratin 19 is often used together with
keratin 8
Keratin, type II cytoskeletal 8 also known as cytokeratin-8 (CK-8) or keratin-8 (K8) is a keratin protein that is encoded in humans by the ''KRT8'' gene. It is often paired with keratin 18.
Utility as an immunohistochemical stain
Antibodies to C ...
and
keratin 18
Keratin 18 is a type I cytokeratin. It is, together with its filament partner keratin 8, perhaps the most commonly found products of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutation ...
to differentiate cells of epithelial origin from hematopoietic cells in tests that enumerate
circulating tumor cell A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become ''seeds'' for the subsequent growth of additio ...
s in blood.
Interactions
Keratin 19 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...
with
Pinin
Pinin is a protein that in humans is encoded by the ''PNN'' gene.
Interactions
Pinin has been shown to interact with Keratin 8, Keratin 18, Keratin 19, CTBP1
C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is en ...
.
References
Further reading
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{{Use dmy dates, date=April 2017
Keratins
Tumor markers