Lympho-epithelial Kazal-type related inhibitor 2 (LEKTI-2) is a protein encoded by the ''SPINK9'' gene in humans. ''SPINK9'' is a member of a gene family cluster located on
chromosome 5
Chromosome 5 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 5 spans about 181 million base pairs (the building blocks of DNA) and represents almost 6% of the total DNA in cells. C ...
q33.1, which includes ''
SPINK5
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the ''SPINK5'' gene.
Structure and function
LEKTI is a large multidomain serine prot ...
'' and ''
SPINK6
Serine protease inhibitor Kazal-type 6 (SPINK6) is a protein encoded by the ''SPINK6'' gene in humans. It is a potent inhibitor of epidermal proteases involved in maintaining skin homeostasis, including KLK5, KLK7 and KLK14. ''SPINK6'' is a membe ...
''.
LEKTI-2 is an inhibitor of
KLK5
Kallikrein-5, formerly known as stratum corneum tryptic enzyme (SCTE), is a serine protease expressed in the epidermis. In humans it is encoded by the ''KLK5'' gene.
This gene is one of the fifteen kallikrein subfamily members located in a clust ...
.
Desquamation
The outer layer of the
epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
is called the
stratum corneum
The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the ''stratum disjunctum'' and ''stratum compact ...
. In the stratum corneum terminally differentiated corneocytes are held together by corneodesmosomes. In order for
desquamation
Desquamation occurs when the outermost layer of a tissue, such as the skin, is shed. The term is . Physiologic desquamation
Keratinocytes are the predominant cells of the epidermis, the outermost layer of the skin. Living keratinocytes reside in ...
to occur, corneodesmosomes need to be fully degraded.
KLK5
Kallikrein-5, formerly known as stratum corneum tryptic enzyme (SCTE), is a serine protease expressed in the epidermis. In humans it is encoded by the ''KLK5'' gene.
This gene is one of the fifteen kallikrein subfamily members located in a clust ...
and
KLK7
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the ''KLK7'' gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as t ...
are two serine proteases that degrade corneodesmosomes. LEKTI-2 regulates corneodesmosome degradation by inhibiting KLK5. In acral (palm and sole) skin, where desquamation needs to be delayed, ''SPINK9'' expression is strongly upregulated.
The resulting high level of LEKTI-2 delays corneodesmosome degradation, thereby allowing the epidermis to form a thick protective stratum corneum layer.
Clinical Significance
SPINK9 is overexpressed in
lichen simplex chronicus
Lichen simplex chronicus (LSC) is thick leathery skin with exaggerated skin markings caused by sudden itching and excessive rubbing and scratching. It generally results in small bumps, patches, scratch marks and scale. It typically affects the ...
,
actinic keratosis
Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . Actinic k ...
, and
squamous cell carcinoma.
See also
*
Kazal-type serine protease inhibitor domain
References
Proteins
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