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Keratins are a diverse group of structural proteins
that form the intermediate filament network
responsible for maintaining the structural integrity
There are around 30 families of keratin proteins
divided into two groups namely acidic and basic
which are arranged in pairs.
A total of 54 functional genes exist which codes
for these keratin families.
The expression of specific keratin genes is
regulated by the differentiation of epithelial cells
within the stratifying squamous epithelium.
Keratins and certain keratin associated proteins are
useful as markers of differentiation because their
expression is both region and differentiation
Most of the eukaryotic cells are composed of
cytoskeleton which is made of three components
microfilaments, intermediate filaments, and
Among the various families and sub-families of
intermediate filament proteins, keratin is an
important type due to its high molecular diversity.
Each keratin is characterized by a chain of amino
acids as the primary structure, which varies in the
number and sequence of amino acid as well as in
polarity, charge and size.
The amino acid sequence of a keratin influences
the properties and function of the keratin
Post translational modifications such as the
formation of disulphide bonds, phosphorylation
and glycosylation can influence the conformation
of the molecule and formation of keratin
Keratin filaments have a tripartite secondary
structure consisting of an N-terminal head
domain, a central α-helical rod domain and C-
terminal tail domain.
The keratins are broadly divided into:
Primary keratins are those keratins which are
always synthesized by the epithelial cells on a
regular basis, e.g., K8/18 in simple epithelia, K5/14
in stratified epithelia.
Secondary keratins are those types of keratins
which are produced by the epithelial cells in
addition to or instead of primary keratins, e.g.,
K7/19 in simple epithelia, K15, and K6/16 in
Based on distribution:
Soft keratin: Found in the epidermis of skin in
the form of flattened non-nucleated scales that
slough continually. The disulfide links are fewer in
number which allows some stretching but returns
to normal upon relaxation of tension.
Hard keratin: These are mainly found in nail, hair
cortex, hair cuticle; the keratin type seen at these
sites have very little flexibility owing to the
presence of many cysteine disulfide crosslinks.
Based on X-ray diffraction pattern:
Alpha : The X-ray diffraction pattern of this type
resembles that of α-helix . The α-helix is right
handed and has 3.6 residues per turn. The
hydrogen bonding occurs within one polypeptide
Beta : The helix is right-handed with an average
of 6 residues. The hydrogen bonding occurs
between neighbouring polypeptide chains.
Based on amino acid sequence
Type I family includes keratins numbered 9-20
which are composed of acidic proteins.
Type II family includes keratins numbered 1-8
which are composed of basic proteins.
Based on molecular weight:
Low molecular weight keratins: Include keratins
with a molecular weight of 40kDa. These keratins
are mainly distributed in glandular and simple
Intermediate molecular weight keratins: Include
keratins with a molecular weight intermediate
between 40kDa and 57kDa and are found in
High molecular weight keratins: Include keratins
with a molecular weight of 57kDa and are seen in
keratinized stratified epithelia.
Keratins fundamentally influence the architecture
and mitotic activity of the epithelial cells.
Keratins and associated filaments provide a
scaffold for epithelial cells and tissues to sustain
mechanical stress, maintain their structural
integrity, ensure mechanical resilience, to protect
against variations in hydrostatic pressure and
establish cell polarity.
Keratins and its filaments are involved in cell
signalling, cell transport, cell compartmentalization
and cell differentiation.
Keratin filaments also influence cell metabolic
processes by regulating protein synthesis and cell
Keratins may also be involved in the transport of
membrane bound vesicles in the cytoplasm of the
Factors regulating Differentiaition
Growth factors like epidermal growth factor,
transforming growth factor alpha and beta
Role of adjacent mesenchymal tissue
Components of extracellular matrix
Effect of Retinoids on various keratins
K1/10 Reduced expression
K13/19 Increased expression
K5, K16, K17 Slightly downregulated
K4,K5, K14 Not affected
Filaggrin Reduced expression
Cornified cell envelope Suppressed
Desmosomes Reduced in number
K8 & K18
Keratins K8 & K18 are co-expressed and constitute
the primary keratin of simple epithelial cells.
They are also the sole keratins of hepatocytes,
acinar cells of pancreas and proximal tubular cells
They are the first keratins to appear in
K7 & K19
They are the secondary or additional keratins of
simple epithelial cells.
They are expressed notably in ductal epithelia of
small and large intestines, gastric foveolar
epithelium, mesothelium, urothelium, as well as
basal cells of non keratinizing stratified squamous
They are frequently co-expressed.
Type I keratin K19 is the smallest keratin.
They are used as tumour markers.
K20 is the simple epithelial keratin with most
restricted expression pattern.
They are expressed in the gastric foveolar
epithelium, small and large intestinal epithelium,
urothelium and merkel cells.
K20 positivity is predictive of a primary tumour in
the gastrointestinal or pancreatobiliary tract.
K5 & K14
K5 & K14 form the primary keratin pair of
keratinocytes of stratified squamous epithelia,
including the epidermis and mucosal non
keratinizing stratified squamous epithelia.
In the follicular outer root sheath they are
uniformly expressed throughout all layers.
Ultrastructurally, K5/K14 keratin filaments are
bundled as tonofilaments and attached to
desmosomes and hemidesmosomes.
Mutations of the K5 / K14 gene is responsible for
the blistering disease – Epidermolysis bullosa
K15 keratin is a basal keratinocyte keratin and hair
follicle stem cell marker.
In comparison to K5 and K14, K15 is completely
restricted to the basal cell layer of stratified
It is also expressed in the basal keratinocytes of
the hair follicle bulge region.
K6 & K16
These keratins are expressed in epidermis of
plantar glabrous skin, hair follicle outer root
sheath and companion layer.
They are the constitutive components of nail
Mutations in K6/K16 give rise to pachyonychia
congenita type I.
These keratins are inducible upon stress, injury or
K17 is a basal/myoepithelial cell keratin.
It is expressed in myoepithelial cells of complex
tissues, including various glands (sweat glands),
respiratory epithelium and urothelium.
It is a prominent component of the suprabasal cell
layers of outer follicular root sheath.
After skin injury, K17 is switched on in
regenerating and migrating epidermal keratinocytes
upon wound healing.
K17 mutations have been identified in
pachyonychia congenita type II and steatocystoma
Like K6/K16, these keratins are also inducible
upon stress, injury or inflammation.
K1 & K10
In the epidermis, the transition of keratinocytes
from basal cell layer to suprabasal spinous cell
layer is characterised by a profound change in
This involves a switch from expression of basal
cell keratins ( K5, K14, K15 ) to suprabasal epidermal
keratins, k1 and subsequently K10.
Keratin filaments composed of K1/K10 pair form
particularly dense bundles which are so
characteristic of suprabasal epidermal
This imparts mechanical integrity to the cells and
the whole epidermis.
K10 specifically inhibits proliferation and cell cycle
progression of keratinocytes.
Loss of K10 leads to increased keratinocyte
Mutations in K1 and K10 are associated with
blistering disorder – bullous congenital icthyosiform
Therefore, K1 and K10 are regarded as
keratinization markers of keratinocytes.
K9 is a highly specific keratin of terminally
differentiating keratinocytes of palmoplantar
Mutations in K9 gene are associated with skin
disorder – epidermolytic palmoplantar keratoderma.
Keratin specific for advanced terminal
differentiation process of epidermal keratinocytes.
It is expressed in the uppermost epidermal layers -
upper stratum spinosum, stratum granulosum.
Mutations in K2 are associated with icthyosis
bullosa of Siemens.
K3 & K12
K3/ K12 are the keratin pair of the corneal
They are expressed in all corneal epithelial cell
Mutations in these keratins give rise to
Meesmann’s corneal dystrophy.
K4 & K13
They are a highly characteristic keratin pair
indicating mucosal path of keratin differentiation.
They are expressed in the entire suprabasal
compartment of mucosal stratified squamous
They are absent in the epidermis and adnexa.
Mutations in these keratins cause the disorder
white sponge nevus of Cannon.
K76 is a highly specific keratin expressed in
suprabasal cell layers of oral masticatory
They are found in the slightly orthokeratinized
stratified squamous epithelium lining the gingiva
and hard palate.
Highly specific keratin restricted to the luminal
cells of eccrine sweat glands.
Used as an eccrine duct marker.
Hair follicle specific keratins
K25 - 28, K71 - 75
These keratins are specifically expressed in the
companion layer, Henle’s layer, Huxley’s layer and
inner root sheath of the hair follicle.
Mutations in K75 predispose to the hair disorder
Keratins of Hair Fiber
K31 - 40, K81 - 86.
These keartins are expressed within the cuticle
and the cortex of the hair follicle.
Mutations in some of these keratins leads to
disorders like monilethrix and ectodermal dysplasia
of hair and nail type.
Keratins with unknown expression
K23, K24, K78, K79, K80
These five, very different keratins complete the
family of human keratin proteins.
But their expression patterns and functions are