Trichohyalin is a
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, respo ...
that in
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s is encoded by the ''TCHH''
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 ba ...
.
Discovery
In 1903 the name ''trichohyalin'' was assigned to the granules of the
inner root sheath The inner root sheath or internal root sheath of the hair follicle is located between the outer root sheath and the hair shaft.James, William; Berger, Timothy; Elston, Dirk (2005) ''Andrews' Diseases of the Skin: Clinical Dermatology'' (10th ed.). S ...
(IRS) of
hair follicle
The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between h ...
s discovered by Hans Vörner. In 1986 the name was reassigned to a protein isolated from sheep wool follicles.
Gene location
The human TCHH is located on the long (q) arm of
chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
1 at region 2 band 1 sub-band 3 (1q21.3), from base pair 152,105,403 to base pair 152,116,368
map. This region in chromosome 1q21 is known as the
epidermal differentiation complex
The epidermal differentiation complex (EDC) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the comple ...
, since it harbors over fifty other genes involved in keratinocyte differentiation.
Gene
coding sequence
The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to no ...
contains 5829 nucleotides. Gene
orthologs
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...
were identified in most mammals including mice, chickens, rats, pigs, sheep, horses and other species.
Protein localisation
Trichohyalin is highly expressed in the inner root sheath cells of the hair follicle and
medulla
Medulla or Medullary may refer to:
Science
* Medulla oblongata, a part of the brain stem
* Renal medulla, a part of the kidney
* Adrenal medulla, a part of the adrenal gland
* Medulla of ovary, a stroma in the center of the ovary
* Medulla of th ...
.
It was also detected in the
granular layer and
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 ...
of normal epidermis, newborn human foreskin
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 ...
, the
hard palate
The hard palate is a thin horizontal bony plate made up of two bones of the facial skeleton, located in the roof of the mouth. The bones are the palatine process of the maxilla and the horizontal plate of palatine bone. The hard palate spans ...
, in the
nail matrix
A nail is a claw-like plate found at the tip of the fingers and toes on most primates. Nails correspond to the claws found in other animals. Fingernails and toenails are made of a tough protective protein called alpha-keratin, which is a polymer ...
, the
filiform papillae
Lingual papillae (singular papilla) are small structures on the upper surface of the tongue that give it its characteristic rough texture. The four types of papillae on the human tongue have different structures and are accordingly classified as c ...
of dorsal tongue epithelium and in rodent
forestomach
The rumen, also known as a paunch, is the largest stomach compartment in ruminants and the larger part of the reticulorumen, which is the first chamber in the alimentary canal of ruminant animals. The rumen's microbial favoring environment allows ...
.
Function
The protein forms frequent links between the heads and tails 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, ho ...
chains and, thus, participates in keratin intermediate filaments (KIF) inter-filamentous cross-linking. It also carries a function of a major reinforcement cross-bridging protein for the
cell envelope
The cell envelope comprises the inner cell membrane and the cell wall of a bacterium. In gram-negative bacteria an outer membrane is also included. This envelope is not present in the Mollicutes where the cell wall is absent.
Bacterial cell env ...
(CE) barrier structure of the IRS and participates in coordination of CE structure.
Overall, trichohyalin confers mechanical strength to the hair follicle inner root sheath and to other toughened
epithelial tissue
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 intercellu ...
s.
Structure
Trichohyalin belongs to the
S100-fused protein family. It is a monomer, containing 1943
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s,
and has elongated (>200 nm) single-stranded
alpha-helical
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
conformation based on its unusually high content of charged residues.
Molecular mass of the human trichohyalin is 253925 Da.
The protein includes nine
domains. Domain 1 contains two
EF-hand
The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins.
The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...
calcium-binding domains. Domains 2-4, 6, and 8 are almost entirely alpha-helical, configured as a series of
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
repeats of varying regularity, and are thought to form a single-stranded alpha-helical rod stabilised by ionic interactions. Domain 6 is the most regular and may bind KIF directly by ionic interactions. Domains 5 and 7 are less well organised and may induce folds in the molecule. Domain 9 contains the C-terminus, conserved among different species.
Post-translational modifications
*
Peptidylarginine deiminases
In enzymology, a protein-arginine deiminase () is an enzyme that catalyzes a form of post translational modification called arginine de-imination or citrullination:
:protein L-arginine + H2O \rightleftharpoons protein L-citrulline + NH3
Thus, ...
(PAD) catalyse the
deimination
Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. Citrulline is not one of the 20 standard amino acids encoded by DNA in the genetic code. Instead, it is the result of a post-tr ...
of arginine residues to
citrulline
The organic compound citrulline is an α-amino acid. Its name is derived from ''citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in 1 ...
s.
* Cross-linking by
transglutaminase
Transglutaminases are enzymes that in nature primarily catalyze the formation of an isopeptide bond between γ-carboxamide groups ( -(C=O)NH2 ) of glutamine residue side chains and the ε-amino groups ( -NH2 ) of lysine residue side cha ...
(TGase) enzymes results in the formation of an
isopeptide bond between peptide-bound
glutamine
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, ...
and
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
residues and provide insolubility and the rigid structure to trichohyalin.
Interactions
TCHH protein is extensively cross-linked to itself in the IRS tissue as well as to keratin intermediate filaments (KIF). All TCHH-keratin links involved only domain 6 or 8 sequences.
The protein can also form cross-links to all other CE proteins including
involucrin
Involucrin is a protein component of human skin and in humans is encoded by the ''IVL'' gene. In binding the protein loricrin, involucrin contributes to the formation of a cell envelope that protects corneocytes in the skin.
Gene
This gene i ...
,
envoplakin
Envoplakin is a protein that in humans is encoded by the ''EVPL'' gene.
Interactions
Envoplakin has been shown to interact
Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c) ...
, keratin,
repetin
Repetin is an extracellular matrix protein expressed in the epidermis. In humans it is encoded by the ''RPTN'' gene. Repetin is part of the S100 fused-type protein family and contains an EF hand structural domain.
It functions in the cornified cel ...
,
desmoplakin
Desmoplakin is a protein in humans that is encoded by the ''DSP'' gene. Desmoplakin is a critical component of desmosome structures in cardiac muscle and epidermal cells, which function to maintain the structural integrity at adjacent cell contact ...
,
SPR1, SPR2, and
LEP.
TCHH-TCHH and TCHH-CE protein links are distributed among domains 2–5, but are uncommon in domains 6 and 8. Most intra-THH cross-links occurred in the least organised domain 5 region at a 3.5-fold higher frequency.
Clinical significance
Trichohyalin is associated with
uncombable hair syndrome
Uncombable hair syndrome (UHS) is a rare structural anomaly of the hair with a variable degree of effect. It is characterized by hair that is silvery, dry, frizzy, wiry, and impossible to comb. It was first reported in the early 20th century. It ...
,
human alopecia areata and also may be linked to
curly hair
Curly is a surname, given name, nickname or stage name. It may refer to:
First name, nickname or stage name
* Crazy Horse (1840–1877), Oglala Sioux war chief nicknamed "Curly"
* Curly (scout), nickname of Ashishishe (c. 1856–1923), Crow Ind ...
phenotype in Europeans.
A weak expression of the protein was discovered in the horny layer of
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
,
ichthyosis
Ichthyosis is a family of genetic skin disorders characterized by dry, thickened, scaly skin. The more than 20 types of ichthyosis range in severity of symptoms, outward appearance, underlying genetic cause and mode of inheritance (e.g., dominan ...
,
keratosis pilaris
Keratosis pilaris (KP; also follicular keratosis, lichen pilaris, or colloquially chicken skin) is a common, autosomal- dominant, genetic condition of the skin's hair follicles characterized by the appearance of possibly itchy, small, goosefle ...
,
porokeratosis,
chronic dermatitis and
callus
A callus is an area of thickened and sometimes hardened skin that forms as a response to repeated friction, pressure, or other irritation. Since repeated contact is required, calluses are most often found on the feet and hands, but they may o ...
.
The same level of trichohyalin expression was found in
epidermal tumours (
seborrheic keratosis
A seborrheic keratosis is a non-cancerous (benign) skin tumour that originates from cells, namely keratinocytes, in the outer layer of the skin called the epidermis. Like liver spots, seborrheic keratoses are seen more often as people age.
The tum ...
,
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 ...
,
Bowen's disease
Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. ...
, well-differentiated
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
) and follicular tumours (
trichoepithelioma
Trichoepithelioma is a neoplasm of the adnexa of the skin. Its appearance is similar to basal cell carcinoma.
One form has been mapped to chromosome 9p21.
Types
Trichoepitheliomas may be divided into the following types:
:* Multiple familial ...
, keratotic basal cell
epithelioma
Epithelioma is an abnormal growth of the epithelium, which is the layer of tissue that covers the surfaces of organs and other structures of the body.
Classification
Epitheliomas can be benign growths or malignant carcinomas. They are classifi ...
, proliferating
trichilemmal
The inner or epidermic coat of the hair follicle is closely adherent to the root of the hair, and consists of two strata named respectively the outer and inner root sheaths.
Outer root sheath
The outer root sheath corresponds with the stratum m ...
tumour,
trichilemmoma
Trichilemmoma (also known as "tricholemmoma"Busam Klaus J., ''Dermatopathology'' s.386; 2010 Saunders ) is a benign cutaneous neoplasm
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or pr ...
,
pilomatricoma
Pilomatricoma, is a benign skin tumor derived from the hair matrix. These neoplasms are relatively uncommon and typically occur on the scalp, face, and upper extremities. Clinically, pilomatricomas present as a subcutaneous nodule or cyst with un ...
and
keratoacanthoma
Keratoacanthoma (KA) is a common low-grade (unlikely to metastasize or invade) rapidly-growing skin tumour that is believed to originate from the hair follicle (pilosebaceous unit) and can resemble squamous cell carcinoma.
The defining characteris ...
).
References
Further reading
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{{refend
S100 fused-type proteins