Amelogenins are a group of

protein isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

produced by

alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...

from the '' AMELX'' gene, on the

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

, and also the '' AMELY'' gene in males, on the

Y chromosome The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...

. They are involved in amelogenesis, the development of enamel. Amelogenins are type of

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

protein, which, together with ameloblastins,

enamelin Enamelin is an enamel matrix protein (EMPs), that in humans is encoded by the ''ENAM'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA ...

s and tuftelins, direct the mineralization of enamel to form a highly organized matrix of rods, interrod crystal and proteins. Although the precise role of amelogenin(s) in regulating the mineralization process is unknown, it is known that amelogenins are abundant during amelogenesis. Developing human enamel contains about 70% protein, 90% of which are amelogenins.

Function

Amelogenins are believed to be involved in the organizing of

enamel rod An enamel prism, or enamel rod, is the basic unit of tooth enamel. Measuring 3-6 μm in diameter in primates, enamel prism are tightly packed hydroxyapatite crystals structures. The hydroxyapatite crystals are hexagonal in shape, providing rigidi ...

s during tooth development. The latest research indicates that these proteins regulate the initiation and growth of

hydroxyapatite Hydroxyapatite (International Mineralogical Association, IMA name: hydroxylapatite) (Hap, HAp, or HA) is a naturally occurring mineral form of calcium apatite with the Chemical formula, formula , often written to denote that the Crystal struc ...

crystals during the mineralization of enamel. In addition, amelogenins appear to aid in the development of

cementum Cementum is a specialized calcified substance covering the root of a tooth. The cementum is the part of the periodontium that attaches the teeth to the alveolar bone by anchoring the periodontal ligament. Structure The cells of cementum are ...

by directing cementoblasts to the tooth's root surface.

Variants

The amelogenin

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

has been most widely studied in humans, where it is a single copy gene, located on the X and

s at Xp22.1–Xp22.3 and Yp 11.2 The amelogenin gene's location on sex chromosomes has implications for variability both between the X chromosome form ( AMELX) and the Y chromosome form ( AMELY), and between alleles of AMELY among different populations. This is because AMELY exists in the non-recombining region of chromosome Y, effectively isolating it from normal selection pressures. Other sources of amelogenin variation arise from the various

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

of AMELX obtained from alternative splicing of mRNA transcripts. Specific roles for isoforms have yet to be established. Among other organisms, amelogenin is well conserved among

eutheria Eutheria (from Greek , 'good, right' and , 'beast'; ), also called Pan-Placentalia, is the clade consisting of Placentalia, placental mammals and all therian mammals that are more closely related to placentals than to marsupials. Eutherians ...

ns, and has homologs in

monotreme Monotremes () are mammals of the order Monotremata. They are the only group of living mammals that lay eggs, rather than bearing live young. The extant monotreme species are the platypus and the four species of echidnas. Monotremes are typified ...

s, reptiles and amphibians.

Application in sex determination

Differences between the

and

versions of the amelogenin gene (AMELX and AMELY respectively) enable it to be used in sex determination of unknown human samples. AMELX’s intron 1 contains a 6-base-pair deletion relative to

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

1 of AMELY. This can be detected at low cost using

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...

(PCR) of intron 1, followed by

gel electrophoresis Gel electrophoresis is an electrophoresis method for separation and analysis of biomacromolecules (DNA, RNA, proteins, etc.) and their fragments, based on their size and charge through a gel. It is used in clinical chemistry to separate ...

. Two bands of DNA, at 555 bps and 371 bps, are resolved if both the AMELX and AMELY versions of the gene are present (i.e. the sample is from a male) or one band of DNA, at 555 bps, if the AMELX version only is present (i.e. the sample is from a female). However, because of AMELY variation among individuals and populations, this method of sex determination is not 100% accurate. Mutation in regions of AMELY intron 1 commonly used as primer annealing sites may disable PCR amplification. A 6bp insertion to AMELY intron 1 results in an amplicon identical in length to that of AMELX. In some males AMELY may be deleted entirely. In any of these cases only one band is visualized during gel electrophoresis of PCR products, causing misidentification of the sample as female. The misidentification rate may vary among populations, but in general appears to be low. In one study in Spain, the amelogenin sex determination test using AMELX (977bps) and AMELY (790bps) bands was performed for 1224 individuals of known gender with a 99.84% (1222/1224) accuracy rate. Another study in India, however, found 5 of its 270 men studied (1.85%) possessed an AMELY deletion, terming them "deleted-amelogenin males" (DAMs). In response the authors suggested that while the amelogenin sex test may be accurate in general, other Y chromosome markers such as SRY, STR, or 50f2 can be used for less ambiguous gender identification. In archaeology where DNA is too broken down to be analyzed by PCR, Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is used to directly detect the presence of the peptides corresponding to either version from tooth enamel samples. This method has been used on samples as old as the

Gravettian The Gravettian is an archaeological industry of the European Upper Paleolithic that succeeded the Aurignacian circa 33,000 years BP. It is archaeologically the last European culture many consider unified, and had mostly disappeared by ...

Clinical significance

Mutations in AMELX can cause amelogenesis imperfecta, a disorder of tooth enamel development.

References

{{reflist Human proteins Teeth Genetics