Anosmin-1 is a secreted, EM associated

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

found in

humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

and other

organisms In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fungi; ...

responsible for normal

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped *Photographi ...

, which is expressed in the brain, spinal cord and kidney. Absence or damage to the protein results in

Kallmann syndrome Kallmann syndrome (KS) is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypog ...

in humans, which is characterized by loss of

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a grey matter, neural structure of the vertebrate forebrain involved in olfaction, the sense of odor, smell. It sends olfactory information to be further processed in the amygdala, the orbitof ...

s and

GnRH Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released f ...

secretion leading to

anosmia Anosmia, also known as smell blindness, is the loss of the ability to detect one or more smells. Anosmia may be temporary or permanent. It differs from hyposmia, which is a decreased sensitivity to some or all smells. Anosmia can be due to a num ...

and

hypothalamic The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...

hypogonadotropic hypogonadism Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis). Hypothalamic disorders result from a deficiency in the release of gonadotropic r ...

. Anosmin-1 is coded by the

KAL-1 gene Anosmin-1 is a secreted, EM associated glycoprotein found in humans and other organisms responsible for normal development, which is expressed in the brain, spinal cord and kidney. Absence or damage to the protein results in Kallmann syndrome in ...

, which is found on the

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...

. Anosmin-1 is 100

kilodalton The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...

s and is expressed on the outside of cells. Because of this and because of its contribution to normal migration of

nerve cell A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. No ...

s, a role in the

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

has been postulated. During

neural crest cell Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

development, anosmin-1 plays a role in cranial neural cell formation by spatiotemporal regulation. Secreated anosmin-1 enhances FGF activity by promoting FGF8-FGFR1 complex formation, whereas inhibits both

BMP5 Bone morphogenetic protein 5 is a protein that in humans is encoded by the ''BMP5'' gene. The protein encoded by this gene is member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce bone and cartilage d ...

and

WNT3A Protein Wnt-3a is a protein that in humans is encoded by the ''WNT3A'' gene. The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have are critical in tissue homeostasis, embryonic de ...

activities. As a results, orchestrated regulation of FGF, BMP, and WNT by anosmin-1 control EMT and MET during neural crest cell development. In human retinal pigment epithelial cell (RPE), the expression of anosmin-1 is regulated by

TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...

which remain to be investigated. Anosmin-1 is encoded by a gene ''ANOS1'' (earlier called ''ADMLX, KAL, KAL1, KALIG1''). In human it is located on the

at Xp22.3 and is affected in some male individuals with

. This gene codes for 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 ...

of the

named anosmin-1, which is involved in the migration of certain

precursors (neuroendocrine GnRH cells) during

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

. Deletion or

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

of this gene results in loss of the functional protein and affects the proper development of the

olfactory nerves The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell. The afferent nerve fibers of the olfactory receptor neurons tr ...

and

olfactory bulbs The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OFC ...

. In addition, neural cells that produce

fail to migrate to the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

. Clinically, mutation results in the

X-linked Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...

form of Kallmann syndrome. Individuals with Kallmann syndrome experience

(lack of smell) and do not go through

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...

(hypothalamic

). ANOS1 is made of 14

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s and spans 120-200

kilobase A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s. Mutations of ANOS1 may account for 14% of the cases of familial Kallmann syndrome and 11% of male sporadic cases.

References

{{reflist

External links

GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome

NextBio.com

GenAtlas
Proteins