PDB rendering based on 1m4u.
|Symbols||; SYM1; SYNS1|
Noggin, also known as NOG, is a protein that is involved in the development of many body tissues, including nerve tissue, muscles, and bones. In humans is encoded by the NOG gene. The amino acid sequence of human noggin is highly homologous to that of rat, mouse, and Xenopus (an aquatic-frog genus).
The protein's name, which is a slang English-language word for "head," was coined in reference to its ability to produce embryos with large heads when exposed at high concentrations.
Noggin is a signaling molecule that plays an important role in promoting somite patterning in the developing embryo. It is released from the notochord and regulates bone morphogenic protein during development. The absence of BMP4 will cause the patterning of the neural tube and somites from the neural plate in the developing embryo. It also causes formation of the head and other dorsal structures.
Noggin function is required for correct nervous system, somite, and skeletal development. Experiments in mice have shown that noggin also plays a role in learning, cognition, bone development, and neural tube fusion. Heterozygous missense mutations in the noggin gene can cause deformities such as joint fusions and syndromes such as multiple synostosis syndrome (SYNS1) and proximal symphalangism (SIM1). SYNS1 is different from SYM1 by causing hip and vertebral fusions. The embryo may also develop shorter bones, miss any skeletal elements, or lack multiple articulating joints.
Noggin is essential for proper bone and limb development, and it carries out many processes that are essential for proper neural development in the embryo.
Mechanism of action
The secreted polypeptide noggin, encoded by the NOG gene, binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signaling proteins, such as bone morphogenetic protein-4 (BMP4).
By diffusing through extracellular matrices more efficiently than members of the TGF-beta superfamily, noggin may have a principal role in creating morphogenic gradients. Noggin appears to have pleiotropic effects, both early in development as well as in later stages. The results of the mouse knockout of noggin suggest that it is involved in numerous developmental processes, such as neural tube fusion and joint formation.
Recently, several heterozygous missense human NOG mutations in unrelated families with proximal symphalangism (SYM1) and multiple synostoses syndrome (SYNS1) have been identified; both SYM1 and SYNS1 have multiple joint fusion as their principal feature, and map to the same region on chromosome 17 (17q22) as NOG. These mutations indicate functional haploinsufficiency where the homozygous forms are embryonically lethal.
Noggin was originally isolated from the aquatic-frog genus Xenopus. The discovery was based on the organism's ability to restore normal dorsal-ventral body axis in embryos that had been artificially ventralized by UV treatment. Noggin was discovered in the laboratory of Richard M. Harland and William C. Smith at the University of California, Berkeley because of this ability to induce secondary axis formation in frog embryos.
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- BMPedia - the Bone Morphogenetic Protein Wiki
- Noggin publications, gene expression data, sequences and interactants from Xenbase
- NOG human gene location in the UCSC Genome Browser.
- NOG human gene details in the UCSC Genome Browser.