This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants.
Noggin is a secreted homodimeric glycoprotein that is an antagonist of bone morphogenetic proteins (BMPs). Mature Human Noggin contains an N-terminal acidic region; a central basic heparin-binding segment and a C-terminal cysteine-knot structure. Noggin is very highly conserved among vertebrates; such that mature human Noggin shares 99%; 99%; 98%; 97% and 89% aa sequence identity with mouse; rat bovine; equine and chicken Noggin; respectively. Secreted Noggin probably remains close to the cell surface due to its binding of heparin-containing proteoglycans. Noggin binds some BMPs such as BMP4 with high affinity and others such as BMP7 with lower affinity. It antagonizes BMP bioactivities by blocking epitopes on BMPs that are needed for binding to both type I and type II receptors. Noggin is expressed in defined areas of the adult central nervous system and peripheral tissues such as lung; skeletal muscle and skin. During culture of human embryonic stem cells (hESC) or neural stem cells under certain conditions; addition of Noggin to antagonize BMP activity may allow stem cells to proliferate while maintaining their undifferentiated state; or alternatively; to differentiate into dopaminergic neurons.
Noggin is a secreted protein involved at multiple stages of vertebrate embryonic development including neural induction and is known to exert its effects by inhibiting the bone morphogenetic protein (BMP)-signaling pathway. It binds several BMPs with very high (picomolar) affinities; with a marked preference for BMP2 and BMP4 over BMP7. By binding tightly to BMPs; Noggin prevents BMPs from binding their receptors. Noggin binds the bone morphogenetic proteins (BMP) such as BMP-4 and BMP-7; and inhibits BMP signaling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. Interaction of BMP and its antagonist Noggin governs various developmental and cellular processes; including embryonic dorsal-ventral axis; induction of neural tissue; formation of joints in the skeletal system and neurogenesis in the adult brain. Noggin plays a key role in neural induction by inhibiting BMP4; along with other TGF-β signaling inhibitors such as chordin and follistatin. Mouse knockout experiments have demonstrated that noggin also plays a crucial role in bone development; joint formation; and neural tube fusion.
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