Exostosin-like 3 (EXTL3) encodes the glycosyltransferases responsible for the biosynthesis of the backbone structure of heparan sulfate (HS), a sulfated polysaccharide that is ubiquitously distributed on the animal cell surface and in the extracellular matrix. A lack of EXTL3 reduces HS levels and causes embryonic lethality, indicating its indispensable role in the biosynthesis of HS. EXTL3 has also been identified as a receptor molecule for regenerating islet-derived (REG) protein ligands, which have been shown to stimulate islet β-cell growth. REG proteins also play roles in keratinocyte proliferation and/or differentiation, tissue regeneration and immune defenses in the gut as well as neurite outgrowth in the central nervous system. Compared with the established function of EXTL3 as a glycosyltransferase in HS biosynthesis, the REG-receptor function of EXTL3 is not conclusive. Genetic diseases caused by biallelic mutations in the EXTL3 gene were recently reported to result in a neuro-immuno-skeletal dysplasia syndrome. EXTL3 is a key molecule for the biosynthesis of HS and may be involved in the signal transduction of REG proteins.

中文翻译：

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Exostosin-like 3（EXTL3）基因产物的特定功能。

像Exostosin-like 3（EXTL3）编码的糖基转移酶负责硫酸乙酰肝素（HS）骨架结构的生物合成，硫酸乙酰肝素是一种普遍存在于动物细胞表面和细胞外基质中的硫酸化多糖。缺少EXTL3会降低HS水平并引起胚胎致死性，表明其在HS生物合成中不可或缺的作用。EXTL3还被鉴定为用于再生胰岛衍生（REG）蛋白配体的受体分子，已显示出该蛋白配体可刺激胰岛β细胞的生长。REG蛋白还在肠道角质形成细胞增殖和/或分化，组织再生和免疫防御以及中枢神经系统中的神经突增生中起作用。与已确定的EXTL3作为HS生物合成中的糖基转移酶的功能相比，EXTL3的REG受体功能不是决定性的。最近有报道说，由EXTL3基因的双等位基因突变引起的遗传性疾病会导致神经免疫骨骼发育异常综合征。EXTL3是HS生物合成的关键分子，可能参与REG蛋白的信号转导。