Yousef G M, Ordon M H, Foussias G, Diamandis E P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Biochem Biophys Res Commun. 2001 Jun 22;284(4):900-10. doi: 10.1006/bbrc.2001.5053.
The sialic acid binding immunglobulin-like lectin (Siglec) family is a recently described member of the immunoglobulin superfamily. Within the Siglec family, there exists a subgroup, which bears a high degree of homology with the molecule CD33 (Siglec-3), and has thus been designated the CD33-like subgroup of Siglecs. Members of this subgroup have been localized to chromosome 19q13.4. Through the positional candidate approach, we identified a novel potential member of this subgroup of Siglecs. We have characterized the complete genomic structure of this gene, determined its chromosomal localization, its homology to other members of the Siglec family, and its tissue expression profile. This new Siglec-like gene is comprised of 11 exons, with 10 intervening introns, and is localized 278 kb telomeric to Siglec-9 and 35 kb centromeric to Siglec-8 and on chromosome 19q13.4. The coding region consists of 2094 base pairs, and encodes for a putative 76.6 kDa protein. All Siglec-conserved structural features, including V-set domain, three C-set domains, transmembrane domain, ITIM and SLAM motifs, were found in this Siglec-like gene. Also, it has the conserved amino acids essential for sialic acid binding. The Siglec-like gene has 40-66% homology with members of the CD33-like subgroup, including Siglecs 5-9. Through RT-PCR we have examined the expression profile of this new gene in a panel of human tissues and found it to be primarily expressed in the bone marrow, spleen, brain, small intestine, colon, and spinal cord. We were also able to identify three different splice variants of the new gene. This gene may represent the latest novel member of the CD33-like subgroup of Siglecs, and, given its high degree of homology, it may also serve a regulatory role in the proliferation and survival of a particular hematopoietic stem cell lineage, as has been found for CD33 and Siglec-7.
唾液酸结合免疫球蛋白样凝集素(Siglec)家族是免疫球蛋白超家族中最近被描述的成员。在Siglec家族中,存在一个亚组,它与分子CD33(Siglec-3)具有高度同源性,因此被指定为Siglec的CD33样亚组。该亚组的成员已被定位到染色体19q13.4。通过定位候选方法,我们鉴定出了这个Siglec亚组的一个新的潜在成员。我们已经对该基因的完整基因组结构进行了表征,确定了其染色体定位、与Siglec家族其他成员的同源性以及其组织表达谱。这个新的类Siglec基因由11个外显子组成,有10个间隔内含子,位于Siglec-9的端粒278 kb处、Siglec-8的着丝粒35 kb处,位于染色体19q13.4上。编码区由2094个碱基对组成,编码一种推定的76.6 kDa蛋白质。在这个类Siglec基因中发现了所有Siglec保守的结构特征,包括V-set结构域、三个C-set结构域、跨膜结构域、免疫受体酪氨酸抑制基序(ITIM)和信号淋巴细胞激活分子(SLAM)基序。此外,它具有唾液酸结合所必需的保守氨基酸。该类Siglec基因与CD33样亚组的成员,包括Siglec 5 - 9,具有40 - 66%的同源性。通过逆转录聚合酶链反应(RT-PCR),我们检测了这个新基因在一组人类组织中的表达谱,发现它主要在骨髓、脾脏、大脑、小肠、结肠和脊髓中表达。我们还能够鉴定出该新基因的三种不同剪接变体。这个基因可能代表了Siglec的CD33样亚组的最新成员,并且鉴于其高度同源性,它也可能在特定造血干细胞谱系的增殖和存活中发挥调节作用,正如在CD33和Siglec-7中所发现的那样。