Identification and characterization of K12 (SECTM1), a novel human gene that encodes a Golgi-associated protein with transmembrane and secreted isoforms

Identification and characterization of K12 (SECTM1), a novel human gene that encodes a Golgi-associated protein with transmembrane and secreted isoforms
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DOI:
10.1006/geno.1997.5151
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发表时间:
1998-02-01
期刊:
影响因子:
4.4
通讯作者:
Kaufman, RE
Kaufman, RE
中科院分区:
生物学3区
文献类型:
--
作者:
Slentz-Kesler, KA;Hale, LP;Kaufman, RE

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对染色体17 q25上CD 7基因上游的DNA酶超敏位点的研究导致发现了一种新的人类基因,命名为K12(SECTM 1,HGMW分配)。该基因跨度类似于14 kb,编码1.8 kb mRNA,在外周血白细胞和乳腺癌细胞系中检测到最高水平。开放阅读框预测了一种具有la型膜蛋白亲水特征的248个氨基酸的蛋白质。Western印迹显示K12蛋白作为27 kDa左右的条带簇存在,并且使用非离子去污剂或高pH条件的提取证明其表现为完整的膜蛋白。免疫荧光定位研究表明,K12在细胞表面上是不可检测的,而是在核周高尔基体样模式中被发现,并与一个众所周知的高尔基体标记共定位。此外,类似于20-kDa的可溶形式的K12蛋白衍生自N-末端结构域是由细胞特异性分泌到培养基中。外周血细胞的免疫组织化学分析显示,K12存在于骨髓系的白细胞中,在粒细胞中观察到最强的染色,在淋巴细胞中未检测到表达。基于其表达范围,其类似细胞因子和生长因子的广泛结构特征,以及该基因在已经与髓性白血病和其他恶性肿瘤相关的区域中的染色体位置,本研究得出结论,K12是一种在造血和/或免疫系统过程中具有潜在重要性的新型分子。(C)北京:科学出版社.
The investigation of a DNase-hypersensitive site upstream of the CD7 gene on chromosome 17q25 has led to the discovery of a novel human gene designated K12 (SECTM1, the HGMW assignment). This gene spans similar to 14 kb and encodes a 1.8-kb mRNA detected at the highest levels in peripheral blood leukocytes and breast cancer cell lines. The open reading frame predicts a 248-amino-acid protein with the hydropathic characteristics of a type la membrane protein. Western blots show that the K12 protein exists as a cluster of bands around 27 kDa, and extractions using nonionic detergents or high pH conditions demonstrate that it behaves as an integral membrane protein. Immunofluorescence localization studies reveal that K12 is not detectable on the cell surface, but instead is found in a perinuclear Golgi-like pattern and colocalizes with a well-known Golgi marker. In addition, an similar to 20-kDa soluble form of the K12 protein derived from the N-terminal domain is specifically secreted by cells into the culture medium. Immunohistochemical analysis of peripheral blood cells shows that K12 is found in leukocytes of the myeloid lineage, with the strongest staining observed in granulocytes and no detectable expression in lymphocytes. Based on its range of expression, its broad structural characteristics that resemble cytokines and growth factors, and the chromosomal location of the gene in an area already associated with myelogenous leukemias and other malignant neoplasms, this study concludes that K12 is a novel molecule with potential importance in hematopoietic and/or immune system processes. (C) 1998 Academic Press.