生长抑素Ⅱ型受体SSTR2蛋白的理化性质及生物信息学分析

doi:10.16088/j.issn.1001-6600.2021121402

广西师范大学学报（自然科学版） ›› 2023, Vol. 41 ›› Issue (1): 164-173.doi: 10.16088/j.issn.1001-6600.2021121402

生长抑素Ⅱ型受体SSTR2蛋白的理化性质及生物信息学分析

张丽萌^1,2, 李闰婷¹, 聂晓宁¹, 李玉华², 李林², 李亚蒙², 陈龙欣^1,2*, 王林青^1*

1.郑州师范学院分子生物学实验室, 河南郑州 450044;
2.郑州师范学院生命科学学院, 河南郑州 450044

收稿日期:2021-12-14 修回日期:2022-03-22 出版日期:2023-01-25 发布日期:2023-03-07
通讯作者: 陈龙欣(1984—),男,河南郑州人,郑州师范学院副教授,博士。E-mail:chen_longxin@163.com; 王林青(1978—),男,河南郑州人,郑州师范学院副教授,博士。E-mail:wanglintsing@163.com
基金资助:
国家自然科学基金(32071447); 河南省高等学校重点科研项目资助计划(22A180031); 河南省高校科技创新人才支持计划(22HASTIT041); 河南省科技厅科技发展计划(科技攻关)项目(212102310901); 郑州师范学院大学生科研创新基金(2021013); 德阳市科技局社会领域重点研发项目(2021SZ018)

Physicochemical Properties and Bioinformatics Analysis of Somatostatin Receptor 2 (SSTR2)

ZHANG Limeng^1,2, LI Runting¹, NIE Xiaoning¹, LI Yuhua², LI Lin², LI Yameng², CHEN Longxin^1,2*, WANG Linqing^1*

1. Laboratory of Molecular Biology, Zhengzhou Normal University, Zhengzhou Henan 450044, China;
2. School of Life Science, Zhengzhou Normal University, Zhengzhou Henan 450044, China

Received:2021-12-14 Revised:2022-03-22 Online:2023-01-25 Published:2023-03-07

摘要/Abstract

摘要： 利用生物信息学方法在线分析生长抑素Ⅱ型受体SSTR2的理化性质、信号肽、跨膜结构、分泌蛋白类型、亚细胞定位、磷酸化位点修饰、空间结构及蛋白互作网络等,并通过MEGA5.0软件建立SSTR2蛋白的系统进化树。结果显示,该基因编码369个氨基酸,分子式为C₁₈₉₈H₂₉₈₄N₄₇₀O₅₁₃S₂₃,相对分子质量为41 332.79,等电点理论值为9.15,不稳定系数为37.16。SSTR2是一种碱性稳定亲水蛋白,无信号肽,存在7个跨膜区,作用于质膜结构;二级结构主要为α-螺旋,属7tmGPCRs超家族,且含有1个7tmA_SSTR2结构域;与SSTR2相互作用的蛋白质包括CORT、SST、NPY、GHRL、GNAI1、GNAI2、GNAI3、SHANK1、HIVEP2。SSTR2基因及其编码蛋白在进化上高度保守,可能参与G蛋白偶联受体信号通路,进而发挥其作用。本研究通过对SSTR2蛋白的理化性质及生物学功能进行分析,为深入研究该蛋白在疾病发生中的机制以及为靶向治疗神经内分泌肿瘤等肿瘤药物研发提供理论依据。

关键词: 生长抑素Ⅱ型受体, SSTR2蛋白, 神经内分泌肿瘤, 生物信息学, 生物学功能

Abstract: The physical and chemical properties, signal peptides, transmembrane structure, secretory protein types, subcellular localization, phosphorylation site modification, secondary structure and protein interaction of the human somatostatin type Ⅱ receptor (SSTR2) were analyzed by online bioinformatics software such as NCBI, ExPASy, SignalP, PSORTII, SOPMA, STRING, SWISS-MODEL, and the phylogenetic tree of SSTR2 protein was established by MegAlign software. The results showed that, the protein encoded by the gene contains 369 amino acids, the molecular formula was C₁₈₉₈H₂₉₈₄N₄₇₀O₅₁₃S₂₃, the relative molecular weight was 41 332.79, the theoretical value of isoelectric point was 9.15 and the instability coefficient was 37.16. SSTR2 was a stable alkaline hydrophilic protein with no signal peptide and 7 transmembrane regions, which acts on the plasma membrane structure. The secondary structure was mainly α-Helix belonging to 7tmGPCRs superfamily and containing one 7tmA_SSTR2 domain; proteins interacting with SSTR2 include CORT, SST, NPY, GHRL, GNAI1, GNAI2, GNAI3, SHANK1, HIVEP2. SSTR2 gene and its encoding protein were highly conserved in evolution, and may be involved in the G protein coupled receptor signal pathway and play its role. In this study, the physical and chemical properties and biological functions of SSTR2 gene were analyzed to provide theoretical basis for the in-depth study of the mechanism of SSTR2 protein in the occurrence of diseases and the research and development of targets therapies for neuroendocrine tumors and other cancer drugs.

Key words: somatostatin receptor, SSTR2 protein, NETs, bioinformatics, biological function

中图分类号:

Q811.4

张丽萌, 李闰婷, 聂晓宁, 李玉华, 李林, 李亚蒙, 陈龙欣, 王林青. 生长抑素Ⅱ型受体SSTR2蛋白的理化性质及生物信息学分析[J]. 广西师范大学学报（自然科学版）, 2023, 41(1): 164-173.

ZHANG Limeng, LI Runting, NIE Xiaoning, LI Yuhua, LI Lin, LI Yameng, CHEN Longxin, WANG Linqing. Physicochemical Properties and Bioinformatics Analysis of Somatostatin Receptor 2 (SSTR2)[J]. Journal of Guangxi Normal University(Natural Science Edition), 2023, 41(1): 164-173.

参考文献

[1] CRACOLICI V,WANG E W,GARDNER P A,et al. SSTR2 expression in olfactory neuroblastoma:clinical and therapeutic implications[J]. Head and Neck Pathology,2021,15(4):1185-1191.
[2]STUEVEN A K,KAYSER A,WETZ C,et al. Somatostatin analogues in the treatment of neuroendocrine tumors:past,present and future[J]. International Journal of Molecular Sciences,2019,20(12):3049.
[3]SHIBA S,MORIZANE C,HIRAOKA N,et al. Pancreatic neuroendocrine tumors:a single-center 20-year experience with 100 patients[J]. Pancreatology,2016,16(1):99-105.
[4]顾倩倩,刘翠,方伟彬,等. 一种靶向于生长抑素受体2的药物筛选模型的建立与应用[J]. 中国药理学通报,2019,35(11):1539-1544.
[5]HAGEMEISTER A L,KITTILSON J D,BERGAN H E,et al. Rainbow trout somatostatin receptor subtypes SSTR1A,SSTR1B,and SSTR2 differentially activate the extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling pathways in transfected cells[J]. Journal of Molecular Endocrinology,2010,45(5):317-327.
[6]RADOJEVIC V,BODMER D. Expression and localization of somatostatin receptor types 3,4 and 5 in the wild-type,SSTR1 and SSTR1/SSTR2 knockout mouse cochlea[J]. Cell and Tissue Research,2014,358(3):717-727.
[7]ISHIDA A,TAJIMA Y,OKABE Y,et al. Discovery and SAR studies of orally active somatostatin receptor subtype-2(SSTR2) agonists for the treatment of acromegaly[J]. ACS Chemical Neuroscience,2020,11(10):1482-1494.
[8]YAMADA Y,POST S R,WANG K,et al. Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain,gastrointestinal tract,and kidney[J]. Proceedings of the National Academy of Sciences of the United States of America,1992,89(1):251-255.
[9]YAMASHITA S,MORINE Y,IMURA S,et al. A new pathological classification of intrahepatic cholangiocarcinoma according to protein expression of SSTR2 and Bcl2[J]. World Journal of Surgical Oncology,2021,19(1):142.
[10]李彦楠,朱晓莉. SSTR2在小细胞肺癌中的表达及其意义[J]. 东南大学学报(医学版),2016,35:156(2):269-271.
[11]ALEXANDER N,MARRANO P,THORNER P,et al. Prevalence and clinical correlations of somatostatin receptor-2(SSTR2) expression in neuroblastoma[J]. Journal of Pediatric Hematology/Oncology,2019,41(3):222-227.
[12]YU B X,ZHANG Z S,SONG H,et al. Retracted:clinical importance of somatostatin receptor 2 (SSTR2) and somatostatin receptor 5 (SSTR5) expression in thyrotropin-producing pituitary adenoma (TSHoma)[J]. Medical Science Monitor:International Medical Journal of Experimental and Clinical Research,2018,24:5904.
[13]ZHANG B L,QIN D Y,MO Z M,et al. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors[J]. Science China Life Sciences,2016,59(4):340-348.
[14]周俊,陈舒曼,邢兵,等. 正常来源CD4⁺CD25⁺细胞在小鼠肺癌模型中的抗肿瘤作用[J]. 广西师范大学学报(自然科学版),2022,40(2):191-199.
[15]SI Y N,KIM S,OU J F,et al. Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy[J]. Cancer Gene Therapy,2021,28(7/8):799-812.
[16]邢加彰,程月鹃,白春梅. 生长抑素类似物治疗神经内分泌肿瘤进展[J]. 临床药物治疗杂志,2019,17(8):26-31.
[17]BRUNNER P,JRG A C,GLATZ K,et al. The prognostic and predictive value of sstr2-immunohistochemistry and sstr2-targeted imaging in neuroendocrine tumors[J]. European Journal of Nuclear Medicine and Molecular Imaging,2017,44(3):468-475.
[18]WAR S A,KUMAR U. Coexpression of human somatostatin receptor-2(SSTR2) and SSTR3 modulates antiproliferative signaling and apoptosis[J]. Journal of Molecular Signaling,2012,7(1):5.
[19]JIANG H,DENG X F,DUAN C M,et al. Somatostatin receptors SSTR2 and SSTR5 are expressed in the human thoracic duct[J]. Lymphology,2011,44(1):21-28.
[20]WU W,ZHOU Y X,WANG Y L,et al. Clinical significance of somatostatin receptor (SSTR) 2 in veningioma[J]. Frontiers in Oncology,2020,10:1633.
[21]林晓茹,方建阳,李靖超,等. 靶向生长抑素受体SSTR2的新型白蛋白亲和放射性碘标记分子探针的制备与评价[J]. 厦门大学学报(自然科学版),2022,61(1):96-104.
[22]LEIJON H,REMES S,HAGSTROM J,et al. Variable somatostatin receptor subtype expression in 151 primary pheochromocytomas and paragangliomas[J]. Human Pathology,2019,86:66-75.
[23]张方亮,邓小红,朱晓彤,等. 翘嘴鳜USP7基因cDNA的克隆及饥饿对其表达影响分析[J]. 广西师范大学学报(自然科学版),2018,36(2):141-147.
[24]JI J X,JIN T H,LOU A G,et al. The effect of miR-10b on growth hormone in pituitary cells of Yanbian yellow cattle by somatostatin receptor 2[J]. Animal Science Journal =Nihon chikusan Gakkaiho,2020,91(1):e13420.
[25]LI Z W,SUN B C,GONG T,et al. GNAI1 and GNAI3 reduce colitis-associated tumorigenesis in mice by blocking IL6 signaling and down-regulating expression of GNAI2[J]. Gastroenterology,2019,156(8):2297-2312.
[26]WANG L,LV Y,LIU G Q. The roles of SHANK1 in the development of colon cancer[J]. Cell Biochemistry and Function,2020,38(5):669-675.

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生长抑素Ⅱ型受体SSTR2蛋白的理化性质及生物信息学分析

Physicochemical Properties and Bioinformatics Analysis of Somatostatin Receptor 2 (SSTR2)

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