人源二肽基肽酶 IV 已应用于藜麦浓缩蛋白水解物的 DPP-IV 抑制活性检测。 人源二肽基肽酶 IV 曾用于研究,评估抑制该酶与抑制血管紧张素转换酶二者联用对血流动力学的协同作用;同时也被用于鉴定、表征膜翅目蜂毒中分子量 100 kDa 的高分子过敏原 Api m 5 与 Ves v 3。
生化与生理功能
二肽基肽酶 IV(DPP4)参与介导 T 细胞活化;同时可作为淋巴瘤、甲状腺癌、前列腺癌与结肠癌潜在生物标志物。DPPIV 具备脯氨酸后二肽氨基肽酶活性:可从多肽游离 N 端切割二肽,底物序列满足 X-Pro-Z、X-Ala-Z;其中 X 为 N 端任意氨基酸残基,Z 不能为脯氨酸或羟脯氨酸。天然 DPPIV 是广泛存在的 II 型跨膜糖蛋白,属于 S9 脯氨酰寡肽酶家族丝氨酸蛋白酶。在体内合成时带有信号肽,该序列同时充当膜锚定结构域。人源 DPPIV 与猪肾来源 DPPIV 氨基酸序列同源性达 88%;二者均以同源二聚体形式存在,亚基分子量约 30 kDa。 高甘露糖型 100 kDa 的 DPPIV 前体蛋白在高尔基体加工,形成 124 kDa、带有大量 N - 连接与 O - 连接糖链的成熟糖蛋白。随后依靠 N - 糖链、O - 糖链协同作用并结合脂质微区,分选转运至细胞膜顶端。 DPPIV 高表达于内皮细胞、上皮细胞与淋巴细胞;血浆中还存在可溶性形式的 DPPIV。
Dipeptidyl Peptidase IV (DPP4) is mapped to human chromosome 2q24.2. It comprises the N-glycosylation sites located in the β-propeller domain.
Application:
Dipeptidyl Peptidase IV human has been used in DPP-IV inhibitory activity assay of quinoa protein concentrate digest.Human dipeptidyl peptidase IV has been used in a study to assess the interactive hemodynamic effects of its inhibition as well as the angiotensin-converting enzyme inhibition. Human dipeptidyl peptidase IV has also been used in a study to identify and characterize the 100 kDa High Molecular Weight Hymenoptera Venom Allergens Api m 5 and Ves v 3.
Biochem/physiol Actions
Dipeptidyl Peptidase IV (DPP4) mediates the activation of T-cells. It is also a potential biomarker for lymphoma, thyroid, prostate and colon cancer.DPPIV has a post-proline dipeptidyl aminopeptidase activity that hydrolyzes N-terminal dipeptides from the unsubstituted N-terminus of peptides with the sequence of X-Pro-Z and X-Ala-Z. Where X is a nonspecific residue at the N terminus and Z cannot be proline or hydroxyproline.Native DPPIV is a ubiquitous type II transmembrane glycoprotein and a serine protease of the S9 prolyl-oligopeptidase family. In vivo, it is synthesized with a signal peptide, which functions as the membrane anchoring domain. There is an 88% sequence homology between the human and porcine kidney enzymes. Both exist as homodimers with a subunit molecular weight of ~30 kDa. The high mannose 100 kDa DPPIV precursor is processed in the Golgi to yield a 124 kDa heavily N-and O-linked mature glycoprotein. It is then sorted to the apical membrane through the concerted action of both N- and O-linked glycans and its association with lipid microdomains. DPPIV is highly expressed on endothelial cells, epithelial cells, and lymphocytes. It is also present in plasma in its soluble form.
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Also acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones such as brain natriuretic peptide 32. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.11 Publications(Microbial infection) Acts as a receptor for human coronavirus MERS-CoV-2. Miscellaneous: Level of plasma concentrations of the soluble form (SDPP) can be managed as a colon carcinoma diagnostic and prognostic marker. Catalytic activity: Release of an N-terminal dipeptide, Xaa-Yaa-|-Zaa-, from a polypeptide, preferentially when Yaa is Pro, provided Zaa is neither Pro nor hydroxyproline. Activity regulation: Inhibited by GPC3 and diprotin A.
Post-translational: The soluble form (Dipeptidyl peptidase 4 soluble form also named SDPP) derives from the membrane form (Dipeptidyl peptidase 4 membrane form also named MDPP) by proteolytic processing. N- and O-Glycosylated. Phosphorylated. Mannose 6-phosphate residues in the carbohydrate moiety are necessary for interaction with IGF2R in activated T-cells. Mannose 6-phosphorylation is induced during T-cell activation.