妊娠相关血浆蛋白A

妊娠相关血浆蛋白A（英語：pregnancy-associated plasma protein A，或Pappalysin-1，缩写PAPP-A）是一种由人类基因 PAPPA 编码的蛋白质，PAPP-A是一种分泌蛋白酶，其主要底物是胰岛素样生长因子结合蛋白。PAPP-A也用于唐氏综合征的筛查试验。^[5][6]

妊娠相关血浆蛋白A
識別號
别名	PAPPA；, ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPPA1, pappalysin 1
外部ID	OMIM：176385 MGI：97479 HomoloGene：31097 GeneCards：PAPPA
基因位置（人类） 染色体 9號染色體[1] 基因座 9q33.1 起始 116,153,791 bp[1] 终止 116,402,321 bp[1]
基因位置（小鼠） 染色体 小鼠4号染色体[2] 基因座 4 C1|4 34.14 cM 起始 65,042,411 bp[2] 终止 65,275,746 bp[2]
RNA表达模式
查阅更多表达数据
基因本體 分子功能 • 鋅離子結合 • 肽酶活性 • endopeptidase activity • 水解酶活性 • metallopeptidase activity • 金屬離子結合 • metalloendopeptidase activity 細胞組分 • 細胞外區域 • 細胞外空間 生物學過程 • 蛋白酶解 • response to follicle-stimulating hormone • female pregnancy • response to glucocorticoid Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	5069	18491
Ensembl	ENSG00000182752	ENSMUSG00000028370
UniProt	Q13219	Q8R4K8
mRNA​序列	​NM_002581	NM_021362
蛋白序列	NP_002572	NP_067337
基因位置​（UCSC）	Chr 9: 116.15 – 116.4 Mb	Chr 4: 65.04 – 65.28 Mb
PubMed​查找	[3]	[4]
維基數據
檢視/編輯人類 檢視/編輯小鼠

功能

此基因编码一种分泌的金属蛋白酶，主要用于切割胰岛素样生长因子的结合蛋白（IGFBPs）。PAPP-A的蛋白水解活性在与膠原蛋白结合后被激活，参与许多局部增生过程，比如傷口癒合和骨重塑。血浆中出现低水平的此蛋白被认为是妊娠中出现非整倍體胎兒（胎兒拥有不正常的染色体数）的生化标志物^[6]，比如在唐氏综合征的產前診斷中，低水平的PAPP-A是一个重要标志^[5]。低水平的PAPP-A也可表明胎盤存在问题，并导致不良并发症如宫内生长受限、妊娠毒血症、胎盤早期剝離、早產乃至死產。

相互作用

妊娠相关血浆蛋白A已知可与主要碱性蛋白发生蛋白質交互作用。^[7][8][9]

参考文献

1. GRCh38: Ensembl release 89: ENSG00000182752 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028370 - Ensembl, May 2017
3. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Breathnach FM, Malone FD. Screening for aneuploidy in first and second trimesters: is there an optimal paradigm?. Curr. Opin. Obstet. Gynecol. 2007, 19 (2): 176–82. PMID 17353686. doi:10.1097/GCO.0b013e3280895e00.
6. Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1.
7. Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, Gleich GJ, Sottrup-Jensen L, Conover CA, Oxvig C. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. J. Biol. Chem. October 2000, 275 (40): 31128–33. PMID 10913121. doi:10.1074/jbc.M001384200.
8. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C. Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. J. Biol. Chem. January 2003, 278 (4): 2106–17. PMID 12421832. doi:10.1074/jbc.M208777200.
9. Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L. Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein. J. Biol. Chem. June 1993, 268 (17): 12243–6. PMID 7685339.

延伸阅读

• Sinosich MJ, Zakher A. Pregnancy-associated plasma protein A interaction with heparin: a critical appraisal.. Gynecol. Obstet. Invest. 1992, 32 (2): 72–7. PMID 1721035. doi:10.1159/000292998.
• Bischof P, Tseng L. In vitro release of pregnancy-associated plasma protein-A (PAPP-A) by human endometrial cells.. American Journal of Reproductive Immunology and Microbiology : AJRIM. 1986, 10 (4): 139–42. PMID 2422961. doi:10.1111/j.1600-0897.1986.tb00013.x.
• Bolton AE, Pinto-Furtado LG, Andrew CE, Chapman MG. Measurement of the pregnancy-associated proteins, placental protein 14 and pregnancy-associated plasma protein A in human seminal plasma.. Clinical Reproduction and Fertility. 1986, 4 (3): 233–40. PMID 2427179.
• Sinosich MJ, Saunders DM. Potential role of pregnancy-associated plasma protein-A in human reproduction.. J. Reprod. Immunol. 1987, 10 (1): 55–65. PMID 2438405. doi:10.1016/0165-0378(87)90050-7.
• Tornehave D, Chemnitz J, Teisner B, et al. Immunohistochemical demonstration of pregnancy-associated plasma protein A (PAPP-A) in the syncytiotrophoblast of the normal placenta at different gestational ages.. Placenta. 1985, 5 (5): 427–31. PMID 6084247. doi:10.1016/S0143-4004(84)80023-5.
• McIntyre JA, Hsi B, Faulk WP, et al. Immunological studies of the human placenta: functional and morphological analysis of pregnancy-associated plasma protein A (PAPP-A).. Immunology. 1982, 44 (3): 577–83. PMC 1554973 . PMID 6172371.
• Bischof P, Geinoz A, Herrmann WL, Sizonenko PC. Pregnancy-associated plasma protein A (PAPP-A) specifically inhibits the third component of human complement (C3).. Placenta. 1984, 5 (1): 1–7. PMID 6203109. doi:10.1016/S0143-4004(84)80044-2.
• Schindler AM, Bischof P. Histochemical localization of pregnancy-associated plasma protein A in fetal, infant, and adult organs and comparison between antisera.. Gynecol. Obstet. Invest. 1984, 18 (2): 88–94. PMID 6207082. doi:10.1159/000299055.
• Kristensen T, Oxvig C, Sand O, et al. Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA.. Biochemistry. 1994, 33 (6): 1592–8. PMID 7508748. doi:10.1021/bi00172a040.
• Durham SK, Kiefer MC, Riggs BL, Conover CA. Regulation of insulin-like growth factor binding protein 4 by a specific insulin-like growth factor binding protein 4 proteinase in normal human osteoblast-like cells: implications in bone cell physiology.. J. Bone Miner. Res. 1994, 9 (1): 111–7. PMID 7512304. doi:10.1002/jbmr.5650090115.
• Bonno M, Oxvig C, Kephart GM, et al. Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta.. Lab. Invest. 1994, 71 (4): 560–6. PMID 7526035.
• Oxvig C, Haaning J, Kristensen L, et al. Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma.. J. Biol. Chem. 1995, 270 (23): 13645–51. PMID 7539791. doi:10.1074/jbc.270.23.13645.
• Zorin NA, Zhabin SG, Semenkov NN. Interaction of human pregnancy-associated plasma protein-A with serine proteinases.. Clin. Chim. Acta. 1995, 239 (1): 47–55. PMID 7586586. doi:10.1016/0009-8981(95)06098-X.
• Silahtaroglu AN, Tümer Z, Kristensen T, et al. Assignment of the human gene for pregnancy-associated plasma protein A (PAPPA) to 9q33.1 by fluorescence in situ hybridization to mitotic and meiotic chromosomes.. Cytogenet. Cell Genet. 1993, 62 (4): 214–6. PMID 7679961. doi:10.1159/000133479.
• Oxvig C, Sand O, Kristensen T, et al. Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein.. J. Biol. Chem. 1993, 268 (17): 12243–6. PMID 7685339.
• Haaning J, Oxvig C, Overgaard MT, et al. Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP.. Eur. J. Biochem. 1996, 237 (1): 159–63. PMID 8620868. doi:10.1111/j.1432-1033.1996.0159n.x.
• Lawrence JB, Oxvig C, Overgaard MT, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A.. Proc. Natl. Acad. Sci. U.S.A. 1999, 96 (6): 3149–53. PMC 15910 . PMID 10077652. doi:10.1073/pnas.96.6.3149.
• Overgaard MT, Oxvig C, Christiansen M, et al. Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues.. Biol. Reprod. 1999, 61 (4): 1083–9. PMID 10491647. doi:10.1095/biolreprod61.4.1083.
• Overgaard MT, Haaning J, Boldt HB, et al. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor.. J. Biol. Chem. 2000, 275 (40): 31128–33. PMID 10913121. doi:10.1074/jbc.M001384200.
• Hourvitz A, Widger AE, Filho FL, et al. Pregnancy-associated plasma protein-A gene expression in human ovaries is restricted to healthy follicles and corpora lutea.. J. Clin. Endocrinol. Metab. 2001, 85 (12): 4916–20. PMID 11134163. doi:10.1210/jc.85.12.4916.

外部链接

• The MEROPS online database for peptidases and their inhibitors: M43.004