妊娠相关血浆蛋白A

妊娠相关血浆蛋白A
识别号
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号染色体
终止	116,402,321 bp
基因位置（小鼠）
染色体	小鼠4号染色体
终止	65,275,746 bp
RNA表达模式
	; ;
	查阅更多表达数据
基因本体
分子功能	• 锌离子结合; • 肽酶活性; • endopeptidase activity; • 水解酶活性; • metallopeptidase activity; • 金属离子结合; • metalloendopeptidase activity;
细胞组分	• 细胞外区域; • 细胞外空间;
生物学过程	• 蛋白酶解; • response to follicle-stimulating hormone; • female pregnancy; • response to glucocorticoid;
	Sources:Amigo / QuickGO
直系同源
	5069
	18491
	ENSG00000182752
	ENSMUSG00000028370
	Q13219
	Q8R4K8
	NM_002581
	NM_021362
	NP_002572
	NP_067337
	维基数据
查看/编辑人类	查看/编辑小鼠

妊娠相关血浆蛋白A（英语：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]

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胶原蛋白结合后被激活，参与许多局部增生过程，比如伤口愈合和骨重塑。血浆中出现低水平的此蛋白被认为是妊娠中出现非整倍体胎儿（胎儿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产前诊断中，低水平的PAPP-A是一个重要标志^[5]。低水平的PAPP-A也可表明胎盘存在问题，并导致不良并发症如宫内生长受限、妊娠毒血症、胎盘早期剥离、早产乃至死产。

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质交互作用。^[7]^[8]^[9]

参考文献

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000182752 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000028370 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^5.0 ^5.1 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.
^ ^6.0 ^6.1 Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1.
^ 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.
^ 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.
^ 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

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000182752 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 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.

[breathnach-5] 5.0 ^5.1 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.

[entrez-6] 6.0 ^6.1 Entrez Gene: PAPPA pregnancy-associated plasma protein A, pappalysin 1.

[pmid10913121-7] 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.

[pmid12421832-8] 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.

[pmid7685339-9] 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.

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查论编蛋白酶类：金属内肽酶类（EC 3.4.24）
ADAM蛋白	α分泌酶 ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
基质金属蛋白酶	胶原酶 MMP1 MMP8 明胶酶 MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23A MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
其它	脑啡肽酶前胶原肽酶嗜热菌蛋白酶妊娠相关血浆蛋白A 骨形态发生蛋白1 溶葡球菌酶胰岛素降解酶 ZMPSTE24
EC 1.1/2/3/4/5/6/7/8/9/10/11/12/13/14/15/16/17/18/19/20/21/22 · 2.1/2/3/4/5/6/7(2.7.10/11-12)/8/9 · 3.1/2/3/4(3.4.21/22/23/24)/5/6/7/8/9/10/11/12/13 · 4.1/2/3/4/5/6 · 5.1/2/3/4/5/99 · 6.1-3（英语：Template:Ligases CO CS and CN）/4/5-6