妊娠相關血漿蛋白A

妊娠相關血漿蛋白A
識別號
別名	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（人類）
染色體	9號染色體
終止	116,402,321 bp
基因位置（小鼠）
染色體	小鼠4號染色體
終止	65,275,746 bp
RNA表達模式
	; ;
	查閱更多表達數據
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
	5069
	18491
	ENSG00000182752
	ENSMUSG00000028370
	Q13219
	Q8R4K8
	NM_002581
	NM_021362
	NP_002572
	NP_067337
	維基數據
檢視/編輯人類	檢視/編輯小鼠

妊娠相關血漿蛋白A（英語：pregnancy-associated plasma protein A，或Pappalysin-1，縮寫PAPP-A）是一種由人類基因 PAPPA 編碼的蛋白質，PAPP-A是一種分泌蛋白酶，其主要基質是胰島素樣生長因子結合蛋白。PAPP-A也用於唐氏綜合症的篩查試驗。^[5]^[6]

功能

此基因編碼一種分泌的金屬蛋白酶，主要用於切割胰島素樣生長因子的結合蛋白（IGFBPs）。PAPP-A的蛋白水解活性在與膠原蛋白結合後被活化，參與許多局部增生過程，比如傷口癒合和骨重塑。血漿中出現低水平的此蛋白被認為是妊娠中出現非整倍體胎兒（胎兒擁有不正常的染色體數）的生化標誌物^[6]，比如在唐氏綜合症的產前診斷中，低水平的PAPP-A是一個重要標誌^[5]。低水平的PAPP-A也可表明胎盤存在問題，並導致不良併發症如宮內生長受限、妊娠毒血症、胎盤早期剝離、早產乃至死產。

相互作用

妊娠相關血漿蛋白A已知可與主要鹼性蛋白發生蛋白質交互作用。^[7]^[8]^[9]

參考文獻

^ ^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.

延伸閱讀

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.

外部連結

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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閱論編蛋白酶類：金屬內肽酶類（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
基質金屬蛋白酶	膠原酶 MMP1 MMP8 明膠酶 MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23A MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
其它	腦啡肽酶前膠原肽酶嗜熱菌蛋白酶妊娠相關血漿蛋白A 骨形態發生蛋白1 溶葡球菌酶胰島素降解酶 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（英語：Template:Ligases CO CS and CN）/4/5-6