CYP17A1

17,20裂解酶
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	3RUK、3SWZ、4NKV、4NKW、4NKX、4NKY、4NKZ
識別號
别名	CYP17A1；, CPT7, CYP17, P450C17, S17AH, cytochrome P450 family 17 subfamily A member 1
外部ID	OMIM：609300 MGI：88586 HomoloGene：73875 GeneCards：CYP17A1
EC number	1.14.14.19、1.14.14.32
為以下藥物的標靶
	阿比特龙、seviteronel
基因位置（人类）
染色体	10號染色體
终止	102,837,472 bp
基因位置（小鼠）
染色体	小鼠19号染色体
终止	46,661,611 bp
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• iron ion binding; • oxygen binding; • 金屬離子結合; • steroid 17-alpha-monooxygenase activity; • monooxygenase activity; • heme binding; • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; • lyase activity; • oxidoreductase activity; • 17-alpha-hydroxyprogesterone aldolase activity;
細胞組分	• endoplasmic reticulum membrane; • 膜; • 轴突; • soma; • 内质网;
生物學過程	• progesterone metabolic process; • androgen biosynthetic process; • glucocorticoid biosynthetic process; • sterol metabolic process; • hormone biosynthetic process; • steroid biosynthetic process; • steroid metabolic process; • sex differentiation;
	Sources:Amigo / QuickGO
直系同源
	1586
	13074
	ENSG00000148795
	ENSMUSG00000003555
	P05093
	P27786
	NM_000102
	NM_007809
	NP_000093
	NP_031835
	維基數據
檢視/編輯人類	檢視/編輯小鼠

细胞色素 P450 17A1（英語：Cytochrome P450 17A1）也被称为甾体17α-单加氧酶（steroid 17α-monooxygenase），17α-羟基化酶（17α-hydroxylase），17,20-碳链裂解酶（17,20-lyase 或 17,20-desmolase）是一种羟基化酶，由位于人类10号染色体的 CYP17A1 基因编码^[6]。这一基因在许多组织与细胞中都有表达，特别是肾上腺皮质的网状带（英语：zona reticularis）和肾上腺束状带（英语：zona fasciculata）以及生殖腺组织^[7]^[8]。CYP17A1蛋白属于细胞色素P450氧化酶超家族的一员，定位于内质网，既有甾体的17α-羟化酶也有17,20-裂解酶活性，在类固醇生成途径中将孕烯醇酮或孕酮的D环上17号C原子上α位加上一个羟基（-OH）基团，生成17α-羟孕烯醇酮或17α-羟孕酮（17α-羟基化活性）；之后再断裂在17号C原子20号C原子之间的碳碳键，生成脱氢表雄酮（DHEA）或雄烯二酮（17,20-裂合酶活性）^[8]。

CYP17A1 基因上包含有增加冠狀動脈疾病患病风险的27个SNPs之一^[9]。

结构

基因

CYP17A1 基因位于10号染色体的10q24.3带上包含有8个外显子^[6]，其cDNA全长为1527bp。^[10]

蛋白

CYP17A1蛋白大小为57.4kDa^[11]，包含有508个氨基酸残基，属于CYP450超家族^[12]，带有一个血基質相关活性位点以催化相关生物反应^[10]。

CYP17A1可被两种甾类抑制剂阿比特龙（英语：abiraterone）和galeterone特异地抑制，CYP17A1和其它参与甾体生成与胆固醇代谢的细胞色素P450氧化酶一样有着经典的P450酶结构，但其结合甾类配体的位置位于F和G螺旋之间，垂直于血红素基团，而通常的非β1折叠^[13]^[14]。

参考文献

^ 對CYP17A1起作用的藥物；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000148795 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000003555 - 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.
^ ^6.0 ^6.1 CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI. www.ncbi.nlm.nih.gov. [2016-09-27]. （原始内容存档于2015-06-23）.
^ BioGPS - your Gene Portal System. biogps.org. [2016-10-11]. （原始内容存档于2011-08-20）.
^ ^8.0 ^8.1 Boulpaep EL; Boron, WF. Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. 2005: 1180. ISBN 1-4160-2328-3.
^ Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. June 2015, 385 (9984): 2264–71. PMC 4608367  . PMID 25748612. doi:10.1016/S0140-6736(14)61730-X.
^ ^10.0 ^10.1 Vasaitis TS, Bruno RD, Njar VC. CYP17 inhibitors for prostate cancer therapy. The Journal of Steroid Biochemistry and Molecular Biology. May 2011, 125 (1-2): 23–31. PMC 3047603  . PMID 21092758. doi:10.1016/j.jsbmb.2010.11.005.
^ CYP17A1 - Steroid 17-alpha-hydroxylase/17,20 lyase - Homo sapiens (Human) - CYP17A1 gene & protein. www.uniprot.org. [2016-10-11]. （原始内容存档于2016-10-12）.
^ Estrada DF, Laurence JS, Scott EE. Cytochrome P450 17A1 Interactions with the FMN Domain of Its Reductase as Characterized by NMR. The Journal of Biological Chemistry. February 2016, 291 (8): 3990–4003. PMC 4759177  . PMID 26719338. doi:10.1074/jbc.M115.677294.
^ DeVore NM, Scott EE. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature. February 2012, 482 (7383): 116–9. PMC 3271139  . PMID 22266943. doi:10.1038/nature10743.
^ Petrunak EM, DeVore NM, Porubsky PR, Scott EE. Structures of human steroidogenic cytochrome P450 17A1 with substrates. The Journal of Biological Chemistry. November 2014, 289 (47): 32952–64. PMC 4239641  . PMID 25301938. doi:10.1074/jbc.M114.610998.

外部链接

醫學主題詞表（MeSH）：CYP17A1+protein,+human
Human CYP17A1 genome location and CYP17A1 gene details page in the UCSC Genome Browser（英语：UCSC Genome Browser）.

[1] 對CYP17A1起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000148795 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000003555 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[:0-6] 6.0 ^6.1 CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI. www.ncbi.nlm.nih.gov. [2016-09-27]. （原始内容存档于2015-06-23）.

[7] BioGPS - your Gene Portal System. biogps.org. [2016-10-11]. （原始内容存档于2011-08-20）.

[isbn1-4160-2328-3-8] 8.0 ^8.1 Boulpaep EL; Boron, WF. Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. 2005: 1180. ISBN 1-4160-2328-3.

[ReferenceA-9] Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. June 2015, 385 (9984): 2264–71. PMC 4608367  . PMID 25748612. doi:10.1016/S0140-6736(14)61730-X.

[:1-10] 10.0 ^10.1 Vasaitis TS, Bruno RD, Njar VC. CYP17 inhibitors for prostate cancer therapy. The Journal of Steroid Biochemistry and Molecular Biology. May 2011, 125 (1-2): 23–31. PMC 3047603  . PMID 21092758. doi:10.1016/j.jsbmb.2010.11.005.

[11] CYP17A1 - Steroid 17-alpha-hydroxylase/17,20 lyase - Homo sapiens (Human) - CYP17A1 gene & protein. www.uniprot.org. [2016-10-11]. （原始内容存档于2016-10-12）.

[12] Estrada DF, Laurence JS, Scott EE. Cytochrome P450 17A1 Interactions with the FMN Domain of Its Reductase as Characterized by NMR. The Journal of Biological Chemistry. February 2016, 291 (8): 3990–4003. PMC 4759177  . PMID 26719338. doi:10.1074/jbc.M115.677294.

[13] DeVore NM, Scott EE. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature. February 2012, 482 (7383): 116–9. PMC 3271139  . PMID 22266943. doi:10.1038/nature10743.

[14] Petrunak EM, DeVore NM, Porubsky PR, Scott EE. Structures of human steroidogenic cytochrome P450 17A1 with substrates. The Journal of Biological Chemistry. November 2014, 289 (47): 32952–64. PMC 4239641  . PMID 25301938. doi:10.1074/jbc.M114.610998.

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