CYP17A1

17,20裂解酶
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	3RUK、3SWZ、4NKV、4NKW、4NKX、4NKY、4NKZ
識別號
別名	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
	阿比特龍、seviteronel
基因位置（人類）
染色體	10號染色體
終止	102,837,472 bp
基因位置（小鼠）
染色體	小鼠19號染色體
終止	46,661,611 bp
RNA表達模式
	查閱更多表達數據
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; • 軸突; • neuronal cell body; • 內質網;
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

細胞色素 P450 17A1（英語：Cytochrome P450 17A1）也被稱為甾體17α-單加氧酶（steroid 17α-monooxygenase），17α-羥基化酶（17α-hydroxylase），17,20-碳鏈裂解酶（17,20-lyase 或 17,20-desmolase）是一種羥基化酶，由位於人類10號染色體的 CYP17A1 基因編碼^[6]。這一基因在許多組織與細胞中都有表達，特別是腎上腺皮質的網狀帶（英語：zona reticularis）和腎上腺束狀帶（英語：zona fasciculata）以及生殖腺組織^[7]^[8]。CYP17A1蛋白屬於細胞色素P450氧化酶超家族的一員，定位於內質網，既有甾體的17α-羥化酶也有17,20-裂解酶活性，在類固醇生成途徑中將孕烯醇酮或孕酮的D環上17號C原子上α位加上一個羥基（-OH）基團，生成17α-羥孕烯醇酮或17α-羥孕酮（17α-羥基化活性）；之後再斷裂在17號C原子20號C原子之間的碳碳鍵，生成脫氫表雄酮（DHEA）或雄烯二酮（17,20-裂解酶活性）^[8]。

Quick Facts 17,20裂解酶, 已知的結構 ...

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CYP17A1 基因上包含有增加冠狀動脈疾病患病風險的27個SNPs之一^[9]。

結構

基因

CYP17A1 基因位於10號染色體的10q24.3帶上包含有8個外顯子^[6]，其cDNA全長為1527bp。^[10]

蛋白

CYP17A1蛋白大小為57.4kDa^[11]，包含有508個氨基酸殘基，屬於CYP450超家族^[12]，帶有一個血基質相關活性位點以催化相關生物反應^[10]。

CYP17A1可被兩種甾類抑制劑阿比特龍（英語：abiraterone）和galeterone特異地抑制，CYP17A1和其它參與甾體生成與膽固醇代謝的細胞色素P450氧化酶一樣有着經典的P450酶結構，但其結合甾類配體的位置位於F和G螺旋之間，垂直於血紅素基團，而通常的非β1摺疊^[13]^[14]。

參考文獻

[1]
對CYP17A1起作用的藥物；在維基數據上查看/編輯參考.
[2]
GRCh38: Ensembl release 89: ENSG00000148795 - Ensembl, May 2017
[3]
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.
[6]
CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI. www.ncbi.nlm.nih.gov. [2016-09-27]. （原始內容存檔於2015-06-23）.
[7]
BioGPS - your Gene Portal System. biogps.org. [2016-10-11]. （原始內容存檔於2011-08-20）.
[8]
Boulpaep EL; Boron, WF. Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. 2005: 1180. ISBN 1-4160-2328-3.
[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.
[10]
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]. （原始內容存檔於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.

外部連結

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

[1] [1]
對CYP17A1起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] [2]
GRCh38: Ensembl release 89: ENSG00000148795 - Ensembl, May 2017

[refGRCm38Ensembl-3] [3]
GRCm38: Ensembl release 89: ENSMUSG00000003555 - Ensembl, May 2017

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

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

[:0-6] [6]
CYP17A1 cytochrome P450 family 17 subfamily A member 1 [Homo sapiens (human)] - Gene - NCBI. www.ncbi.nlm.nih.gov. [2016-09-27]. （原始內容存檔於2015-06-23）.

[7] [7]
BioGPS - your Gene Portal System. biogps.org. [2016-10-11]. （原始內容存檔於2011-08-20）.

[isbn1-4160-2328-3-8] [8]
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] [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]
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] [11]
CYP17A1 - Steroid 17-alpha-hydroxylase/17,20 lyase - Homo sapiens (Human) - CYP17A1 gene & protein. www.uniprot.org. [2016-10-11]. （原始內容存檔於2016-10-12）.

[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] [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] [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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