CCR5

CCR5
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	2L87、2RLL、2RRS、2MZX、4MBS
識別號
別名	CCR5；, CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5, CMKBR5, IDDM22, C-C motif chemokine receptor 5 (gene/pseudogene), C-C motif chemokine receptor 5
外部ID	OMIM：601373 MGI：107182 HomoloGene：37325 GeneCards：CCR5
相關疾病
	type 1 diabetes mellitus 22、人類免疫缺陷病毒傳染性疾病
為以下藥物的標靶
	阿拉韋羅、cenicriviroc、馬拉韋羅、vicriviroc、aplaviroc hydrochloride、AZD5672
基因位置（人類）
染色體	3號染色體
終止	46,376,206 bp
基因位置（小鼠）
染色體	小鼠9號染色體
終止	123,947,736 bp
基因本體
分子功能	• G protein-coupled receptor activity; • coreceptor activity; • chemokine (C-C motif) ligand 5 binding; • virus receptor activity; • signal transducer activity; • 血漿蛋白結合; • chemokine receptor activity; • C-C chemokine receptor activity; • actin binding; • phosphatidylinositol phospholipase C activity; • C-C chemokine binding; • chemokine binding;
細胞組分	• 細胞質; • integral component of membrane; • 核內體; • 膜; • 細胞膜; • integral component of plasma membrane; • external side of plasma membrane; • cell surface;
生物學過程	• G protein-coupled receptor signaling pathway; • signaling; • response to cholesterol; • release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; • positive regulation of cytosolic calcium ion concentration; • cell-cell signaling; • dendritic cell chemotaxis; • MAPK cascade; • 趨化性; • cellular defense response; • cell surface receptor signaling pathway; • 免疫反應; • inflammatory response; • cellular response to lipopolysaccharide; • calcium ion transport; • calcium-mediated signaling; • 信號轉導; • fusion of virus membrane with host plasma membrane; • chemokine-mediated signaling pathway; • viral process; • defense response; • negative regulation of macrophage apoptotic process; • cytokine-mediated signaling pathway; • cell chemotaxis;
	Sources:Amigo / QuickGO
直系同源
	1234
	12774
	ENSG00000160791
	ENSMUSG00000079227
	P51681
	P51682
	NM_001100168; NM_000579; NM_001394783
	NM_009917
	NP_000570; NP_001093638
	NP_034047
	維基數據
檢視/編輯人類	檢視/編輯小鼠

CCR5（C-C chemokine receptor type 5），中文名：趨化因子受體5^[7]或趨化因子C－C亞族受體5^[8]，也稱為CD195。是白血球表面的一種蛋白質，因此也稱為CCR5蛋白質，R5型HIV進入並感染宿主細胞的過程需要藉助CCR5蛋白質，控制CCR5蛋白質的基因稱為CCR5基因，該基因在人體內的基因座是3p21.31（意為位於3號染色體短臂的2區－1帶－子帶31上）。^[9]^[10]^[11]^[12]^[13]^[14]^[15]

某些人群的基因組中含有此基因的一個突變型，稱為CCR5-Δ32，與普通CCR5基因相比，有一段長為 32 鹼基對的缺失，其表達產物無法被HIV識別和結合，因此可對R5型HIV引起的愛滋病免疫，^[10]^[11]^[12]^[13]^[14]^[15]但對於僅使用CXCR4受體蛋白的X4型HIV卻沒有免疫能力^[16]^[17]。CCR5的另外一種突變CCR5-893（−）亦同樣對部分愛滋病具有免疫作用^[18]。

功能[編輯]

CCR5是一種G蛋白偶聯受體，屬於整合型膜蛋白的β趨化因子受體家族成員^[7]^[19]^[20]，在CC趨化因子組中起趨化因子受體的作用^[19]。

CCR5主要在T細胞，巨噬細胞，樹突細胞，嗜曙紅顆粒白血球，小膠質細胞和乳腺癌或前列腺癌的細胞亞群中表達。^[21]^[22]CCR5在癌症變性過程中被選擇性誘導表達，且不在正常乳腺或前列腺上皮細胞中表達。大約50％的人類乳腺癌表達了CCR5，主要是三陰性乳腺癌。^[21]CCR5抑制劑阻斷了表達CCR5的乳腺癌細胞和前列腺癌細胞的轉移，表明CCR5或可作為一種新的治療靶點。^[21]^[22]^[23]最近的研究表明，CCR5在癌細胞亞群中表達，具有癌症幹細胞的特徵，後者已知可激發對治療的抗性，而CCR5抑制劑可以增強現有化療技術的細胞殺傷作用^[24]。

CCR5在正常免疫中的作用尚不清楚^[25]，《複雜疾病遺傳學》（Genetics of Complex Disease）這一本書籍指出：「一般而言，CCR5並不會影響免疫反應，但它在對西尼羅河病毒感染的免疫反應中扮演重要的角色」^[26]。CCR5-Δ32基因雖對部分愛滋病具有免疫作用，但一篇2015年的綜述指其與多發性硬化相關^[27]，不過在整體研究中它跟自體免疫性疾病的關係存有矛盾^[28]。其跟腫瘤的關係則欠詳細記錄^[29]。此外CCR5-Δ32可能會使攜帶者在感染西尼羅河病毒後出現更嚴重的神經系統疾病^[26]。

參考資料[編輯]

^ 與CCR5相關的疾病；在維基數據上查看/編輯參考.
^ 對CCR5起作用的藥物；在維基數據上查看/編輯參考.
^ ^3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000160791 - Ensembl, May 2017
^ ^4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000079227 - 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.
^ ^7.0 ^7.1 邱磊. 超氧化物歧化酶介导趋化因子受体 5 的功能. 第二軍醫大學. [2018-12-02]. （原始內容存檔於2019-06-03）.
^ 朱平,王彥宏,樊春梅,張浩,黃向陽,吳振彪,/冷南. 趋化因子受体 CCR5 及其配体在类风湿关节炎患者滑液及滑膜中的表达. 中華醫學雜誌. 2001, (17) [2018-12-02]. （原始內容存檔於2018-12-03）.
^ GRCh38: Ensembl release 89: ENSG00000160791 Summary - Homo sapiens. Ensembl. [2018-11-27]. （原始內容存檔於2022-03-21）（英國英語）.
^ ^10.0 ^10.1 de Silva E, Stumpf MP. HIV and the CCR5-Delta32 resistance allele. FEMS Microbiology Letters. Dec 2004, 241 (1): 1–12. PMID 15556703. doi:10.1016/j.femsle.2004.09.040.
^ ^11.0 ^11.1 Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. The New England Journal of Medicine. Feb 2009, 360 (7): 692–8. PMID 19213682. doi:10.1056/NEJMoa0802905.
^ ^12.0 ^12.1 Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood. Mar 2011, 117 (10): 2791–9. PMID 21148083. doi:10.1182/blood-2010-09-309591.
^ ^13.0 ^13.1 Zhen A, Kitchen S. Stem-cell-based gene therapy for HIV infection. Viruses. Jan 2014, 6 (1): 1–12. PMC 3917429 . PMID 24368413. doi:10.3390/v6010001.
^ ^14.0 ^14.1 Kay MA, Walker BD. Engineering cellular resistance to HIV. The New England Journal of Medicine. Mar 2014, 370 (10): 968–9. PMID 24597871. doi:10.1056/NEJMe1400593.
^ ^15.0 ^15.1 Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. The New England Journal of Medicine. Mar 2014, 370 (10): 901–10. PMC 4084652 . PMID 24597865. doi:10.1056/NEJMoa1300662.
^ Coakley, E., Petropoulos, C. J. and Whitcomb, J. M. Assessing chemokine co-receptor usage in HIV. Curr. Opin. Infect. Dis. 2005, 18 (1): 9–15. PMID 15647694. doi:10.1097/00001432-200502000-00003.
^ Berger, EA; Doms, RW; Fenyö, EM; Korber, BT; Littman, DR; Moore, JP; Sattentau, QJ; Schuitemaker, H; et al. A new classification for HIV-1. Nature. 1998, 391 (6664): 240. PMID 9440686. doi:10.1038/34571.
^ Schweneker, Marc; Bachmann, André S; Moelling, Karin. JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Letters. 2005-03-14, 579 (7): 1751–58 [2018-12-02]. PMID 15757671. doi:10.1016/j.febslet.2005.02.037. （原始內容存檔於2019-02-15）（英語）.
^ ^19.0 ^19.1 CCR5 - chemokine (C-C motif) receptor 5 (gene/pseudogene). Genetics Home Reference. （原始內容存檔於2009-09-24）.
^ Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. Mar 1996, 35 (11): 3362–7. PMID 8639485. doi:10.1021/bi952950g.
^ ^21.0 ^21.1 ^21.2 Velasco-Velázquez M, Jiao X, De La Fuente M, Pestell TG, Ertel A, Lisanti MP, Pestell RG. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Research. Aug 2012, 72 (15): 3839–50. PMID 22637726. doi:10.1158/0008-5472.CAN-11-3917.
^ ^22.0 ^22.1 Sicoli D, Jiao X, Ju X, Velasco-Velazquez M, Ertel A, Addya S, Li Z, Andò S, Fatatis A, Paudyal B, Cristofanilli M, Thakur ML, Lisanti MP, Pestell RG. CCR5 receptor antagonists block metastasis to bone of v-Src oncogene-transformed metastatic prostate cancer cell lines. Cancer Research. Dec 2014, 74 (23): 7103–14. PMC 4294544 . PMID 25452256. doi:10.1158/0008-5472.CAN-14-0612.
^ Velasco-Velázquez M, Xolalpa W, Pestell RG. CCL5/CCR5 in breast cancer. Expert Opin Ther Targets. Nov 2014, 18 (11): 1265–75. PMID 25256399. doi:10.1517/14728222.2014.949238.
^ Jiao X, Velasco-Velázquez MA, Wang M, Li Z, Rui H, Peck AR, Korkola JE, Chen X, Xu S, DuHadaway JB, Guerrero-Rodriguez S, Addya S, Sicoli D, Mu Z, Zhang G, Stucky A, Zhang X, Cristofanilli M, Fatatis A, Gray JW, Zhong JF, Prendergast GC, Pestell RG. CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion. Cancer Res. Apr 2018, 78 (7): 1657–71. PMID 29358169. doi:10.1158/0008-5472.CAN-17-0915.
^ Barmania F, Pepper MS. C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection. Applied & Translational Genomics. 2013, 2 (a): 3–16. doi:10.1016/j.atg.2013.05.004.
^ ^26.0 ^26.1 Donaldson, Peter; Daly, Ann; Ermini, Luca; Debra, Bevitt. Genetics of Complex Disease. Garland Science. 2015: 241 [2018-12-02]. ISBN 9780815344919. （原始內容存檔於2018-11-29）.
^ Ghorba, Khodayar; Hassanshahi, Gholamhossein; Momeni, Mohammad; Zare-Bidaki, Mohammad; Arababadi, Mohammad Kazemi; Kennedy, Derek. Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?. Inflammation. 2013-06, 36 (3): 633–42 [2018-11-27]. PMID 23250822. doi:10.1007/s10753-012-9585-8. （原始內容存檔於2018-06-17）（英語）.
^ Ascierto, PA; Stroncek, DF; Wang, E. Developments in T Cell Based Cancer Immunotherapies. Humana Press. 2015: 117 [2018-12-02]. ISBN 978-3-319-21167-1. （原始內容存檔於2018-11-29）.
^ Rezaei, Nima. Cancer Immunology: A Translational Medicine Context. Springer. 2015: 135 [2020-09-25]. ISBN 978-3-662-44006-3. （原始內容存檔於2019-02-15）.

[1] 與CCR5相關的疾病；在維基數據上查看/編輯參考.

[2] 對CCR5起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000160791 - Ensembl, May 2017

[refGRCm38Ensembl-4] 4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000079227 - Ensembl, May 2017

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

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

[:0-7] 7.0 ^7.1 邱磊. 超氧化物歧化酶介导趋化因子受体 5 的功能. 第二軍醫大學. [2018-12-02]. （原始內容存檔於2019-06-03）.

[8] 朱平,王彥宏,樊春梅,張浩,黃向陽,吳振彪,/冷南. 趋化因子受体 CCR5 及其配体在类风湿关节炎患者滑液及滑膜中的表达. 中華醫學雜誌. 2001, (17) [2018-12-02]. （原始內容存檔於2018-12-03）.

[9] GRCh38: Ensembl release 89: ENSG00000160791 Summary - Homo sapiens. Ensembl. [2018-11-27]. （原始內容存檔於2022-03-21）（英國英語）.

[pmid15556703-10] 10.0 ^10.1 de Silva E, Stumpf MP. HIV and the CCR5-Delta32 resistance allele. FEMS Microbiology Letters. Dec 2004, 241 (1): 1–12. PMID 15556703. doi:10.1016/j.femsle.2004.09.040.

[pmid19213682-11] 11.0 ^11.1 Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K, Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. The New England Journal of Medicine. Feb 2009, 360 (7): 692–8. PMID 19213682. doi:10.1056/NEJMoa0802905.

[pmid21148083-12] 12.0 ^12.1 Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood. Mar 2011, 117 (10): 2791–9. PMID 21148083. doi:10.1182/blood-2010-09-309591.

[pmid24368413-13] 13.0 ^13.1 Zhen A, Kitchen S. Stem-cell-based gene therapy for HIV infection. Viruses. Jan 2014, 6 (1): 1–12. PMC 3917429 . PMID 24368413. doi:10.3390/v6010001.

[pmid24597871-14] 14.0 ^14.1 Kay MA, Walker BD. Engineering cellular resistance to HIV. The New England Journal of Medicine. Mar 2014, 370 (10): 968–9. PMID 24597871. doi:10.1056/NEJMe1400593.

[pmid24597865-15] 15.0 ^15.1 Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. The New England Journal of Medicine. Mar 2014, 370 (10): 901–10. PMC 4084652 . PMID 24597865. doi:10.1056/NEJMoa1300662.

[Coakley-16] Coakley, E., Petropoulos, C. J. and Whitcomb, J. M. Assessing chemokine co-receptor usage in HIV. Curr. Opin. Infect. Dis. 2005, 18 (1): 9–15. PMID 15647694. doi:10.1097/00001432-200502000-00003.

[classification-17] Berger, EA; Doms, RW; Fenyö, EM; Korber, BT; Littman, DR; Moore, JP; Sattentau, QJ; Schuitemaker, H; et al. A new classification for HIV-1. Nature. 1998, 391 (6664): 240. PMID 9440686. doi:10.1038/34571.

[18] Schweneker, Marc; Bachmann, André S; Moelling, Karin. JM4 is a four-transmembrane protein binding to the CCR5 receptor. FEBS Letters. 2005-03-14, 579 (7): 1751–58 [2018-12-02]. PMID 15757671. doi:10.1016/j.febslet.2005.02.037. （原始內容存檔於2019-02-15）（英語）.

[Home-19] 19.0 ^19.1 CCR5 - chemokine (C-C motif) receptor 5 (gene/pseudogene). Genetics Home Reference. （原始內容存檔於2009-09-24）.

[pmid8639485-20] Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. Mar 1996, 35 (11): 3362–7. PMID 8639485. doi:10.1021/bi952950g.

[pmid22637726-21] 21.0 ^21.1 ^21.2 Velasco-Velázquez M, Jiao X, De La Fuente M, Pestell TG, Ertel A, Lisanti MP, Pestell RG. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Research. Aug 2012, 72 (15): 3839–50. PMID 22637726. doi:10.1158/0008-5472.CAN-11-3917.

[pmid25452256-22] 22.0 ^22.1 Sicoli D, Jiao X, Ju X, Velasco-Velazquez M, Ertel A, Addya S, Li Z, Andò S, Fatatis A, Paudyal B, Cristofanilli M, Thakur ML, Lisanti MP, Pestell RG. CCR5 receptor antagonists block metastasis to bone of v-Src oncogene-transformed metastatic prostate cancer cell lines. Cancer Research. Dec 2014, 74 (23): 7103–14. PMC 4294544 . PMID 25452256. doi:10.1158/0008-5472.CAN-14-0612.

[pmid25256399-23] Velasco-Velázquez M, Xolalpa W, Pestell RG. CCL5/CCR5 in breast cancer. Expert Opin Ther Targets. Nov 2014, 18 (11): 1265–75. PMID 25256399. doi:10.1517/14728222.2014.949238.

[pmid29358169-24] Jiao X, Velasco-Velázquez MA, Wang M, Li Z, Rui H, Peck AR, Korkola JE, Chen X, Xu S, DuHadaway JB, Guerrero-Rodriguez S, Addya S, Sicoli D, Mu Z, Zhang G, Stucky A, Zhang X, Cristofanilli M, Fatatis A, Gray JW, Zhong JF, Prendergast GC, Pestell RG. CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion. Cancer Res. Apr 2018, 78 (7): 1657–71. PMID 29358169. doi:10.1158/0008-5472.CAN-17-0915.

[25] Barmania F, Pepper MS. C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection. Applied & Translational Genomics. 2013, 2 (a): 3–16. doi:10.1016/j.atg.2013.05.004.

[Complex_Disease-26] 26.0 ^26.1 Donaldson, Peter; Daly, Ann; Ermini, Luca; Debra, Bevitt. Genetics of Complex Disease. Garland Science. 2015: 241 [2018-12-02]. ISBN 9780815344919. （原始內容存檔於2018-11-29）.

[27] Ghorba, Khodayar; Hassanshahi, Gholamhossein; Momeni, Mohammad; Zare-Bidaki, Mohammad; Arababadi, Mohammad Kazemi; Kennedy, Derek. Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?. Inflammation. 2013-06, 36 (3): 633–42 [2018-11-27]. PMID 23250822. doi:10.1007/s10753-012-9585-8. （原始內容存檔於2018-06-17）（英語）.

[28] Ascierto, PA; Stroncek, DF; Wang, E. Developments in T Cell Based Cancer Immunotherapies. Humana Press. 2015: 117 [2018-12-02]. ISBN 978-3-319-21167-1. （原始內容存檔於2018-11-29）.

[29] Rezaei, Nima. Cancer Immunology: A Translational Medicine Context. Springer. 2015: 135 [2020-09-25]. ISBN 978-3-662-44006-3. （原始內容存檔於2019-02-15）.

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[4]

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[6]

[7]

[8]

[9]

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[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

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[29]