CCR5：修订间差异

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'''CCR5'''（'''C-C [[趋化因子受体|chemokine receptor]] type 5'''），也称为'''CD195'''。是白细胞表面的一种蛋白质，因此也称为'''CCR5蛋白质'''，R5型[[人類免疫缺陷病毒|HIV病毒]]进入并感染宿主细胞的过程需要借助CCR5蛋白质，控制CCR5蛋白质的基因称为'''CCR5基因'''，该基因在人体内的[[基因座]]是3p21.31（意为位于3号染色体短臂的2区－1带－子带31上）。<ref>{{Cite web|url=http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000160791;r=3:46370854-46376206|title=GRCh38: Ensembl release 89: ENSG00000160791 Summary - Homo sapiens|accessdate=2018-11-27|author=|date=|work=|publisher=[[Ensembl]]|language=en-gb}}</ref><ref name="pmid15556703" /><ref name="pmid19213682" /><ref name="pmid21148083" /><ref name="pmid24368413" /><ref name="pmid24597871" /><ref name="pmid24597865" />
'''CCR5'''（'''C-C [[趋化因子受体|chemokine receptor]] type 5'''），也称为'''CD195'''。是白细胞表面的一种蛋白质，因此也称为'''CCR5蛋白质'''，R5型[[人類免疫缺陷病毒|HIV病毒]]进入并感染宿主细胞的过程需要借助CCR5蛋白质，控制CCR5蛋白质的基因称为'''CCR5基因'''，该基因在人体内的[[基因座]]是3p21.31（意为位于3号染色体短臂的2区－1带－子带31上）。<ref>{{Cite web|url=http://may2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000160791;r=3:46370854-46376206|title=GRCh38: Ensembl release 89: ENSG00000160791 Summary - Homo sapiens|accessdate=2018-11-27|author=|date=|work=|publisher=[[Ensembl]]|language=en-gb}}</ref><ref name="pmid15556703" /><ref name="pmid19213682" /><ref name="pmid21148083" /><ref name="pmid24368413" /><ref name="pmid24597871" /><ref name="pmid24597865" />


某些人群的基因组中含有此基因的一个突变型，称为CCR5-Δ32，与普通CCR5基因相比，有一段长为 32 [[鹼基對|碱基对]]的[[突变#%E7%BC%BA%E5%A4%B1|缺失]]，其表达产物无法被HIV病毒识别和结合，因此可对R5型HIV病毒引起的艾滋病免疫，<ref name="pmid15556703">{{cite journal|title=HIV and the CCR5-Delta32 resistance allele|date=Dec 2004|journal=FEMS Microbiology Letters|issue=1|doi=10.1016/j.femsle.2004.09.040|volume=241|pages=1–12|pmid=15556703|vauthors=de Silva E, Stumpf MP}}</ref><ref name="pmid19213682">{{cite journal|title=Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation|date=Feb 2009|journal=The New England Journal of Medicine|issue=7|doi=10.1056/NEJMoa0802905|volume=360|pages=692–8|pmid=19213682|vauthors=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}}</ref><ref name="pmid21148083">{{cite journal|title=Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation|date=Mar 2011|journal=Blood|issue=10|doi=10.1182/blood-2010-09-309591|volume=117|pages=2791–9|pmid=21148083|vauthors=Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T}}</ref><ref name="pmid24368413">{{cite journal|title=Stem-cell-based gene therapy for HIV infection|date=Jan 2014|journal=Viruses|issue=1|doi=10.3390/v6010001|volume=6|pages=1–12|pmc=3917429|pmid=24368413|vauthors=Zhen A, Kitchen S}}</ref><ref name="pmid24597871">{{cite journal|title=Engineering cellular resistance to HIV|date=Mar 2014|journal=The New England Journal of Medicine|issue=10|doi=10.1056/NEJMe1400593|volume=370|pages=968–9|pmid=24597871|vauthors=Kay MA, Walker BD}}</ref><ref name="pmid24597865">{{cite journal|title=Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV|date=Mar 2014|journal=The New England Journal of Medicine|issue=10|doi=10.1056/NEJMoa1300662|volume=370|pages=901–10|pmc=4084652|pmid=24597865|display-authors=6|vauthors=Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH}}</ref>但对于仅使用CXCR4受体蛋白的X4型HIV病毒却没有免疫能力<ref name="Coakley">{{cite journal|title=Assessing chemokine co-receptor usage in HIV|author=Coakley, E., Petropoulos, C. J. and Whitcomb, J. M.|journal=Curr. Opin. Infect. Dis.|issue=1|doi=10.1097/00001432-200502000-00003|year=2005|volume=18|pages=9–15|pmid=15647694}}</ref><ref name="classification">{{cite journal|title=A new classification for HIV-1|first1=EA|last2=Doms|first2=RW|journal=Nature|issue=6664|doi=10.1038/34571|year=1998|volume=391|pages=240|pmid=9440686|last3=Fenyö|first3=EM|last4=Korber|first4=BT|last5=Littman|first5=DR|last6=Moore|first6=JP|last7=Sattentau|first7=QJ|last8=Schuitemaker|first8=H|last9=Sodroski|first9=J|display-authors=8|last1=Berger|last10=Weiss|first10=R. A.}}</ref>。CCR5-Δ32基因虽对部分艾滋病具有免疫作用，但有研究指其与多发性硬化<ref>{{Cite journal|title=CCR5-Delta32 Allele is Associated with the Risk of Developing Multiple Sclerosis in the Iranian Population|author=|url=https://link.springer.com/article/10.1007%2Fs10571-009-9415-1|last=Shahbazi|first=Majid|last2=Ebadi|first2=Hamid|date=2009-05-29|journal=Cellular and Molecular Neurobiology|issue=8|doi=10.1007/s10571-009-9415-1|volume=29|pages=1205–1209|language=en|issn=0272-4340|last3=Fathi|first3=Davood|last4=Roshandel|first4=Danial|last5=Mahamadhoseeni|first5=Mana|last6=Rashidbaghan|first6=Azam|last7=Mahammadi|first7=Narges|last8=Mahammadi|first8=Mahammad Reza|last9=Zamani|first9=Mahdi|access-date=2018-11-26|archive-url=https://web.archive.org/web/20180610094523/https://link.springer.com/article/10.1007%2Fs10571-009-9415-1#|archive-date=2018-06-10|dead-url=no}}</ref>、子宫颈癌<ref>{{Cite journal|title=CCR5-Delta32 polymorphism and susceptibility to cervical cancer: association with early stage of cervical cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/18543610|last=Singh|first=Hariom|last2=Sachan|first2=Rekha|date=2008|journal=Oncology Research|issue=2|volume=17|pages=87–91|issn=0965-0407|pmid=18543610|last3=Jain|first3=Meenu|last4=Mittal|first4=Balraj}}</ref>、精神分裂症<ref>{{Cite journal|title=Association between the CCR5 32-bp deletion allele and late onset of schizophrenia|url=https://www.ncbi.nlm.nih.gov/pubmed/16513874|last=Rasmussen|first=Henrik Berg|last2=Timm|first2=Sally|date=2006-3|journal=The American Journal of Psychiatry|issue=3|doi=10.1176/appi.ajp.163.3.507|volume=163|pages=507–511|issn=0002-953X|pmid=16513874|last3=Wang|first3=August G.|last4=Søeby|first4=Karen|last5=Lublin|first5=Henrik|last6=Fenger|first6=Mogens|last7=Hemmingsen|first7=Ralf|last8=Werge|first8=Thomas}}</ref>等疾病相关。
某些人群的基因组中含有此基因的一个突变型，称为CCR5-Δ32，与普通CCR5基因相比，有一段长为 32 [[鹼基對|碱基对]]的[[突变#%E7%BC%BA%E5%A4%B1|缺失]]，其表达产物无法被HIV病毒识别和结合，因此可对R5型HIV病毒引起的艾滋病免疫，<ref name="pmid15556703">{{cite journal|title=HIV and the CCR5-Delta32 resistance allele|date=Dec 2004|journal=FEMS Microbiology Letters|issue=1|doi=10.1016/j.femsle.2004.09.040|volume=241|pages=1–12|pmid=15556703|vauthors=de Silva E, Stumpf MP}}</ref><ref name="pmid19213682">{{cite journal|title=Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation|date=Feb 2009|journal=The New England Journal of Medicine|issue=7|doi=10.1056/NEJMoa0802905|volume=360|pages=692–8|pmid=19213682|vauthors=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}}</ref><ref name="pmid21148083">{{cite journal|title=Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation|date=Mar 2011|journal=Blood|issue=10|doi=10.1182/blood-2010-09-309591|volume=117|pages=2791–9|pmid=21148083|vauthors=Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T}}</ref><ref name="pmid24368413">{{cite journal|title=Stem-cell-based gene therapy for HIV infection|date=Jan 2014|journal=Viruses|issue=1|doi=10.3390/v6010001|volume=6|pages=1–12|pmc=3917429|pmid=24368413|vauthors=Zhen A, Kitchen S}}</ref><ref name="pmid24597871">{{cite journal|title=Engineering cellular resistance to HIV|date=Mar 2014|journal=The New England Journal of Medicine|issue=10|doi=10.1056/NEJMe1400593|volume=370|pages=968–9|pmid=24597871|vauthors=Kay MA, Walker BD}}</ref><ref name="pmid24597865">{{cite journal|title=Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV|date=Mar 2014|journal=The New England Journal of Medicine|issue=10|doi=10.1056/NEJMoa1300662|volume=370|pages=901–10|pmc=4084652|pmid=24597865|display-authors=6|vauthors=Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH}}</ref>但对于仅使用CXCR4受体蛋白的X4型HIV病毒却没有免疫能力<ref name="Coakley">{{cite journal|title=Assessing chemokine co-receptor usage in HIV|author=Coakley, E., Petropoulos, C. J. and Whitcomb, J. M.|journal=Curr. Opin. Infect. Dis.|issue=1|doi=10.1097/00001432-200502000-00003|year=2005|volume=18|pages=9–15|pmid=15647694}}</ref><ref name="classification">{{cite journal|title=A new classification for HIV-1|first1=EA|last2=Doms|first2=RW|journal=Nature|issue=6664|doi=10.1038/34571|year=1998|volume=391|pages=240|pmid=9440686|last3=Fenyö|first3=EM|last4=Korber|first4=BT|last5=Littman|first5=DR|last6=Moore|first6=JP|last7=Sattentau|first7=QJ|last8=Schuitemaker|first8=H|last9=Sodroski|first9=J|display-authors=8|last1=Berger|last10=Weiss|first10=R. A.}}</ref>。CCR5在正常免疫中的作用尚不清楚<ref>{{cite journal | title=C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection | journal=Applied & Translational Genomics | volume = 2 | issue = a | pages=3–16 | vauthors = Barmania F, Pepper MS | doi = 10.1016/j.atg.2013.05.004 | year=2013 }}</ref>。《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，但它在對西尼罗河病毒感染的免疫反應中扮演重要的角色」<ref name="Complex Disease"/>。
CCR5-Δ32基因虽对部分艾滋病具有免疫作用，但一篇2015年的綜述指其与多发性硬化相关<ref>{{Cite journal|pmid=23250822|doi=10.1007/s10753-012-9585-8|title=Is the CCR5 Δ 32 Mutation Associated with Immune System-Related Diseases?|url=https://link.springer.com/article/10.1007/s10753-012-9585-8|last=Ghorba|first=Khodayar|last2=Hassanshahi|first2=Gholamhossein|date=2013-06|journal=Inflammation|issue=3|volume=36|pages=633-42|language=en|last3=Momeni|first3=Mohammad|last4=Zare-Bidaki|first4=Mohammad|last5=Arababadi|first5=Mohammad Kazemi|last6=Kennedy|first6=Derek|author=|access-date=2018-11-27|archive-url=https://web.archive.org/web/20180617180553/https://link.springer.com/article/10.1007%2Fs10753-012-9585-8|archive-date=2018-06-17|dead-url=no}}</ref>，不過在整體研究中它跟自體免疫性疾病的關係存有矛盾<ref>{{Cite book|title=Developments in T Cell Based Cancer Immunotherapies|year=2015|last1=Ascierto|first1=PA|last2=Stroncek|first2=DF|last3=Wang|first3=E|url=https://books.google.com.hk/books?id=GNULCwAAQBAJ&pg=PA117|page=117 |publisher=Humana Press|isbn=978-3-319-21167-1}}</ref>。其跟腫瘤的關係則欠詳細記錄<ref>{{Cite book|title=Cancer Immunology: A Translational Medicine Context|year=2015|first=Nima|last=Rezaei|url=https://books.google.com.hk/books?id=L8uoBQAAQBAJ&pg=PA135&lpg=PA135&dq=cervical+cancer+CCR5Δ32&source=bl&ots=StXWE4H4ED&sig=WS5dE0CvyN1H6fKDBGxhCEUKPHY&hl=zh-TW&sa=X&ved=2ahUKEwiB2qnb3fPeAhUYeisKHR9TA9gQ6AEwA3oECAgQAQ#v=onepage|page=135 |publisher=Springer|isbn=978-3-662-44006-3}}</ref>。此外CCR5-Δ32可能會使携带者在感染西尼罗河病毒後出現更嚴重的神經系统疾病<ref name="Complex Disease">{{Cite book|title=Genetics of Complex Disease|year=2015|last1= Donaldson|first1=Peter|last2=Daly|first2=Ann|last3=Ermini|first3=Luca|first4=Bevitt|last4=Debra|url=https://books.google.com.hk/books?id=5JVwCgAAQBAJ&pg=PA241&lpg=PA241|page=241|publisher=Garland Science|isbn=9780815344919}}</ref>。CCR5的另外一種突變CCR5-893（−）亦同樣对部分艾滋病具有免疫作用<ref>{{Cite journal|pmid=15757671|doi=10.1016/j.febslet.2005.02.037|title=JM4 is a four-transmembrane protein binding to the CCR5 receptor|url=https://www.sciencedirect.com/science/article/pii/S0014579305002449|last=Schweneker|first=Marc|last2=Bachmann|first2=André S|date=2005-03-14|journal=FEBS Letters|issue=7|volume=579|pages=1751-58|language=en|last3=Moelling|first3=Karin|access-date=2018-12-02}}</ref>。


== 功能 ==
== 功能 ==

2018年12月2日 (日) 15:08的版本

CCR5
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名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IDOMIM：601373 MGI：107182 HomoloGene：37325 GeneCards：CCR5
相關疾病
type 1 diabetes mellitus 22、​人类免疫缺陷病毒传染性疾病[1]
為以下藥物的標靶
阿拉韦罗、​cenicriviroc、​马拉韦罗、​vicriviroc、​aplaviroc hydrochloride、​AZD5672[2]
基因位置（人类）
3號染色體
染色体3號染色體[3]
3號染色體
CCR5的基因位置
CCR5的基因位置
基因座3p21.31起始46,370,946 bp[3]
终止46,376,206 bp[3]
直系同源
物種人類小鼠
Entrez

1234

12774

Ensembl

ENSG00000160791

ENSMUSG00000079227

UniProt

P51681

P51682

mRNA​序列

NM_001100168
​NM_000579
​NM_001394783

NM_009917

蛋白序列

NP_000570
​NP_001093638

NP_034047

基因位置​（UCSC）Chr 3: 46.37 – 46.38 MbChr 9: 123.92 – 123.95 Mb
PubMed​查找[5][6]
維基數據
檢視/編輯人類檢視/編輯小鼠
HIV-1作用于CD4+辅助性T细胞

CCR5（C-C chemokine receptor type 5），也称为CD195。是白细胞表面的一种蛋白质，因此也称为CCR5蛋白质，R5型HIV病毒进入并感染宿主细胞的过程需要借助CCR5蛋白质，控制CCR5蛋白质的基因称为CCR5基因，该基因在人体内的基因座是3p21.31（意为位于3号染色体短臂的2区－1带－子带31上）。[7][8][9][10][11][12][13]

某些人群的基因组中含有此基因的一个突变型，称为CCR5-Δ32，与普通CCR5基因相比，有一段长为 32 碱基对的缺失，其表达产物无法被HIV病毒识别和结合，因此可对R5型HIV病毒引起的艾滋病免疫，[8][9][10][11][12][13]但对于仅使用CXCR4受体蛋白的X4型HIV病毒却没有免疫能力[14][15]。CCR5在正常免疫中的作用尚不清楚[16]。《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，但它在對西尼罗河病毒感染的免疫反應中扮演重要的角色」[17]。 CCR5-Δ32基因虽对部分艾滋病具有免疫作用，但一篇2015年的綜述指其与多发性硬化相关[18]，不過在整體研究中它跟自體免疫性疾病的關係存有矛盾[19]。其跟腫瘤的關係則欠詳細記錄[20]。此外CCR5-Δ32可能會使携带者在感染西尼罗河病毒後出現更嚴重的神經系统疾病[17]。CCR5的另外一種突變CCR5-893（−）亦同樣对部分艾滋病具有免疫作用[21]。

功能

参考资料

趋化因子受体
(G蛋白偶联受体)
CC
CXC
其它
肿瘤坏死因子受体
1-10
11-20
21-25
JAK-STAT信号通路
I型
细胞因子受体
共用γ-链
共用β-链
gp130
IL12RB1
其它
II型
细胞因子受体
免疫球蛋白超家族
IL-17 family
酶联受体
 
描述
  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. 
  3. ^ 3.0 3.1 3.2 GRCh38: Ensembl release 89: ENSG00000160791 - Ensembl, May 2017
  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. 
  7. ^ GRCh38: Ensembl release 89: ENSG00000160791 Summary - Homo sapiens. Ensembl. [2018-11-27] （英国英语）. 
  8. ^ 8.0 8.1 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. 
  9. ^ 9.0 9.1 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. 
  10. ^ 10.0 10.1 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. 
  11. ^ 11.0 11.1 Zhen A, Kitchen S. Stem-cell-based gene therapy for HIV infection. Viruses. Jan 2014, 6 (1): 1–12. PMC 3917429 可免费查阅. PMID 24368413. doi:10.3390/v6010001. 
  12. ^ 12.0 12.1 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. 
  13. ^ 13.0 13.1 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 可免费查阅. PMID 24597865. doi:10.1056/NEJMoa1300662. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 17.0 17.1 Donaldson, Peter; Daly, Ann; Ermini, Luca; Debra, Bevitt. Genetics of Complex Disease. Garland Science. 2015: 241. ISBN 9780815344919. 
  18. ^ 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. （原始内容存档于2018-06-17） （英语）. 
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  21. ^ 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 （英语）. 
取自“https://zh.wikipedia.org/w/index.php?title=CCR5&oldid=52238551”