Chemokine (C-X-C motif) receptor 4 |
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CXCR4 in complex with IT1t(PDB 3OE9) |
有效结构 | PDB | 直系同源检索:PDBe, RCSB | PDB查询代码列表 | 2K03, 2K04, 2K05, 3ODU, 3OE0, 3OE6, 3OE8, 3OE9 | | |
标识 |
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代号 | CXCR4; CD184; D2S201E; FB22; HM89; HSY3RR; LAP3; LCR1; LESTR; NPY3R; NPYR; NPYRL; NPYY3R; WHIM |
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扩展标识 | 遗传学:162643 鼠基因:109563 同源基因:20739 IUPHAR: CXCR4 ChEMBL: 2107 GeneCards: CXCR4 Gene |
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基因本体论描述 | 分子功能 | · actin binding · G-protein coupled receptor activity · protein binding · coreceptor activity · C-X-C chemokine receptor activity · C-X-C chemokine binding · ubiquitin protein ligase binding · myosin light chain binding · ubiquitin binding
| 细胞成分 | · cytoplasm · plasma membrane · external side of plasma membrane · cell surface · integral to membrane · cytoplasmic membrane-bounded vesicle · growth cone · cell leading edge · cytoplasmic vesicle
| 生物过程 | · activation of MAPK activity · patterning of blood vessels · response to hypoxia · ameboidal cell migration · neuron migration · dendritic cell chemotaxis · apoptotic process · inflammatory response · G-protein coupled receptor signaling pathway · elevation of cytosolic calcium ion concentration · germ cell development · brain development · motor neuron axon guidance · germ cell migration · response to virus · viral reproduction · virus-host interaction · calcium-mediated signaling · viral reproductive process · entry into host cell · regulation of cell migration · T cell proliferation · neutrophil activation · myelin maintenance · positive regulation of oligodendrocyte differentiation · regulation of chemotaxis · neural precursor cell proliferation
| Sources: Amigo / QuickGO | |
RNA表达模式 |
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直系同源体 |
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物种 | 人类 | 小鼠 |
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Entrez | 7852 | 12767 |
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Ensembl | ENSG00000121966 | ENSMUSG00000045382 |
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UniProt | P61073 | P70658 |
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mRNA序列 | NM_001008540 | NM_009911 |
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蛋白序列 | NP_001008540 | NP_034041 |
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基因位置 | Chr 2: 136.87 – 136.88 Mb | Chr 1: 128.59 – 128.59 Mb |
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PubMed查询 | [1] | [2] |
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趋化因子受体CXCR4是趋化因子基质细胞衍生因子-1(CXCL12)的特异受体[1][2]。CXCL12对淋巴细胞有强烈的趋化作用。该受体是用来提取纯化艾滋病毒的几个趋化因子受体之一。现在还不清楚是否出现使用CXCR4的人类免疫缺乏病毒是免疫缺乏的原因还是后果。
另外,CXCR4还可能人类胚胎发育中的着床过程中起作用。
作为趋化因子受体与配体,CXCR4和CXCL12比较特殊,他们是一配一的受体配体关系。绝大数趋化因子受体有多个配体,一个趋化因子可以结合到两个或多个受体。
CXCR4的配体CXCL12在造血干细胞移居骨髓在起重要作用[3]。影响或阻断CXCR4受体配体结合,可以调节造血干细胞的迁徙,这对骨髓造血干细胞移植可能十分有用。目前的试验药物有:粒细胞集落刺激因子(Granulocyte colony-stimulating factor)和Plerixafor(AMD3100)。但这些药物尚未临床使用。
CXCR4在体内大部分组织和器官上都有表达,它是由352个氨基酸组成的GPCR(G蛋白偶联受体),具有七次穿膜结构。 CXCR4参与体内多种生理机制,包括参与HIV-1病毒侵染【1】,造血功能【2】,胚胎发育【3-7】,及肿瘤迁移等【8】。
参考文献
- ^ Deng H, et al., Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661-6.
- ^ Oberlin E, et al., The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996 Aug 29;382(6594):833
- ^ Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998 Jun 11;393(6685):595-9.
- Dragic, T., An overview of the determinants of CCR5 and CXCR4 co-receptor function. J Gen Virol, 2001. 82(Pt 8): p. 1807-14.
- Maekawa, T. and T. Ishii, Chemokine/receptor dynamics in the regulation of hematopoiesis. Intern Med, 2000. 39(2): p. 90-100.
- Nagasawa, T., et al., Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature, 1996. 382(6592): p. 635-8.
- Tachibana, K., et al., The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature, 1998. 393(6685): p. 591-4.
- Zou, Y.R., et al., Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature, 1998. 393(6685): p. 595-9.
- McGrath, K.E., et al., Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4. Dev Biol, 1999. 213(2): p. 442-56.
- Lu, M., E.A. Grove, and R.J. Miller, Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A, 2002. 99(10): p. 7090-5.
- Burger, J.A. and T.J. Kipps, CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood, 2006. 107(5): p. 1761-7.
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| 趋化因子受体 (G蛋白偶联受体) | CC | - CCR1/CCRL1
- CCR2
- CCRL2
- CCR3
- CCR4
- CCR5
- CCR6
- CCR7
- CCR8
- CCR9
- CCR10
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| CXC | |
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| 其它 | |
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| 肿瘤坏死因子受体 | 1-10 | - TNFRSF1 (CD120)
- TNFRSF1A (CD120a)
- TNFRSF1B (CD120b)
- TNFRSF3(淋巴毒素β受体)
- TNFRSF4(CD134)
- TNFRSF5(CD40)
- TNFRSF6(FAS)
- TNFRSF6B
- TNFRSF7 (CD27)
- TNFRSF8 (CD30)
- TNFRSF9 (CD137)
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| 11-20 | - TNFRSF10A (CD261)
- TNFRSF10B (CD262)
- TNFRSF10C (CD263)
- TNFRSF10D (CD264)
- TNFRSF11A (CD265/RANK)
- TNFRSF11B(骨保护素)
- TNFRSF12A (CD266)
- TNFRSF13B (CD267)
- TNFRSF13C
- TNFRSF14 (CD268)
- TNFRSF16 (神经生长因子受体)
- TNFRSF17 (CD269)
- TNFRSF18
- TNFRSF19
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| 21-25 | - TNFRSF21
- TNFRSF25
- TNFRSF27
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| JAK-STAT信号通路 | I型 细胞因子受体 | 共用γ-链 | - 白介素受体
- IL2R/IL2RA/IL2RB/IL15R
- IL4R/IL13R/IL13RA1/IL13RA2
- IL7R/IL7RA
- IL9R
- IL21R
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| 共用β-链 | |
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| gp130 | - 白介素受体
- IL6RA
- 11/IL11RA
- 27/IL27RA
- OSMR
- LIFR
- CNTFR
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| IL12RB1 | - Interleukin receptors
- IL12R/IL12RB1/IL12RB2
- IL23R23
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| 其它 | |
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| II型 细胞因子受体 | - 白介素受体
- IL10R/IL10RA/IL10RB/IL22R/IL22RA2
- IL20R/IL20RA/IL20RB
- IL28R
- 干扰素受体
- -α/β/IFNAR1/IFNAR2
- -γ/IFNGR1/IFNGR2
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| 免疫球蛋白超家族 | |
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| IL-17 family | - IL-17
- IL17RA
- IL17RB
- IL17RC
- IL17RD
- IL17RE
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| 酶联受体 | - 受体蛋白丝氨酸/苏氨酸激酶:CSF1R
- KIT
- 受体蛋白丝氨酸/苏氨酸激酶:TGF-beta
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| 信号转导索引 |
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| 描述 | - 胞外
- 細胞表面受體(英语:Template:Cell surface receptors)
- 配体门控离子通道
- 酶联受體
- G蛋白偶聯受體
- 免疫球蛋白超家族(英语:Template:Immunoglobulin superfamily immune receptors)
- 整合素
- 神經肽受體
- 生長因子受體
- 细胞因子受體
- 胞內
- 受體蛋白(英语:Template:Signal transducing adaptor proteins)
- GTP-binding(英语:Template:GTP-binding protein regulators)
- MAP激酶
- 鈣信號
- 脂質系號
- 路徑
- hedgehog
- Wnt
- TGF-β
- MAPK ERK(英语:Template:MAPK ERK signaling pathway)
- notch(英语:Template:Notch signaling pathway)
- JAK-STAT
- 細胞凋亡
- hippo(英语:Template:Hippo signaling pathway)
- TLR
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