在Reactome数据库中，“JAK2 in IL12RB2:IL12RB2受体被磷酸化”转化为BioPAX途径。 从左到右 IL12RB2中的JAK2:IL12RB2受体被磷酸化 白介素35 (IL35)可能通过一个复合物发出信号，该复合物包括与白介素12受体β 2 (IL12RB2)二聚体相关的酪氨酸蛋白激酶JAK2 (JAK2) (Collison et al. 2012)。JAKs被认为可以磷酸化信号转导和转录激活因子(STATs) (Stark GR和Darnell JE, 2012)。由于针对IL35诱导JAK/STAT磷酸化事件的一系列事件尚不清楚，这一事件被表示为一个黑盒子。 作者：Varusai，Thawfeek，2016-12-15 评论:辛格，冈拉什，2017-07-05 评论:Pylayeva-Gupta, Yuliya, 2017-08-09 编辑日期:Varusai, Thawfeek, 2016-12-15 三磷酸腺苷 腺苷5 '三磷酸 ATP（4-） 反应数据库ID:113592 胞质 基因本体论 去:0005829 ATP (4 -) (ChEBI: 30616) ATP（4-） 三磷酸腺苷 三磷酸腺苷 腺苷5 '三磷酸 ChEBI CHEBI: 30616 Reactome数据库ID Release 77 113592 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=113592 Reactome r - - 113592 5 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.5 Reactome //www.joaskin.com 复合 C00002 额外的信息 心肌梗死 小姐:0361 2 IL35:(IL12RB2: JAK2二聚体) Reactome DB_ID: 8983520 质膜 基因本体论 去:0005886 IL12RB2: JAK2 反应数据库ID:8950039 IL12RB2 白细胞介素-12受体β-2链 I12R2_HUMAN Reactome DB_ID: 447249 UniProt: Q99665 IL12RB2 IL12RB2 白细胞介素-12的功能受体。该亚基是与JAK2/STAT4通路耦合的信号元件。促进t细胞和NK细胞的增殖。通过强烈增强ifn - γ的产生，诱导t细胞向Th1表型的促进。亚基异质二聚体/ heterooligomer;disulfide-linked。功能高亲和力IL12受体由I12RB1和IL12RB2组成。Il12RB2通过胞质结构域的膜近端与JAK2结合(通过其n端)。在体内和体外，与SOCS3的相互作用(通过其SH2结构域)抑制了stat4介导的激活。通过膜末端c端区域与STAT4结合。组织特异性亚型2在幼稚和活化的t细胞中表达相似水平。发育阶段Th1细胞在激活的第3天和第8天的最高水平。体外诱导，ifn - α上调。DOMAIN The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.DOMAIN The box 1 motif is required for JAK interaction and/or activation.PTM On IL12 binding, phosphorylated on C-terminal tyrosine residues by JAK2. Phosphorylation on Tyr-800 is required for STAT4 binding and activation, and for SOCS3 binding.POLYMORPHISM Heterozygotic variants Gly-313 and Arg-720 are associated with atopy, an immunological condition that can lead to clinical symptoms such as allergic rhinitis, sinusitis, asthma and eczema.SIMILARITY Belongs to the type I cytokine receptor family. Type 2 subfamily. 智人 NCBI分类法 9606 UniProt Q99665 24 相等的 862 相等的 Reactome数据库ID Release 77 447249 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=447249 Reactome R-HSA-447249 2 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-447249.2 1 JAK2 酪氨酸受体激酶JAK2 Reactome DB_ID: 210620 UniProt: O60674 JAK2 JAK2 功能:参与细胞生长、发育、分化或组蛋白修饰等过程的非受体酪氨酸激酶。介导先天免疫和适应性免疫中的重要信号事件。在细胞质中，通过与生长激素(GHR)、催乳素(PRLR)、瘦素(LEPR)、促红细胞生成素(EPOR)、血小板生成素(THPO)等I型受体的关联，在信号转导中起关键作用;或II型受体，包括ifn - α、ifn - β、ifn - γ和多种白细胞介素(PubMed:7615558)。在配体结合到细胞表面受体之后，磷酸化受体细胞质尾部的特定酪氨酸残基，为STATs蛋白创建对接位点(PubMed:9618263)。随后，一旦STATs蛋白被招募到受体，它们就被磷酸化。磷酸化的STATs会形成同源二聚体或异源二聚体，并转移到细胞核中激活基因转录。例如，在红细胞生成过程中，促红细胞生成素(EPO)对细胞的刺激导致JAK2的自磷酸化、激活，以及它与促红细胞生成素受体(EPOR)的关联，后者在其胞浆结构域被磷酸化。然后，STAT5 (STAT5A或STAT5B)被JAK2招募、磷酸化并激活。一旦激活，二聚态STAT5易位到细胞核，并促进参与调节红细胞生成的几个关键基因的转录。 Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980).ACTIVITY REGULATION Regulated by autophosphorylation, can both activate or decrease activity (By similarity). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (PubMed:21036157).SUBUNIT Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC (By similarity). Interacts with IL23R (PubMed:12023369). Interacts with SKB1 (PubMed:10531356). Interacts with STAM2 (PubMed:10899310). Interacts with IFNGR2 (via intracellular domain) (PubMed:7673114, PubMed:7615558). Interacts with LEPR (Isoform B) (By similarity). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (PubMed:20353823). Interacts with STRA6 (PubMed:21368206). Interacts with RHEX; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874).TISSUE SPECIFICITY Ubiquitously expressed throughout most tissues.DOMAIN Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1 (By similarity).PTM Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (By similarity). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (By similarity). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (By similarity). Also phosphorylated by TEC (By similarity). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558, PubMed:7673114). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206).DISEASE Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9;12)(p24;p13) with ETV6.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. UniProt O60674 1 相等的 1132 相等的 Reactome数据库ID Release 77 210620 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=210620 Reactome r - hsa - 210620 2 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-210620.2 1 Reactome数据库ID Release 77 8950039 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8950039 Reactome r - hsa - 8950039 1 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8950039.1 2 IL35 Interleukin-35 IL12A: EBI3 Reactome DB_ID: 622267 细胞外区域 基因本体论 去:0005576 EBI3 eb病毒诱导基因3蛋白 IL27B_HUMAN IL27B Interleukin-27β亚基 Reactome DB_ID: 448418 UniProt: Q14213 EBI3 EBI3 IL27B 功能与IL-27结合形成IL-27白细胞介素，一种在先天免疫中起作用的异二聚体细胞因子。IL-27具有促炎和抗炎特性，可调节辅助性T细胞发育，抑制T细胞增殖，刺激细胞毒性T细胞活性，诱导B细胞中的同种型转换，并对天然免疫细胞具有多种作用。其靶细胞包括CD4辅助性T细胞，其可在1型效应细胞（TH1）、2型效应细胞（TH2）和产生IL17的辅助性T细胞（TH17）中分化。它驱动幼稚但不记忆的CD4 T细胞的快速克隆扩增。它还与IL-12强烈协同，触发原始CD4 T细胞的干扰素-γ/干扰素-γ产生，与细胞因子受体WSX-1/TCCR结合。IL-27的另一个重要作用是其抗肿瘤活性和抗血管生成活性，同时激活抗血管生成趋化因子的产生；非二硫键连接（PubMed:12121660）。这种异二聚体被称为白细胞介素-27（PubMed:12121660）。IL12A异二聚体；非二硫键连接（PubMed:9342359）。这种异二聚体被称为白细胞介素-35（PubMed:9342359）。与SQSTM1（PubMed:8551575）相互作用。由EB病毒（EBV）诱导。相似性属于I型细胞因子受体家族。类型3亚科。 UniProt Q14213 21 相等的 229 相等的 Reactome数据库ID Release 77 448418 数据库标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=448418 Reactome r - hsa - 448418 2 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-448418.2 1 IL12A IL12p35 IL12-p35 Interleukin-12α亚基 IL12A_HUMAN 反应数据库ID:447212 UniProt: P29459 IL12A IL12A NKSF1 作为活化的T细胞和NK细胞的生长因子，增强NK/淋巴因子激活的杀伤细胞的溶解活性，并通过静息的PBMC刺激ifn - γ的产生的细胞因子。亚基异二聚体与IL12B;disulfide-linked (PubMed: 1674604, PubMed: 10899108)。这种异源二聚体被称为白介素IL-12 (PubMed:1674604)。异质二聚体与EBI3 / IL27B;不是disulfide-linked (PubMed: 9342359)。这种异源二聚体称为白介素IL-35 (PubMed:9342359)。诱导(微生物感染)对肠病毒71型(EV71)感染反应下调。属于IL-6超家族。 UniProt P29459 23 相等的 219 相等的 Reactome数据库ID Release 77 447212 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=447212 Reactome r - hsa - 447212 2 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-447212.2 1 Reactome数据库ID Release 77 622267 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=622267 Reactome r - hsa - 622267 3. Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-622267.3 1 Reactome数据库ID Release 77 8983520 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8983520 Reactome R-HSA-8983520 1 反应稳定标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8983520.1 ADP 腺苷5 '磷酸氢盐 ADP (3 -) Reactome DB_ID: 29370 ADP (3 -) (ChEBI: 456216) ADP (3 -) ADP 5&apos-O-[（膦氧基）膦酸]腺苷 ADP trianion ChEBI CHEBI: 456216 Reactome数据库ID Release 77 29370 数据库标识符。使用此URL连接到Reactome中此实例的网页：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=29370 Reactome R-ALL-29370 5 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.5 复合 C00008 2 IL35:(IL12RB2: p-JAK2)二聚体 Reactome DB_ID: 8983873 1 p-JAK2 磷JAK2 Reactome DB_ID: 210621 磷酸化残基 摩登派青年 国防部：00696 1 相等的 1132 相等的 Reactome数据库ID Release 77 210621 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=210621 Reactome r - hsa - 210621 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-210621.1 2 2 Reactome数据库ID Release 77 8983873 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8983873 Reactome r - hsa - 8983873 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8983873.1 Reactome数据库ID Release 77 8983870 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=8983870 Reactome r - hsa - 8983870 1 Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8983870.1 22306691 Pubmed 2012 IL-35受体的组成和信号通路是非常规的 克里森,劳伦W Delgoffe,格雷格•米 盖伊，克利福德 维格纳利，凯特M 查图尔维迪,这个 费尔韦瑟,DeLisa 萨托斯卡 加西亚,K克里斯托弗 猎人,克里斯托弗 查尔斯·G·德雷克 穆雷,彼得·J 达里奥·A·A·维纳利 Nat。Immunol 13:290-9 22520844 Pubmed 2012 JAK-STAT通路在20 斯塔克,乔治·R 达内尔,詹姆斯E 免疫36:503-14