在Reactome数据库中，“JAK2 in IL12RB2:IL12RB2受体被磷酸化”转化为BioPAX途径。 IL12RB2中的JAK2:IL12RB2受体被磷酸化

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

Reactome DB_ID: 113592

胞质去 0005829

ATP (4 -) (ChEBI: 30616)

ATP (4)

腺苷5 '三磷酸三磷酸腺苷三磷酸腺苷 Reactome //www.joaskin.com ChEBI 30616

Reactome DB_ID: 8983520

等离子体膜去 0005886 IL35:(IL12RB2:JAK2二聚体)[质膜]

IL35:(IL12RB2: JAK2二聚体)

Reactome DB_ID: 8950039

IL12RB2: JAK2(质膜)

IL12RB2: JAK2

Reactome DB_ID: 447249

UniProt: Q99665 IL12RB2

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

链坐标

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862

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Reactome DB_ID: 210620

UniProt: O60674 JAK2

JAK2

JAK2 参与各种过程，如细胞生长，发育，分化或组蛋白修饰FUNCTION非受体酪氨酸激酶。介导先天免疫和适应性免疫基础的信令事件。在细胞质中，通过其关联在信号传导中起关键作用与I型受体如生长激素（GHR），催乳素（PRLR），瘦素（LEPR），促红细胞生成素（EPOR），血小板生成素（THPO）;或II型受体，包括IFN-α，IFN-β，IFN-γ和多个白介素（搜索PubMed：7615558）。下列配体结合至细胞表面受体，磷酸化在受体上的胞质尾的特定酪氨酸残基，产生停泊位点的STAT蛋白（搜索PubMed：9618263）。随后，磷酸化的STAT蛋白一旦被招募到受体。磷酸化的STAT然后形成同型二聚体或异源二聚体和易位至细胞核，激活基因转录。例如，促红细胞生成素（EPO）中红细胞生成导致JAK2自磷酸化，活化，以及其与促红细胞生成素受体（EPOR）协会，变得在其胞质结构域中磷酸化细胞刺激。然后，STAT5（STAT5A或STAT5B）被募集，通过JAK2磷酸化和激活。一旦被激活，二聚STAT5进入细胞核，促进参与红细胞生成的调制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

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1132

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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

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-8950039.1

Reactome DB_ID: 622267

细胞外区域去 0005576 IL35(细胞外地区)

IL35

IL12A: EBI3 Interleukin-35

Reactome DB_ID: 448418

UniProt: Q14213 EBI3

EBI3

IL27B EBI3 功能与IL27相关，形成IL-27白介素，一种在先天免疫中起作用的异源二聚体细胞因子。IL-27具有促进和抗炎的特性，可以调节t辅助细胞的发育，抑制t细胞增殖，刺激细胞毒性t细胞活性，诱导b细胞的同型转换，并且对固有免疫细胞有不同的影响。其靶细胞为CD4 t辅助细胞，可分化为1型效应细胞(TH1)、2型效应细胞(TH2)和IL17生成辅助t细胞(TH17)。它促使幼稚的但不是记忆性CD4 t细胞的快速克隆扩张。它还与IL-12强烈协同，触发幼稚CD4 t细胞产生干扰素- γ / ifn - γ，并与细胞因子受体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，可激活抗血管生成趋化因子的产生。亚基异源二聚体与IL27/IL27A;不是disulfide-linked (PubMed: 12121660)。这种异源二聚体被称为白介素IL-27 (PubMed:12121660)。与IL12A异质二聚体;不是disulfide-linked (PubMed: 9342359)。 This heterodimer is known as interleukin IL-35 (PubMed:9342359). Interacts with SQSTM1 (PubMed:8551575).INDUCTION By Epstein-Barr virus (EBV).SIMILARITY Belongs to the type I cytokine receptor family. Type 3 subfamily. UniProt Q14213

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229

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Reactome DB_ID: 447212

UniProt: P29459 IL12A

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

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219

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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

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 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

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-8983520.1

Reactome DB_ID: 29370

ADP (3 -) (ChEBI: 456216)

ADP (3 -)

ADP trianion 事情就让它5,- o - [(phosphonatooxy) phosphinato]腺苷 ADP ChEBI 456216

Reactome DB_ID: 8983873

IL35:(IL12RB2:p-JAK2)二聚体[质膜]

IL35:(IL12RB2: p-JAK2)二聚体

Reactome DB_ID: 447249

平等的

862

平等的

Reactome DB_ID: 210621

位置不明的磷酸化残基磷酸化残渣(MOD: 00696)

平等的

1132

平等的

Reactome DB_ID: 622267

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

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

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•米家伙,Clifford年代 Vignali,凯特米查图尔维迪,这个费尔韦瑟,DeLisa Satoskar Abhay R 加西亚,K克里斯托弗猎人,克里斯托弗德雷克,查尔斯·G 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