BioPAX通路从 “活化的寡聚物NOD RIP2 recruites（RICK）” 中的Reactome数据库转换。 从左到右 活化NOD寡聚物招募RIP2 (RICK) NOD1和NOD2（NOD）通过卡片结构域之间的同性恋关联与炎性激酶RIP2（RICK）相互作用（Inohara等，1999，Ogura等，2001）。这具有使多个RIP2分子在近距离接近的效果，增强RIP2-RIP2相互作用（Inohara等人，2000），是由NFKappab的NOD激活所谓的“诱导的接近模型”的关键步骤。请注意，虽然在此暗示每个NOD与RIP2的交互暗示，但RIP2激活可能是不需要的。RIP2招聘导致后续激活NFKappab。RIP2的激酶活性最初描述为不需要（Inohara等，2000），但随后建议参与确定信号强度（Windheim等，2007），最近发现对维持RIP2稳定性至关重要，并且在调解中的作用是必不可少的点燃信令（NEMBRIINE等人2009）。 作者:朱普，S, 2010-04-22 综述：Kufer，TA，2011-04-28 来自：Rittinger，K，2011-06-06 来自：黄，爱德蒙，2011-06-06 编辑：朱浦，S，2011-04-28 从反垃圾中的EntitySet转换 PAMP：NOD低聚物 反应DB_ID：708346 NOD1：IE-DAP低聚物 Reactome DB_ID：622306 cytosol. 基因本体论 去：0005829. NOD1: iE-DAP Reactome DB_ID: 168408 NOD1 Caspase招生域蛋白4 Reactome DB_ID: 168407 UNIPROT：Q9Y239 NOD1 NOD1 CARD4 功能增强Caspase-9介导的细胞凋亡。通过RIPK2和IKK-GAMMA诱导NF-KAPPA-B活性。赋予细胞内细菌脂多糖（LPS）的反应。形成细胞内传感系统以及arhgef2，用于在细胞侵袭过程中检测微生物效应。rhOA和RIPK2所需的NF-Kappa-B信号传导途径激活S.FlexNeri细胞侵袭。不仅涉及感测肽聚糖（PGN）的杂鼠，而且在Shigella效应蛋白IPGB2和OSPB中的NF-Kappa-B的激活中。在细菌感染后募集NLRP10至细胞膜。津属同杂草。自主联系人。通过卡片相互作用绑定到Caspase-9和RIPK2。与Arhgef2互动。 Interacts with NLRP10 and recruits it to the cell membrane following invasive bacterial infection. Interacts with RNF34.TISSUE SPECIFICITY Highly expressed in adult heart, skeletal muscle, pancreas, spleen and ovary. Also detected in placenta, lung, liver, kidney, thymus, testis, small intestine and colon.PTM Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF34 promotes proteasomal degradation and thereby negatively regulates NOD1 for instance in NF-kappa-B activition. HOMO SAPIENS. NCBI分类学 9606 uniprot. Q9Y239. 1 平等的 953. 平等的 Reactome数据库ID Release 77 168407. 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=168407 Reactome R-HSA-168407 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-168407.1 Reactome http://www.reacectome.org. 1 IE-DAP. 细胞内D-gamma-Glutamyl-meso-diamino-pimelic酸 gamma-D-glutamyl-meso-diaminopimelic酸 Reactome DB_ID：622271 γ-D-戊酰胺 - 甲基二氨基丙二酸[Chebi：59271] gamma-D-glutamyl-meso-diaminopimelic酸 Chebi. Chebi：59271 Reactome数据库ID Release 77 622271 数据库标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=622271 Reactome R-ALL-622271 4. Reactome稳定的标识符。使用此URL在反弹中连接到此实例的网页：http：//www.reacontome.org/cgi-bin/eventbrowser_st_id?st_id=r-all-622271.4 1 Reactome数据库ID Release 77 168408. 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=168408 Reactome R-HSA-168408 1 Reactome稳定的标识符。使用此URL将此实例的Web页面连接到Reactome：http：//www.reacontome.org/cgi-bin/eventbrowser_st_id?st_id=r-hsa-168408.1 6. Reactome数据库ID Release 77 622306 数据库标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=622306 Reactome R-HSA-622306 1 Reactome稳定的标识符。使用此URL在反垃圾中连接到此实例的网页：http：//www.reacectome.org/cgi-bin/eventbrowser_st_id?st_id=r-hsa-622306.1 MDP: NOD2低聚物 反应DB_ID：708350 MDP：NOD2 Reactome DB_ID: 168414 MDP. Muramyl二肽 反应DB_ID：708341 Muramyl Dipeptide [Chebi：59414] Muramyl二肽 Chebi. Chebi：59414 Reactome数据库ID Release 77 708341 数据库标识符。使用此URL在反弹中连接到此实例的网页：http：//www.reacontome.org/cgi-bin/eventbrowser?db=gk_current&id=708341 Reactome r - - 708341 4. Reactome稳定的标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-708341.4 1 NOD2 Caspase招生域蛋白15 Reactome DB_ID: 168411 UNIPROT：Q9HC29 NOD2 NOD2 卡15. IBD1. 功能胃肠免疫力参与。当通过胞壁酰二肽（MDP），细菌肽聚糖的片段刺激，结合近端适配器受体相互作用RIPK2，其募集泛素连接酶如XIAP，BIRC2，BIRC3，INAVA和LUBAC复杂，引发MAP激酶的活化和活化的NF-κ-B的信令。这反过来又导致数百个基因的转录激活参与免疫应答。需要MDP诱导NLRP1依赖性CASP1激活和释放IL1B在巨噬细胞（PUBMED：18511561）。成分的自噬体介导抗菌通路与ATG16L1一起的（PUBMED：20637199）。还在来自病毒感测单链RNA（ssRNA）的作用。与之交互线粒体抗病毒信号/ MAVS，导致活化干扰素调节因子-3 / IRF3和类型的表达我干扰素（PUBMED：19701189）的信号复合物选自由ARHGEF2，NOD2和RIPK2的.SUBUNIT组分（PUBMED：21887730）。相互作用（通过CARD结构域）与RIPK2（通过CARD结构域）（PUBMED：19592251，PUBMED：21887730，PubMed的：27812135）。化与ATG16L1（考研：20637199，考研：23376921）。相互作用（通过NACHT结构域）与CARD9（搜索PubMed：24960071）。 Interacts with ANKRD17 (via N-terminus) (PubMed:23711367). Interacts with HSPA1A; the interaction enhances NOD2 stability (PubMed:24790089). Interacts (via both CARD domains) with HSP90; the interaction enhances NOD2 stability (PubMed:23019338). Interacts (via CARD domain) with SOCS3; the interaction promotes NOD2 degradation (PubMed:23019338). Interacts (via CARD domain) with ERBBI2P; the interaction inhibits activation of NOD2 (PubMed:16203728). Interacts (via CARD domain) with CASP1; this interaction leads to IL1B processing. Also interacts with CASP4. Interacts with NLRP1; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and leads to increased IL1B release (PubMed:18511561). Interacts with MAPKBP1; the interaction is enhanced in the presence of muramyl dipeptide (MDP) (PubMed:22700971). Interacts with INAVA; the interaction takes place upon PRR stimulation (PubMed:28436939). Interacts with ANKHD1, C10ORF67, CHMP5, DOCK7, ENTR1, KRT15, LDOC1, PPP1R12C, PPP2R3B, TRIM41 and VIM (PubMed:27812135). Interacts with NLRP12; this interaction promotes degradation of NOD2 through the ubiquitin-proteasome pathway (PubMed:30559449).TISSUE SPECIFICITY Expressed in intestinal mucosa, mainly in Paneth cells and, at lower extent, in the glandular epithelium.INDUCTION Up-regulated by muramyl-dipeptide and lipopolysaccharide.DOMAIN The ATG16L1-binding motif mediates interaction with ATG16L1.DOMAIN Intramolecular interactions between the N-terminal moiety and the leucine-rich repeats (LRR) may be important for autoinhibition in the absence of activating signal. In the absence of LRRs, the protein becomes a constitutive activator of CASP1 cleavage and proIL1B processing.PTM Polyubiquitinated following MDP stimulation, leading to proteasome-mediated degradation (PubMed:23019338). uniprot. Q9HC29 1 平等的 1040 平等的 Reactome数据库ID Release 77 168411 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=168411 Reactome R-HSA-168411 1 Reactome稳定的标识符。使用此URL在反垃圾邮件中连接到此实例的网页：http：//www.reacontome.org/cgi-bin/eventbrowser_st_id?st_id=r-hsa-168411.1 1 Reactome数据库ID Release 77 168414 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=168414 Reactome R-HSA-168414 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-168414.1 6. Reactome数据库ID Release 77 708350 数据库标识符。使用此URL将此实例的网页连接到Reactome：http：//www.reacectome.org/cgi-bin/eventbrowser?db=gk_current&id = 708350 Reactome R-HSA-708350 1 Reactome稳定的标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-708350.1 Reactome数据库ID Release 77 708346 数据库标识符。使用此URL将此实例的网页连接到反乐中：http：//www.reacectome.org/cgi-bin/eventbrowser?db=gk_current&id=708346 Reactome r - hsa - 708346 1 Reactome稳定的标识符。使用此URL在反弹中连接到此实例的网页：http：//www.reacontome.org/cgi-bin/eventbrowser_st_id?st_id=r-hsa-708346.1 RIP2 ripk2. 瑞克 受体 - 相互作用丝氨酸 - 苏氨酸激酶2 Reactome DB_ID: 168402 UNIPROT：O43353 RIPK2 ripk2. CARDIAK 瑞克 RIP2 UNQ277 / PRO314 / PRO34092 丝氨酸/苏氨酸/酪氨酸激酶，在调节先天性和适应性免疫反应中起重要作用。在细菌肽聚糖的刺激下，NOD1和NOD2被激活，通过CARD-CARD域寡聚和招募RIPK2。通过Src酪氨酸激酶促进鸟嘌呤交换因子ARHGEF2的酪氨酸磷酸化，导致NOD2激活NF-kappaB。一旦被招募，RIPK2自磷酸化，并通过E3泛素连接酶XIAP、BIRC2和BIRC3进行'Lys-63'连接的多聚泛素化。多聚泛素化蛋白介导MAP3K7/TAK1向IKBKG/NEMO的募集，并诱导IKBKG/NEMO的' lys63 '连接多聚泛素化和随后IKBKB/IKKB的激活。反过来，NF-kappa-B从NF-kappa-B抑制剂中释放出来，并易位到细胞核中，在那里它激活了数百个参与免疫反应、生长控制或防止凋亡的基因的转录。在t细胞受体(TCR)参与促进BCL10磷酸化和随后的NF-kappa-B活化过程中也起作用。在应答NGFR信号的RHOA失活中发挥作用(PubMed:26646181)。亚单位存在于至少由ARHGEF2, NOD2和RIPK2组成的信号复合物中。与ARHGEF2交互;这种相互作用通过Src激酶CSK介导RIPK2的酪氨酸磷酸化。 Binds to CFLAR/CLARP and CASP1 via their CARD domains. Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6. May be a component of both the TNFRSF1A and TNRFSF5/CD40 receptor complex. Interacts with NOD1. Interacts (via CARD domain) with NOD2 (via CARD domain) (PubMed:19592251, PubMed:21887730, PubMed:27812135). Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway. Interacts with IKBKG/NEMO. The polyubiquitinated protein interacts with MAP3K7/TAK1. Interacts with XIAP/BIRC4. Interacts with NLRP10. Interacts with CARD9. Interacts with INAVA; the interaction takes place upon PRR stimulation (PubMed:28436939). Interacts (via CARD domain) with NGFR (via death domain) (PubMed:26646181).TISSUE SPECIFICITY Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.DOMAIN Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins.PTM Autophosphorylated. Autophosphorylation at Tyr-474 is necessary for effective NOD2 signaling. Phosphorylated. Phosphorylation at Tyr-381 by Src kinase CSK occurs in a ARHGEF2-dependent manner and is required for NOD2-dependent innate immune activation.PTM Ubiquitinated on Lys-209; undergoes 'Lys-63'-linked polyubiquitination catalyzed by ITCH. Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Also undergoes 'Met-1'-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation. Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent proinflammatory signaling activation of NF-kappa-B. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to attenuate NOD2-mediated inflammation and tissue damage (By similarity).PTM (Microbial infection) Acetylation of Ser-174, Ser-176 and Ser-178 by Yersinia YopJ prevents phosphorylation and activation, thereby promoting cell death.SIMILARITY Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. uniprot. O43353 1 平等的 540. 平等的 Reactome数据库ID Release 77 168402 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=168402 Reactome R-HSA-168402 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-168402.1 6. PAMP：NOD Oligomer：RIP2 Reactome DB_ID: 168409 1 6. Reactome数据库ID Release 77 168409. 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=168409 Reactome R-HSA-168409 1 Reactome稳定的标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-168409.1 Reactome数据库ID Release 77 168405. 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=168405 Reactome R-HSA-168405 1 Reactome稳定的标识符。使用此URL连接到该实例的网页中Reactome：//www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-168405.1 11087742 Pubmed 2001年 NOD2，NOD1 / APAF-1家族构件仅限于单核细胞并激活NF-κB ogura，Y. Inohara，N 贝尼托，A 陈,FF 山冈,年代 Nunez，G. J Biol Chem 276：4812-8 19473975 Pubmed 2009 RIP2的激酶活性决定了其稳定性，从而确定了NOD1和NOD2介导的免疫反应 NEMBRINI，C. Kisielow J Shamshiev，AT 托托拉岛, Coyle，AJ. 科夫，男 Marsland，BJ. J Biol Chem 284:19183-8 10329646. Pubmed 1999年 NOD1，一个激活因子1样活化胱天蛋白酶-9和核因子-κB的 Inohara，N 小关，T del peso，l 胡，y 议，C 陈,年代 卡里奥,R Merino，J. 刘，D 倪J Nunez，G. J Biol Chem 274:14560-7 10224040 Pubmed 1999年 人类CARD4蛋白是一种新的CED-4/Apaf-1细胞死亡家族成员，可激活NF-kappaB 贝尔坦，J NIR，WJ. 菲舍尔，CM 泰伯，ov. Errada,公关 格兰特，Jr. Keilty，JJ Gosselin,毫升 罗宾逊,客 Wong，GH. 格鲁克斯曼，MA 迪斯泰法诺，PS J Biol Chem 274:12955-8 10880512 Pubmed 2000年 NOD1 / RICK和RIP信令路径中NF-Kappa B激活的诱导近似模型 Inohara，N 小关，T 林,我 del peso，l 卢卡斯,电脑 陈,FF ogura，Y. Nunez，G. J Biol Chem 275：27823-31 17348859 Pubmed 2007 由Muramyl Dipeptide进行细胞因子产生调节的分子机制 Windheim，男 郎，C 药,M Platet，La. 科恩,P 生物化学杂志404：179-90