BioPAX通路从“CBL结合B细胞连接蛋白”在Reactome数据库转换。 CBL结合B细胞接头蛋白 CBL结合B细胞接头蛋白 CBL通过募集信号分子，例如BTK，磷脂脂酶Cγ2，VAV和GRB2，将分子支架桥接Syk与下游信号传导途径结合到下游信号途径中以形成信号组络合物。CBL被认为是从该复合物中产生负调节信号传导。符合此，CBL Inactivation在BlnK缺陷小鼠中看到的早期B细胞分化中的许多关键缺陷（Song等人。2007）。 撰写：Ray，KP，2010-05-17 来自：洛佩兹，AF，2010-09-06 来自：赫克斯，TR，2010-09-06 编辑：Jupe，S，2010-08-06 反应DB_ID：912750 1 cytosol. 走 0005829. UniProt的：Q8WV28 BLNK BLNK SLP65 BLNK 抨击 功能用作中央接头蛋白，B细胞受体（BCR）下游，将Syk激酶桥接到多种信号通路和调节B细胞功能和发育的生物学结果。在激活ERK / EPHB2，MAP激酶P38和JNK中发挥作用。调制AP1激活。对NF-Kappa-B和NFAT的激活很重要。在BCR介导的PLCG1和PLCG2活化和CA（2+）动员中起重要作用，并且是将BCR贩运到晚期的贩运所必需的。然而，预BCR介导的MAP激酶和磷脂酰 - 肌醇3（PI3）激酶信号传导的激活似乎似乎似乎不需要。可能需要RAC1-JNK途径。在向前B细胞转换中扮演Pro-B单元的关键作用。可能在BCR诱导的B细胞凋亡中发挥重要作用。用PLCG1，VAV1和NCK1以B细胞抗原受体依赖性方式缔合的作用。与VAV3，PLCG2和GRB2交互。 Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-131' (PubMed:21930792).TISSUE SPECIFICITY Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.PTM Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca(2+) and MAPK signaling pathways. 反应 http://www.reacectome.org. HOMO SAPIENS. NCBI分类学 9606 uniprot. Q8WV28 链坐标 1 平等的 456. 平等的 反应DB_ID：912656 1 UNIPROT：P22681 CBL CBL. RNF55 CBL2 CBL. 功能转接蛋白，其功能如同由细胞表面受体的活化而触发许多信号传导途径的负调节物。充当E3泛素 - 蛋白连接酶，其来自特定E2泛素接受泛素结合酶，然后将其转移到被蛋白酶体促进它们的降解底物（PUBMED：17094949）。泛素化SPRY2（考研：17094949，考研：17974561）。泛素化EGFR（考研：17974561）。识别激活的受体酪氨酸激酶，包括KIT，FLT1，FGFR1，FGFR2，PDGFRA，PDGFRB，CSF1R，EPHA8和KDR和终止信号。确认膜结合HCK，SRC和SRC家族的其他激酶，介导的泛素化和降解。参与造血细胞信号转导。扮演成骨细胞分化和凋亡的调控具有重要作用。至关重要的破骨细胞。在“的Tyr-731”磷酸化形式诱导的活化和磷脂酰肌醇3-激酶的募集到细胞膜在对于破骨细胞功能的关键的信号通路。 May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Forms homodimers; IFT20 promotes the formation of stable homodimers (PubMed:29237719). Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2 (By similarity). Interacts with CBLB (PubMed:29237719). Interacts with ALK, AXL, BLK, FGR and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with ATX2 (By similarity). Interacts with TEK/TIE2 (tyrosine phosphorylated). Interacts with SH3KBP1 and this interaction is inhibited in the presence of SHKBP1 (By similarity). Interacts with SIGLEC10 (By similarity). Interacts with IFT20 (PubMed:29237719). Interacts with SPRY2; the interaction inhibits CBL-mediated ubiquitination of EGFR (PubMed:17974561).SUBUNIT (Microbial infection) Interacts with M.tuberculosis LpqN, which influences the balance between intrinsic antibacterial and antiviral defense.DOMAIN The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.DOMAIN The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.PTM Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine residues by HCK.PTM Ubiquitinated, leading to its degradation via the proteasome (PubMed:11896602, PubMed:20094046). Ubiquitination is negatively regulated by IFT20 (PubMed:29237719).MISCELLANEOUS This protein has one functional calcium-binding site. uniprot. P22681 O4'-磷酸-1-酪氨酸在731 731. 平等的 O4'-磷酸-1-酪氨酸[MOD：00048] O4'-磷酸-1-酪氨酸在700 700 平等的 O4'-磷酸-1-酪氨酸在774 774. 平等的 1 平等的 906. 平等的 Reactome DB_ID：912760 1 B细胞连接蛋白：P（Y700,731,774）-CBL [胞质溶胶] B细胞接头蛋白：P（Y700,731,774）-CBL 反应DB_ID：912750 1 1 平等的 456. 平等的 反应DB_ID：912656 1 O4'-磷酸-1-酪氨酸在731 731. 平等的 O4'-磷酸-1-酪氨酸在700 700 平等的 O4'-磷酸-1-酪氨酸在774 774. 平等的 1 平等的 906. 平等的 反应数据库ID版本77 912760. 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=912760 反应 R-HSA-912760 1 反应稳定标识符。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-912760.1 反应数据库ID版本77 912724. 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=912724 反应 R-HSA-912724 1 反应稳定标识符。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-912724.1 17202354 PubMed. 2007年 冗余在B细胞发育途径：C-CBL灭活通过B细胞连接蛋白依赖途径拯救早期B细胞发育 宋，H 张，J. 蒋，yj. Siraganian，RP 霍兹，RJ J免疫素178：926-35