bioax途径由Reactome数据库中“SOS介导的RAS核苷酸交换(SHC)”转化而来。 SOS介导的RAS核苷酸交换(SHC)

SOS介导的RAS核苷酸交换(SHC)

grb2结合的SOS促进gtp结合RAS的形成。这激活了丝裂原活化蛋白激酶(MAPK)级联，导致细胞生长和分化。

作者:Garapati, P V, 2012-05-25 中国海洋大学学报(自然科学版)，2012-08 编辑:Garapati, P V, 2012-05-25

Reactome DB_ID: 29438

胞质去 0005829

三磷酸鸟苷(ChEBI: 15996)

三磷酸鸟苷

鸟嘌呤核苷5 '三磷酸 Reactome //www.joaskin.com ChEBI 15996

Reactome DB_ID: 109796

等离子体膜去 0005886 p21 RAS:GDP[质膜]

RAS p21:国内生产总值

Reactome DB_ID: 29420

国内生产总值(ChEBI: 17552)

国内生产总值

鸟嘌呤核苷5 '磷酸氢盐鸟苷二磷酸 ChEBI 17552 从Reactome中的EntitySet转换而来

Reactome DB_ID: 9649715

成熟的p21 RAS[质膜] 从Reactome中的EntitySet转换而来。每个同义词是一个PhysicalEntity的名称，每个XREF指向一个PhysicalEntity S-Farn-Me PalmS NRAS S-Farn-Me-PalmS KRAS4A[质膜] S-Farn-Me KRAS4B[质膜] HRAS[质膜] UniProt P01111 UniProt P01116-1 UniProt P01116-2 UniProt P01112 智人

NCBI分类法 9606 Reactome数据库ID Release 77 109796 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=109796 Reactome r - hsa - 109796

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-109796.2

Reactome DB_ID: 29420

Reactome DB_ID: 109783

p21 RAS:GTP[质膜]

RAS p21:三磷酸鸟苷

Reactome DB_ID: 29438

从Reactome中的EntitySet转换而来

Reactome DB_ID: 9649715

Reactome数据库ID Release 77 109783 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=109783 Reactome r - hsa - 109783

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-109783.2 PHYSIOL-LEFT-TO-RIGHT

激活

Reactome DB_ID: 2424468 p-5Y-LAT: p-SHC1: GRB2: SOS1(质膜)

p-5Y-LAT: p-SHC1: GRB2: SOS1

Reactome DB_ID: 2396597

UniProt: O43561-2纬度

纬度

纬度 TCR (t细胞抗原受体)和TCR前介导的信号转导所必需的功能，无论是在成熟t细胞中还是在它们的发育过程中。参与自然杀伤细胞中FCGR3(低亲和力免疫球蛋白γ Fc区域受体III)介导的信号传导，肥大细胞中FCER1(高亲和力免疫球蛋白epsilon受体)介导的信号传导。这些受体及其相关激酶的激活与细胞内远端事件，如通过PLCG1、GRB2、GRAP2和其他信号分子的招募，动员细胞内钙库、PKC激活、MAPK激活或细胞骨架重组等相互作用。亚基磷酸化后直接与肌磷脂3-激酶的PIK3R1亚基和GRB2、GRAP、GRAP2、PLCG1和PLCG2的SH2结构域相互作用。与CBL、SOS、VAV和LCP2间接相互作用。与SHB, SKAP2和CLNK相互作用(通过相似性)。与FCGR1A交互。在胸腺细胞TCR激活时与GRB2, PLCG1和THEMIS相互作用(相似)。组织特异性在胸腺，t细胞，NK细胞，肥大细胞和脾脏中表达。存在于t细胞而不存在于b细胞(在蛋白质水平上)。PTM在TCR激活时被ZAP70磷酸化在酪氨酸上，或被SYK磷酸化在其他免疫受体上; which leads to the recruitment of multiple signaling molecules. Is one of the most prominently tyrosine-phosphorylated proteins detected following TCR engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK leading to the recruitment of VAV1 to LAT-containing complexes.PTM Palmitoylation of Cys-26 and Cys-29 is required for raft targeting and efficient phosphorylation.MISCELLANEOUS Engagement of killer inhibitory receptors (KIR) disrupts the interaction of PLCG1 with LAT and blocks target cell-induced activation of PLC, maybe by inducing the dephosphorylation of LAT. UniProt O43561-2

O4 -phospho-L-tyrosine 127

127

平等的

O4的-phospho-L-tyrosine (MOD: 00048)

O4 -phospho-L-tyrosine 132

132

平等的

O4 -phospho-L-tyrosine 171

171

平等的

O4 -phospho-L-tyrosine 191

191

平等的

O4 -phospho-L-tyrosine 226

226

平等的

链坐标

平等的

262

平等的

Reactome DB_ID: 2685672

p-SHC1: GRB2: SOS(胞质)

p-SHC1: GRB2: SOS

Reactome DB_ID: 109797

GRB2-1: SOS1(胞质)

GRB2-1: SOS1

Reactome DB_ID: 64847

UniProt: Q07889 SOS1

SOS1

SOS1 功能通过GTP促进Ras-bound GDP的交换(PubMed:8493579)。可能是通过促进Ras激活，调节对EGF响应的MAP激酶MAPK3的磷酸化(PubMed:17339331)。三聚体复合物的催化成分，通过促进Rac特异性鸟嘌呤核苷酸交换因子(GEF)活性，参与从Ras到Rac的信号转导(通过相似性)。亚基(通过c端)与GRB2(通过SH3结构域)相互作用(PubMed:8493579, PubMed:7664271)。与磷酸化的MUC1和GRB2形成复合物(通过其SH3结构域)(PubMed:7664271)。与磷酸化LAT2相互作用(PubMed:12486104)。与NCK1和NCK2相互作用(PubMed:10026169)。由ABI1, EPS8和SOS1组成的复合物的一部分(通过相似性)。与YWHAB和YWHAE相互作用(ser1134和ser1161磷酸化形式)(PubMed:22827337)。牙龈组织表达的组织特异性。PTM通过RPS6KA3在Ser-1134和Ser-1161位点磷酸化，产生YWHAB和YWHAE结合位点，并参与egf诱导的MAPK1/3磷酸化的负调控。 UniProt Q07889

平等的

1333

平等的

Reactome DB_ID: 74686

UniProt: P62993-1 GRB2

GRB2

灰 GRB2 其提供细胞表面生长因子受体和Ras信号pathway.SUBUNIT协会（通过SH2结构域）之间的关键环节功能转接蛋白与活化EGF和PDGF受体（酪氨酸磷酸化）（PUBMED：10026169，PUBMED：19836242）。与PDGFRA（酪氨酸磷酸）相互作用;的相互作用可以是间接的（通过相似性）。也同伙其它细胞酪氨酸 - 磷酸化的蛋白质，如SIT1，IRS1，IRS4，SHC和LNK;可能是通过其两个SH2和SH3结构域的一致行动（PUBMED：8388384，PUBMED：8491186，PUBMED：9553137，PUBMED：11433379）。它也似乎在信号通路，导致DNA合成与RAS进行交互。化与SOS1（考研：8493579，考研：7664271）。形成复合物MUC1和SOS1，通过SH3结构域与SOS1和与磷酸化MUC1的SH2结构域的相互作用（PUBMED：7664271）。化与磷酸化MET（考研：11063574，考研：11827484）。化与磷酸化TOM1L1（通过相似）。 Interacts with the phosphorylated C-terminus of SH2B2 (PubMed:9233773). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:9489702, PubMed:12359715, PubMed:12486104, PubMed:12514734). Interacts with NISCH, PTPNS1 and REPS2 (PubMed:9062191, PubMed:9422736, PubMed:11912194). Interacts with syntrophin SNTA1 (By similarity). Interacts (via SH3 domains) with REPS1 (By similarity). Interacts (via SH3 domains) with PIK3C2B (PubMed:11533253). Interacts with CBL and CBLB (PubMed:10022120, PubMed:10086340). Interacts with AJUBA and CLNK (By similarity). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (PubMed:8723348, PubMed:9108392, PubMed:9484780, PubMed:10942756, PubMed:12171928). Interacts with PTPN11 (By similarity). Interacts with PRNP (By similarity). Interacts with RALGPS1 (PubMed:10747847). Interacts with HCST (PubMed:16582911). Interacts with KDR (By similarity). Interacts with FLT1 (tyrosine-phosphorylated) (By similarity). Interacts with GAPT and PTPRE (PubMed:10980613, PubMed:18559951). Interacts (via SH2 domain) with KIF26A (PubMed:19914172). Interacts (via SH3 2) with GAB2 (PubMed:19523899). Interacts with ADAM15 (PubMed:18296648). Interacts with THEMIS2 (By similarity). Interacts (via SH2 domain) with AXL (phosphorylated) (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:15526160, PubMed:16129412). Interacts with PTPRJ and BCR (PubMed:12475979, PubMed:15302586). Interacts with PTPN23 (PubMed:21179510). Interacts with FLT4 (tyrosine phosphorylated) (PubMed:15102829). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:8798570, PubMed:12925710). Part of a complex including TNK2, GRB2, LTK and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:8262059). Interacts with ERBB4 (PubMed:10867024). Interacts with NTRK1 (phosphorylated upon ligand-binding) (PubMed:15488758). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:9148935). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (PubMed:20521079). Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (PubMed:19509291). Interacts with DAB2 (By similarity). Interacts with TESPA1 (PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (By similarity). Interacts with CD28 (PubMed:24098653). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (By similarity). Interacts with ASAP3 (phosphorylated form) (PubMed:22027826). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (PubMed:27041574). Interacts with FCRL6 (tyrosine phosphorylated form) (PubMed:20933011). Interacts with RHEX (via tyrosine-phosphorylated form) (PubMed:25092874). Interacts with DENND2B (PubMed:29030480). Interacts with SPRY2 (PubMed:17974561). Interacts with LRRC8A (By similarity).SUBUNIT (Microbial infection) Interacts (via SH3 domain) with hepatitis E virus/HEV ORF3 protein.SUBUNIT (Microbial infection) Interacts with hepatitis C virus/HCV protein NS5A via its SH3 domains.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 protein UL46.DOMAIN The SH3 domains mediate interaction with RALGPS1 and SHB.SIMILARITY Belongs to the GRB2/sem-5/DRK family.CAUTION Was shown to interact with ZDHHC19, leading to recruitment of STAT3. However, this study was later retracted. UniProt P62993-1

平等的

217

平等的

Reactome数据库ID Release 77 109797 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=109797 Reactome r - hsa - 109797

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-109797.3

Reactome DB_ID: 1433505

UniProt: P29353-2 SHC1

SHC1

SHC1 SHCA 人体自燃将激活的生长因子受体与信号通路结合的信号转接器。参与由激活的KIT和KITLG/SCF发起的信号级联。亚型p46Shc和亚型p52Shc一旦磷酸化，通过GRB2/SOS复合物的募集，将激活的受体酪氨酸激酶与Ras结合，并参与有丝分裂信号的细胞质传播。亚型p46Shc和亚型p52Shc可能在各种非神经元系统中作为Ras信号级联的启动子。Isoform p66Shc不介导Ras激活，但参与信号转导途径，调节细胞对氧化应激和寿命的反应。亚型p66Shc作为肿瘤抑制因子p53的下游靶点，对于应激激活的p53诱导细胞内氧化剂升高、细胞色素c释放和凋亡的能力必不可少。p66Shc亚型的表达与寿命相关(通过相似性)。参与血管生成素受体TEK/TIE2下游信号转导，调控内皮细胞迁移和新生血管生成。亚基与CPNE3相互作用;这种相互作用可能介导CPNE3与ERBB2的结合(PubMed:20010870)。在体外通过PID结构域与酪氨酸磷酸化IGF1R和INSR的NPXY motif相互作用。 Once activated, binds to GRB2. Interacts with tyrosine-phosphorylated CD3T and DDR2. Interacts with the N-terminal region of SH2B2. Interacts with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with TRIM31. Interacts with PTPN6/SHP (tyrosine phosphorylated). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTT (By similarity). Interacts with ALK, GAB2, GRB7 and KIT. Interacts with FLT4 (tyrosine-phosphorylated). Interacts with EPHB1 and GRB2; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PDGFRB (tyrosine-phosphorylated). Interacts with ERBB4. Interacts with TEK/TIE2 (tyrosine-phosphorylated). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. Interacts with PTK2/FAK1. Interacts with CEACAM1; this interaction is CEACAM1-phosphorylation-dependent and mediates interaction with EGFR or INSR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Interacts (via PID domain) with PEAK1 (when phosphorylated at 'Tyr-1188') (PubMed:23846654). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 UL46.TISSUE SPECIFICITY Widely expressed. Expressed in neural stem cells but absent in mature neurons.DOMAIN In response to a variety of growth factors, isoform p46Shc and isoform p52Shc bind to phosphorylated Trk receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif of the Trk receptors. Isoform p46Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation (By similarity).PTM Phosphorylated by activated epidermal growth factor receptor. Phosphorylated in response to FLT4 and KIT signaling. Isoform p46Shc and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-rich domain. Isoform p66Shc is phosphorylated on Ser-36 by PRKCB upon treatment with insulin, hydrogen peroxide or irradiation with ultraviolet light (By similarity). Tyrosine phosphorylated in response to FLT3 signaling (By similarity). Tyrosine phosphorylated by activated PTK2B/PYK2 (By similarity). Tyrosine phosphorylated by ligand-activated ALK. Tyrosine phosphorylated by ligand-activated PDGFRB. Tyrosine phosphorylated by TEK/TIE2. May be tyrosine phosphorylated by activated PTK2/FAK1; tyrosine phosphorylation was seen in an astrocytoma biopsy, where PTK2/FAK1 kinase activity is high, but not in normal brain tissue. Isoform p52Shc dephosphorylation by PTPN2 may regulate interaction with GRB2. UniProt P29353-2

O4 -phospho-L-tyrosine 239

239

平等的

O4 -phospho-L-tyrosine 240

240

平等的

O4 -phospho-L-tyrosine 317

317

平等的

111

平等的

583

平等的

Reactome数据库ID Release 77 2685672 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=2685672 Reactome r - hsa - 2685672

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-2685672.1 Reactome数据库ID Release 77 2424468 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=2424468 Reactome r - hsa - 2424468

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-2424468.1 去 0005085

去分子功能

Reactome数据库ID Release 77 2424479 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=2424479 Reactome数据库ID Release 77 2424477 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=2424477 Reactome r - hsa - 2424477

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-2424477.1 9690470 Pubmed 1998 Sos激活Ras的结构基础 Boriack-Sjodin,爸爸 Margarit, SM Bar-Sagi,莱 Kuriyan J 自然394:337-43