BIoPAX路径从反应数据库中的“Chek1磷酸盐Rad51”转换。

2.7.11

Chek1磷酸化Rad51.

在苏氨酸残留T309上活化Chek1磷酸化rad51，这对于染色质（Sorensen等人2005）是必要的。

撰写：Orlic-Milacic，Marija，2015-05-12 审查：Borowiec，James A，2015-06-12 编辑：Orlic-Milacic，Marija，2015-05-12

Reactome DB_ID: 62637

骨髓去 0005654.

UNIPROT：Q06609 RAD51

RAD51

Rad51a. RAD51 RECA 功能在同源斯坦克交换中起重要作用，通过同源重组（HR）进行DNA修复的关键步骤（PubMed：28575658）。与单链和双链DNA结合，并表现出DNA依赖性的ATP酶活性。催化同源DNA合作伙伴之间的同源性和链交换的识别，在加工的DNA断裂和修复模板之间形成关节分子。以ATP依赖性方式与单链DNA结合以形成对同源搜索和斯特兰替交换（PubMed：26681308）必不可少的核蛋白丝。含有BRCA2和RAD51C的PALB2-脚手架HR复合物的一部分，并且被认为在DNA修复中发挥作用。在RAD51C和XRCC3存在下在氧化应激条件下调节线粒体DNA拷贝数的作用。也涉及Interstrand Cross-Link修复（PubMed：26253028）.subunit形成线性碘聚物，产生了Rad51核蛋白丝，这对于DNA重组期间的链对反应至关重要。与BRCA1相互作用，直接或间接与P53。与XRCC3，RAD54L和RAD54B交互。与BCDX2子码头RAD51C：RAD51B交互。 Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with RAD51AP1 and RAD51AP2. Interacts with CHEK1, and this may require prior phosphorylation of CHEK1. Interacts with the MND1-PSMC3IP heterodimer. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with SPIDR; the interaction is direct and recruits RAD51 to DNA damage sites. Interacts with FIGNL1 (via N-terminal one-half region); the interaction is direct. Interacts with RAD51AP1 (via C-terminal region); the interaction is direct. Interacts with NABP2, RPA1, PALB2 and RAD51. Interacts with SWI5/C9orf119, and at lower level with SFR1/MEIR5. Interacts with hyperphosphorylated RPA2; this interaction is necessary for efficient recruitment to chromatin in response to DNA damage. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with PARPBP, BRCA2 and RECQL5; these interactions interfere with the formation of the RAD51-DNA homologous recombination structure. Interacts with POLQ; POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). Interacts with FBH1 (PubMed:23393192). Interacts with POLN (PubMed:19995904). Interacts with RFWD3 (PubMed:28575658). Interacts with the MCM8-MCM9 complex; the interaction recruits RAD51 to DNA damage sites (PubMed:23401855). Component of a multiprotein complex with MEIOB and SPATA22. Interacts with the complex BRME1:HSF2BP:BRCA2 (By similarity).TISSUE SPECIFICITY Highly expressed in testis and thymus, followed by small intestine, placenta, colon, pancreas and ovary. Weakly expressed in breast.INDUCTION Stress-induced increase in the mitochondrial levels is seen.DOMAIN The nuclear localization may reside in the C-terminus (between 259 and 339 AA).PTM Ubiquitinated by the SCF(FBH1) E3 ubiquitin ligase complex, regulating RAD51 subcellular location and preventing its association with DNA. Ubiquitinated by RFWD3 in response to DNA damage: ubiquitination leads to degradation by the proteasome, promoting homologous recombination (PubMed:28575658).PTM Phosphorylated. Phosphorylation of Thr-309 by CHEK1 may enhance association with chromatin at sites of DNA damage and promote DNA repair by homologous recombination. Phosphorylation by ABL1 inhibits function.SIMILARITY Belongs to the RecA family. RAD51 subfamily. 反应 http://www.reacectome.org. HOMO SAPIENS.

NCBI分类学 9606 uniprot. Q06609.

链坐标

平等的

339.

平等的

反应DB_ID：29358

ATP（4-）[Chebi：30616]

ATP（4-）

腺苷5'-三磷酸盐 atp. 三磷酸腺苷 Chebi. 30616.

反应DB_ID：113582

ADP（3-）[Chebi：456216]

ADP（3-）

ADP TriaNion. 事情就让它5,- o - [(phosphonatooxy) phosphinato]腺苷 ADP. Chebi. 456216

反应DB_ID：5685231

o-磷酸-1-苏氨酸在309

309

平等的

O-phospho-L-threonine (MOD: 00047)

平等的

339.

平等的

物理体左右

激活

反应DB_ID：113838

UNIPROT：O14757 CHEK1

Chek1.

CHK1 Chek1. 函数丝氨酸/苏氨酸蛋白激酶需要检查点介导的细胞周期停滞和DNA修复的激活响应DNA损伤或不良DNA的存在（PubMed：11535615，PubMed：1244677，PubMed：12399544，PubMed：14559997，PubMed：14988723，PubMed：15311285，PubMed：15665856，PubMed：15650047）。也可以在未受干扰的细胞周期中调节细胞周期进展（PubMed：11535615，PubMed：12446774，PubMed：12399544，Pubmed：14559997，PubMed：14988723，PubMed：15311285，PubMed：15665856，PubMed：15650047）。该调节通过多种机制实现，其中一些机制有助于保持基因组的完整性（PUBMED：11535615，PUBMED：1244677，PUBMED：12399544，PUBMED：14559997，PUBMED：14988723，PubMed：15311285，PubMed：15665856，PubMed：15650047）。识别基板共识序列[R-X-X-S / T]（PubMed：11535615，PubMed：12446774，PubMed：12399544，PubMed：14559997，PubMed：14988723，PubMed：15311285，PubMed：15665856，PubMed：15650047）。结合和磷酸化CDC25A，CDC25B和CDC25C（PubMed：9278511，PubMed：12676583，PubMed：14681206，PubMed：12676925，PubMed：12759351，PubMed：19734889，PubMed：14559997）。CDC25A在“Ser-178”和“Ser-216”中的CDC25C磷酸化的磷酸化产生14-3-3蛋白的结合位点，抑制CDC25A和CDC25C（PubMed：9278511）。CDC25A在“SER-76”，“SER-124”，“SER-178”，“SER-279”和“SER-293”中的磷酸化促进CDC25A的蛋白水解（PUBMED：9278511，PUBMED：12676583，PUBMED：14681206，PubMed：12676925，PubMed：12759351，PubMed：19734889）。NEK11在“SER-79”，“SER-82”，“SER-82”和“SER-88”中的磷酸化蛋白质磷酸化的磷酸化，这是CDCD25A的多共涵化和降解所需的（Pubmed：9278511， PubMed:19734889, PubMed:20090422). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758).ACTIVITY REGULATION Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication (PubMed:11390642, PubMed:12588868, PubMed:12676583, PubMed:12676962, PubMed:15665856, PubMed:19716789). Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B (PubMed:11836499, PubMed:12766152, PubMed:16963448, PubMed:19330022). Proteolytic cleavage at the C-terminus by SPRTN during normal DNA replication activates the protein kinase activity (PubMed:31316063).SUBUNIT Interacts (phosphorylated by ATR) with RAD51 (PubMed:15665856). Interacts with and phosphorylates CLSPN, an adapter protein that regulates the ATR-dependent phosphorylation of CHEK1 (PubMed:16963448). Interacts with BRCA1 (PubMed:11836499). Interacts with and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:9278511). Interacts with FBXO6, which regulates CHEK1 (PubMed:19716789). Interacts with PPM1D, which regulates CHEK1 through dephosphorylation (PubMed:15870257). Interacts with TIMELESS; DNA damage-dependent (PubMed:15798197). Interacts with FEM1B; activates CHEK1 in response to stress (PubMed:19330022). Interacts with TLK1 (PubMed:12660173). Interacts with XPO1 and YWHAZ (PubMed:12676962). Interacts with CDK5RAP3; antagonizes CHEK1 (PubMed:19223857).TISSUE SPECIFICITY Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon.DOMAIN The autoinhibitory region (AIR) inhibits the activity of the kinase domain.PTM Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation. ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity. Phosphorylation at Ser-345 induces a change in the conformation of the protein, activates the kinase activity and is a prerequisite for interaction with FBXO6 and subsequent ubiquitination at Lys-436. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention. Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest. Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination. Also phosphorylated at undefined residues during mitotic arrest, resulting in decreased activity.PTM Ubiquitinated. Mono or diubiquitination promotes nuclear exclusion (By similarity). The activated form (phosphorylated on Ser-345) is polyubiquitinated at Lys-436 by some SCF-type E3 ubiquitin ligase complex containing FBXO6 promoting its degradation. Ubiquitination and degradation are required to terminate the checkpoint and ensure that activated CHEK1 does not accumulate as cells progress through S phase, when replication forks encounter transient impediments during normal DNA replication.PTM Proteolytically cleaved at the C-terminus by SPRTN during normal DNA replication, thereby promoting CHEK1 removal from chromatin and activating the protein kinase activity.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily. uniprot. O14757.

o-磷酸-1-丝氨酸在317

317.

平等的

O-phospho-L-serine (MOD: 00046)

O-phospho-L-serine在345

345

平等的

476.

平等的

去 0004674.

去分子功能

反应数据库ID版本77 182636 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=182636 反应数据库ID版本77 5685230 数据库标识符。使用此URL将此实例的网页连接到Reactome：http：//www.reacontome.org/cgi-bin/eventbrowser?db=gk_current&id=5685230 反应 r - hsa - 5685230

反应稳定标识符。使用此URL将此实例的网页连接到Reactome：http：//www.reacontome.org/cgi-bin/eventbrowser_st_id?st_id=r-hsa -5685230.1 15665856 Pubmed 2005年哺乳动物同源重组修复需要细胞周期检查点激酶CHK1 Sørensen，克劳斯商店汉森，Lasse tengbjerg Dziegielewski雅罗斯瓦夫 syljuåsen，randi g 伦丁，塞西莉亚 Bartek Jiri 地狱，托马斯 NAT。细胞生物。7：195-201