bioax途径由Reactome数据库中的“BAP1结合BRCA1:BARD1异源二聚体”转化而来。 左到右 BAP1结合BRCA1:BARD1异源二聚体 BAP1主要通过与BARD1的相互作用与BRCA1:BARD1复合物结合，尽管BRCA1增强了相互作用。BAP1的182-365氨基酸残基与BARD1的RING结构域结合，但位于BARD1 RING结构域的brca1结合位点之外(Nishikawa et al. 2009)。 作者:Orlic-Milacic, Marija, 2020-09-30 评论:Baer, Richard J, 2020-11-04 编者按:Orlic-Milacic, Marija, 2020-11-09 BRCA1：BARD1. Reactome DB_ID: 5659802 核浆 基因本体论 去:0005654 乳腺癌易感基因1 乳腺癌1型易感蛋白 反应DB_ID：50949 UniProt: P38398 BRCA1 乳腺癌易感基因1 RNF53 FUNCTION E3泛素 - 蛋白连接酶特异性介导“的Lys -6'-联聚泛素链的形成和通过促进DNA损伤的细胞应答在DNA修复中心作用（PUBMED：12890688，PUBMED：14976165，PUBMED：16818604，PubMed的：17525340，考研：12887909，考研：10500182，考研：19261748）。目前还不清楚其是否也介导其它类型的多泛素链（搜索PubMed：12890688）的形成。的BRCA1-BARD1异二聚体坐标细胞途径如DNA损伤修复，泛素化和转录调节来维持基因组稳定性的不同范围（PUBMED：12890688，PUBMED：14976165，PUBMED：20351172）。调控对中心体微核（考研：18056443）。在S相和细胞周期的G2期既电离辐射后需要进行适当的细胞周期阻滞（：10724175，PUBMED：PUBMED 12183412，PUBMED：11836499，PUBMED：19261748）。需要FANCD2靶向DNA损伤的位点（PUBMED：12887909）。通过结合到磷酸化的无活性和ACACA防止其去磷酸化抑制脂质合成（PUBMED：16326698）。部分是通过在DNA断裂BRCA2-RAD51修复机制的PALB2依赖加载其调节作用，有助于通过与PALB2，微调重组修复的直接互动同源重组修复（HRR）（PUBMED：19369211）。的BRCA1-RBBP8复杂，其调节CHEK1激活和控制细胞周期G2 /经由RBBP8的BRCA1介导的泛素化DNA损伤中号检查站的组分（PUBMED：16818604）。作为转录激活因子（PUBMED：20160719）.ACTIVITY调节E3泛素 - 蛋白连接酶的活性是通过磷酸化的抑制通过AURKA。 Activity is increased by phosphatase treatment.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Heterodimer with BARD1 (PubMed:11573085, PubMed:12890688, PubMed:14976165). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165). Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19261746, PubMed:19261748, PubMed:19261749, PubMed:20351172). Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage (PubMed:17525340, PubMed:17643121, PubMed:17643122, PubMed:24316840, PubMed:26778126, PubMed:23269703). Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form) (PubMed:26778126). Component of the BRCA1-RBBP8 complex (PubMed:16101277). Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage (PubMed:16818604, PubMed:9811458). Associates with RNA polymerase II holoenzyme (PubMed:9662397). Interacts with SMC1A, NELFB, DCLRE1C, CLSPN (PubMed:11877377, PubMed:15096610, PubMed:15456891, PubMed:11739404). Interacts with CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF (PubMed:10724175, PubMed:11836499, PubMed:14636569, PubMed:20351172, PubMed:21673012). Interacts (via BRCT domains) with BRIP1 (phosphorylated form) (PubMed:11301010, PubMed:15133502, PubMed:21473589). Interacts with FANCD2 (ubiquitinated form) (PubMed:11239454). Interacts with H2AX (phosphorylated on 'Ser-140') (PubMed:12419185). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA (PubMed:12360400, PubMed:16326698, PubMed:16698035, PubMed:18452305). Part of a BRCA complex containing BRCA1, BRCA2 and PALB2 (PubMed:19369211). Interacts directly with PALB2; the interaction is essential for its function in HRR (PubMed:19369211, PubMed:28319063). Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein (PubMed:19369211). Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1 (PubMed:11751867). Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Interacts with EXD2 (PubMed:26807646). Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme (PubMed:9662397).TISSUE SPECIFICITY Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines.DOMAIN The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of ABRAXAS1, recruits BRCA1 at DNA damage sites.DOMAIN The RING-type zinc finger domain interacts with BAP1.PTM Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR (PubMed:11114888, PubMed:12183412, PubMed:21144835). Phosphorylation at Ser-988 by CHEK2 regulates mitotic spindle assembly (PubMed:10724175, PubMed:20364141). Phosphorylation by AURKA regulates centrosomal microtubule nucleation (PubMed:18056443).PTM Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation.POLYMORPHISM There is evidence that the presence of the rare form of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated with an increased risk for developing ovarian cancer.CAUTION An article that concluded that AURKA-mediated phosphorylation of BRCA1 Ser-308 plays a role in the normal cell cycle G2/M transition was withdrawn due to data manipulation of flow cytometry data. 智人 NCBI分类法 9606. UniProt P38398 1 平等的 1863 平等的 Reactome数据库ID Release 77 50949 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=50949 Reactome R-HSA-50949 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-50949.1 Reactome http://www.reacectome.org. 1 BARD1 brca1相关环状结构域蛋白1 Reactome DB_ID: 5659775 UniProt: Q99728 BARD1 BARD1 E3泛素蛋白连接酶。BRCA1-BARD1异源二聚体特异性介导'Lys-6'链接多聚泛素链的形成，并协调多种细胞途径，如DNA损伤修复、泛素化和转录调节，以维持基因组稳定性。在控制细胞周期以应对DNA损伤中起着核心作用。通过介导泛素E3连接酶的活性发挥作用，泛素E3连接酶是其肿瘤抑制功能所必需的。还与CSTF1/CSTF-50形成异源二聚体，通过抑制pre-mRNA 3'切割来调节mRNA加工和RNAP II的稳定性。通道蛋白改性;蛋白质泛素化。亚基Homo和异源二聚体。异源二聚体(环型锌指)与BRCA1。异源二聚体(通过ANK重复序列和BRCT结构域)与CSTF1/CSTF-50。BRCA1- a复合物的成分，至少由BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2和BABAM1/NBA1组成。 Interacts with UBXN1.PTM Processed during apoptosis. The homodimer is more susceptible to proteolytic cleavage than the BARD1/BRCA1 heterodimer.CAUTION It is uncertain whether Met-1 or Met-26 is the initiator. UniProt Q99728 1 平等的 777 平等的 Reactome数据库ID Release 77 5659775. 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=5659775 Reactome r - hsa - 5659775 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-5659775.1 1 Reactome数据库ID Release 77 5659802 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=5659802 Reactome R-HSA-5659802 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-5659802.1 ComplexPortal CPX-715 额外的信息 心肌梗死 小姐:0361 BAP1. 泛素羧基端水解酶BAP1 ecNumber3.4.19.12/ecNumber BAP1_HUMAN 反弹DB_ID：5689665 UniProt: Q92560 BAP1 BAP1. Kiaa0272. hucep-6 功能脱硫酶通过介导组蛋白H2A和HCFC1的脱水培养蛋白在染色质中发挥关键作用（PubMed：12485996，PubMed：18757409，PubMed：20436459，PubMed：25451922）。PR-DUB络合物的催化组分，一种特异性地介导在'Lys-119'（H2AK119UB1）的组蛋白H2A单体化脱硫的复合物（Hubmed：20436459，Pubmed：25451922）。不脱硫结酶单胞质组蛋白H2B（PubMed：20436459）。通过介导HCFC1 N-末端和C末端链的脱水，与'Lys-48'-Lixed泛素链的脱水，与'Lys-63'连接的多泛素链（PubMed：19188440，PubMed：19815555）。HCFC1的脱硫不会导致HCFC1的稳定性增加（PubMed：19188440，PubMed：19815555）。通过抑制其介导遍染和自动素化的能力（PubMed：19117993），通过干扰BRCA1和BARD1异二聚体活性。然而，它不介导BRCA1和BARD1的脱水（PUBMED：19117993）。能够通过分子内相互作用在核定位信号（NLS）中的分子内相互作用来介导静氢化，从而保护其免受细胞质封存（PubMed：24703950）。作为肿瘤抑制器（PubMed：9528852）。PR-DUB复合物的组分，至少由BAP1和ASXL1组成（PUBMED：20436459）。 Interacts with BRCA1 (via the RING finger) (PubMed:19117993, PubMed:9528852). Interacts (via HBM-like motif) with HCFC1 (PubMed:19188440, PubMed:19815555). Interacts (when phosphorylated at Thr-493) with FOXK1 (PubMed:25451922). Interacts (when phosphorylated at Thr-493) with FOXK2; leading to recruit the PR-DUB complex and repress FOXK2 target genes (PubMed:24748658, PubMed:25451922).TISSUE SPECIFICITY Highly expressed in testis, placenta and ovary. Expressed in breast.PTM Ubiquitinated: monoubiquitinated at multiple site of its nuclear localization signal (NLS) BY UBE2O, leading to cytoplasmic retention. Able to mediate autodeubiquitination via intramolecular interactions to couteract cytoplasmic retention.SIMILARITY Belongs to the peptidase C12 family. BAP1 subfamily.CAUTION According to a report, interaction with FOXK2 is not dependent on phosphorylation of BAP1 (PubMed:24748658). However, it was later shown that phosphorylation at Thr-493 promotes interaction with FOXK2 (PubMed:25451922). UniProt Q92560 1 平等的 729 平等的 Reactome数据库ID Release 77 5689665 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=5689665 Reactome R-HSA-5689665 2 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-5689665.2 BRCA1: BARD1: BAP1 Reactome DB_ID: 9701007 1 1 Reactome数据库ID Release 77 9701007 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=9701007 Reactome r - hsa - 9701007 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 -9701007.1 Reactome数据库ID Release 77 9701003 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=9701003 Reactome r - hsa - 9701003 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 -9701003.1 19117993 PubMed. 2009 BRCA1相关蛋白1干扰BRCA1/BARD1环异源二聚体活性 Nishikawa,) 吴，文文 Koike，Ayaka Kojima，Ryoko Gomi，Hiromichi 福田康夫守 太,Tomohiko 癌症res。69：111-9