In budding yeast, TIP41 interacts with TAP42 to regulate protein phosphatase activity []. In mammalian cells, TIP41-like protein (TIPRL) does not directly bind TAP42, but rather primarily interacts with PP2A, PP4 or PP6 catalytic subunits. TIPRL inhibits PP4 activity to allow for H2AX phosphorylation and the subsequent DNA damage response [].
OTUB1 (also known as otubain-1) is a deubiquitinating enzyme that belongs to the OTU family of cysteine proteases []. OTUB1 can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation []. It also plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites [, ]. Mutations in OTUB1 cause tumour predisposition syndrome (TPDS), characterised by predisposition to develop a variety of tumours [].
BRISC and BRCA1-A complex member 1 (BABAM1, also known as MERIT40 and NBA1) was initially identified as a gene required for resistance to ionizing radiation []. It is a component of the BRCA1-A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE []. The BRCA1-A complex recognises 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at double-strand breaks (DSBs), facilitating DNA damage repair. The BRCA1-A complex is also involved in G2/M transition DNA damage checkpoint control. BABAM1 may also play a role as a component of the BRISC complex (contains the FAM175B/ABRO1, BRCC3/BRCC36, BRE/BRCC45 and MERIT40/NBA1 proteins), a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin. In these 2 complexes, BABAM1 is probably required to maintain the stability of BRE/BRCC45 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component [, ].
This entry represents the catalytic domain found in TOPK, which belongs to a superfamily that contains other protein kinases, such as RIO kinases, aminoglycoside phosphotransferase, choline kinase and phosphoinositide 3-kinase.Lymphokine-activated killer T-cell-originated protein kinase (TOPK), also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis []. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX [, ]. It contributes to cancer development and progression by downregulating the function of tumour suppressor p53 and reducing cell-cycle regulatory proteins [, ].
Brain and reproductive organ-expressed (BRE, also known as BRCC45) is a component of the BRCA1-A complex, a complex that specifically recognises 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs) []. It acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer [, ]. It is also part of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates [, , , ]. Within the BRISC complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity [].
