This entry represents the DNA damage-binding protein 1 (DDB1) family, whose members are involved in DNA repair.The fission yeast members in this family includes Rik1 and Ddb1. Rik1 is a component of the Rik1-associated E3 ubiquitin ligase complex that shows ubiquitin ligase activity and is required for histone H3K9 methylation []. Ddb1 is a component of cullin 4A ubiquitin ligases, which regulates the selective proteolysis of key proteins in DNA repair, replication and transcription [, ].Mammalian Ddb1 is apart of the CUL4-DDB1 ubiquitin E3 ligase that regulates cell-cycle progression, replication and DNA damage response. The CUL4-DDB1 ubiquitin E3 ligase interacts with multiple WD40-repeat proteins and regulates histone methylation []. This complex also regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 [].The plant Ddb1 is part of the CUL4-DDB1-DDB2 E3 ligase involved in maintaining genome integrity upon UV stress [].
This entry represents Det1 family proteins []. Det1 (de-etiolated-1) is an essential negative regulator of plant light responses, and it is a component of the Arabidopsis CDD complex containing DDB1 and COP10 ubiquitin E2 variant. Mammalian Det1 forms stable DDD-E2 complexes, consisting of DDB1, DDA1 (DET1, DDB1 Associated 1), is a member of the UBE2E group of canonical ubiquitin conjugating enzymes and modulates Cul4A function [].
DNA damage-binding protein 2 (DDB2) is required for DNA repair. It binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair []. It is also involved in the initiation of nucleotide excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A (cullin 4A) [].
This entry represents the N-terminal domain of DDA1 (DET1- and DDB1-associated protein 1) ubiquitin ligase, which binds strongly with Det1 (De-etiolated 1) and DDB1 (Damaged DNA binding protein 1 associated 1). Together DDA1, DDB1 and Det1 form the DDD core complex, which recruits a specific UBE2E enzyme to form specific DDD-E2 complexes []. Component of the DDD-E2 complexes which may provide a platform for interaction with cul4a and WD repeat proteins. These proteins may be involved in ubiquitination and subsequent proteasomal degradation of target proteins.
DDA1 is a core subunit of multiple Cul4-based E3 ligases (CRL4s), involved in ubiquitination and subsequent proteasomal degradation of target proteins, which regulate key developmental and stress responses in eukaryotes [, ]. In mammals, DDA1 binds to DET1 and DDB1 to form DDD complexes, which recruit specific ubiquitin-conjugating UBE2E enzymes to form DDD-E2 complexes []. The DDD-E2 complex provides a platform for interaction with Cul4A and beta-transducing (also called WD40) repeat proteins. DDA1 is conserved in higher eukaryotes, including Arabidopsis [].
The paramyxoviruses, which include such respiroviruses as para-influenzae and measles, produce phosphoproteins - protein P - that are integral to the polymerase transcription-replication complex. Protein P consists of two functionally distinct moieties, an N-terminal PNT, and a C-terminal PCT [].The P mRNA encodes a variety of proteins beyond P. Protein V consists of PNT fused to a C-terminal zinc-binding region. This conserved region consists of the two-zinc-binding section sandwiched between beta sheets 6 and 7 of the overall V protein. It is the binding of this core domain of V protein with the DDB1 protein (part of the ubiquitin-ligase complex) of eukaryotes which represents the key element of the virus-host protein interaction []. In the Henipavirus family, which includes Nipah and Hendra viruses, the V protein is able to block IFN (interferon) signalling by preventing IFN-induced STAT phosphorylation and nuclear translocation [].
In Arabidopsis, SPA1/2/3/4 play a central role in suppression of photomorphogenesis. SPA1 and SPA2 predominate in dark-grown seedlings, whereas SPA3 and SPA4 prevalently regulate the elongation growth in adult plants []. SPAs contain a kinase-like domain, a coiled-coil domain and the WD-repeats. SPAs and COP1 (a ring finger E3 ubiquitin ligase) can form homo- and heterodimers via their respective coiled-coil domains, and the COP1/SPA complex forms a tetramer of two COP1 and two SPA proteins []. The SPA proteins can self-associate or interact with each other, forming a heterogeneous group of SPA-COP1 complexes []. Besides recognizing substrates, both COP1 and SPA bind DDB1 in the CUL4 complex through their C-terminal WD-repeat domains. They serve as DDB1-CUL4-associated factors (DCAFs) similar to other substrate adaptors in CUL4-based E3 ligases. SPA1 interacts with photoreceptor cry2 via its kinase-like domain, with cry1 via its WD-repeat domain and with phytochromes possibly via both []. SPAs have also been shown to regulate the phyB-PIF4 module at high ambient temperature [].
