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CUL4A
Cullin-4A is a protein that in humans is encoded by the ''CUL4A'' gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide. Structure CUL4A protein is 759 amino acids long and forms an extended, rigid structure primarily consisting of alpha-helices. At the N-terminus, CUL4A binds to the beta-propeller of the DDB1 adaptor protein which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). As a result, the N-terminus is crucial for the recruitment of substrates for the ubiquitin ligase complex. At the C-terminal end, CUL4A interacts with the RBX1/RO ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL4B
Cullin-4B is a protein that in humans is encoded by the ''CUL4B'' gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, ''CUL4B'' has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide. Structure Human CUL4B is 913 amino acids long and shares a high degree of sequence identity (84%) with CUL4A with the exception of its unique N-terminal region. The extreme N-terminus of CUL4B is disordered and, currently, it is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DDB1
DNA damage-binding protein 1 is a protein that in humans is encoded by the ''DDB1'' gene. Gene The gene's position is on chromosome 11q12-q13. Protein The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed of a large and a small ( DDB2) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa. Function As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as nucleotide excision repair. Since then, researchers have found that DDB1 primarily functions as a core component of the CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs). These DCAFs are often ubiquitin ligase substrates and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling ( Cdt2) and more. Interactions DDB1 has be ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DTL (gene)
Denticleless protein homolog is a protein that in humans is encoded by the ''DTL'' gene. Interactions DTL (gene) has been shown to interact with P21 p21Cip1 (alternatively p21Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated .... References Further reading * * * * * * * {{gene-1-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DDB2
DNA damage-binding protein 2 is a protein that in humans is encoded by the ''DDB2'' gene. Structure As indicated by Rapić-Otrin et al. in 2003, the ''DDB2'' gene is located on human chromosome 11p11.2, spans a region of approximately 24 – 26 kb and includes 10 exons. The DDB2 protein contains five putative WD40 repeats (sequences of about 40 amino acids that can interact with each other) positioned downstream from the second exon. The WD40 motif identified in DDB2 is characteristic of proteins involved in the recognition of chromatin proteins. The C-terminal region of DDB2 (a 48 kDa molecular weight protein) is essential for binding to DDB1 (a larger 127 kDa protein). Together, the two proteins form a UV-damaged DNA binding protein complex (UV-DDB). Deficiency in humans If humans have a mutation in each copy of their ''DDB2'' gene, this causes a mild form of the human disease xeroderma pigmentosum, called XPE. Patients in the XPE group have mild dermatological manifestatio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RBX1
RING-box protein 1 is a protein that in humans is encoded by the ''RBX1'' gene. Function This gene encodes an evolutionarily conserved protein that interacts with cullins. The protein plays a unique role in the ubiquitination reaction by heterodimerizing with cullin-1 to catalyze ubiquitin polymerization. It also may be involved in the regulation of protein turn-over. Interactions RBX1 has been shown to interact with: * CAND1, * CUL1, * CUL2, * CUL4A, * CUL5 * CUL7, * DCUN1D1, and * P70-S6 Kinase 1 Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase (p70S6K, p70-S6K), is an enzyme (specifically, a protein kinase) that in humans is encoded by the ''RPS6KB1'' gene. It is a serine/threonine kinase that acts downstream of PIP3 .... References Further reading * * * * * * * * * * * * * * * * * * {{PDB Gallery, geneid=9978 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cullin
Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form ''Cullin-RING ubiquitin ligases'' (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination. The human genome contains eight cullin genes * CUL1, part of SCF complex * CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box) * CUL3, part of CUL3-BTB complex * CUL4A * CUL4B * CUL5 * CUL7 * CUL9, also known as PARC There is also a more distant member called ANAPC2 (or APC2), part of the Anaphase-promoting complex. CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromatin Remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NEDD8
NEDD8 is a protein that in humans is encoded by the ''NEDD8'' gene. (in ''saccharomyces cerevisiae'' this protein is known as Rub1) This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation. Activation and conjugation As with ubiquitin and SUMO, NEDD8 is conjugated to cellular proteins after its C-terminal tail is processed. The NEDD8 activating E1 enzyme is a heterodimer composed of APPBP1 and UBA3 subunits. The APPBP1/UBA3 enzyme has homolog ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Replication Factor CDT1
CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the ''CDT1'' gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle. Role in pre-replication complexes The protein encoded by this gene is a key licensing factor in the assembly of pre-replication complexes (pre-RC), which occurs during the G1 phase of the cell cycle. In the assembly of pre-RCs, origin recognition complexes (ORC1-6) recognize and bind to DNA replication origins. CDT1, along with the protein CDC6, are then recruited to the forming pre-RC, followed by minichromosome maintenance complexes (MCM2-7). The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin, which inhibits it, and by SCFSKP2, which ubiquinates the protein to tag it for proteasomal degradation. This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cyc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
S Phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved. Regulation Entry into S-phase is controlled by the G1 restriction point (R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling. This transition is essentially irreversible; after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable. Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. In yeast, for instance, cell growth induces accumulation of Cln3 cyclin, which complexes with the cyclin dependent kinase CDK2. The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PCNA
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics. Many proteins interact with PCNA via the two known PCNA-interacting motifs PCNA-interacting peptide (PIP) box and AlkB homologue 2 PCNA interacting motif (APIM). Proteins binding to PCNA via the PIP-box are mainly involved in DNA replication whereas proteins binding to PCNA via APIM are mainly important in the context of genotoxic stress. Function The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SETD8
N-lysine methyltransferase KMT5A is an enzyme that in humans is encoded by the ''KMT5A'' gene. The enzyme is a histone methyltransferase, SET domain-containing and lysine-specific. The enzyme transfers one methyl group to histone H4 lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ... residue at position 20. ''S''-Adenosyl methionine (SAM) is both the cofactor and the methyl group donor. The lysine residue is converted to ''N''6-methyllysine residue. none, Leftmost: side chain of lysine. Next: ''N''6-methyllysine side chain. This histone modification is often abbreviated H4K20me1: * H4 - type of histone * K - symbol of lysine * 20 - position of the lysine residue modified * me - abbreviation for methyl group * 1 - number of methyl groups transferred References Furthe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
