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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, r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL3
Cullin 3 is a protein that in humans is encoded by the ''CUL3'' gene. Cullin 3 protein belongs to the family of cullins which in mammals contains eight proteins (Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, Cullin 7 and Cullin 9). Cullin proteins are an evolutionarily conserved family of proteins throughout yeast, plants and mammals. Protein function Cullin 3 is a component of Cullin- RING E3 ubiquitin ligases complexes (CRLs) which are involved in protein ubiquitylation and represent a part of ubiquitin–proteasome system (UPS). Added ubiquitin moieties to the lysine residue by CRLs then target the protein for the proteasomal degradation. Cullin- RING E3 ubiquitin ligases are involved in many cellular processes responsible for cell cycle regulation, stress response, protein trafficking, signal transduction, DNA replication, transcription, protein quality control, circadian clock and development. Deletion of ''CUL3'' gene in mice causes embryonic lethality ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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/ ... [...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 i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL2
Cullin-2 is a protein that in humans is encoded by the ''CUL2'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b .... Interactions CUL2 has been shown to interact with: * CAND1, * DCUN1D1, * RBX1, * SAP130, * TCEB2 and * Von Hippel-Lindau tumor suppressor. References External links * Further reading * * * * * * * * * * * * * * * * {{gene-10-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL5
Cullin-5 is a protein that in humans is encoded by the ''CUL5'' gene. Discovery The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor. Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5. Tissue distribution Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules. Function Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation. One study have shown that Cul5 plays a role in Reelin signaling cascade, participating ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL7
Cullin-7 is a RING-E3 ligase protein that in humans is encoded by the ''CUL7'' gene. Clinical significance It is associated with 3-M syndrome. Interactions CUL7 has been shown to interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ... with RBX1. References Further reading * * * * * * * * * * * * * External links GeneReviews/NIH/NCBI/UW entry on 3-M syndrome OMIM entries entry on 3-M syndrome * * {{gene-6-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anaphase-promoting Complex
Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C have unknown functions but are highly conserved. It was the discovery of the APC/C (and SCF) and their key role in eukaryotic cell-cycle regulation that established the importance of ubiquitin-mediated proteolysis in cell biology. Once perceived as a system exclusively involved in removing damaged protein from the cell, ubiquitination and subsequent protein degradation by the proteasome is now perceived as a universal regulatory mechanism for signal transduction whose importance approaches that of protein phosphorylation. In 2014, the APC/C was mapped in 3D at a resolution of less than a nanometre, which also uncovered its secondary structure. This finding c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ANAPC2
Anaphase-promoting complex subunit 2 is an enzyme that in humans is encoded by the ''ANAPC2'' gene. A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The product of this gene is a component of the complex and shares sequence similarity with a recently identified family of proteins called cullins, which may also be involved in ubiquitin-mediated degradation. Interactions ANAPC2 has been shown to interact with ANAPC1 and ANAPC11 Anaphase-promoting complex subunit 11 is an enzyme that in humans is encoded by the ''ANAPC11'' gene. Interactions ANAPC11 has been shown to interact with ANAPC2 and CDC27 C ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SCF Complex
Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has important roles in the ubiquitination of proteins involved in the cell cycle. The SCF complex also marks various other cellular proteins for destruction. Core components SCF contains a variable F-box protein and three core subunits: * F-box protein (FBP) – FBP contributes to the substrate specificity of the SCF complex by first aggregating to target proteins independently of the complex. Each FBP (e.g. Skp2) may recognize several different substrates in a manner that is dependent on post-translational modifications such as phosphorylation or glycosylation. FBP then binds to Skp1 of the SCF complex using an F-box motif, bringing the target protein into proximity with the functional E2 ubiquitin-conjugating enzyme. FBP is also essential in re ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Elongin C
Elongin C is a protein that in humans is encoded by the ''ELOC'' gene. Function Elongin C is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Interactions TCEB1 has been shown to interact with: * TCEB2 and * Von Hippel-Lindau tumor suppressor The term ''von'' () is used in German language surnames either as a nobiliary particle indicating a noble patrilineality, or as a simple preposition used by commoners tha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CUL9
Cullin-9 is a protein that in humans is encoded by the ''CUL9'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b .... Interactions PARC (gene) has been shown to interact with P53. References Further reading * * * * * * * * {{gene-6-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PARC (gene)
Cullin-9 is a protein that in humans is encoded by the ''CUL9'' gene. Interactions PARC (gene) has been shown to interact with P53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s .... References Further reading * * * * * * * * {{gene-6-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |