This entry represents the N-terminal unstructured domain of protein angel homolog 2 (ANGEL2) []. This protein is a member of the CCR4 nocturin family of deadenylases and has 2',3'-cyclic phosphatase activity involved in RNA processing and modification [].
This entry represents the C-terminal catalytic domain of the deadenylase CCR4a, also known as CCR4-NOT transcription complex subunit 6 (CNOT6). CCR4 belongs to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In S. cerevisiae, Ccr4 is the major deadenylase subunit of the CCR4-NOT transcription complex, which contains two deadenylase subunits and several noncatalytic subunits [, ].There are two vertebrate CCR4 proteins, CCR4a and CCR4b (also called CNOT6-like or CNOT6L). CCR4a associates with other components, such as CNOT1-3 and Caf1, to form a CCR4-NOT multisubunit complex, which regulates transcription and mRNA degradation []. CCR4a is a component of P-bodies and is necessary for foci formation of various P-body components [, ]. It also plays a role in cellular responses to DNA damage, by regulating Chk2 activity [].
Macrophage-derived chemokine or CC chemokine 22 (MDC/CCL22) is a chemokine produced by macrophages and dendritic cells []. It is a chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells []. It binds to receptor CCR4 [, ]. MDC/CCL2 may play an important role in the recruitment of TH2 cells into the inflammatory sites and the regulation of T helper type 2 (TH2)-related immune responses [, ].
This entry represents the C-terminal catalytic domain of the deadenylase CCR4b, also known as CCR4-NOT transcription complex subunit 6-like (CNOT6L). CCR4 belongs to the large EEP (exonuclease/endonuclease/phosphatase) superfamily that contains functionally diverse enzymes that share a common catalytic mechanism of cleaving phosphodiester bonds. In S. cerevisiae, CCR4 is the major deadenylase subunit of the CCR4-NOT transcription complex, which contains two deadenylase subunits and several noncatalytic subunits [, ].There are two vertebrate CCR4 proteins, CCR4a (also called CCR4-NOT transcription complex subunit 6 or CNOT6) and CCR4b. CCR4b associates with other components, such as CNOT1-3 and Caf1, to form a CCR4-NOT multisubunit complex, which regulates transcription and mRNA degradation []. The nuclease domain of CCR4b exhibits Mg2+-dependent deadenylase activity with strict specificity for poly (A) RNA as substrate []. CCR4b is mainly localized in the cytoplasm. It regulates cell growth and influences cell cycle progression by regulating p27/Kip1 mRNA levels []. It contributes to the prevention of cell death by regulating insulin-like growth factor-binding protein 5 [].
The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 []. The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress []. Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex []. Pop2, a component of the Ccr4-Not complex, functions as a deadenylase [].This group represents CCR4-NOT complex, subunits 3 and 5.
The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 []. The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress []. Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex []. Pop2, a component of the Ccr4-Not complex, functions as a deadenylase [].This entry includes CCR4-NOT complex subunits Not2, Not3, Not5 and related proteins.
The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 []. The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress []. Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex []. Pop2, a component of the Ccr4-Not complex, functions as a deadenylase [].This entry represents a domain of unknown function found in the Not1 subunit of the CCR4-Not complex.
The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 []. The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress []. Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex []. Pop2, a component of the Ccr4-Not complex, functions as a deadenylase [].The Ccr4-Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to regulate transcription factor TFIID [].
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role []. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [], and endothelial cells, where they may act as either angiogenic or angiostatic factors [].The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors []. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [, ]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).CC chemokine receptors are a subfamily of the chemokine receptors that specifically bind and respond to cytokines of the CC chemokine family. There are currently ten members of the CC chemokine receptor subfamily, named CCR1 to 10. The receptors receptors are found in monocytes, lymphocytes, basophils and eosinophils.This entry represents CC chemokine receptor 4 (CCR4), it is expressed on T(h)2 cells []and is up-regulated by T cell receptor activation. CCR4 is also found in the brain microvascular and coronary artery endothelial cells []and in blood dentric cells []. It has been suggested the receptor is invloved in trafficking of dendritic cells []. CCR4 is noted as playing a role in allergic reactions, particularly in asthma [, , ].
This family includes plant serine/threonine receptor-like kinases related to CRINKLY4 (CR4), a protein involved in developmental processes in plant and endosperm that was first isolated in maize [, ]. Mutations in this protein affects the cell wall thickness and structure, cuticle formation, and vesicle trafficking, and tumor like outgrowths, with similar effects seen in rice [, , ]. Arabidopsis thaliana contains an orthologue of CR4, ACR4, and four CRINKLY4-related proteins (CRR or CCR) AtCRR1, AtCRR2, AtCRR3 and AtCRR4 (also known as CRINKLY 4-related kinase 1, AtCRK1) []. Phylogenetic analysis showed that the CR4 family of receptor kinases can be divided in three clades, one including CR4, CCR1 and CCR2, a second including CCR3 and CCR4 family members, and a third and more distant clade including members from algae and Selaginella moellendorffii sequences with transmembrane and/or kinase domains []. Kinase assays showed that ACR4 is an active serine/threonine kinase, while CCR1 and CCR2 are nearly inactive in autophosphorylation assays []. CR4 family are characterised by the presence of seven 'crinkly' repeats in the extracellular part which is required both for signalling and normal protein internalisation, including a conserved C(X~10)CWG sequence motif. The Cys residues in the extracellular 'crinkly' repeat domain are likely to form stabilizing disulfide bridges []. Another feature of the CR4 family is that the extracellular domain shows homology to the three Cys-rich repeats of the TUMOR NECROSIS FACTOR RECEPTOR (TNFR) extracellular domain [].This family represents the CRINKLE4-related proteins CCR3 and CCR4.
Not1 is the core component of the CCR4/NOT complex, which plays roles in the negative regulation of gene expression at transcriptional and post-transcriptional levels. This entry includes Not1 (also known as Cdc39) and its homologues, such as LET-711 from Caenorhabditis elegans []. De novo variants in CNOT1 have been shown to cause neurodevelopmental delay []. The Ccr4-Not complex is a global regulator of gene expression that is conserved from yeast to human. It affects genes positively and negatively and is thought to regulate transcription factor IID function. In Saccharomyces cerevisiae, it exists in two prominent forms and consists of at least nine core subunits: the five Not proteins (Not1 to Not5), Caf1, Caf40, Caf130 and Ccr4 []. The Ccr4-Not complex regulates many different cellular functions, including RNA degradation and transcription initiation. It may be a regulatory platform that senses nutrient levels and stress []. Caf1 and Ccr4, are directly involved in mRNA deadenylation, and Caf1p is associated with Dhh1, a putative RNA helicase thought to be a component of the decapping complex []. Pop2, a component of the Ccr4-Not complex, functions as a deadenylase [].
