Activated leucocyte cell adhesion molecule (ALCAM/CD166) is a transmembrane adhesion protein that belongs to the immunoglobulin superfamily []. It is involved in many functions, including the maintenance of tissue architecture, immune responses, leukocyte intravasation, monocyte migration, angiogenesis, and tumour progression [, ]. It functions as a co-stimulatory molecule for T cells [, ].
ICOS is an inducible T-cell co-stimulator with homology to CD28 []. CD28 and ICOS function similarly during expansion, survival and differentiation of T cells. They are necessary for proper IgG responses. However, CD28 induces IL-2 production, while ICOS is more potent in the induction of IL-10 production [].
V-set and Ig domain-containing 4 (VSIG4) is a strong negative regulator of T cell proliferation and IL-2 production []. It also negatively regulates macrophage activation by activating the PI3K/Akt-STAT3 pathway, leading to pyruvate dehydrogenase kinase-2 (PDK2) upregulation and subsequent phosphorylation of pyruvate dehydrogenase, which results in reduction in pyruvate/acetyl-CoA conversion, reduction in mitochondrialreactive oxygen species secretion, and macrophage inhibition [].
This entry represents interleukin 31 (IL-31), it is a four-helix bundle cytokine that is preferentially produced by T helper type 2 cells [, ]. It is associated with pruritus, a characteristic feature of atopic dermatitis [], and with other types of allergic contact dermatitis-provoked skin inflammation [].
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.This superfamily represents MHC class I and II-like antigen-recognition domains from:MHC class II, N-terminal domains of alpha and beta chains []MHC class I, alpha-1 and alpha-2 domains []MHC class I related proteins, such as gammadelta T-cell ligand [], Ulbp3 [], Fc (IgG) receptor (alpha-1 and -2 domains) [], CD1 (alpha-1 and -2 domains) [], zinc-alpha-2-glycoprotein ZAG (fat depleting factor) []Immunomodulatory protein m144, alpha-1 and alpha-2 domains []Haemochromatosis protein Hfe, alpha-1 and alpha-2 domains []NK cell ligand RAE-1 beta []Endothelial protein C receptor (phospholipid-binding protein) []
This domain is found N-terminal in various melanoma associated antigens from eukaryotes, and is typically between 82 and 96 amino acids in length. These are tumour rejection antigens which are expressed on HLA-A1 of tumour cells and they are recognised by cytotoxic T lymphocytes (CTLs) [].
This entry includes glycine cleavage system T proteins (GcvT) and the bacterial tRNA-modifying protein YgfZ.YgfZ is a folate-binding protein []involved in regulating the level of ATP-dnaA and in the modification of some tRNAs. It is probably a key factor in regulatory networks that act via tRNA modification, such as initiation of chromosomal replication [].
This entry represents an uncharacterised domain of unknown function found at the C-terminal region of Zinc finger SWIM domain-containing proteins 1/3 (ZSWIM1/3) from vertebrates. The function of these proteins is currently unknown. ZSWIM1 may play a role in the development or function of T helper cells [].
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.Class I MHC glycoproteins are expressed on the surface of all somatic nucleated cells, with the exception of neurons. MHC class I receptors present peptide antigens that are synthesised in the cytoplasm, which includes self-peptides (presented for self-tolerance) as well as foreign peptides (such as viral proteins). These antigens are generated from degraded protein fragments that are transported to the endoplasmic reticulum by TAP proteins (transporter of antigenic peptides), where they can bind MHC I molecules, before being transported to the cell surface via the Golgi apparatus [, ]. MHC class I receptors display antigens for recognition by cytotoxic T cells, which have the ability to destroy viral-infected or malignant (surfeit of self-peptides) cells.MHC class I molecules are comprised of two chains: a MHC alpha chain (heavy chain), and a beta2-microglobulin chain(light chain), where only the alpha chain spans the membrane. The alpha chain has three extracellular domains (alpha 1-3, with alpha1 being at the N terminus), a transmembrane region and a C-terminal cytoplasmic tail. The soluble extracellular beta-2 microglobulin chain associates primarily with the alpha-3 domain and is necessary for MHC stability. The alpha1 and alpha2 domains of the alpha chain are referred to as the recognition region, because the peptide antigen binds in a deep groove between these two domains. This entry represents the alpha chain C-terminal tail domain.
Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [, , ]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [, ]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine []. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers []. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [].There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [, , ]: Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [, ]is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo []. T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells. CD30L, a cytokine which induces proliferation of T cells.FASL, a cytokine involved in cell death [].4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production [].TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [].TNF-alpha is synthesised as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-beta, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-alpha is a secreted protein. All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The PROSITE pattern for this family is located in a β-strand in the central section of the protein which is conserved across all members.
Dimethlysulfonioproprionate (DMS) is catabolised in marine bacterioplankton through a pathway in which the initial step involves demethylation to methylmercaptopropionate (MMPA), which is then further catabolised to methane thiol and acetate. The enzyme responsible for the first step is dimethylsulfonioproprionate demethylase DmdA [, ].The overall fold of DmdA is not similar to other enzymes that typically utilise the cofactor tetrahydrofolate (THF). Instead DmdA has a triple domain structure similar to that observed for the glycine cleavage T protein []. Glycine cleavage T protein is an aminomethyltransferase which is part of the glycine cleavage complex responsible for the reversible oxidation of glycine [].This entry also includes YgfZ, which is a folate-binding protein []involved in regulating the level of ATP-dnaA and in the modification of some tRNAs. It is probably a key factor in regulatory networks that act via tRNA modification, such as initiation of chromosomal replication [].
This entry includes submaxillary gland androgen-regulated proteins SMR1,SMR2, SMR3. This entry also includes opiorphin prepropeptide from humans. SMR1 gene gives rise to four related peptides: SMR1-undecapeptide, SMR1-hexapeptide, SMR1-pentapeptide []and submandibular gland peptide T [].Submandibular gland peptide T is able to down-regulate cardiovascular depression induced by septic or anaphylactic shock [].SMR1-pentapeptide (also called Sialorphin) may be involved in the modulation of mineral balance between at least four systems: kidney, bone, tooth and circulation. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. It is an endogenous inhibitor of neprilysin. It inhibits the breakdown of Met-enkephalin and substance P in isolated tissue from the dorsal zone of the rat spinal cord. It has an analgesic effect when administered to rats by intravenous injection [, , ].
This entry represents the catalytic domain of ST17B (Serine/threonine-protein kinase 17B), also known as DRAK2 [].STKs (serine/threonine-protein kinases) catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed [, ]. It is involved in regulating many immune processes including the germinal centre (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses [, , , , ]. It may be involved in the development of autoimmunity [].
Homer (also known as Vesl) family members, including Homer1/2/3, are synaptic scaffolding proteins that regulate localisation of group 1 metabotropic glutamate receptors (mGluRs), which are known to play major roles in neural signal transduction. Homer family members contain the EVH1 domain at the N terminus for receptor binding, two leucine zipper motifs at the C terminus for clustering, and a linking region whose function is unclear. Besides binding to mGluR, Homer family members also recognise the PPXXF motif found in other binding partners []. Homer2 and Homer3, but not Homer1, have been shown to bind to nuclear factor of activated T cells (NFAT) and serve as negative regulators of NFAT-dependent signaling in T cells [].This entry represents the N-terminal EVH1 domain found in the Homer family members [, ].
The development of B and T cells depends on the rearrangement of variable (V),diversity (D), and joining (J) gene segments to produce mature Ig and T cellreceptor coding regions. This rearrangement process, known as V(D)Jrecombination is initiated by a complex consisting of multi-domain proteins RAG1 and RAG2. The RAG proteins catalyse DNA cleavage in the first phase of thereaction using a recombination signal sequence (RSS) that flanks V, D and Jsegments [, , ].Recombination activating protein 1 (RAG1) is the catalytic component of the RAG complex []. RAG1 contains a RING finger domain that can act as a ubiquitin ligase (E3), and can promote its own ubiquitylation and targets both karyopherin alpha 1 (KPNA1) and histone 3 (H3) [, ].Many of the proteins recognised by this entry are fragments.
This C-type lectin-like domain (CTLD) is found in human and mouse attractin (AtrN) and attractin-like protein (ALP). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Mouse AtrN (the product of the mahogany gene) has been shown to bind Agouti protein and to function in agouti-induced pigmentation and obesity []. Mutations in AtrN have also been shown to cause spongiform encephalopathy and hypomyelination in rats and hamsters [, , ]. The cytoplasmic region of mouse ALP has been shown to bind to melanocortin receptor (MCR4) []. Signaling through MCR4 plays a role in appetite suppression. Attractin may have therapeutic potential in the treatment of obesity []. Human attractin (hAtrN) has been shown to be expressed on activated T cells and released extracellularly. The circulating serum attractin induces the spreading of monocytes that become the focus of the clustering of non-proliferating T cells [, , ].
CD4 is a glycoprotein found on the surface of T cells. It is a co-receptor that assists the T cell receptor (TCR) in communicating with an antigen-presenting cell (APC). The structure of a soluble fragment of CD4 has been determined to 2.3 A and reveals that the molecule has two intimately-associated immunoglobulin-like domains connected by a continuous beta strand. Residues implicated in HIV recognition reside in domain D1. Domain D2 is distinguished by a variation in the β-strand topologies of antibody domains that results in a truncated β-barrel with a non-standard intra-sheet disulphide bond [, ]. The binding sites for monoclonal antibodies, class II major histocompatibility complex molecules, and HIV gp120 can be mapped on the molecular surface. Ligation of CD4 by MHC-II on blood monocytes mediates macrophage differentiation and it also increases the susceptibility of blood-derived monocytes to HIV binding and subsequent infection [].
This entry represents interleukin-23 subunit alpha, IL-23A (also known as Interleukin-23 subunit p19) associates with IL-12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity []. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis []. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells [].
Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Interleukin-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses []. It is required for division of CD8+ T cells of memory phenotype, a process that is increased by inhibition of IL-2 []. The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2. IL-15 has been identified in mammals, birds and fish. Recombinant fish IL-15 has been shown to stimulate splenic leukocytes, inducing a large increase in the expression of the antiviral, immunoregulatory cytokine, interferon-gamma [].This entry represents interleukin-15 found in fish.
Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Interleukin-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses []. It is required for division of CD8+ T cells of memory phenotype, a process that is increased by inhibition of IL-2 []. The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2. IL-15 has been identified in mammals, birds and fish. Avian IL-15s are expressed in a wide variety of tissues and cell types, including liver, muscle, heart, and intraepithelial lymphocytes []. They have been shown to stimulate the growth of spleen T-cells and to enhance the activity of natural killer (NK) cells []. Thsi entry represents IL-15 found in birds.
Interleukins (IL) are a group of cytokinesthat play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Interleukin-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses []. It is required for division of CD8+ T cells of memory phenotype - a process that is increased by inhibition of IL-2 []. The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2. IL-15 has been identified in mammals, birds and fish. This entry represents Mammalian IL-15s, that are expressed in a number of different tissues and cell types. Within the immune system, they are mainly produced by monocytes and macrophages []. This entry represents interleukin-15 found in mammals.
The development of B and T cells depends on the rearrangement of variable (V),diversity (D), and joining(J) gene segments to produce mature Ig and T cellreceptor coding regions. This rearrangement process, known as V(D)Jrecombination is initiated by the complex, multi-domain proteins RAG1 andRAG2. The RAG proteins catalyze DNA cleavage in the first phase of thereaction using a recombination signal sequence (RSS) that flanks V, D and Jsegments [, , ].RAG1 contains a zinc-binding dimerization domain immediately N-terminal to thecatalytic core region, which in turn contains a putative DNA-binding domain at its N terminus. The dimerization domain consists of azinc C3HC4 RING finger and a C2H2 zinc RAG1-type finger.The C2H2 RAG1-type zinc finger contains the hallmarks of a classical zincfinger structure with a two stranded β-sheet and an α-helix [].
CD8 on thymocytes and thymus-derived T cells consists of disulfide-linked CD8alpha and CD8 beta chains, which are transmembrane proteins containing N-terminal Ig domains, extended and glycosylated hinge and stalk regions and transmembrane and cytoplasmic portions []. CD8alphabeta plays important roles in thymic selection, CD8 T-cell differentiation, and antigen recognition []. CD8 also can be expressed as a CD8alphaalpha homodimer. Both CD8alphaalpha and CD8alphabeta bind similarly to MHC class I molecules. However, CD8alphabeta, but not CD8alphaalpha, associates with TCR/CD3, strengthens pMHC binding, and promotes CD8 association with lipid rafts and p56lck (lymphocyte-specific tyrosine kinase, lck) and hence TCR signaling via lck-mediated phosphorylation of CD3 ITAMs []. This entry represents CD8 beta. Disruption of the CD8 beta gene or deletion of the cytoplasmic tail of CD8 beta results in severe reduction of positive selection of CD8 T cells [, ].
C-C chemokine ligand 5 (CCL5), also known as RANTES, is a target gene of NF-kappaB, and is expressed by T lymphocytes, macrophages, platelets, synovial fibroblasts, tubular epithelium, and certain types of tumour cells [, ]. CCL5 plays a role in recruiting a variety of leukocytes into inflammatory sites including T cells, macrophages, eosinophils, and basophils. CCL5 activity is mediated through its binding to CCR1, CCR3, and mainly CCR5 [, ].CCR5 is a G-protein-coupled receptor for CCL3, CCL4 and CCL5. CCR5 is also the major coreceptor for HIV-1 entry into target cells and is thought to be a suitable therapeutic target for HIV-1 blockade []. However, the affinity between CCR5 and natural CCL5 is low and has limited viral entry inhibiting activity. Therefore, several CCL5 derivatives with high anti-HIV-1 potency have been produced to act as entry inhibitors and CCR5 antagonists [, ].
EcfA1 is an ATP-binding (A) component of a common energy-coupling factor (ECF) transport systems []. It shares homology with the ATP-binding cassette (ABC) protein [].ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea [].
EcfA2 is an ATP-binding (A) component of a common energy-coupling factor (ECF) transport systems []. It shares homology with the ATP-binding cassette (ABC) protein [].ECF transporters usually contain two ATPase subunits (or a double-length fusion protein), a T component, and a substrate capture (S) component that is highly variable, and may be interchangeable in genomes with only one T component.ECF transporters can be classified into two groups: group I includes transporters that have a dedicated AT module encoded in the same gene cluster as an S component, while group II employs a universal energy-coupling module (EcfAA'T) that is encoded by a separate gene cassette and shared by many different unlinked S components. Group II is ubiquitous in the phyla Firmicutes and Thermotogales and also occurs in some members of the Archaea [].
Homer (also known as Vesl) family members, including Homer1/2/3, are synaptic scaffolding proteins that regulate localisation of group 1 metabotropic glutamate receptors (mGluRs), which are known to play major roles in neural signal transduction. Homer family members contain the EVH1 domain at the N terminus for receptor binding, two leucine zipper motifs at the C terminus for clustering, and a linking region whose function is unclear. Besides binding to mGluR, Homer family members also recognise the PPXXF motif found in other binding partners []. Homer2 and Homer3, but not Homer1, have been shown to bind to nuclear factor of activated T cells (NFAT) and serve as negative regulators of NFAT-dependent signaling in T cells [].
This entry represents the SiaC family regulatory phosphoprotein which undergoes a regulatory phosphorylation at Thr-68 of founder protein PA0170 from Pseudomonas aeruginosa, but in more distant homologs, T can be S. Also, it is part of motif NTSS, so may contain more than one phosphorylation site. Phosphorylation causes regulatory change to protein-protein interaction, in a pathway that seems broadly distributed, involves a diguanylate cyclase, and in the case of Pseudomonas aeruginosa affects aggregation and biofilm formation responses [].
The adaptor protein linker activator of T-cells 2 (LAT2), also called non-T-cell activation linker (NTAL), linker activator for B-cells (LAB) or Williams Beuren Syndrome critical region 5 (WBSCR5), is expressed in various myeloid and lymphoid cells []. Given the wide expression pattern, it may modulate signalling in most types of leukocytes []. It has been shown to be involved in immunoreceptor signaling [], B cell activation [], negative regulation of T cell activation [], and regulation of mast cell physiology [].
Protein GPR15L is a chemotactic factor and an agonistic ligand for GPR15, a G protein-coupled receptor (GPCR) that is found in lymphocytes. GPR15L is found on colon and skin, especially cervix, epithelia []and squamous mucosa of the oral cavity and esophagus []. GPR15L attracts GPR15-expressing T cells including lymphocytes []. GPR15L is also a SUSD2 binding factor, and the interaction inhibits colon cancer cell growth and induce G1 cell cycle arrest by down-regulating cyclin D and cyclin-dependent kinase 6 [].
This entry represents the retinoblastoma-like protein 1 (RBL1, also known as p107). Members of this family contain a conserved domain named the 'pocket' that interacts with the LXCXE motif found in viral proteins, such as SV40 large T antigen []. RBL1 is a component of the DREAM complex, which represses cell cycle-dependent genes in quiescent cells and plays a role in the cell cycle-dependent activation of G2/M genes [, ].
Synaptotagmin-like protein 1 (Slp1/Jfc1) acts as a Rab27a effector and plays a role in vesicle trafficking [, ]. Through its interaction with Rab27a, Slp1 also contributes to secretory lysosome exocytosis from cytotoxic T lymphocytes. Slp1 (and Slp2) may form part of a docking complex, capturing secretory lysosomes at the immunological synapse [].Slp1 possesses two C2 domains in tandem, domain C2A showing homology with the C2B domain of synaptotagmins [].
This entry represents an agenet domain found in EMSY-like (AtEML) proteins, which have possible roles in chromatin regulation and are related to the BRCA2-interacting human oncoprotein EMSY []. Proteins containing this domain also include MRG2 (AT1G02740) from Arabidopsis and PHD finger protein 20-like protein 1 (PHF20L1) from animals. MRG2 binds to the FLOWERING LOCUS T locus and elevates the expression in an H3K36me3-dependent manner []. The function of PHF20L1 is not clear.
This entry represents interleukin-7 (IL7), it is a hematopoietic growth factor produced by bone marrow stromal cells. It promotes growth of B- and T-cell precursors and functions with IL2 in the activation of mature T-cells [, ]. IL-7 and IL-7Ralpha bind the gamma-c receptor forming a complex required for the development and homeostasis of T and B cells []. Interleukin-7 and Interleukin-9 belong to the same larger family.
Ycf54 is found encoded in the chloroplast genomes of algae, it is also found in plants and in the cyanobacteria. Ycf54 is a component of the MgPME-cyclase complex. Ycf54 plays two roles in the function of the MgPME-cyclase. First, it plays a critical role in t assembly/stability of the Mg-cyclase complex and its constituents and, secondly, is required for normal Pchlide formation. Both functions indicate that this protein is required for optimal MgPME-cyclase activity, although it is not absolutely essential [].
2B4 is a transmembrane receptor which is expressed primarily on natural killer (NK) cells. It plays a role in activating NK-mediated cytotoxicity through its interaction with CD48 on target cells in a subset of CD8 T cells []. The structure of 2B4 consists of an immunoglobulin variable domain fold and contains two β-sheets. One of the β-sheets, the six-stranded sheet, contains structural features that may have a role in ligand recognition and receptor function [].This entry represents the 2B4 immunoglobulin domain.
2B4 is a transmembrane receptor which is expressed primarily on natural killer (NK) cells. It plays a role in activating NK-mediated cytotoxicity through its interaction with CD48 on target cells in a subset of CD8 T cells []. The structure of 2B4 consists of an immunoglobulin variable domain fold and contains two β-sheets. One of the β-sheets, the six-stranded sheet, contains structural features that may have a role in ligand recognition and receptor function [].
This entry represents the RNA recognition motif 3 (RRM3) of hnRNP-LL. hnRNP-LL plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells [, ]. It is closely related in domain structure and sequence to heterogeneous nuclear ribonucleoprotein L (hnRNP-L), which is an abundant nuclear, multifunctional RNA-binding protein with three RNA-recognition motifs (RRMs).
This entry represents the RNA recognition motif 1 (RRM1) of hnRNP-LL. hnRNP-LL plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells [, ]. It is closely related in domain structure and sequence to heterogeneous nuclear ribonucleoprotein L (hnRNP-L), which is an abundant nuclear, multifunctional RNA-binding protein with three RNA-recognition motifs (RRMs).
This entry represents the RNA recognition motif 2 (RRM2) of hnRNP-LL. hnRNP-LL plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells [, ]. It is closely related in domain structure and sequence to heterogeneous nuclear ribonucleoprotein L (hnRNP-L), which is an abundant nuclear, multifunctional RNA-binding protein with three RNA-recognition motifs (RRMs).
STKs (serine/threonine-protein kinases) catalyse the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK, also called polo-like kinase kinase 1 in Xenopus (xPlkk1) [], is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion []. It plays a role in regulating the CD28 responsive element in T cells [], and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumour types [].
This is a family of unknown function found in Alphabaculovirus. It includes the ECORI-T site protein ETS, which was identified as a 1.7-kb transcript from the coding region within the EcoRI T fragment (29.0 to 30.1 map units) in Autographa californica nuclear polyhedrosis virus (AcMNPV) []. This protein is produced as an early stage transcript and persists throughout infection, although its function is unknown [].
This entry represents the RNA recognition motif 4 (RRM4) of hnRNP-LL. hnRNP-LL plays a critical and unique role in the signal-induced regulation of CD45 and acts as a global regulator of alternative splicing in activated T cells [, ]. It is closely related in domain structure and sequence to heterogeneous nuclear ribonucleoprotein L (hnRNP-L), which is an abundant nuclear, multifunctional RNA-binding protein with three RNA-recognition motifs (RRMs).
Phosphatidylinositol-glycan biosynthesis class T protein (PIG-T, also known as Gpi16 in budding yeasts) is a component of the glycosylphosphatidylinositol (GPI) trans-amidase complex that adds GPIs to newly synthesized proteins []. Mammalian GPI transamidase consists of at least five components: Gaa1, Gpi8, PIG-S, PIG-T, and PIG-U, all five of which are required for its function. It is possible that Gaa1, Gpi8, PIG-S, and PIG-T form a tightly associated core that is only weakly associated with PIG-U. The exact function of PIG-S is unclear [].
Ycf54 is found encoded in the chloroplast genomes of algae, it is also found in plants and in the cyanobacteria. Ycf54 is a component of the MgPME-cyclase complex. Ycf54 plays two roles in the function of the MgPME-cyclase. First, it plays a critical role in t assembly/stability of the Mg-cyclase complex and its constituents and, secondly, is required for normal Pchlide formation. Both functions indicate that this protein is required for optimal MgPME-cyclase activity, although it is not absolutely essential [].
Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Interleukin-9 (IL-9) is expressed primarily by activated T cells []. The growth factor and anti apoptotic activities of IL-9 on multiple transformed cells suggest a potential role for the cytokine in tumourigenesis []. IL-9 has also been proposed as a candidate gene for asthma []. This entry represents interleukin-9.
Nepoviruses are plant viruses that, together with comoviruses and picornaviruses, are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. Its genome consist of two single-stranded RNAs, both required for infection []. This family aligns several nepovirus coat protein sequences. In several cases, this is found at the C terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped β-barrel domains, and forms a pseudo T = 3 icosahedral capsid structure [].
Mycoplasma arthritidis-derived mitogen (MA-Mit) adopts a completely α-helical structure consisting of ten alpha helices arranged in two orthogonal bundles. MA-Mit is a superantigen that can activate large fractions of T cells bearing particular TCR V-beta elements. Two MA-Mit molecules form an asymmetric dimer and cross-link two MHC antigens to form a dimerised MA-Mit-MHC complex [].This superfamily represents the C-terminal domain found in Mycoplasma arthritidis-derived mitogen.
Glia maturation factor gamma (GMFG) belongs to the GMF family, whose members sever actin-Arp2/3 complex branch junctions by a cofilin-like mechanism [, ]. Mammals express two GMF isoforms, GMF-beta and GMF-gamma, which display different tissue distributions []. GMF-gamma is expressed in microvascular endothelial and inflammatory cells, and has been implicated in promoting neutrophil and T cell migration [, ]. GMF-gamma may facilitate smooth muscle contraction through regulating actin dynamics [].
CD160 is a GPI-anchored MHC-class I activating receptor mainly expressed on peripheral blood NK cells. It is also expressed on both cytolytic lymphocytes and some unstimulated CD4 T cells []. CD160 has different isoforms, including GPI-anchored isoform, a transmembrane isoform, and a secreted isoform. Upon specific engagement of CD160 by its physiological ligand HLA-C, or by mAb cross-linking, CD160 PB-NK cells produce significant levels of IFN-gamma, TNF-alpha, IL-6 as well as IL-8 and MIP-1beta [].
Members of this group are known as retinoic acid early inducible proteins (RAE-1) [, ]. They are ligands for the activating immunoreceptor NKG2D, which is widely expressed on natural killer cells, T cells, and macrophages []. There is a considerable diversity of NKG2D ligands. In mice, the ligands include, among others, five members of the retinoic acid early inducible gene 1 (RAE-1; α-ε) [].RAE-1 proteins are distant major histocompatibility complex (MHC) class I homologues, comprising isolated alpha1-alpha2 platform domains [].
Nepoviruses are plant viruses that, together with comoviruses and picornaviruses, are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. Its genome consist of two single-stranded RNAs, both required for infection []. This domain aligns several nepovirus coat protein sequences. In several cases, this is found at the C terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped β-barrel domains, and forms a pseudo T = 3 icosahedral capsid structure [].
Nepoviruses are plant viruses that, together with comoviruses and picornaviruses, are classified in the picornavirus superfamily of plus strand single-stranded RNA viruses. Its genome consist of two single-stranded RNAs, both required for infection []. This family includes several nepovirus coat protein sequences. In several cases, this is found at the C terminus of the RNA2-encoded viral polyprotein. The coat protein consists of three trapezoid-shaped β-barrel domains, and forms a pseudo T = 3 icosahedral capsid structure [].
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 [, ].
CD226, also known as DNAM-1, is a nectin receptor that contains two extracellular Ig-like domains (CD226-D1 and CD226-D2), and is widely expressed in monocytes, platelets, T cells, and most of the resting NK cells. The interactions between CD226and its nectin/Necl family ligands, CD155 (also known as Necl-5) and CD112 (nectin-2), play important roles in modulating NK cell adhesion and cytotoxicity, facilitating immunological synapse formation and promoting cytokine secretion during inflammation [, , ].
This entry represents a group of Cdc42-binding proteins known as SPECs (for small protein effector of Cdc42), including SPEC1 and SPEC2 from humans. SPECs modulate the activity of the Rho GTPase Cdc42, which plays important roles in actin polymerization and kinase signaling []. SPEC1 and SPEC2 play a role in F-actin accumulation in activated T lymphocytes and may play a role in early contractile events in phagocytosis [].
The closely related CD3 epsilon, gamma and delta subunits constitute part of the invariant portion of the T cell receptor (TCR) complex. Both are transmembrane proteins with immunoglobulin-like domains in their extracellular regions. Each protein contains a single immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain that becomes phosphorylated upon ligation of the invariant TCR chains and provides binding sites for various downstream effectors [].
The closely related CD3 gamma and delta subunits constitute part of the invariant portion of the T cell receptor (TCR) complex. Both are transmembrane proteins with immunoglobulin-like domains in their extracellular regions. Each protein contains a single immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain that becomes phosphorylated upon ligation of the invariant TCR chains and provides binding sites for various downstream effectors [].
T-cell immunoglobulin and ITIM domain receptor (TIGIT) is a surface protein and an inhibitory receptor that suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells []. It contains an immunoglobulin tail tyrosine (ITT)-like phosphorylation motif and an ITIM (immunoreceptor tyrosine-based inhibition motif) in its cytoplasmic tail. The identified ligands of TIGIT include the poliovirus receptor (PVR or CD155) and PVRL2 (Nectin2 or CD112). The TIGIT/PVR signaling has been shown to suppresses granule polarization and NK cell cytotoxicity [].
FKBP-type peptidylprolyl isomerases () in vertebrates, are receptors for the two immunosuppressants, FK506 and rapamycin. The drugs inhibit T cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. Peptidylprolyl isomerases accelerate protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides. These proteins are found in a variety of organisms [].This entry represents a domain found in FKBP-type peptidylprolyl isomerases.
This entry represents interleukin-7 (IL7), it is a hematopoietic growth factor produced by bone marrow stromal cells. It promotes growth of B- and T-cell precursors and functions with IL2 in the activation of mature T-cells [, ]. IL-7 and IL-7Ralpha bind the gamma-c receptor forming a complex required for the development and homeostasis of T and B cells []. Interleukin-7 and Interleukin-9 belong to the same larger family.
GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway []. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease []. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain.
SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity []. It is involved in the signaling of T cell receptors []. It was the first described member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains [].This entry represents the SH3 domain of SASH3.
Interleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Structure of IL-3 receptor alpha chain (IL3Ra) in complex with the anti-leukemia antibody CSL362 reveals that the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), contains the CSL362 binding epitope. Furthermore, NTD of IL3Ra adopts a typical fibronectin type III (FnIII) fold [].
SASH3, also called SLY/SLY1 (SH3-domain containing protein expressed in lymphocytes), is expressed exclusively in lymhocytes and is essential in the full activation of adaptive immunity []. It is involved in the signaling of T cell receptors []. It was the first described member of the SLY family of proteins, which are adaptor proteins containing a central conserved region with a bipartite nuclear localization signal (NLS) as well as SAM (sterile alpha motif) and SH3 domains [].
Secreted and transmembrane protein 1 (SECTM1), also known as protein K-12, has been identified as a ligand for CD7, an immunoglobulin superfamily molecule with a role in T- and NK-cell activation and cytokine production []. SECTM1 is a potent costimulatory ligand for T cell proliferation and is induced by IFN-gamma [, , ].The human genome contains only one SECTM gene, while the mouse genome contains two (SECTM1A and SECTM1B) [].
CD48 (also known as Blast-1 or SLAMF2) is a coactivator and adhesion molecule on cells with a hematopoietic origin []. It contains a glycosylphosphatidylinositol membrane anchor and can serve as a receptor for SLAMF4 (also known as CD244) []. It regulates adaptive immune responses by providing longer access of putative antigen presenting cells to virus-specific effector T cells by prolonging the time frame of effective stimulation [].
Calcipressin-3 (RCAN3) is a member of the calcipressin family. Overexpressed RCAN3 has been found to bind and inhibit the Ca2+/calmodulin-dependent phosphatase calcineurin, and further down-regulates nuclear factor of activated T cells (NFAT)-dependent cytokine gene expression in activated human Jurkat T cells []. RCAN3 can also interact with cardiac troponin I (TNNI3), a heart-specific inhibitory subunit of the troponin complex, and may play a role in cardiac contraction [].Calcipressins (RCANs) are a novel family of calcineurin regulators that have been suggested as key factors contributing to Down syndrome in humans. Three human calcipressins have been identified, calcipressin 1-3. Calcipressin 1 is also known as modulatory calcineurin-interacting protein 1 (MCIP1), Adapt78 and Down syndrome critical region 1 (DSCR1). Calcipressin 2 is variously known as MCIP2, ZAKI-4 and DSCR1-like 1. Calcipressin 3 is also called MCIP3 and DSCR1-like 2 []. Calcipressins contain an N-terminal RNA recognition motif (RRM), a highly conserved SP repeat domain containing the phosphorylation site by GSK-3, a well-known PxIxIT motif responsible for docking many substrates to calcineurin, and a C-terminal TxxP motif [].Calcineurin is a calcium-responsive enzyme that dephosphorylates the nuclear factor of activated T cells (NFAT). In doing so, it promotes its nuclear translocation and uniquely links calcium signalling to transcriptional regulation [].
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as OX40, ACT35, CD134, IMD16 or TXGP1L, activates NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5 []. It also promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis []. It is primarily expressed on activated CD4+ and CD8+ T cells, where it is transiently expressed and upregulated on the most recently antigen-activated T cells within inflammatory lesions. This makes it an attractive target to modulate immune responses, i.e. TNFRSF4 (OX40) blocking agents to inhibit adverse inflammation or agonists to enhance immune responses [, ]. An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Some single nucleotide polymorphisms (SNPs) of its natural ligand OX40 ligand (OX40L, CD252), which is also found on activated T cells, have been associated with systemic lupus erythematosus [].This entry represents the N-terminal domain of TNFRSF4. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number of modules can vary in number and type in different members of the family [, , ].
ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells []. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function []. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands []. This entry contains the N terminus SH2 domains of both Syk and Zap70.
Diphtheria toxin () is a 58kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis []. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows: NAD++ peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamideThe crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution []. The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the α+β type; a transmembrane (TM) domain, which consists of 9 α-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened β-barrel with a jelly-roll-like topology []. The TM- and receptor binding-domains together constitute fragment B.This entry represents the translocation domain (also known as the T domain) found in the middle of the Diphtheria toxin protein. The T domain has a multi-helical globin-like fold with two additional helices at N-termini, but which has no counterpart to the first globin helix. This domain is thought to unfold in the membrane []. pH-induced conformational change in the T domain triggers insertion into the endosomal membrane and facilitates the transfer of the catalytic domain into the cytoplasm [, ].
Diphtheria toxin () is a 58kDa protein secreted by lysogenic strains of Corynebacterium diphtheriae. The toxin causes the disease diphtheria in humans by gaining entry into the cell cytoplasm and inhibiting protein synthesis []. The mechanism of inhibition involves transfer of the ADP-ribose group of NAD to elongation factor-2 (EF-2), rendering EF-2 inactive. The catalysed reaction is as follows: NAD++ peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamideThe crystal structure of the diphtheria toxin homodimer has been determined to 2.5A resolution []. The structure reveals a Y-shaped molecule of 3 domains, a catalytic domain (fragment A), whose fold is of the α+β type; a transmembrane (TM) domain, which consists of 9 α-helices, 2 pairs of which may participate in pH-triggered membrane insertion and translocation; and a receptor-binding domain, which forms a flattened β-barrel with a jelly-roll-like topology []. The TM- and receptor binding-domains together constitute fragment B.This entry represents the translocation domain (also known as the T domain) found as the central domain in the Diphtheria toxin protein. The T domain has a multi-helical globin-like fold with two additional helices at N-termini, but which has no counterpart to the first globin helix. This domain is thought to unfold in the membrane []. pH-induced conformational change in the T domain triggers insertion into the endosomal membrane and facilitates the transfer of the catalytic domain into the cytoplasm [, ].
The protein is a member of the nuclear factors of activated T (NFAT) cells family of transcription factors. Proteins belonging to this group of transcription factors play a central role in inducible gene transcription during the immune response. The product of this gene is a pre-existing cytosolic component. It is present in the cytosolic fraction of un-stimulated T cells. After T-cell activation it is found in the nucleus as a part of the DNA-binding transcription complex. Two transcript variants encoding distinct isoforms have been identified for this gene, []Mus musculus (Mouse) and Homo sapiens (Human).NFAT proteins appear to be regulated primarily at the level of their subcellular localisation []. They are found exclusively in the cytoplasm of resting T cells, and consist of 2 components: a pre-existing cytoplasmic component that translocates into the nucleus on calcium mobilisation, and an inducible nuclear component comprising members of the activating protein-1 (AP-1) family of transcription factors. In response to antigen receptor signalling, the calcium-regulated phosphatase calcineurin acts directly to dephosphorylate NFAT proteins, causing their rapid translocation from the cytoplasm to the nucleus, where they cooperatively bind their target.Synonym(s): NFATp,NFATC2
The capsid of spherical viruses is built from a limited number of proteins and often displays icosahedral symmetry. Rotaviruses have a segmented double-stranded RNA genome enclosed in a complex capsid formed by three concentric protein layers. The proteins forming the capsid are VP2 (internal layer, with triangulation T = 1 and an asymmetric dimer in the icosahedral repeating unit), VP6 (intermediate layer, T = 13 symmetry), VP7 (external layer, T = 13) and VP4, which forms a spike inserted in the outermost two layers. The major capsid protein VP6 self-assembles into spherical or helical particles mainly depending upon pH. VP6 assemblies arise from different pickings of a unique dimer of trimers. The repeating unit of the helix contains a pair of trimers related by a radial dyad []. The VP6 trimer is composed of two domains: a head (external) and a base (internal), leaving a central cavity, these are formed by a distal β-barrel domain and a proximal α-helical domain, which interact with the outer and inner layer of the virion, respectively [].
Major Histocompatibility Complex (MHC) glycoproteins are heterodimeric cell surface receptors that function to present antigen peptide fragments to T cells responsible for cell-mediated immune responses. MHC molecules can be subdivided into two groups on the basis of structure and function: class I molecules present intracellular antigen peptide fragments (~10 amino acids) on the surface of the host cells to cytotoxic T cells; class II molecules present exogenously derived antigenic peptides (~15 amino acids) to helper T cells. MHC class I and II molecules are assembled and loaded with their peptide ligands via different mechanisms. However, both present peptide fragments rather than entire proteins to T cells, and are required to mount an immune response.Class I MHC glycoproteins are expressed on the surface of all somatic nucleated cells, with the exception of neurons. MHC class I receptors present peptide antigens that are synthesised in the cytoplasm, which includes self-peptides (presented for self-tolerance) as well as foreign peptides (such as viral proteins). These antigens are generated from degraded protein fragments that are transported to the endoplasmic reticulum by TAP proteins (transporter of antigenic peptides), where they can bind MHC I molecules, before being transported to the cell surface via the Golgi apparatus [, ]. MHC class I receptors display antigens for recognition by cytotoxic T cells, which have the ability to destroy viral-infected or malignant (surfeit of self-peptides) cells.MHC class I molecules are comprised of two chains: a MHC alpha chain (heavy chain), and a beta2-microglobulin chain (light chain), where only the alpha chain spans the membrane. The alpha chain has three extracellular domains (alpha 1-3, with alpha1 being at the N terminus), a transmembrane region and a C-terminal cytoplasmic tail. The soluble extracellular beta-2 microglobulin chain associates primarily with the alpha-3 domain and is necessary for MHC stability. The alpha1 and alpha2 domains of the alpha chain are referred to as the recognition region, because the peptide antigen binds in a deep groove between these two domains. This entry represents the alpha chain domains alpha1 and alpha2 that make up this recognition region (the alpha3 domain is represented by ().
Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [, , ]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [, ]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine []. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers []. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [].There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [, , ]: Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [, ]is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo []. T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulatedT cells and enhances the generation of cytolytic T cells. CD30L, a cytokine which induces proliferation of T cells.FASL, a cytokine involved in cell death [].4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production [].TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [].TNF-alpha is synthesised as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-beta, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-alpha is a secreted protein. All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The PROSITE pattern for this family is located in a β-strand in the central section of the protein which is conserved across all members.This entry represents Tumor Necrosis Factor, conserved site.
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents CXC chemokine receptor 6 (CXCR6) also known as cluster of differentiation 186 and is a receptor for chemokine CXCL16. CXCL16 does not activate any other known chemokine receptor, this interaction is highly specific and unique []. Binding of CXCL16 to CXCR6 causes chemotactic migration in activated T cells [, ]however, CXCR6 is a weak mediator of chemotaxis []. The resultant chemotactic response is sensitive to pertussis toxin and results in calcium mobilisation [, ]. CXCR6 is expressed in lymphoid tissues and activated T cells and is induced in peripheral blood leukocytes []and found on natural killer cells []. A number of roles have been suggested for CXCR6 and subset-specific immune responses may be regulated by cell-cell contacts between activated subsets of T cells expressing CXCR6 and antigen presenting cells expressing CXCL16. CXCR6 may also be involved in cell-cell contacts during chronic inflammation []. Additional roles for the receptor include T cell migration in the splenic red pulp, thymocyte development and effector T cell trafficking []. It has been shown that CXCR6 acts as a coreceptor for T cell line-tropic and macrophage-tropic HIV-1 strains, and may play a role in the establishment and progression of HIV infection [, ].
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).The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.This entry represents CXCR3, which is expressed in natural killer cells and activated T lymphocytes but not in resting T lymphocytes, B lymphocytes, monocytes or granulocytes [, ]. CXCR3 also appears to be constitutively expressed on endothelial cells of medium and large blood vessels []. CXCR3 is able to regulate leukocyte trafficking and binding to various chemokines inducing various cellular responses, most notably integrin activation, cytoskeletal changes and chemotactic migration [, , , ]. The main role of CXCR3 is the selective recruitment of effector T cells in both normal tissues and inflammation []and it is involved in a number of T cell-mediated inflammatory diseases, such as autoimmune diseases, delayed-type hypersensitivity responses, certain viral diseases and acute transplant rejection []. It has been implicated in atherosclerosis [], pulmonary fibrosis [], type 1 diabetes []and nephrotoxic nephritis [], and has been implicated in wound healing [].CXCR3 is the receptor for CXCL9 (Mig), CXCL10 (IP10) and CXCL11 (I-TAC), [, , , ], which are upregulated in response to interferon-gamma and are potent chemoattractants for activated T cells [, ]. All three chemokines elicit an increase in intracellular Ca2+ levels and activate phosphoinositide 3-kinase and mitogen-activated protein kinase (MAPK) []. CXCR3 is also capable of binding a number of CC chemokines with moderate affinity, including CCL11 (eotaxin), CCL13, CCL20, CCL7, CCL5 []. However, it has been reported that CCL11, despite binding with high affinity, may be neither an agonist or an antagonist of the CXCR3 receptor, but sequesters available CCL11 resulting in a lowered response at other receptors [].
Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [, , ]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [, ]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine []. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers []. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [].There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The following cytokines can be grouped into a family on the basis of sequence, functional, and structural similarities [, , ]: Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) [, ]is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes and which are cytotoxic for a wide range of tumor cells in vitro and in vivo []. T cell antigen gp39 (CD40L), a cytokine which seems to be important in B-cell development and activation.CD27L, a cytokine which plays a role in T-cell activation. It induces the proliferation of costimulated T cells and enhances the generation of cytolytic T cells. CD30L, a cytokine which induces proliferation of T cells.FASL, a cytokine involved in cell death [].4-1BBL, a inducible T cell surface molecule that contributes to T-cell stimulation.OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production [].TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis [].TNF-alpha is synthesised as a type II membrane protein which then undergoes post-translational cleavage liberating the extracellular domain. CD27L, CD30L, CD40L, FASL, LT-beta, 4-1BBL and TRAIL also appear to be type II membrane proteins. LT-alpha is a secreted protein. All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. The PROSITE pattern for this family is located in a β-strand in the central section of the protein which is conserved across all members.This group represents a tumour necrosis factor family protein, CD30 ligand type, also known as Tumor necrosis factor ligand superfamily member 8. It is a cytokine that binds to TNFRSF8/CD30, inducing proliferation of T-cell [].
Like all apoptotic cell death, T cell receptor (TCR)-mediated death can bedivided into two phases: an inductive phase and an effector phase. The effector phase includes a sequence of steps that are common to apoptosis inmany cell types, which, if not interrupted, will lead to cell death. Theinduction phase, which often requires the expression of new genes, consistsof a set of signals that activate the effector phase. Outside the thymus,most, if not all, of the TCR-mediated apoptosis of mature T cells (sometimesreferred to as activation-induced cell death (AICD)) is induced through thesurface antigen Fas pathway: activation through the TCR induces expressionof the Fas (CD95) ligand (FasL); the expression of FasL on either aneighbouring cell, or on the Fas-bearing cell, induces trimerisation of Fas,which then initiates a signal-transduction cascade, leading to apoptosis of the Fas-bearing cell. This commitment stage requires the activation of keydeath-inducing enzymes, termed caspases, which act by cleaving proteins that are essential for cell survival and proliferation[, ].Fas is also known to be essential in the death of hyperactivated peripheralCD4+ cells: in the absence of Fas, mature peripheral T cells do not die, butthe activated cells continue to proliferate, producing cytokines that leadto grossly enlarged lymph nodes and spleen. Fas belongs to the tumournecrosis factor receptor (TNFR) family of cysteine-rich type I membranereceptors; its ligand (FasL) is expressed on activated lymphocytes, NK cells,platelets, certain immune-privileged cells and some tumour cells [, ].Defects in the Fas-FasL system are associated with various disease syndromes.Mice with non-functional Fas or FasL display characteristics of lympho-proliferative disorder, such as lymphadenopathy, splenomegaly, and elevated secretion of IgM and IgG. These mice also secrete anti-DNA autoantibodiesand rheumatoid factor [].
The lysosome associated protein transmembrane (LAPTM) family is comprised of three members: LAPTM5, LAPTM4a and LAPTM4b; they are lysosome-associated transmembrane proteins, found in mammals, insects and nematodes.This entry represents LAPTM5, which is a lysosomal protein expressed in cells of lymphoid and myeloid origin. LAPTM5 trafficking from the Golgi to the lysosome requires its association with the ubiquitin ligase Nedd4 and the clathrin adaptor GGA3 []. LAPTM5 negatively regulates T and B cell receptor signaling by directly interacting with these receptors and mediating their down-regulation [, ]. It is also a positive regulator of NF-kB and MAPK signaling allowing efficient proinflammatory cytokine production in response to macrophage activation [].
NF-kappa-B-activating protein (Nkap) is a highly conserved protein which functions as a transcriptional repressor on Notch target genes. It is required for T cell development and acquisition of functional competency [, , ]. It also plays a role in RNA splicing and processing involved in transcriptional repression, maintenance and survival of adult haematopoietic stem cells.Nkap is divided into three domains, an N-terminal domain containing RS repeats, a highly basic middle domain and the C-terminal domain () [, ].This entry represents uncharacterised proteins that contain Nkap domain 1.
This entry represents Capsid proteins from Bacteriophage P2 (GpN) and similar proteins from tailed bacteriophages and bacterial prophages mainly among Proteobacteria. GpN undergoes proteolytic cleavage into three products: Minor capsid protein H1, a 39 kDa proteinMinor capsid protein H2, 38.6 kDaMajor capsid protein N*, 36.7 kDa []The capsid of P4, the satellite phage of P2, consists of those same gene products encoded by P2, although in this case the resulting capsids are smaller than those usually formed by P2 alone. P2 procapsid have a dextro HK97 fold with T = 7 symmetry [, ].
Intraflagellar transport (IFT) particle, which consists of complex A and B, is involved in assembling and maintaining eukaryotic cilia and flagella. Intraflagellar transport protein 20 (IFT20) is a subunit of the intraflagellar transport complex B (consists of IFT172, 88, 81, 80, 74/72, 57/55, 52, 46, 27, 20) [, ]. IFT20 is associated with the Golgi complex and may play a role in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium [, ]. Besides its function in cilia, IFT20 also regulates immune synapse assembly in T cells []. In an yeast two hybrid experiment, IFT20 exhibited a strong interaction with IFT57/Hippi and the kinesin II subunit, KIF3B [].
Phospholipase C gamma (PLCg), also known as 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma, is a member of the family of phosphoinositide specific PLCs that convert phosphatidylinositol 4,5-bisphosphate into second messengers 1,2-diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), thereby initiating and propagating numerous cellular signaling events [].There are two forms of phospholipase C-gamma, PLCg1 and PLCg2. PLCg1 is widely distributed but the expression of PLCg2 is primarily limited to cells of haematopoietic lineage []. PLCg1 is critical in many cells, and in haematopoietic systems it is required for T cell and NK cell function, whereas PLCg2 is important in mast cells, NK cells, B cells, and platelets. A third form, plc-3, is known from Caenorhabditis elegans [].
Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS1 plays a key role in the negative regulation of interferon-gamma signaling and in T cell differentiation [, , ].
PR domain zinc finger protein 1 (PRDM1, also known as BLIMP-1) is a transcriptional repressor that is essential for cellular development. This entry includes BLIMP-1 from vertebrates and its homologues from invertebrates. In vertebrates, PRDM1 is also known as B lymphocyte-induced maturation protein 1 (BLIMP-1) or positive regulatory domain I-binding factor (PRDI-BF1). It is essential for the differentiation of B and T cells []. In Caenorhabditis elegans, it regulates the spatiotemporal cell migration pattern []. The degradation of PRDM1 by DRE-1/FBXO11-dependent mechanism regulates the C. elegans developmental timing and maturation [].
Interleukin-4 (IL-4) is a cytokine that plays a central role in the control and regulation of the immune and inflammatory system [, ]. IL-4 is a participant in several B-cell activation processes. It also stimulates othercell types such as T cells or mast cells. IL-4 is a glycoprotein that contains three disulphide bonds [].Interleukin-13 (IL-13) is a pleiotropic cytokine which may be important in the regulation of the inflammatory and immune responses []. The sequences of IL-4 and IL-13 are distantly related. This entry represetns both IL-4 and IL-13.
UBP5, also known as isopeptidase T or USP5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell []. Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (Znf) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. Znf domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin [, ]. This entry represents the UBA1 domain.
Recoverin is a Ca(2+) -binding protein that controls phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase (GRK-1) in photoreceptor cells [, ]. It serves as a cancer-retina antigen that is expressed in retina and tumour cells and evokes antibodies and/or T cells in patients with cancer [, ].A number of other proteins including visinin, hippocalcin, neurocalcin,S-modulin, visinin-like protein, frequenin, guanylyl cyclase-activating proteins GCAP-1 and GCAP-2 []belong to this family. All of the family members are generally small N-myristoylated proteins containing four EF-hand calcium-binding consensus motifs.
Hepatitis B X-interacting protein (HBXIP, also known as LAMTOR5) was originally recognised for its association with the X protein of hepatitis B virus (HBV) and ability to down-regulate HBV replication []. When complexed to the anti-apoptotic protein survivin, HBXIP interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerised APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway []. HBXIP is one of the Ragulator components that are required for mTORC1 activation by amino acids []. It is also part of the AA (amino acid) sensing machinery in human CD4+ T cells [].
CAMPATH-1 antigen (also known as CD52) is a very small glycosylphosphatidylinositol (GPI)-anchored glycoprotein present in lymphocytes , male reproductive tracts and female cumulus cells [, , , , ]. CD52 on the lymphocyte membrane surface induces regulatory T cells with immunosuppressive activities []. In the male reproductive tract, CD52 may protect sperm function from complement attack if antisperm antibody is generated in the female reproductive tracts []. It has also been suggested that CD52 has some functional roles around fertilisation in females as well as in males [].
Cytoplasmic tRNA 2-thiolation protein 1 (also known as Ncs6/Tuc1 in budding yeasts) is responsible for 2-thiolation of mcm5S2U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln) [, ]. It directly bind tRNAs and probably acts by catalysing adenylation of tRNAs, an intermediate required for 2-thiolation. Its fission yeast homologue, Ctu1 forms a complex with Ctu2 (Ncs2/Tuc2 homologue) and serves as a putative enzyme for the formation of 2-thiouridine []. This family also includes tRNA-5-methyluridine(54) 2-sulfurtransferase, which catalyzes the 2-thiolation of 5-methyluridine residue at position 54 in the T loop of tRNAs, leading to 5-methyl-2-thiouridine [].
Bacteriocin AS-48 is a cyclic peptide antibiotic produced by the eubacteria Enterococcus faecalis (Streptococcus faecalis) that shows a broad antimicrobial spectrum against both Gram-positive and Gram-negative bacteria. Bacteriocin AS-48 is encoded by the pheromone-responsive plasmid pMB2, and acts on the plasma membrane in which it opens pores leading to ion leakage and cell death []. The globular structure of bacteriocin AS-48 is comprised of five alpha helices enclosing a hydrophobic core. The mammalian NK-lysin effector protein of T and natural killer cells has a similar structure, though it lacks sequence homology with bacteriocins AS-48.This entry represents the characteristic domain of bacteriocin AS-48.
Elf (E74-like-factor) is a subfamily of the ETS transcription factor family []. Elf-1 is an immune cell specific transcription factor. It is found in T cells, B cells, megakaryocytes,and mast cells and is involved in the control of transcription for various immune proteins []. Included in the Elf subfamily are also Elf-2 (NERF) []and Elf4 (MEF) [].This entry represents a domain found in the N terminus of Elf transcription factors. It is approximately 110 amino acids in length and is found in association with . It contains a conserved PAVIVE sequence motif.
This entry represents the SH2 domain found in SLAP/SLAP2.Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling. They negatively regulate T cell receptor signaling []and act as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke []. They contain adjacent Src homology 3 (SH3) and Src homology 2 (SH2) domains. SLAP has been shown to regulate receptor tyrosine kinase (RTK) signaling []. It also binds to the receptor tyrosine kinase Flt3 and plays a role in signal transduction downstream of Flt3 []. SLAP2 acts as a negative regulator of FLT3 signaling [].
Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells. Interleukin-17 (IL-17) is a potent proinflammatory cytokine produced by activated memory T cells []. The IL-17 family (of which there are 6 known members, termed IL-17A to IL-17F) is thought to represent a distinct signalling system that appears to have been highly conserved across vertebrate evolution []. Family members play an active role in inflammatory diseases, autoimmune diseases and cancer []. This entry represents interleukin-17 found in chordata.
Basic leucine zipper transcriptional factor ATF-like (BATF) is a transcription factor that dimerises with Jun class factors to bind AP-1 DNA sites []. It does not only inhibit AP-1-driven transcription, but also has positive transcriptional activities in dendritic cells, B cells and T cells through its interaction with members of the interferon-regulatory factor (IRF) family []. BATF controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8+ dendritic cells and class-switch recombination (CSR) in B-cells [].
Siva binds to the CD27 cytoplasmic tail. It has a DD homology region, a box-B-like ring finger, and a zinc finger-like domain. Overexpression of Siva in various cell lines induces apoptosis, suggesting an important role for Siva in the CD27-transduced apoptotic pathway []. Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis. Indeed, the unique amphipathic helical region (SAH) present in Siva-1 is required for its binding to BCL-X(L) and sensitising cells to UV radiation. Natural complexes of Siva-1/BCL-X(L) are detected in HUT78 and murine thymocyte, suggesting a potential role for Siva-1 in regulating T cell homeostasis [].
Hematopoietic cell signal transducer (HCST, also known as DAP10) is a transmembrane adaptor that associates with an activation receptor, NKG2D, which is found on NK and subsets of T cells. The ligands for this receptor include MHC class I chain-related (MIC) protein A and protein B and UL16-binding proteins []. In activated mouse natural killer (NK) cells, the NKG2D receptor associates with two intracellular adaptors, DAP10 and DAP12, which trigger phosphatidyl inositol 3 kinase (PI3K) and Syk family protein tyrosine kinases, respectively. It has been suggested that the DAP10-PI3K pathway is sufficient to initiate NKG2D-mediated killing of target cells [].
