ligand-binding

NKG2D ligand 1, also called ULBP1, is a member of UL16-binding protein (ULBP) family which has also been termed the retinoic acid early transcript 1 (RAET1) family. Unlike the classical MHC class I molecules and the MIC molecules possess α1, α2 and α3 domains, ULBP/RAET1 family members lack α3 domain. ULBP1 is recognized by the activating receptor NKG2D on the surface of cytotoxic natural killer (NK) and T cells, and then promotes the lysis of cells expressing ULBP1 which is important for the immune surveillance. ULBP1 and several other family members, ULBP2 and ULBP5, own the ability to bind the human cytomegalovirus (CMV) UL16 glycoprotein. The human CMV glycoprotein UL16 binds to intracellular ULBP1 and so inhibits its expression at the cell surface, which reduces the susceptibility of the virus-infected cell to cytotoxic destruction by NK cells. The expression of ULBP1 has been found on some tumor cells and is implicated in tumor surveillance.

C-C Motif Chemokine 3 (MIP-1 alpha,CCL3 ) is a member of the beta or CC subfamily of chemokines and is closely related to CCL4/MIP-1 beta. CCL3 expression can be induced in a variety of hematopoietic cells, fibroblasts, smooth muscle cells, and epithelial cells. Mature mouse CCL3 shares 73%, 91%, and 82% amino acid sequence identity with human, rat, and cotton rat CCL3, respectively. CCL3 exerts its biological functions through interactions with CCR1, CCR3, and CCR5. It is cleared from the extracellular space by internalization via the decoy chemokine receptor D6. CCL3 promotes the chemoattraction, adhesion to activated vascular endothelium, and cellular activation of many hematopoietic cell types including activated T cells, NK cells, neutrophils, monocytes, immature dendritic cells, and eosinophils. CCL3 is also known as stem cell inhibitor (SCI) and can inhibit the proliferation of hematopoietic progenitor cells. CCL3 bioactivity contributes to tumor metastasis and the inflammatory components of viral infection, rheumatoid arthritis, and hepatitis, although it also can suppress the replication of HIV.

APRIL (a proliferation-inducing ligand), also known as TNFSF13, TALL2, TRDL1, and CD256, is a member of the TNF ligand superfamily. It is synthesized as a 32 kDa proprotein which is cleaved by furin in the Golgi to release the active 17 kDa soluble molecule. Secreted human APRIL, which consists almost entirely of a single TNF homology domain, shares 85% amino acid sequence identity with mouse and rat APRIL. Both APRIL and its close relative BAFF bind and signal through the TNF superfamily receptors TACI and BCMA, while BAFF additionally functions through BAFF R. APRIL binds to heparan sulfate proteoglycans (HSPGs) independently of its binding to TACI and BCMA. APRIL can form bioactive heterotrimers with BAFF, and these circulate in the serum of patients with rheumatic immune disorders. APRIL enhances the proliferation and survival of plasma cells and also promotes T cell-dependent humoral responses. APRIL levels are elevated in the serum during coronary artery disease, and it is also elevated in many cancers primarily due to expression by tumor-infiltratin neutrophils.

Receptor activator of NF-κB(RANK,TNFRSF11A) belongs to one member of tumor necrosis factor receptor family.It is a receptor for TNFSF11/RANKL/TRANCE/OPGL. This gene encodes a type 1 membrane protein with a 30 amino acids (aa) signal peptide, 184 aa extracellular region , a 20 aa transmembrane domain and a 391 aa cytoplasmic region. Human and murine RANK share 81% aa identity in their extracellular domains. RANK is ubiquitous highly expressed in trabecular bone, thymus, small intestine, lung, brain and kidney, but weakly expressed in spleen and bone marrow. After binding its ligand RANKL, RANK can activate signaling pathways such as NF-κB, JNK, ERK, p38, and Akt/PKB, through TRAF protein phosphorylation. RANK/TNFRSF11A signaling is largely considered to be growth promoting and apoptosis reducing such as the effects observed in osteoclasts. RANK/TNFRSF11A was also found to be involved in the regulation of interactions between T-cells and dendritic cells.

C-C Motif Chemokine 3-Like 1 (CCL3L1) is a secreted protein that belongs to the intercrine beta (chemokine CC) family. CCL3L1 is a ligand for CCR1, CCR3 and CCR5. CCL3L1 binds to several chemokine receptors including chemokine binding protein 2 and chemokine (C-C motif) receptor 5 (CCR5). CCR5 is a co-receptor for HIV, and binding of this protein to CCR5 inhibits HIV entry. The processed form LD78-beta (3-70) shows a 20-fold to 30-fold higher chemotactic activity and is a very potent inhibitor of HIV-1-infection. The copy number of this gene varies among individuals: most individuals have 1-6 copies in the diploid genome, although rare individuals have zero or more than six copies. The human genome reference assembly contains two full copies of the gene (CCL3L3 and CCL3L1) and a partial pseudogene. This record represents the more centromeric full-length gene.

SCF/C-kit ligand is the ligand of the tyrosine-kinase receptor encoded by the KIT locus. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. In phase I/II clinical studies administration of the combination of SCF and G-CSF resulted in a two- to threefold increase in cells that express the CD34 antigen compared with G-CSF alone.

Low affinity immunoglobulin gamma Fc region receptor III (Fc gamma RIII/CD16) is a member of the Ig superfamily. Based on close relationships in their extracellular domains, the Fc gamma Rs have been divided into three classes composing of Fc gamma RI (CD64), Fc gamma RII (CD32), and Fc gamma RIII (CD16). Each group may be encoded by multiple genes and exist in different isoforms depending on species and cell type. Mouse CD16 is a type I transmembrane protein having two extracellular Ig-like domains consisting of immunoglobulin domain, repeat, signa and transmembrane, transmembrane helix. It is expressed on a variety of myeloid and lymphoid cells and associates with Fc R gamma to deliver an activating signal upon ligand binding. Fcgr3 is IgG binding and activation or inhibition of immune responses such as antibody-dependent cellular cytotoxicity, phagocytosis, cell surface receptor signaling pathway and positive regulation of type I/IIa/III hypersensitivity.

CD40 ligand or CD40L, also called CD154,  is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 (protein) on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. In total CD40L has three binding partners: CD40, α5β1 integrin and αIIbβ3. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells. CD40 Ligand Protein (Primary Amine Labeling), Human, Recombinant (His & Flag), Biotinylated is expressed in HEK293 mammalian cells with N-His-Flag tag. The predicted molecular weight is 52.4 kDa and the accession number is P29965.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate the apoptosis pathway by binding to its associated death receptors DR4 and DR5. The activation of the TRAIL pathway in inducing tumor-selective apoptosis leads to the development of TRAIL-based cancer therapies, which include recombinant forms of TRAIL, TRAIL receptor agonists, and other therapeutic agents.

Human Chemokine (C-C Motif) Ligand 27 (CCL27) is a small cytokine that is a member of the CC chemokine family; it is expressed in numerous tissues, including gonads, thymus, placenta and skin. CCL27 elicits its chemotactic effects by binding to the chemokine receptor CCR10. Predominantly expressed in the skin, CCL27 is associated with T cell-mediated inflammation of the skin. Human and Mouse CCL27 share 84% sequence identity in the mature form.

The epidermal growth factor receptor (EGFR) is overexpressed in a variety of human epithelial tumors, often as a consequence of gene amplification. Tumors with EGFR gene amplification frequently contain EGFR gene rearrangements, with the most common extracellular domain mutation being EGFRvIII. This mutation leads to a deletion of exons 2-7 of the EGFR gene and renders the mutant receptor incapable of binding any known ligand. EGFRVIII Protein, Human, Recombinant (His & Avi), FITC-Labeled is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 41.6 kDa and the accession number is NP_001333870.1.

ULBP6/RAET1L (UL16-binding protein, also known as retinoic acid early transcript), is expressed as a full-lengthtranscript in cells and encodes a protein that is a ligand for bothNKG2D and the UL16 protein of HCMV.

MICB (MHC class I chain-related gene B) is a transmembrane glycoprotein that functions as a ligand for NKG2D. A closely related protein, MICA, shares 85% amino acid identity with MICB.MICB Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis. MICB Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 58.21 kDa and the accession number is Q29980-1.

Hemopexin (HPX) serves as scavenger and transporter of toxic plasma heme to the liver. HPX is formed by two four-bladed beta-propeller domains, resembling two thick disks that lock together at a 90 degrees angle. The heme is bound between the two beta-propeller domains in a pocket formed by the interdomain linker peptide.HPX, acting not only as a heme carrier but also displaying transient heme-based ligand binding and (pseudo-)enzymatic properties, could be considered a 'chronosteric' heme-protein.

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner.; Lacks ligand binding ability and has no or only very low ERE binding activity resulting in the loss of ligand-dependent transactivation ability. ER beta Protein, Human, Recombinant (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 61.1 kDa and the accession number is Q92731.

Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription. Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation. Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry. Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition. During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells.; Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity.

Plays a role as a neuroprotective factor. Protects against neuronal cell death induced by multiple different familial Alzheimer disease genes and amyloid-beta proteins in Alzheimer disease. Mediates its neuroprotective effect by interacting with a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR. Also acts as a ligand for G-protein coupled receptors FPR2/FPRL1 and FPR3/FPRL2. Inhibits amyloid-beta protein 40 fibril formation. Also inhibits amyloid-beta protein 42 fibril formation. Suppresses apoptosis by binding to BAX and preventing the translocation of BAX from the cytosol to mitochondria. Also suppresses apoptosis by binding to BID and inhibiting the interaction of BID with BAX and BAK which prevents oligomerization of BAX and BAK and suppresses release of apoptogenic proteins from mitochondria. Forms fibers with BAX and also with BID, inducing BAX and BID conformational changes and sequestering them into the fibers which prevents their activation. Can also suppress apoptosis by interacting with BIM isoform BimEL, inhibiting BimEL-induced activation of BAX, blocking oligomerization of BAX and BAK, and preventing release of apoptogenic proteins from mitochondria. Plays a role in up-regulation of anti-apoptotic protein BIRC6/APOLLON, leading to inhibition of neuronal cell death. Binds to IGFBP3 and specifically blocks IGFBP3-induced cell death. Competes with importin KPNB1 for binding to IGFBP3 which is likely to block IGFBP3 nuclear import. Induces chemotaxis of mononuclear phagocytes via FPR2/FPRL1. Reduces aggregation and fibrillary formation by suppressing the effect of APP on mononuclear phagocytes and acts by competitively inhibiting the access of FPR2 to APP. Protects retinal pigment epithelium (RPE) cells against oxidative stress-induced and endoplasmic reticulum (ER) stress-induced apoptosis. Promotes mitochondrial biogenesis in RPE cells following oxidative stress and promotes STAT3 phosphorylation which leads to inhibition of CASP3 release. Also reduces CASP4 levels in RPE cells, suppresses ER stress-induced mitochondrial superoxide production and plays a role in up-regulation of mitochondrial glutathione. Reduces testicular hormone deprivation-induced apoptosis of germ cells at the nonandrogen-sensitive stages of the seminiferous epithelium cycle. Protects endothelial cells against free fatty acid-induced inflammation by suppressing oxidative stress, reducing expression of TXNIP and inhibiting activation of the NLRP3 inflammasome which inhibits expression of proinflammatory cytokines IL1B and IL18. Protects against high glucose-induced endothelial cell dysfunction by mediating activation of ERK5 which leads to increased expression of transcription factor KLF2 and prevents monocyte adhesion to endothelial cells. Inhibits the inflammatory response in astrocytes. Increases the expression of PPARGC1A/PGC1A in pancreatic beta cells which promotes mitochondrial biogenesis. Increases insulin sensitivity.

G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system.

The very low density lipoprotein receptor, known as VLDLR, is a single-pass type 1 integral membrance protein and a member of the LDL receptor family. This receptor family includes LDL receptor, LRP, megalin, VLDLR and ApoER2, and is characterized by a cluster of cysteine-rich class A repeats, epidermal growth factor (EGF)-like repeats, YWTD repeats and an O-linked sugar sdomain. VLDLR contains 3 EGF-like domains, 8 LDL-receptor class A domains, as well as 6 LDL-receptor class B repeats, and is abundant in heart, skeletal muscle, also ovary and kidney, but not in liver. VLDLR binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. VLDLR mediates the phosphorylation of mDab1 (mammalian disabled protein) via binding to Reelin, and induces the modulation of Tau phosphorylation. This pathway regulates the migration of neurons along with the radial glial fiber network during brain development. Defects of VLDLR may be the cause of VLDLR-associated cerebellar hypoplasia (VLDLRCH), a syndrome characterized by moderate-to-profound mental retardation, delayed ambulation, and predominantly truncal ataxia.

CCL11 or chemokine (C-C motif) ligand 11 is a member of the chemokine (C-C motif) ligand family. Chemokin (C-C motif) ligand 11 is a member of the chemokine family. There are four members of the chemokine family: C-C kemokines, C kemokines, CXC kemokines and CX3C kemokines. The C-C kemokines have two cysteines nearby the amino terminus. There have been at least 27 distinct members of this subgroup reported for mammals, called C-C chemokine ligands (CCL)-1 to 28. Chemokines are a family of small chemotactic cytokines, or proteins secreted by cells. They share the same structure similarities such as small size, and the presence of four cysteine residues in conserved locations in order to form their 3-dimensional shape. Some of the chemokines are considered pro-inflammatory which can be induced to recruit cells of the immune system to a site of infection during an immune response, while others are considered homeostatic and are implied in controlling the migration of cells during normal processes of tissue maintenance and development. CCL11 is implicated in allergic responses through selectively recruiting eosinophils by inducing their chemotaxis. The effects of CCL11 are mediated by its binding to chemokine receptor. Increased CCL11 levels in blood plasma are associated with aging in mice.

GNG13 is a subunit of heterotrimeric G proteins which consist of alpha, beta, and gamma subunits. Heterotrimeric G proteins are membrane-bound GTPases that are linked to 7-TM receptors. They function as signal transducers for the 7-transmembrane-helix G protein-coupled receptors. They are involved as a modulator or transducer in various transmembrane signaling systems. Each G protein is composed of an alpha-, beta- and gamma-subunit and is bound to GDP in the 'off' state. Ligand-receptor binding results in detachment of the G protein, switching it to an 'on' state and permitting Galpha activation of second messenger signaling cascades. There are several types of Galpha proteins; besides, some Gbetagamma subunits have active functions. Gbetagamma coupled to H1 receptors can activate PLA2 and Gbetagamma coupled to M1 receptors can activate KIR channels. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and G protein-effector interaction. GNG13 is a gamma subunit that is expressed in taste, retinal, and neuronal tissues and plays a key role in taste transduction.

Apolipoprotein E (Apo-E), is a member of the apolipoprotein A1/A4/E family. ApoE is a major protein component of serum LDL, VLDL, HDL, and chylomicrons. APOE may function in mediating the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues. APOE is usually secreted in plasma. Phosphorylation sites are present in the extracellular medium.

Mouse stem cell factor (SCF), is the ligand for the receptor-type protein-tyrosine kinase KIT. It plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. It also promotes phosphorylation of PIK3R1, which is the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5.

Ephrin-B2 is a single-pass type I membrane protein and it contains 1 ephrin RBD (ephrin receptor-binding) domain. Ephrin-B2 belongs to the ephrin (EPH) family and it is cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. The ephrins and EPH-related receptors contain the largest subfamily of receptor protein-tyrosine kinases and have been associated with mediating developmental events, particularly in the nervous system and in erythropoiesis. Based upon their structures and sequence relationships, ephrins are allocated into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. It also binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4 and together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration.

Human Siglec-15 is a transmembrane glycoprotein in the Siglec family. Siglecs are type I transmembrane proteins where the NH3+-terminus is in the extracellular space and the COO−-terminus is cytosolic. Each Siglec contains an N-terminal V-type immunoglobulin domain (Ig domain) which acts as the binding receptor for sialic acid. These lectins are placed into the group of I-type lectins because the lectin domain is an immunoglobulin fold. All Siglecs are extended from the cell surface by C2-type Ig domains which have no binding activity. Siglecs differ in the number of these C2-type domains. Human Siglec-15 consists of a 244 amino acid (aa) extracellular domain (ECD) with two Ig-like domains, a 21 aa transmembrane segment, and a 44 aa cytoplasmic domain. Siglec-15 function is important for osteoclast formation and TRANCE/RANK Ligand signaling in osteoclasts

CD112 is a type I transmembrane glycoprotein belonging to the Immunoglobulin superfamily. It comprises one Ig-like V-type domain and two Ig-like C2-type domains in the extracellular region. The V domain is believed to mediate nectin binding to its ligands. Nectin2 is known to bind the pseudorabies virus, and herpes simplex virus2 (HSV2), involving in cell to cell spreading of these viruses. It does not bind poliovirus. As a homophilic adhesion molecule, CD112 is found concentrated in adherens junctions, and exists on neurons, endothelial cells,epithelial cells and fibroblasts. CD112 has been identified as the ligand for DNAM-1 (CD226), and the interaction of CD226/CD112 mediates cytotoxicity and cytokine secretion by T and NK cells. The costimulatory responses may be a critical component in allergic reactions and may therefore become targets for anti-allergic therapy.

Stem cell factor (SCF), is the ligand for the receptor-type protein-tyrosine kinase KIT. It plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. It also promotes phosphorylation of PIK3R1, which is the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5.

Human Artemin is a GDNF family ligand that is distantly related to the TGF-β superfamily of molecules. It is synthesized as a preproprotein, and contains a variable length pre-, or signal sequence, plus a 68 amino acid (aa) proregion and a 113 aa mature segment. Following synthesis and proteolytic processing, mature ARTN is secreted as a presumably glycosylated, 28 kDa disulfide-linked homodimer that contains three intrachain disulfide bonds and the typical TGF-β signature cysteine-knot motif. In the mature region, human ARTN is 89% and 88% aa identical to rat and mouse ARTN, respectively. Human ARTN is active on rodent cells. The receptor for ARTN has been identified as the ligand binding subunit GFRα-3 plus the signal transducing subunit, RET. The GFRα-1/RET receptor complex has also been suggested to be a ligand binding unit for ARTN. ARTN is known to be a chemoattractant for sympathetic neuron axons innervating the developing cardiovascular system. It also promotes sensory neuron survival and likely plays a role in the development of the peripheral nervous system. Finally, it has been reported to reverse neuropathic pain due to nerve injury, and to help resolve morphological changes associated with nerve damage.

B cell maturation antigen (BCMA) is a member of the TNF receptor superfamily. It has been designated TNFRSF17. Mouse BCMA is a 185 amino acid (aa) protein consisting of a 49 aa extracellular domain, a 23 aa transmembrane domain, and a 113 aa intracellular domain. BCMA is a type III membrane protein containing one extracellular cysteine rich domain. Within the TNFRSF, it shares the highest homology with TACI. BCMA and TACI have both been shown to bind to APRIL and BAFF, members of the TNF ligand superfamily. BCMA expression has been found in immune organs and mature B cell lines. Although some expression has been observed at the cell surface, BCMA appears to be localized to the Golgi compartment. The binding of BCMA to APRIL or BAFF has been shown to stimulate IgM production in peripheral blood B cells and increase the survival of cultured B cells. This data suggests that BCMA may play an important role in B cell development,function and regulation.

Fatty Acid-Binding Protein 6 (FABP6) is cytoplasmic protein that binds long-chain fatty acids and other hydrophobic ligands which belongs to the calycin superfamily. FABP6 expression is restricted in the small intestine to the ileum where it is involved in the enterohepatic circulation of bile acids. FABP6 forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior. Isoform 2 is expressed in colorectal adenocarcinomas and their adjacent normal mucosa (at protein level). Isoform 1 is expressed in the jejunum, ileum, cecum and ascending colon intestine. FABP6 plays a role in fatty acid uptake, transport, and metabolism. FABP6 stimulates gastric acid and pepsinogen secretion. It seems to be able to bind to bile salts and bilirubins.

Neurturin is a member of the GDNF family of ligands, which include glial cell-derived neurotrophic factor (GDNF), Neurturin, Persephin, and Artemin. Neurturin is expressed in both neuronal and nonneuronal tissues. Similarly to other TGFβ family proteins, Neurturin is synthesized as a precursor protein that is cleaved at the dibasic cleavage site (RXXR) to release the carboxyterminal domain. The carboxy terminal domain of Neurturin contains the characteristic seven conserved cysteine residues necessary for the formation of the cysteine-knot and the single interchain disulfide bond. Biologically active human Neurturin is a disulfide-linked homodimer of the carboxy-terminal 102 amino acid residues. Unlike other members of TGF-β family, bioactivities of all GDNF family ligands are mediated through a unique multicomponent receptor complex composed of high affinity ligand binding component (GFRα-1-GFRα-4) and a common signaling component (cRET receptor tyrosine kinase). Each member of the GDNF family ligands has its preferred binding protein. Neurturin preferentially binds to GFRα-2 but can also bind GFRα-1 at higher concentrations. It may play a role in regulating the development and maintenance of the central and peripheral nervous systems and as well as non neuronal systems.

MICB (MHC class I chain-related gene B) is a transmembrane glycoprotein that functions as a ligand for NKG2D. A closely related protein, MICA, shares 85% amino acid identity with MICB.MICB Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis. MICB Protein, Human, Recombinant (His & Avi) is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 34.4 kDa and the accession number is Q29980-1.

The epidermal growth factor receptor (EGFR) is overexpressed in a variety of human epithelial tumors, often as a consequence of gene amplification. Tumors with EGFR gene amplification frequently contain EGFR gene rearrangements, with the most common extracellular domain mutation being EGFRvIII. This mutation leads to a deletion of exons 2-7 of the EGFR gene and renders the mutant receptor incapable of binding any known ligand. EGFRVIII Protein, Human, Recombinant (His & Avi), PE-Labeled is expressed in HEK293 mammalian cells with C-His-Avi tag. The predicted molecular weight is 41.6 kDa and the accession number is NP_001333870.1.

Probable ligand-binding protein. Bla g 4 Protein, Blattella germanica, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 35.8 kDa and the accession number is P54962.

G-protein coupled receptor for glucagon-like peptide 1 (GLP-1). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels. Plays a role in regulating insulin secretion in response to GLP-1. GLP1R Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with N-6xHis tag. The predicted molecular weight is 18.3 kDa and the accession number is P43220.

Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface. ASGR2 Protein, Mouse, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 29.9 kDa and the accession number is P24721.

Adhesion molecule that binds to leukocyte adhesion LFA-1 protein LFA-1 (integrin alpha-L/beta-2). ICAM4 is also a ligand for alpha-4/beta-1 and alpha-V integrins. Isoform 2 may modulate binding of membrane-associated ICAM4. ICAM4 Protein, Mouse, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 39.1 kDa and the accession number is Q9ERM2.

Catalyzes the transfer of CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1). This constitutes the first step in the formation of the ribitol 5-phosphate tandem repeat which links the phosphorylated O-mannosyl trisaccharide to the ligand binding moiety composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1. Required for normal location of POMGNT1 in Golgi membranes, and for normal POMGNT1 activity. May interact with and reinforce a large complex encompassing the outside and inside of muscle membranes. Could be involved in brain development (Probable).

Insulin-like growth factor 2 (IGF-2/IGF-II) is a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumor, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. IGF-2/IGF-II is a mediator of prolactin-induced alveologenesis; prolactin, IGF-2, and cyclin D1, all of which are overexpressed in breast cancers, are components of a developmental pathway in the mammary gland. IGF-2 and exhibited statistically significant, positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short period after enrolment. Circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer. IGF-2/IGF-II appears to be involved in the progression of many tumors. It binds to at least two different types of receptors: IGF type 1 (IGF 1R) and mannose 6-phosphate/IGF type 2 (M6-P/IGF 2R). Ligand binding to IGF 1R provokes mitogenic and anti-apoptotic effects. M6-P/IGF 2R has a tumor suppressor function—it mediates IGF 2 degradation. Mutation of M6-P/IGF 2R causes both diminished growth suppression and augmented growth stimulation. This study aimed to investigate the role of IGF 2 and its receptors (IGF 1R and IGF 2R) in human gastric cancer.

Lipocalin-1, also known as Von Ebner gland protein, VEG protein, Tear Prealbumin, VEGP, Tear lipocalin, and LCN1 is a secreted protein that belongs to the calycin superfamily and Lipocalin family. Human Lipocalin-1 / VEGP was originally described as a major protein of human tear fluid, which was thought to be tear specific. Lipocalin-1 / VEGP is identical to lingual von Ebner's gland protein and is also produced in the prostate, nasal mucosa, and tracheal mucosa. Homologous proteins have been found in the rat, pig, and probably dog and horse. Lipocalin-1 / VEGP is an unusual lipocalin member, because of its high promiscuity for relative insoluble lipids and binding characteristics that differ from other members. Lipocalin-1 / VEGP acts as the principal lipid-binding protein in tear fluid, a more general physiological function has to be proposed due to its wide distribution and properties. Lipocalin-1 / VEGP would be ideally suited for scavenging of lipophilic, potentially harmful substances and thus might act as a general protection factor of epithelia. Lipocalin-1 / LCN1 could play a role in taste reception. It could be necessary for the concentration and delivery of sapid molecules in the gustatory system. Lipocalin-1 / LCN1 can bind various ligands, with chemical structures ranging from lipids and retinoids to the macrocyclic antibiotic rifampicin and even to microbial siderophores. It exhibits an extremely wide ligand pocket.

The tyrosine kinase receptor, macrophage-stimulating 1 receptor (MST1R), a c-met-related tyrosine kinase, also known as the Ron receptor or CD136, controls cell survival and motility programs related to invasive growth. As the tyrosine kinase receptor is comprised of an extracellular domain, MST1R protein contains the ligand-binding pocket and an intracellular region where the kinase domain is located. MST1R signaling may be involved in the regulation of macrophage and T-lymphocyte activation in vivo during injury. This assessment of gene expression indicates the importance of genetic factors in contributing to lung injury and points to strategies for intervention in the progression of inflammatory diseases. It had been shown that MST1R/CD136 plays a critical role in Ni-induced lung injury in mice. The overexpression of MSP, MT-SP1, and MST1R was a strong independent indicator of both metastasis and death in human breast cancer patients and significantly increased the accuracy of an existing gene expression signature for poor prognosis. Stimulation of MST1R leads to its transphosphorylation and the ultimate activation of numerous intracellular signaling pathways, such as the classical mitogen-activated protein kinase pathway, the phosphatidylinositol (PI)3-kinase pathway, and the JNK pathway.

ACBD7, acyl-CoA-binding domain-containing protein 7, is a small (1 Kd) protein that contains 1 ACB (acyl-CoA-binding) domain. The ACB domain consists of four alpha-helices arranged in a bowl shape with a highly exposed acyl-CoA-binding site. The ligand is bound through specific interactions with residues on the protein, most notably several conserved positive charges that interact with the phosphate group on the adenosine-3'phosphate moiety, and the acyl chain is sandwiched between the hydrophobic surfaces of CoA and the protein. Other proteins containing an ACB domain include: ACBP (acyl-CoA-binding protein), ACBD3, ACBD4, ACBD5, ACBD6.

The enzyme BirA is a key reagent because of its ability to biotinylate proteins at a specific residue in a recognition sequence. This enzyme is used to biotinylate the C termini of membrane proteins, allowing these proteins to be tetramerized by binding to streptavidin. Because of the specificity of the biotinylation at the C terminus, the orientation of the membrane proteins on the streptavidin is equivalent to that of the native protein on the cell surface. These tetrameric proteins can be used to study protein receptor-ligand interactions at the cell surface, and site-specific biotinylation can be used to study proteins in vitro using a defined orientation. The biotinylation of histones by BirA ligase is consistent with the proposed role of human HCS in chromatin. The N-terminal BirA domain is required for both transcriptional regulation of biotin synthesis and biotin protein ligase activity.

Transforming growth factor beta 1 (TGFβ1) is the prototype of a growing superfamily of peptide growth factors and plays a prominent role in a variety of cellular processes, including cell-cycle progression, cell differentiation, reproductive function, development, motility, adhesion, neuronal growth, bone morphogenesis, wound healing, and immune surveillance. TGF-β1, TGF-β2 and TGF-β3 signal via the same heteromeric receptor complex, consisting of a ligand binding TGF-β receptor type II (TβR-II), and a TGF-β receptor type I (TβR-I). Signal transduction from the receptor to the nucleus is mediated via SMADs. TGF-β expression is found in cartilage, bone, teeth, muscle, heart, blood vessels, haematopoitic cells, lung, kidney, gut, liver, eye, ear, skin, and the nervous system.

Chemokine (C-X-C motif) ligand 9 (CXCL9, MIG), is a small cytokine belonging to the CXC chemokine family. CXCL9 functions as one of the three ligands of chemokine receptor CXCR3 which is a G protein-coupled receptor found predominantly on T cells. It together with CXCL10 and CXCL11, may activate CXCR3 by binding to it. CXCL9 serves as a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. It has been observed that tumour endothelial cells secrete high levels of CXCL9 in all, and CXCL10 in most melanoma metastases. it plays an important role in CD4+ T lymphocyte recruitment and development of CAV, MOMA-2+ macrophages are the predominant recipient-derived source of CXCL9, and recipient CD4 lymphocytes are necessary for sustained CXCL9 production and CAV development in this model.

Atrial Natriuretic Peptide Receptor-3 (NPR3), also known as NPRC or ANPR-C, is one of the three natriuretic peptide receptors, is a type I transmembrane glycoprotein. The natriuretic system is key to the maintenance of vascular tone and cardiovascular homeostasis. Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP. May function as a clearance receptor for NPPA, NPPB and NPPC, regulating their local concentrations and effects. Osteocrin was found to be a specific ligand to NPR3. NPR3 is necessary for Osteocrin to regulate femoral, tibial, and metatarsal bone elongation.

Sclerostin (SOST) is a member of the cerberus/DAN family, a group of secreted glycoproteins characterized by a cysteine-knot motif. Cerberus/DAN family members are putative BMP antagonists, and include Dan, Cerberus, Gremlin, PRDC, and Caronte. While the overall sequence identity between members of the family is low, they have conserved spacing of six cysteine residues. Cerberus and Dan have an additional cysteine residue used for dimerization; however, SOST does not and is secreted as a monomer. SOST was originally identified as an important regulator of bone homeostasis. SOST is expressed by osteoclasts in developing bones of mouse embryos, including both intramembranously forming skull bones and endochondrally forming long bones. SOST plays a physiological role as a negative regulator of bone formation by repressing BMP-induced osteogenesis. SOST has been shown to have unique ligand specificity, binding BMP-5, -6, and -7 with high affinity and BMP-2 and -4 with low affinity.

Fibronectin1(FN1) is a secreted protein and contains 12 fibronectin type-I domains,fibronectin type-II domains and 16 fibronectin type-III domains.Recombinant human fibronectin fragment, is a protein of ~63 kDa containing a central cell-binding domain, a high affinity heparin-binding domain II,and CS1 site within the alternatively spliced III CS region of human fibronectin. Cells bind to a VLA-4 ligand, a CS-I site, and a VLA-5 ligand, a cell attachment domain, and virus vectors binds to a heparin binding domain II, which co-locates the cell and the virus vector on NovoNectin. This process enhances the density of both cells and vectors, and facilitates the gene transduction in the result.

Human Chemokine (C-X-C motif) Ligand 4 (CXCL4) is expressed in megakaryocytes and stored in the alpha-granules of platelets. CXCL4 contains several heparin-binding sites at the C-terminal region and binds heparin with high affinity. The active CXCL4 protein is a tetramer. Human and mouse CXCL4 share 64% sequence identity. CXCL4 is chemotactic for neutrophils, fibroblasts and monocytes and plays a critical role in inflammation and wound repair. CXCL4 functions via a splice variant of the chemokine receptor CXCR3, known as CXCR3B. The major physiologic role of CXCL4 appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. In contrast to other CXC chemokines, CXCL4 lacks chemotactic activity for polymorphonuclear granulocytes.