endosome

Endosome lysosome-associated apoptosis and autophagy regulator (ELAPOR1), also known as EIG121 protein, is a type I transmembrane protein induced by estrogen. The estrogen-induced gene 121 (EIG121) has been associated with breast and endometrial cancers,but its mechanism of action remains unknown.May protect cells from cell death by inducing cytosolic vacuolization and upregulating the autophagy pathway. That EIG121 is a good endometrial biomarker associated with a hyperestrogenic state and estrogen-related type I endometrial adenocarcinoma.

Cathepsin E (CTSE) is a gastric aspartyl protease that functions as a disulfide-linked homodimer. It is a member of the Peptidase C1 family, and has a specificity similar to that of Pepsin A and Cathepsin D. CTSE is localized to the endoplasmic reticulum and Golgi apparatus, while the mature enzyme is localized to the endosome. It is expressed abundantly in the stomach, the Clara cells of the lung and activated B-lymphocytes, and at lower levels in lymph nodes, skin and spleen. CTSE is an intracellular proteinase that have a role in immune function, activation-induced lymphocyte depletion in the thymus, neuronal degeneration and glial cell activation in the brain. Futhermore, it probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation.

Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation.

Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells. Rabies virus (RABV) (strain ERA) Glycoprotein (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 55.0 kDa and the accession number is P03524.

Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of the eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin F which may have 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins found in synaptic vesicles. Receptor proteins are exposed on host presynaptic cell membrane during neurotransmitter release, when the toxin heavy chain (HC) binds to them. Upon synaptic vesicle recycling the toxin is taken up via the endocytic pathway. When the pH of the toxin-containing endosome drops a structural rearrangement occurs so that the N-terminus of the HC forms pores that allows the light chain (LC) to translocate into the cytosol. Once in the cytosol the disulfide bond linking the 2 subunits is reduced and LC cleaves its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release. Whole toxin only has protease activity after reduction, which releases LC. Requires complex eukaryotic host polysialogangliosides for full neurotoxicity. It is not clear whether a synaptic vesicle protein acts as its receptor; there is evidence for and against SV2 fulfilling this function.; Has proteolytic activity. After translocation into the eukaryotic host cytosol, inhibits neurotransmitter release by acting as a zinc endopeptidase that catalyzes the hydrolysis of the '60-Gln-|-Lys-61' bond of synaptobrevin-1 VAMP1 and the equivalent 'Gln-|-Lys' sites in VAMP2 and VAMP3. Cleaves the '48-Gln-|-Lys-49' bond of A.californica synaptobrevin (AC P35589).; Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol. Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD). The RBD is responsible for the adherence of the toxin to the cell surface. It simultaneously recognizes 2 coreceptors; polysialated gangliosides and the receptor protein SV2A, SV2B and SV2C in close proximity on host synaptic vesicles; although not all evidence indicates these are the receptors. The N-terminus of the TD wraps an extended belt around the perimeter of the LC, protecting Zn(2+) in the active site; it may also prevent premature LC dissociation from the translocation channel and protect toxin prior to translocation. The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol.

LMAN2 (Lectin, Mannose Binding 2, also known as VIP36) is a Protein Coding gene. This gene encodes a type I transmembrane lectin that shuttles between the endoplasmic reticulum, the Golgi apparatus, and the plasma membrane. The encoded protein binds high mannose type glycoproteins and may facilitate their sorting, trafficking, and quality control. The L-type lectin LMAN2 appears to be specifically required for the accumulation of GPRC5B in the Golgi complex and restriction of GPRC5B transport along the exosomal pathway. This may occur due to interference with the adaptor protein GGA1-mediated trans-Golgi network-to-endosome transport of GPRC5B. A Golgi-traversing pathway for the exosomal release of the cargo protein GPRC5B in which CD2AP facilitates the entry and LMAN2 impedes the exit of the flux, respectively.

It is involved in the regulation of the biosynthesis and biological function of glycoprotein oligosaccharides. Catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked sugar chains, called bisecting N-acetylglucosamine (GlcNAc). It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. The addition of this bisecting GlcNAc residue alters not only the composition, but also the conformation of the N-glycan. The introduction of the bisecting GlcNAc residue results in the suppression of further processing and elongation of N-glycans, precluding the formation of beta-1,6 GlcNAc branching, catalyzed by MGAT5 since it is unable to use the bisected oligosaccharide as a substrate. Addition of bisecting N-acetylglucosamine to CDH1 E-cadherin modulates CDH1 cell membrane location. Inhibits NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc- formation which modulates sialylation levels and plays a role in cell migration regulation. In brain, addition of bisecting N-acetylglucosamine to BACE1 blocks its lysosomal targeting in response to oxidative stress and further degradation which increases its location to early endosome and the APP cleavage.

Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells. Rabies virus (RABV) (strain India) Glycoprotein (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 65.4 kDa and the accession number is A3RM22.

Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells. Rabies virus (RABV) (strain HEP-Flury) Glycoprotein (E. coli, His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 55.5 kDa and the accession number is P19462.

Attaches the virus to host cellular receptor, inducing clathrin-dependent endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and endosomal membrane. VSIV (strain Mudd-Summers) Glycoprotein G Protein (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 54.8 kDa and the accession number is P0C2X0.

VPS1 domain-containing receptor SorCS1, also known as SORCS1 and SORCS, is a single-pass type I membrane protein that belongs to the SORCS family and SORCS1 subfamily. SORCS1 contains five BNR repeats and one PKD domain. SorCS1 is a member of the Vps1p-domain receptor family comprised of Sortilin, SorCS1, SorCS2, SorCS3, and SorLA. The common characteristic of these receptors is an N-terminal Vps1p domain, which either represents the only module of the luminal extracellular moiety or is combined with additional domains. Family members play roles in protein transport and signal transduction. The individual receptors bind and internalize a variety of ligands, such as neuropeptides and trophic factors, and Sortilin and SorLA mediate trans-Golgi network-to-endosome sorting. Their prominent neuronal expression, several of the identified ligands, and results support the notion that members of this receptor family have important functions in neurogenesis, plasticity-related processes, and functional maintenance of the nervous system. Sortilin and SorLA mediate intracellular protein trafficking and sorting. SorCS1 binds platelet-derived growth factor-BB (PDGF-BB) and is expressed in isoforms differing only in their cytoplasmic domains. SorCS1 binds platelet-derived growth factor, a growth factor crucial for pericyte recruitment to the microvasculature, and may thus have a role in expanding or maintaining the islet vasculature.

PTP4A2, also known as PRL2 or PTPCAAX2, is short for Protein tyrosine phosphatase type IVA 2. This protein exists in cell membrane, cytoplasm,endosome and membrane. PTP4A2 is often farnesylated during post-translational modification. Farnesylation is required for membrane targeting and for interaction with RABGGTB. The unfarnesylated forms are redirected to the nucleus and cytosol. It can stimulate progression from G1 into S phase during mitosis and promotes tumors. It also inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.

Lysosome-Associated Membrane Glycoprotein 1 (LAMP1) is a single-pass type I membrane protein belonging to the LAMP family. LAMP1 is expressed largely in the endosome-lysosome membranes of cells.It shuttles between lysosomes, endosomes, and the plasma membrane. LAMP1 functions to present carbohydrate ligands to selectins and it has also been implicated in tumor cell metastasis. It has been proposed LAMP1 can be used as a therapeutic agent for certain cancers, as well as a marker for lysosomal storage disorders and degranulation on lymphocytes such as CD8+ and NK cells. Cell surface LAMP1 and LAMP2 have been shown to promote adhesion of human peripheral blood mononuclear cells(PBMC) to vascular endothelium, therefore they are possibly involved in the adhesion of PBMCs to the site of inflammation.

Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for endosomal localization of WASHC2C. Mediates the association of the CSC with the WASH complex via WASHC2. Required for the endosomal localization of TBC1D5.; (Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirus from the early endosome and the delivery to the Golgi apparatus.

May be involved in several stages of intracellular trafficking. Plays a role in protein transport from early to late endosomes. Plays a role in protein transport to the lysosome. Promotes degradation of EGFR after EGF signaling. Plays a role in intracellular transport of vesicular stomatitis virus nucleocapsids from the endosome to the cytoplasm.

Serine threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1 ERK2 and MAPK3 ERK1 are the 2 MAPKs which play an important role in the MAPK ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG SCF. Depending on the cellular context, the MAPK ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1 RSK1, RPS6KA3 RSK2, RPS6KA2 RSK3, RPS6KA6 RSK4, SYK, MKNK1 MNK1, MKNK2 MNK2, RPS6KA5 MSK1, RPS6KA4 MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.

Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation.

class I viral fusion protein that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversible conformational changes induced upon acidification in the endosome.; Stable signal peptide (SSP): cleaved and functions as a signal peptide. In addition, it is also retained as the third component of the GP complex. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of GP1 and GP2, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.; interacts with the host receptor.

Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells. Rabies virus (RABV) (strain India) Glycoprotein (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 51.4 kDa and the accession number is A3RM22.

Plays a central role in autophagy. Acts as core subunit of different PI3K complex forms that mediate formation of phosphatidylinositol 3-phosphate and are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis including endosome formation in neuronal cells. May play a role in antiviral host defense.; Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors.

Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells. Rabies virus (RABV) (strain CVS-11) Glycoprotein (His & Myc & SUMO) is expressed in E. coli expression system with N-10xHis-SUMO and C-Myc tag. The predicted molecular weight is 69.7 kDa and the accession number is O92284.

Attaches the virus to host cellular receptor, inducing endocytosis of the virion. In the endosome, the acidic pH induces conformational changes in the glycoprotein trimer, which trigger fusion between virus and cell membrane. There is convincing in vitro evidence that the muscular form of the nicotinic acetylcholine receptor (nAChR), the neuronal cell adhesion molecule (NCAM), and the p75 neurotrophin receptor (p75NTR) bind glycoprotein and thereby facilitate rabies virus entry into cells. Rabies virus (RABV) (strain HEP-Flury) Glycoprotein (His) is expressed in Baculovirus insect cells with C-9xHis tag. The predicted molecular weight is 51.5 kDa and the accession number is P19462.