目录号 | 产品详情 | 靶点 | |
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T11709 | JAK | ||
JAK3 Covalent Inhibitor-1 is a compound characterized by its potent and selective inhibition of Janus kinase 3 (JAK3), possessing an IC50 of 11 nM and demonstrating a 246-fold selectivity compared to other JAKs. | |||
T3583 | Antibacterial DprE1 | ||
Macozinone (PBTZ169) 是具有杀菌作用的苯并噻嗪酮,也有抗结核作用。它也是一种 DprE1有效抑制剂,可通过与活性位点 Cys387 残基形成共价键来抑制必需的黄素蛋白 DprE1。 | |||
T8371 | Virus Protease SARS-CoV | ||
ML188是一种选择性非共价 SARS-CoV3CLpro 抑制剂,具有抗病毒活性,IC50为 1.5 μM。 | |||
T16143 | Ras | ||
MRTX-1257 是选择性的、可口服的不可逆共价KRAS G12C 抑制剂,其在 H358 细胞中测得 KRAS 依赖 ERK 磷酸化的IC50值为 900 pM。 | |||
T41277 | Others | ||
PACMA 31 是一种不可逆的共价蛋白二硫键异构酶 (PDI) 抑制剂,IC50 为 10 μM。 PACMA 31 显着抑制卵巢肿瘤生长并表现出肿瘤靶向能力。 | |||
T22461 | CDK | ||
YKL-5-124 是选择性不可逆CDK7共价抑制剂,对CDK7和CDK7/Mat1/CycH 的IC50分别为 53.5 nM 和 9.7 nM。它诱导强烈的细胞周期停滞,并抑制 E2F 驱动的基因表达。它对 CDK7 的生化和细胞选择性优于 CDK12/13。它对CDK7的选择性比 CDK9 和 CDK2 高 100 倍以上。 | |||
T7414 | Apoptosis Raf Ras | ||
ARS-853 是一种选择性共价KRAS G12C 抑制剂,IC50为 2.5 μM。它通过与 GDP 结合的癌蛋白结合并阻止激活来抑制突变 KRAS 驱动的信号传导。 | |||
T9061 | c-Myc | ||
EN4 (EN4 MYC inhibitor) 是一种靶向 MYC 的半胱氨酸 171 (C171) 的共价配体。它抑制 MYC 转录活性,下调 MYC 靶标,并具有抗肿瘤作用。它对 c-MYC 的选择性高于 N-MYC 和 L-MYC。 | |||
T8369 | Ras | ||
Adagrasib (MRTX849) 是一种 KRAS G12C 共价抑制剂,具有口服活性和选择性。Adagrasib 与 KRAS G12C 非活性构象的 GDP 状态结合,抑制 KRAS 及其下游信号的传导。Adagrasib 对 KRAS G12C 突变肿瘤具有抑制活性。 | |||
T8684 | Ras | ||
Sotorasib (AMG-510) 是一种 KRAS G12C 共价抑制剂,具有口服活性和选择性。Sotorasib 与 KRAS G12C 非活性构象的 GDP 状态结合,抑制 KRAS 及其下游信号的传导。Sotorasib 对 KRAS G12C 突变肿瘤具有抑制活性。 |
目录号 | 产品名/同用名 | 种属 | 表达系统 | ||
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TMPY-01007 | VEGFC Protein, Human, Recombinant (His) | Human | HEK293 | ||
Vascular endothelial growth factor C (VEGF-C) is a member of the VEGF family. Upon biosynthesis, VEGF-C protein is secreted as a non-covalent momodimer in an anti-parellel fashion. VEGF-C protein is a dimeric glycoprotein, as a ligand for two receptors, VEGFR-3 (Flt4), and VEGFR-2. VEGF-C may function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis. VEGF-C protein is over-expressed in various human cancers including breast cancer and prostate cancer. VEGF-C/VEGFR-3 axis, through different signaling pathways, plays a critical role in cancer progression by regulating different cellular functions, such as invasion, proliferation, and resistance to chemotherapy. Thus, targeting the VEGF-C/VEGFR-3 axis may be therapeutically significant for certain types of tumors.
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TMPY-03156 | VEGFC Protein, Mouse/Rat, Recombinant (aa 108-223, His) | Mouse,Rat | HEK293 | ||
Vascular endothelial growth factor C (VEGF-C) is a member of the VEGF family. Upon biosynthesis, VEGF-C protein is secreted as a non-covalent momodimer in an anti-parellel fashion. VEGF-C protein is a dimeric glycoprotein, as a ligand for two receptors, VEGFR-3 (Flt4), and VEGFR-2. VEGF-C may function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis. VEGF-C protein is over-expressed in various human cancers including breast cancer and prostate cancer. VEGF-C/VEGFR-3 axis, through different signaling pathways, plays a critical role in cancer progression by regulating different cellular functions, such as invasion, proliferation, and resistance to chemotherapy. Thus, targeting the VEGF-C/VEGFR-3 axis may be therapeutically significant for certain types of tumors.
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TMPY-02521 | HIST3H2A Protein, Human, Recombinant | Human | E. coli | ||
Histones are a complex family of highly conserved basic proteins responsible for packaging chromosomal DNA into nucleosomes. There are subtype diversities: H1, H2A, H2B, and H3 or H4. It has become more and more evident that histone modifications are key players in the regulation of chromatin states and dynamics as well as in gene expression. Therefore, histone modifications and the enzymatic machinery that set them are crucial regulators that can control cellular proliferation, differentiation, plasticity, and malignancy processes. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Histone cluster 3, H2a also known as histone H2A (HIST3H2A) is a member of histones. Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. E3 ubiquitin ligase complex is specific for histone H2A (HIST3H2A). Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. DNA damage induces monoubiquitylation of histone H2A (HIST3H2A) in the vicinity of DNA lesions.
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TMPY-01474 | PAI-1 Protein, Human, Recombinant (His) | Human | HEK293 | ||
Plasminogen activator inhibitor 1, also known as PAI-1, Endothelial plasminogen activator inhibitor, SerpinE1 and PLANH1, is a secreted glycoprotein that belongs to the serpin family. SerpinE1 is the primary physiological inhibitor of the two plasminogen activators urokinase (uPA) and tissue plasminogen activator (tPA). Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis. Defects in SerpinE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency) which is characterized by abnormal bleeding due to SerpinE1 defect in the plasma. High concentrations of SerpinE1 have been associated with thrombophilia which is an autosomal dominant disorder in which affected individuals are prone to develop serious spontaneous thrombosis. Studies of PAI-1 have contributed significantly to the elucidation of the protease inhibitory mechanism of serpins, which is based on a metastable native state becoming stabilised by insertion of the RCL into the central beta-sheet A and formation of covalent complexes with target proteases. Greater expression of PAI-1 has been associated with increased survival of cells and resistance to apoptosis. PAI-1 appears to influence apoptosis by decreasing cell adhesion (anoikis) as well as its effect on intracellular signaling. PAI-1, in its active state, also binds to the extracellular protein vitronectin. When in complex with its target proteases, it binds with high affinity to endocytosis receptors of the low density receptor family. The mechanisms of PAI-1 overexpression during obesity are complex, and it is conceivable that several inducers are involved at the same time at several sites of synthesis. PAI-1 is also implicated in adipose tissue development. It suggests that PAI-1 inhibitors serve in the control of atherothrombosis.
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TMPH-00088 | Expansin-B1 Protein, Arabidopsis thaliana, Recombinant (His) | Arabidopsis thaliana | E. coli | ||
May cause loosening and extension of plant cell walls by disrupting non-covalent bonding between cellulose microfibrils and matrix glucans. No enzymatic activity has been found.
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TMPH-00087 | Expansin-A1 Protein, Arabidopsis thaliana, Recombinant (His & Myc) | Arabidopsis thaliana | E. coli | ||
Causes loosening and extension of plant cell walls by disrupting non-covalent bonding between cellulose microfibrils and matrix glucans. No enzymatic activity has been found.
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TMPH-03601 | Streptavidin Protein, S. avidinii, Recombinant (His) | Streptomyces avidinii | Yeast | ||
The biological function of streptavidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of streptavidin).
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TMPJ-01221 | UBE2J2 Protein, Human, Recombinant (GST) | Human | E. coli | ||
Ubiquitin-Conjugating Enzyme E2 J2 (UBE2J2) belongs to the ubiquitin-conjugating enzyme family. UBE2J2 is involved in the ubiquitiantion. UBE2J2 located in the membrane of the endoplasmic reticulum, catalyzes the covalent attachment of ubiquitin to other proteins. UBE2J2 may play a important role in the selective degradation of misfolded membrane protein from the endoplasmic reticulum.
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TMPJ-01278 | SENP8 Protein, Human, Recombinant (His) | Human | E. coli | ||
Sentrin-Specific Protease 8 (SENP8) mediates the reversible covalent modification of proteins by NEDD8. SENP8 catalyzes the full-length NEDD8 to generate its mature form and deconjugation of NEDD8 from targeted proteins such as CUL2 , CUL4A in vivo, or p53. but it does not show activity against ubiquitin or SUMO proteins.
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TMPH-01265 | PELI3 Protein, Human, Recombinant (His) | Human | E. coli | ||
E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1. Can activate AP1/JUN and ELK1. Not required for NF-kappa-B activation.
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TMPJ-01198 | UBE2R2 Protein, Human, Recombinant (His) | Human | E. coli | ||
Ubiquitin-Conjugating Enzyme E2 R2 (UBE2R2) is a modification enzyme that belongs to the ubiquitin-conjugating enzyme family. UBE2R2 is involved in cell growth and transformation. It accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, UBE2R2 catalyzes monoubiquitination and 'Lys-48'-linked polyubiquitination. It may be involved in degradation of katenin.
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TMPJ-00033 | UBE2B Protein, Human, Recombinant (His) | Human | Human Cells | ||
Ubiquitin-Conjugating Enzyme E2 B (UBE2B) is a member of the ubiquitin-conjugating enzyme family. UBE2B accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. It is shown that UBE2B interacts with RAD18, UBR2, and WAC. UBE2B is required for post-replicative DNA damage repair. Additional, UBE2B plays a role in sepsis-induced muscle protein proteolysis and cancer-induced cachexia.
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TMPJ-01334 | UBE2Z Protein, Human, Recombinant (His) | Human | E. coli | ||
Ubiquitin-Conjugating Enzyme E2 Z (ZUBE2Z) is a member of the E2 ubiquitin-conjugating enzyme family. ZUBE2Z is widely expressed in many tissues, with high expression found in the placenta, pancreas, spleen, and testis. It is ubiquitinates proteins that catalyze the covalent attachment of ubiquitin to other proteins. It has shown that ZUBE2Z participate in signaling pathways, and may be involved in apoptosis regulation.
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TMPY-02129 | Transglutaminase 3/TGM3 Protein, Human, Recombinant (His) | Human | Baculovirus-Insect Cells | ||
Transglutaminases (TGase) are a family of calcium-dependent acyl-transfer enzymes ubiquitously expressed in mammalian cells and responsible for catalyzing covalent cross-links between proteins or peptides. Transglutaminase 3 (TGM3) is a member of a family of Ca2+-dependent enzymes that catalyze covalent cross-linking reactions between proteins or peptides. TGM3 isoform is widely expressed and is important for epithelial barrier formation. It is a zymogen, requiring proteolysis for activity. Calcium-activated TGM3 can bind, hydrolyze, and is inhibited by GTP, despite lacking structural homology with other GTP binding proteins. TGM3 displays a diffuse cytoplasmic distribution in vitro consistent with its proposed role in the early phase of cornified cell envelope assembly in the cytoplasm. TGM3-driven specific isopeptide bonds between intermediate filaments and KAPs participate to the progressive scaffolding of the hair shaft. Additionally, TGM3 may be a novel prognostic biomarker for esophageal squamous cell carcinoma (ESCC).
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TMPY-02842 | UBE2L6 Protein, Human, Recombinant (His) | Human | E. coli | ||
UBCH8, also known as UBE2L6, belongs to the ubiquitin-conjugating enzyme family. The family of ubiquitin-conjugating (E2) enzymes is characterized by the presence of a highly conserved ubiquitin-conjugating (UBC) domain. These domains accommodate the ATP-activated ubiquitin (Ub) or ubiquitin-like (UBL) protein via a covalently linked thioester onto its active-site residue. E2 enzymes act via selective protein-protein interactions with the E1 and E3 enzymes and connect activation to covalent modification. By doing so, E2s differentiate effects on downstream substrates, either with a single Ub/UBL molecule or as a chain. UBCH8 is highly similar in primary structure to the enzyme encoded by the UBE2L3 gene. It catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. UBCH8 functions in the E6/E6-AP-induced ubiquitination of p53/TP53 and promotes ubiquitination and subsequent proteasomal degradation of FLT3. At protein level, it is present in natural killer cells.
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TMPJ-01069 | Serpin A1e Protein, Mouse, Recombinant (His) | Mouse | Human Cells | ||
Alpha-1-antitrypsin 1-5(SERPIN A1) is a secreted protein and belongs to the serpin family. Serpins bind the protease active site resulting in a major conformational rearrangement that traps the enzyme in a covalent acyl-enzyme intermediate. Mouse SERPIN A1 is a serine protease inhibitor whose targets include elastase,plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. Defects in this gene can cause emphysema orliver disease. Several transcript variants encoding the same protein have been found for this gene.
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TMPJ-00985 | UBE2A Protein, Human, Recombinant (GST, His) | Human | E. coli | ||
Ubiquitin-Conjugating Enzyme E2 (UBE2A) is a member of the E2 Ubiquitin-Conjugating Enzyme family. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBE2A catalyzes the covalent attachment of ubiquitin to other proteins. UBE2A is required for postreplication repair of UV-damaged DNA. UBE2A Interacts with RAD18 and WAC.
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TMPJ-01362 | UBAP1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Ubiquitin-Associated Protein 1 (UBAP1) belongs to the UBA domain family. Members of this family are related to ubiquitin and the ubiquitination pathway. Because of their cytogenetic location, this UBA domain family member is being studied as a putative target for mutation in nasopharyngeal carcinomas. UBAP1 is highly expressed in the heart, brain, placenta, lung, skeletal muscle, liver, and pancreas. UBAP1 consists of two UBA domains and one UMA domain. The ubiquitin associated domain is throught to be a non-covalent ubiquitin binding domain, including a compact three helix bundle.
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TMPH-01896 | PZP Protein, Human, Recombinant (His) | Human | E. coli | ||
Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.
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TMPH-01264 | PELI1 Protein, Human, Recombinant (His) | Human | Baculovirus | ||
E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation. Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3. Negatively regulates necroptosis by reducing RIPK3 expression. Mediates 'Lys-63'-linked ubiquitination of RIPK1.
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TMPH-03575 | Sortase A Protein, S. aureus, Recombinant (His) | Staphylococcus aureus | E. coli | ||
Transpeptidase that anchors surface proteins to the cell wall. Recognizes and modifies its substrate by proteolytic cleavage of a C-terminal sorting signal. Following cleavage, a covalent intermediate is formed via a thioester bond between the sortase and its substrate, which is then transferred and covalently attached to the cell wall. This sortase recognizes a Leu-Pro-x-Thr-Gly (LPXTG) motif, which is cleaved by the sortase between the threonine and glycine residues. Utilizes lipid II as the peptidoglycan substrate for the sorting reaction. Responsible for the display of important virulence factors. Important for interactions with the host and host colonization during infection.
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TMPJ-01403 | UBE2D4 Protein, Human, Recombinant (GST) | Human | E. coli | ||
Ubiquitin-Conjugating Enzyme E2 D4 (UBE2D4) is a ligase that belongs to the Ubiquitin-Conjugating Enzyme family. UBE2D4 has been proposed to participate in Ubl conjugation pathway. UBE2D4 takes part in post-translational protein modification, protein K6-linked ubiquitination, protein K11-linked ubiquitination, protein K27-linked ubiquitination, protein K29-linked ubiquitination, protein K48-linked ubiquitination, and protein K63-linked ubiquitination. UBE2D4 regulate of protein metabolic process. UBE2D4 accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, UBE2D4 able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11' and 'Lys-48'-linked poly-ubiquitination.
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TMPH-01012 | BMP-1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Metalloprotease that plays key roles in regulating the formation of the extracellular matrix (ECM) via processing of various precursor proteins into mature functional enzymes or structural proteins. Thereby participates in several developmental and physiological processes such as cartilage and bone formation, muscle growth and homeostasis, wound healing and tissue repair. Roles in ECM formation include cleavage of the C-terminal propeptides from procollagens such as procollagen I, II and III or the proteolytic activation of the enzyme lysyl oxidase LOX, necessary to formation of covalent cross-links in collagen and elastic fibers. Additional substrates include matricellular thrombospondin-1/THBS1 whose cleavage leads to cell adhesion disruption and TGF-beta activation.; Plays an important role in bone repair by acting as a coactivator of BMP7.
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TMPY-00323 | Hepatitis C virus (HCV-1a) NS3 protease/helicase immunodominant region Protein (aa 1356-1459, GST) | HCV | E. coli | ||
HCV NS3 displays three enzymatic activities: serine protease, NTPase, and RNA helicase. HCV NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A, and NS5A-NS5B. HCV NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand (By similarity). Cleaves and inhibits the host antiviral protein MAVS. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. One of the HCV proteases, NS3-4A serine protease, is a non-covalent heterodimer consisting of a catalytic subunit (the N-terminal one-third of NS3 protein) and an activating cofactor (NS4A protein) and is responsible for cleavage at four sites of the HCV polyprotein.
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TMPY-03155 | VEGFC Protein, Mouse/Rat, Recombinant (aa 108-223, hFc) | Mouse,Rat | HEK293 | ||
Vascular endothelial growth factor C (VEGF-C) is a member of the VEGF family. Upon biosynthesis, VEGF-C protein is secreted as a non-covalent momodimer in an anti-parellel fashion. VEGF-C protein is a dimeric glycoprotein, as a ligand for two receptors, VEGFR-3 (Flt4), and VEGFR-2. VEGF-C may function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis. VEGF-C protein is over-expressed in various human cancers including breast cancer and prostate cancer. VEGF-C/VEGFR-3 axis, through different signaling pathways, plays a critical role in cancer progression by regulating different cellular functions, such as invasion, proliferation, and resistance to chemotherapy. Thus, targeting the VEGF-C/VEGFR-3 axis may be therapeutically significant for certain types of tumors.
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TMPJ-01089 | TFF1 Protein, Mouse, Recombinant (His) | Mouse | Human Cells | ||
Trefoil Factor 1 (TFF1) belongs to the three structurally related secreted proteins that contain trefoil domains.TFF1 is an approximately peptide that has an important effect in epithelial regeneration and wound healing.It originates from musculus and highly expressed by goblet cells of the gastric and intestinal mucosa and by conjunctival goblet cells. TFF1 is a copper-binding protein that can form disulfide-linked homodimers, associate into disulfide-linked complexes with Gastrokine 2, and form non-covalent complexes with the mucin MUC5AC. TFF1 is down-regulated during the progression from gastritis to gastric dysplasia to gastric cancer, although it is up-regulated in breast and prostate cancers. TFF1 inhibits the formation of calcium oxalate crystals, and its excretion in the urine is reduced in patients with kidney stones.
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TMPJ-01055 | HBA1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Hemoglobin subunit alpha 1 (HBA1), also known as α2β2, is a hetero-tetramer consisting of two α and two β subunits held together by non-covalent interactions. Each subunit contains a heme group with an iron atom in the Fe2+ state. Cooperativity of Hemoglobin (Hb) in binding with O2 and allosteric regulatory binding properties with CO2, H+, Cl−, and 2,3-DPG (2,3-bisphosphoglycerate) are based on subunit interactions. HBA1 is the most common type of Hb in adult humans, which mediates the transport of oxygen and carbon dioxide in the blood. In recent years, Hb α and β chains have been found co-expressed in alveolar cells, mesangial cells of the kidney, retinal ganglion cells, hepatocytes and neurons. Endothelial and peripheral catecholaminergic cells express exclusively the α chain, while macrophages present the β chain only.
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TMPY-03700 | S100A11 Protein, Mouse, Recombinant (His) | Mouse | E. coli | ||
Protein S100-A11, also known as S100 calcium-binding protein A11, S100A11 and MLN70, is a member of theS-100 family. S100A11 is widely expressed in multiple tissues, and is located in cytoplasm, nucleus, and even cell periphery. S100A11 exists as a non-covalent homodimer with an antiparallel conformation. Ca(2+) binding to S100A11 would trigger conformational changes which would expose the hydrophobic cleft of S100A11 and facilitate its interaction with target proteins. As a dual cell growth mediator, S100A11 acts as either a tumor suppressor or promoter in many different types of tumors and would play respective roles in influencing the proliferation of the cancer cells. In the nucleus, S100A11 suppresses the growth of keratinocytes through p21 (CIP1/WAF1) activation and induces cell differentiation. S100A11 is also a novel diagnostic marker in breast carcinoma.
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TMPY-01868 | TIMP-2 Protein, Human, Recombinant | Human | HEK293 | ||
Tissue inhibitors of metalloproteinases (TIMP) family are natural inhibitors of the matrix metalloproteinases (MMPs), the zinc enzymes involved in extracellular matrix maintenance and remodeling. The TIMP family encompasses four members (TIMP1-4), and they inhibit most MMPs by forming non-covalent binary complex. TIMP2 is a 22 kDa non N-glycosylated protein expressed by a variety of cell types, and plays a unique role among TIMP family members owing to its functions to regulate cellular responses to growth factors. Findings establish an unexpected, MMP-independent mechanism for TIMP2 inhibition of endothelial cell proliferation in vitro and reveal an important component of the antiangiogenic effect of TIMP2 in vivo. TIMP-2 thus is critical to the maintenance of tissue homeostasis and is involved in the regulation of tumor microenvironment.
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TMPY-01331 | S100A11 Protein, Human, Recombinant | Human | E. coli | ||
Protein S100-A11, also known as S100 calcium-binding protein A11, S100A11 and MLN70, is a member of theS-100 family. S100A11 is widely expressed in multiple tissues, and is located in cytoplasm, nucleus, and even cell periphery. S100A11 exists as a non-covalent homodimer with an antiparallel conformation. Ca(2+) binding to S100A11 would trigger conformational changes which would expose the hydrophobic cleft of S100A11 and facilitate its interaction with target proteins. As a dual cell growth mediator, S100A11 acts as either a tumor suppressor or promoter in many different types of tumors and would play respective roles in influencing the proliferation of the cancer cells. In the nucleus, S100A11 suppresses the growth of keratinocytes through p21 (CIP1/WAF1) activation and induces cell differentiation. S100A11 is also a novel diagnostic marker in breast carcinoma.
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TMPY-00933 | TIMP-2 Protein, Human, Recombinant (hFc) | Human | HEK293 | ||
Tissue inhibitors of metalloproteinases (TIMP) family are natural inhibitors of the matrix metalloproteinases (MMPs), the zinc enzymes involved in extracellular matrix maintenance and remodeling. The TIMP family encompasses four members (TIMP1-4), and they inhibit most MMPs by forming non-covalent binary complex. TIMP2 is a 22 kDa non N-glycosylated protein expressed by a variety of cell types, and plays a unique role among TIMP family members owing to its functions to regulate cellular responses to growth factors. Findings establish an unexpected, MMP-independent mechanism for TIMP2 inhibition of endothelial cell proliferation in vitro and reveal an important component of the antiangiogenic effect of TIMP2 in vivo. TIMP-2 thus is critical to the maintenance of tissue homeostasis and is involved in the regulation of tumor microenvironment.
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TMPY-03052 | MFAP5 Protein, Human, Recombinant (His) | Human | HEK293 | ||
MFAP5 (Microfibril Associated Protein 5, also known as MAGP2) is a Protein Coding gene. MFAP5 is a component of the elastin-associated microfibrils. It belongs to the MFAP family. As a 25-kD microfibril-associated glycoprotein, MFAP5 is rich in serine and threonine residues. It stimulates the assembly of elastic fibers, a complex structure composed of a tropoelastin inner core and microfibril outer mantle comprising proteins such as fibrillins and microfibril-associated glycoproteins that guide tropoelastin deposition. MFAP5 also stabilizes type 1 procollagen and thus plays an important role in extracellular matrix homeostasis. It has multiple binding regions on fibrillins and has a covalent periodic association with fibrillin-containing microfibrils. Diseases associated with MFAP5 include Aortic Aneurysm, Familial Thoracic 9, and Familial Thoracic Aortic Aneurysm And Aortic Dissection.
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TMPH-01241 | TOP1 Protein, Human, Recombinant (His & Myc) | Human | Baculovirus | ||
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
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TMPJ-00486 | SUMO2 Protein, Human, Recombinant (His) | Human | E. coli | ||
Small Ubiquitin-Related Modifier 2 (SUMO2) is an Ubiquitin-like protein that belongs to the ubiquitin family with SUMO subfamily. It is a family of small, related proteins that can be enzymatically attached to a target protein by a post-translational modification process termed sumoylation. SUMO2 can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptidebond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins.
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TMPJ-01100 | UBE2V1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Ubiquitin-Conjugating Enzyme Variant 1a (UBE2V1) is a member of the Ubiquitin-conjugating (E2) enzyme family. The E2 catalytic core domain of UBE2V1 lacks an active site cysteine residue, rendering it catalytically inactive on its own. However, in the cytoplasm UBE2V1 is able to form a catalytically active complex with UBE2N/Ubc13, which mediates the synthesis Lys63-linked Ubiquitin chains and is required for NF-kappa B activation. UBE2V1 is required for UBE2N (Ubc13)/UBE2V1 Complex-dependent Lys63-linked Ubiquitin chain formation. More specifically, UBE2V1 orients the Ubiquitin molecule to favor linkage at Lys63 via a non-covalent interaction with the Ubiquitin molecule. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. UBE2V1 plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6, and TRAF2. It mediates transcriptional activation of target genes. UBE2V1 also controls the progress through the cell cycle and differentiation, the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.
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TMPY-02642 | UBE2W Protein, Human, Recombinant (His) | Human | E. coli | ||
Ubiquitin-conjugating enzymes, also known as UBE2W, E2 enzymes and more rarely as ubiquitin-carrier enzymes, perform the second step of protein ubiquitination. The modification of protein with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBE2W is a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair. It accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. It also catalyzes monoubiquitination and "Lys-11"-linked polyubiquitination. UBE2W is also considered to regulate FANCD2 monoubiquitination. UBE2W exhibits ubiquitin conjugating enzyme activity and catalyzes the monoubiquitination of PHD domain of Fanconi anemia complementation group L (FANCL). Over-expression of UBE2W in cells promotes the monoubiquitination of FANCD2 and down-regulated UBE2W markedly reduces the UV irradiation-induced but not MMC-induced FANCD2 monoubiquitination.
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TMPY-02348 | ISG15 Protein, Human, Recombinant | Human | E. coli | ||
Interferon-induced 17 kDa protein (ISG15), a 15-kDa protein of unique primary amino acid sequence, functions intracellularly as a ubiquitin homolog and a cytokine that induces production of IFN-gamma and augments NK / lymphokine-activated killer cell proliferation and function. ISG15 is secreted from monocytes and lymphocytes. ISG15 is a ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. Alterations in the ISG15 signaling pathway have also been found in several human tumor entities. In addition to being stimulated by type I interferon, expression of ISG15 is greatly induced by viral or bacterial infection through the Janus kinase/signal transducer and activator of transcription (Jak / STAT) signaling pathway. After induction, ISG15 is secreted by monocytes, B- and T-lymphocytes, and fibroblasts. We demonstrate the novel way in which the function of the ISG15 protein is inhibited by influenza B virus, which strongly induces the ISG15 protein: a specific region of the influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of ISG15 to its target proteins both in vitro and in infected cells.
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TMPY-02467 | ISG15 Protein, Human, Recombinant (mature form) | Human | E. coli | ||
Interferon-induced 17 kDa protein (ISG15), a 15-kDa protein of unique primary amino acid sequence, functions intracellularly as a ubiquitin homolog and a cytokine that induces production of IFN-gamma and augments NK / lymphokine-activated killer cell proliferation and function. ISG15 is secreted from monocytes and lymphocytes. ISG15 is a ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. Alterations in the ISG15 signaling pathway have also been found in several human tumor entities. In addition to being stimulated by type I interferon, expression of ISG15 is greatly induced by viral or bacterial infection through the Janus kinase/signal transducer and activator of transcription (Jak / STAT) signaling pathway. After induction, ISG15 is secreted by monocytes, B- and T-lymphocytes, and fibroblasts. We demonstrate the novel way in which the function of the ISG15 protein is inhibited by influenza B virus, which strongly induces the ISG15 protein: a specific region of the influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of ISG15 to its target proteins both in vitro and in infected cells.
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TMPH-03008 | ENR Protein, Mycobacterium tuberculosis, Recombinant (His) | Mycobacterium tuberculosis | E. coli | ||
Enoyl-ACP reductase of the type II fatty acid syntase (FAS-II) system, which is involved in the biosynthesis of mycolic acids, a major component of mycobacterial cell walls. Catalyzes the NADH-dependent reduction of the double bond of 2-trans-enoyl-[acyl-carrier protein], an essential step in the fatty acid elongation cycle of the FAS-II pathway. Shows preference for long-chain fatty acyl thioester substrates (>C16), and can also use 2-trans-enoyl-CoAs as alternative substrates. The mycobacterial FAS-II system utilizes the products of the FAS-I system as primers to extend fatty acyl chain lengths up to C56, forming the meromycolate chain that serves as the precursor for final mycolic acids.; Is the primary target of the first-line antitubercular drug isoniazid (INH) and of the second-line drug ethionamide (ETH). Overexpressed inhA confers INH and ETH resistance to M.tuberculosis. The mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of NAD and binding of the INH-NAD adduct to the active site of InhA. Similarly, the ETH-NAD adduct binds InhA.
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TMPH-00651 | Lpp Protein, E. coli, Recombinant (His & KSI) | E. coli | E. coli | ||
An outer membrane lipoprotein that controls the distance between the inner and outer membranes; adding residues to Lpp increases the width of the periplasm. The only protein known to be covalently linked to the peptidoglycan network (PGN). Also non-covalently binds the PGN. The link between the cell outer membrane and PGN contributes to the maintenance of the structural and functional integrity of the cell envelope, and maintains the correct distance between the PGN and the outer membrane. The most abundant cellular protein in terms of copy number, there can be up to one million Lpp molecules per cell. About one-third of Lpp is bound to the PGN (called bound or periplasmic) the rest is called free or transmembrane. The 'free' form can be surface labeled by membrane impermeable agents and so must cross the outer membrane; it is thought that this transmembrane form is still anchored in the inner leaflet of the outer membrane. Modeling suggests that non-covalent binding of OmpA (from the outer membrane) and TolR (from the inner membrane) to peptidoglycan maintains the position of the cell wall in the periplasm, holding it approximately equidistant from both the inner and outer membranes. Trimeric Lpp controls the width of the periplasm, adjusts its tilt angle to accommodate to the available space, and can compensate in part for an absence of OmpA (Probable). The role of the cell surface-exposed, free form (transmembrane) of Lpp is unknown.
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TMPH-00385 | Chikungunya virus (strain S27-African prototype) Non-structural protein 4 (His) | CHIKV | E. coli | ||
Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2.; The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs. As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins.; Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and guanylyltransferase. mRNA-capping is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus (Probable). The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping consists in the following reactions: GTP is first methylated into 7-methyl-GMP and then is covalently linked to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. NsP1 is also needed for the initiation of the minus-strand RNAs synthesis. At the initiation of virus replication, mediates the assembly of the viral replication complex made of the non-structural proteins, the association of this complex with the inner face of the plasma membrane and the formation of membranous spherules that serve as replication complex factories. Forms the neck of these spherules with a central channel for mediating communication and the passage of RNA, nucleotides, and small proteins between the viral replication complex and the host cytoplasm. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell.; Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities. NTPase and RNA triphosphatase are involved in viral RNA capping and helicase keeps a check on the dsRNA replication intermediates. The C-terminus harbors a protease that specifically cleaves the polyproteins and releases the mature proteins. Required for the shutoff of minus-strand RNAs synthesis. Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1. Also inhibits host transcription by inducing the rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (Probable).; Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis. Displays mono-ADP-ribosylhydrolase activity. ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication. Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs. The nsp3-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (Probable).; RNA dependent RNA polymerase. Replicates genomic and antigenomic RNA by recognizing replications specific signals. The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs. The late replication complex composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus-strand RNAs.
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TMPH-01270 | TRAIP Protein, Human, Recombinant (His) | Human | E. coli | ||
E3 ubiquitin ligase required to protect genome stability in response to replication stress. Acts as a key regulator of interstrand cross-link repair, which takes place when both strands of duplex DNA are covalently tethered together, thereby blocking replication and transcription. Controls the choice between the two pathways of replication-coupled interstrand-cross-link repair by mediating ubiquitination of MCM7 subunit of the CMG helicase complex. Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3. If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase, enabling the Fanconi anemia DNA repair pathway. Only catalyzes ubiquitination of MCM7 when forks converge. Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: promotes ubiquitination of DPCs, leading to their degradation by the proteasome. Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys-63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity. The function in translesion synthesis is however controversial. Acts as a regulator of the spindle assembly checkpoint. Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF. Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation.
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TMPH-02288 | UBE2D3 Protein, Human, Recombinant (His & SUMO) | Human | E. coli | ||
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction. Together with RNF135, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production.
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TMPY-00629 | PAI-1 Protein, Rat, Recombinant (hFc) | Rat | HEK293 | ||
Plasminogen activator inhibitor 1, also known as PAI-1, Endothelial plasminogen activator inhibitor, SerpinE1 and PLANH1, is a secreted glycoprotein that belongs to the serpin family. SerpinE1 is the primary physiological inhibitor of the two plasminogen activators urokinase (uPA) and tissue plasminogen activator (tPA). Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis. Defects in SerpinE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency) which is characterized by abnormal bleeding due to SerpinE1 defect in the plasma. High concentrations of SerpinE1 have been associated with thrombophilia which is an autosomal dominant disorder in which affected individuals are prone to develop serious spontaneous thrombosis. Studies of PAI-1 have contributed significantly to the elucidation of the protease inhibitory mechanism of serpins, which is based on a metastable native state becoming stabilised by insertion of the RCL into the central beta-sheet A and formation of covalent complexes with target proteases. Greater expression of PAI-1 has been associated with increased survival of cells and resistance to apoptosis. PAI-1 appears to influence apoptosis by decreasing cell adhesion (anoikis) as well as its effect on intracellular signaling. PAI-1, in its active state, also binds to the extracellular protein vitronectin. When in complex with its target proteases, it binds with high affinity to endocytosis receptors of the low density receptor family. The mechanisms of PAI-1 overexpression during obesity are complex, and it is conceivable that several inducers are involved at the same time at several sites of synthesis. PAI-1 is also implicated in adipose tissue development. It suggests that PAI-1 inhibitors serve in the control of atherothrombosis.
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TMPY-02559 | PAI-1 Protein, Rat, Recombinant (His) | Rat | HEK293 | ||
Plasminogen activator inhibitor 1, also known as PAI-1, Endothelial plasminogen activator inhibitor, SerpinE1 and PLANH1, is a secreted glycoprotein that belongs to the serpin family. SerpinE1 is the primary physiological inhibitor of the two plasminogen activators urokinase (uPA) and tissue plasminogen activator (tPA). Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis. Defects in SerpinE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency) which is characterized by abnormal bleeding due to SerpinE1 defect in the plasma. High concentrations of SerpinE1 have been associated with thrombophilia which is an autosomal dominant disorder in which affected individuals are prone to develop serious spontaneous thrombosis. Studies of PAI-1 have contributed significantly to the elucidation of the protease inhibitory mechanism of serpins, which is based on a metastable native state becoming stabilised by insertion of the RCL into the central beta-sheet A and formation of covalent complexes with target proteases. Greater expression of PAI-1 has been associated with increased survival of cells and resistance to apoptosis. PAI-1 appears to influence apoptosis by decreasing cell adhesion (anoikis) as well as its effect on intracellular signaling. PAI-1, in its active state, also binds to the extracellular protein vitronectin. When in complex with its target proteases, it binds with high affinity to endocytosis receptors of the low density receptor family. The mechanisms of PAI-1 overexpression during obesity are complex, and it is conceivable that several inducers are involved at the same time at several sites of synthesis. PAI-1 is also implicated in adipose tissue development. It suggests that PAI-1 inhibitors serve in the control of atherothrombosis.
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TMPH-01263 | PRKN Protein, Human, Recombinant (His & SUMO) | Human | E. coli | ||
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
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TMPH-00698 | OmpA Protein, E. coli, Recombinant (His) | E. coli | in vitro E. coli expression system | ||
With TolR probably plays a role in maintaining the position of the peptidoglycan cell wall in the periplasm (Probable). Plays a role in resistance to environmental stress, and a role in outer membrane functionality and cell shape. Non-covalently binds peptidoglycan (Probable). Acts as a porin with low permeability that allows slow penetration of small solutes. A very abundant protein, there can be up to 210,000 OmpA molecules per cell. Reconstitution in unilamellar lipid vesicles shows only about 3% of the protein is in an open conformation, which allows diffusion of L-arabinose at a rate comparable to that of OmpF porin; the pores interconvert very rarely. Native and reconstituted protein forms ion channels with 2 conductance states of (50-80 pS) and (260-320 pS); the states are interconvertible in this study. Interconversion requires refolding of the periplasmic domain. Small pores are converted into large pores by increasing temperature; in this model the C-terminal periplasmic domain forms 8 more beta sheets to form a larger pore. The center of the isolated beta-barrel is polar and has a central gate (involving Glu-73, Lys-103, Glu-149 and Arg-159, sandwiched between Tyr-29, Phe-40 and Tyr-94), with no obvious passage for water or ions (Probable). Gating involves the Glu-73-Arg-159 salt bridge; gate opening probably involves formation of alternate salt bridges Glu-149-Arg-159 and Glu-73-Lys-103. Modeling suggests that non-covalent binding of OmpA (from the outer membrane) and TolR (from the inner membrane) to peptidoglycan maintains the position of the cell wall in the periplasm, holding it approximately equidistant from both the inner and outer membranes. Trimeric Lpp controls the width of the periplasm, adjusts its tilt angle to accommodate to the available space, and can compensate in part for an absence of OmpA (Probable).; Required for F plasmid cell conjugation; purified protein plus lipopolysaccharide (LPS) inhibits conjugation in a concentration-dependent manner. OmpA probably acts as the receptor on recipient cells (Probable). Required for the stabilization of mating aggregates during F plasmid conjugative transfer, may interact with F plasmid-encoded TraN, but not with TraN from plasmid R100-1. All 4 external, surface-exposed loops are required for F plasmid conjugation.; (Microbial infection) Mutants with decreased or altered protein are resistant to bacteriophage TuII*. Mutants which have no or greatly reduced protein levels are resistant to a number of bacteriophages, including K3, K4, K5, Ox2, Ox3, Ox4, Ox5, Ml, and Ac3 (Probable). Mutations in this protein render the bacteria partially or completely susceptible to a number of bacteriophages for which is it probably the receptor. All but the last external, surface-exposed loops are required for phage K3 infection.; (Microbial infection) A mutation in this locus (called tolG) renders the cell tolerant to bacteriocin JF246 but does not affect its sensitivity to colicins A, C, El, E2, E3, K, Ia, or Ib. Mutations in this protein render the bacteria partially or completely susceptible to colicin K or colicin L, for which is it probably the receptor.
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TMPH-01262 | PRKN Protein, Human, Recombinant (His & Myc) | Human | Baculovirus | ||
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
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TMPH-02631 | PRKN Protein, Mouse, Recombinant (GST) | Mouse | E. coli | ||
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
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TMPH-03281 | PRKN Protein, Rat, Recombinant (His & Myc) | Rat | Baculovirus | ||
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
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