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Product listing: Ubiquityl-Histone H2A (Lys119) (D27C4) XP® Rabbit mAb, UniProt ID Q96QV6 #8240 to USP8 (D18F6) Rabbit mAb, UniProt ID P40818 #11832

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1). Ubiquitin is a conserved 76 amino acid peptide unit that can be covalently linked to many cellular proteins by the ubiquitination process. Three components are involved in this protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thioester complex with the activation component E1; the activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, then from E2 to ubiquitin ligase E3 for final delivery to the epsilon-NH2 of the target protein lysine residue (2). Histone H2A is mono-ubiquitinated at Lys119 by the Polycomb Repressor Complex 1 (PRC1) and is critical for transcriptional silencing of the developmental HOX genes and X chromosome inactivation (3-6). PRC1 is composed of Bmi1 and RING1A (also RING1 or RNF1), both of which act to enhance the E3 ubiquitin ligase activity of the catalytic subunit RING1B (also RING2 or RNF2) (3,4). Histone H2A is also mono-ubiquitinated at Lys119 at sites of DNA damage. This mono-ubiquitination event requires the PRC1 components Bmi1 and RING1B, in addition to another E3 ubiquitin ligase RNF8, and contributes to subsequent recruitment of the BRCA1 complex, via binding of RAP80/UIMC1 (ubiquitin interactive motif containing 1 protein) (7-10).

$364
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Ubiquityl-Histone H2B (Lys120) (D11) XP® Rabbit mAb #5546.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3 and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitylation (1). Ubiquitin is a conserved 76 amino acid peptide unit that can be covalently linked to many cellular proteins by the ubiquitylation process. Three components are involved in this protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thiolester complex with the activation component E1; the activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, then from E2 to ubiquitin ligase E3 for final delivery to the epsilon-NH2 of the target protein lysine residue (2). Histone H2B is mono-ubiquitylated on lysine 120 during transcriptional activation by the RAD6 E2 protein in conjunction with the BRE1A/BRE1B E3 ligase (also known as RNF20/RNF40) (3). The RAD6/BRE1 complex is recruited to gene promoters during activation by the PAF complex, an RNA polymerase II-associated protein complex that regulates transcriptional elongation (3-5). Mono-ubiquitylated histone H2B lysine 120 is associated with the transcribed region of active genes (3,6). Mono-ubiquitylation of histone H2B stimulates transcriptional elongation by facilitating FACT-dependent chromatin remodeling (7,8). In addition, it is essential for subsequent methylation of histone H3 lysines 4 and 79, two additional histone modifications that regulate transcriptional initiation and elongation (9). Interestingly, de-ubiquitylation of histone H2B lysine 120 by USP22, a subunit of the human SAGA histone acetyltransferase complex, is a required step in transcriptional activation (10). Thus, it appears that the ubiquitylation state of histone H2B is dynamic during transcription and may serve as an intermediate step in transcriptional activation.

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Immunofluorescence (Immunocytochemistry), Western Blotting

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3 and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitylation (1). Ubiquitin is a conserved 76 amino acid peptide unit that can be covalently linked to many cellular proteins by the ubiquitylation process. Three components are involved in this protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thiolester complex with the activation component E1; the activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, then from E2 to ubiquitin ligase E3 for final delivery to the epsilon-NH2 of the target protein lysine residue (2). Histone H2B is mono-ubiquitylated on lysine 120 during transcriptional activation by the RAD6 E2 protein in conjunction with the BRE1A/BRE1B E3 ligase (also known as RNF20/RNF40) (3). The RAD6/BRE1 complex is recruited to gene promoters during activation by the PAF complex, an RNA polymerase II-associated protein complex that regulates transcriptional elongation (3-5). Mono-ubiquitylated histone H2B lysine 120 is associated with the transcribed region of active genes (3,6). Mono-ubiquitylation of histone H2B stimulates transcriptional elongation by facilitating FACT-dependent chromatin remodeling (7,8). In addition, it is essential for subsequent methylation of histone H3 lysines 4 and 79, two additional histone modifications that regulate transcriptional initiation and elongation (9). Interestingly, de-ubiquitylation of histone H2B lysine 120 by USP22, a subunit of the human SAGA histone acetyltransferase complex, is a required step in transcriptional activation (10). Thus, it appears that the ubiquitylation state of histone H2B is dynamic during transcription and may serve as an intermediate step in transcriptional activation.

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Proliferating cell nuclear antigen (PCNA) is a member of the DNA sliding clamp family of proteins that assist in DNA replication (1). Crystal structure data suggests that a PCNA homotrimer ring can encircle and slide along the DNA double helix (2). Multiple proteins involved in DNA replication, DNA repair, and cell cycle control bind to PCNA rather than directly associating with DNA, thus facilitating fast processing of DNA (reviewed in 3). PCNA protein expression is a well-accepted marker of proliferation.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquilin 1 (UBQLN1) is a ubiquitously expressed, type 2 ubiquitin like (UBL) protein that contains an amino-terminal UBL domain and a carboxy-terminal Ub-associated (UBA) domain (1). Research studies demonstrate that UBQLN1 associates with poly-Ub chains through its UBA domain, while the UBL domain participates in interactions with proteasome subunits. Evidence suggests that UBQLN1 acts as a shuttling factor during endoplasmic-reticulum-associated protein degradation (ERAD) as it transports misfolded, ubiquitinated proteins from the ER to the proteasome for subsequent degradation (2-5). Additional research studies demonstrate that the UBL domain of UBQLN1 binds UIM-containing endocytic proteins and participates in the sequestration of protein aggregates during aggresome formation (6,7). UBQLN1 regulates presenilin protein levels and is localized in neurofibrillary tangles of Alzheimer's disease-affected brains (8). Polymorphisms in the corresponding UBQLN1 gene may be associated with a risk of Alzheimer's disease (9-11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquilin 2 (UBQLN2) is a broadly expressed member of the ubiquilin family of ubiquitin receptor proteins. UBQLN2 is a type 2 ubiquitin-like (UBL) protein that contains an amino-terminal UBL domain, multiple heat shock chaperonin-binding (STI) motifs, several PXX repeats, and a carboxy-terminal ubiquitin-associated (UBA) domain (1-3). Research studies indicate that the UBL domain of UBQLN2 can interact with proteasome subunits (4). The UBA domain of UBQLN2 can interact with ubiquitinated proteins and the autophagosome and allows UBQLN2 to participate in the ubiquitin-proteasome and autophagy pathways (5-8). Mutations in the PXX repeat region of the corresponding UBQLN2 gene are associated with an X-linked form of amyotrophic lateral sclerosis (ALS15) and dementia with reduced penetrance in females (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Human E3 identified by differential display (UBR5/EDD) is a HECT domain-containing ubiquitin E3 ligase of the N-end rule pathway that promotes the ubiquitination and proteasomal degradation of proteins harboring N-degrons (1-3). UBR5 represents an ortholog of HYD, the Drosophila hyperplastic discs tumor suppressor gene product but has been found to be overexpressed in breast and ovarian cancers, suggesting a possible role in promoting tumor development (4,5). Research studies have demonstrated that UBR5 is functional within the nucleus as it participates in DNA damage signaling by controlling the activities of Chk2, TopBP1, and RNF168 (6-9). Recently, UBR5 was shown to play a novel role in immune cell function by regulating RORγt stability and IL-17 production by Th17 cells (10).

$348
100 µl
This Cell Signaling Technology antibody is conjugated to biotin under optimal conditions. The biotinylated antibody is expected to exhibit the same species cross-reactivity as the unconjugated UCHL1 (D3T2E) XP® Rabbit mAb #13179.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes (UBEs) and deubiquitinating enzymes (DUBs) (1,2). DUBs are categorized into 5 subfamilies: USP, UCH, OTU, MJD, and JAMM. UCHL1, UCHL3, UCHL5/UCH37, and BRCA-1-associated protein-1 (BAP1) belong to the ubiquitin carboxy-terminal hydrolase (UCH) family of DUBs, which all possess a conserved catalytic UCH domain of about 230 amino acids. UCHL5 and BAP1 have unique, extended carboxy-terminal tails. UCHL1 is abundantly expressed in neuronal tissues and testes, while UCHL3 expression is more widely distributed (3,4). Although UCHL1 and UCHL3 are the most closely related UCH family members with about 53% identity, their biochemical properties differ in that UCHL1 binds monoubiquitin and UCHL3 shows dual specificity toward both ubiquitin (Ub) and NEDD8, a Ub-like molecule.UCHL1 (PGP 9.5/PARK5) functions as a deubiquitinating enzyme and monoubiquitin stabilizer. In vitro studies have demonstrated that UCHL1 can hydrolyze isopeptide bonds between the carboxy-terminal glycine of Ub and the ε-amino group of lysine on target proteins. UCHL1 is also involved in the cotranslational processing of pro-ubiquitin and ribosomal proteins translated as ubiquitin fusions (5-7). Mice deficient in UCHL1 experience spasticity, suggesting that UCHL1 activity is required for the normal neuromuscular junction structure and function (5-7). Research studies have described loss of UCHL1 expression in numerous human malignancies, such as prostate, colorectal, renal, and breast carcinomas. Investigators have shown that loss of UCHL1 expression in breast carcinomas can be attributed to hyper-methylation of the UCHL1 gene promoter (8). While loss of UCHL1 expression is implicated in human carcinogenesis, mutation of UCHL1 has been implicated in neurodegenerative diseases such as Parkinson's and Alzheimer's (6,7).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes (UBEs) and deubiquitinating enzymes (DUBs) (1,2). DUBs are categorized into 5 subfamilies: USP, UCH, OTU, MJD, and JAMM. UCHL1, UCHL3, UCHL5/UCH37, and BRCA-1-associated protein-1 (BAP1) belong to the ubiquitin carboxy-terminal hydrolase (UCH) family of DUBs, which all possess a conserved catalytic UCH domain of about 230 amino acids. UCHL5 and BAP1 have unique, extended carboxy-terminal tails. UCHL1 is abundantly expressed in neuronal tissues and testes, while UCHL3 expression is more widely distributed (3,4). Although UCHL1 and UCHL3 are the most closely related UCH family members with about 53% identity, their biochemical properties differ in that UCHL1 binds monoubiquitin and UCHL3 shows dual specificity toward both ubiquitin (Ub) and NEDD8, a Ub-like molecule.UCHL1 (PGP 9.5/PARK5) functions as a deubiquitinating enzyme and monoubiquitin stabilizer. In vitro studies have demonstrated that UCHL1 can hydrolyze isopeptide bonds between the carboxy-terminal glycine of Ub and the ε-amino group of lysine on target proteins. UCHL1 is also involved in the cotranslational processing of pro-ubiquitin and ribosomal proteins translated as ubiquitin fusions (5-7). Mice deficient in UCHL1 experience spasticity, suggesting that UCHL1 activity is required for the normal neuromuscular junction structure and function (5-7). Research studies have described loss of UCHL1 expression in numerous human malignancies, such as prostate, colorectal, renal, and breast carcinomas. Investigators have shown that loss of UCHL1 expression in breast carcinomas can be attributed to hyper-methylation of the UCHL1 gene promoter (8). While loss of UCHL1 expression is implicated in human carcinogenesis, mutation of UCHL1 has been implicated in neurodegenerative diseases such as Parkinson's and Alzheimer's (6,7).

$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes (UBEs) and deubiquitinating enzymes (DUBs) (1,2). DUBs are categorized into 5 subfamilies: USP, UCH, OTU, MJD, and JAMM. UCHL1, UCHL3, UCHL5/UCH37, and BRCA-1-associated protein-1 (BAP1) belong to the ubiquitin carboxy-terminal hydrolase (UCH) family of DUBs, which all possess a conserved catalytic UCH domain of about 230 amino acids. UCHL5 and BAP1 have unique, extended carboxy-terminal tails. UCHL1 is abundantly expressed in neuronal tissues and testes, while UCHL3 expression is more widely distributed (3,4). Although UCHL1 and UCHL3 are the most closely related UCH family members with about 53% identity, their biochemical properties differ in that UCHL1 binds monoubiquitin and UCHL3 shows dual specificity toward both ubiquitin (Ub) and NEDD8, a Ub-like molecule.UCHL1 (PGP 9.5/PARK5) functions as a deubiquitinating enzyme and monoubiquitin stabilizer. In vitro studies have demonstrated that UCHL1 can hydrolyze isopeptide bonds between the carboxy-terminal glycine of Ub and the ε-amino group of lysine on target proteins. UCHL1 is also involved in the cotranslational processing of pro-ubiquitin and ribosomal proteins translated as ubiquitin fusions (5-7). Mice deficient in UCHL1 experience spasticity, suggesting that UCHL1 activity is required for the normal neuromuscular junction structure and function (5-7). Research studies have described loss of UCHL1 expression in numerous human malignancies, such as prostate, colorectal, renal, and breast carcinomas. Investigators have shown that loss of UCHL1 expression in breast carcinomas can be attributed to hyper-methylation of the UCHL1 gene promoter (8). While loss of UCHL1 expression is implicated in human carcinogenesis, mutation of UCHL1 has been implicated in neurodegenerative diseases such as Parkinson's and Alzheimer's (6,7).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes (UBEs) and deubiquitinating enzymes (DUBs) (1,2). DUBs are categorized into 5 subfamilies: USP, UCH, OTU, MJD, and JAMM. UCHL1, UCHL3, UCHL5/UCH37, and BRCA-1-associated protein-1 (BAP1) belong to the UCH family of DUBs, which all posses a conserved catalytic domain (UCH domain) of about 230 amino acids. UCHL5 and BAP1 have unique extended C-terminal tails. UCHL1 is abundantly expressed in neuronal tissues and testes, while UCHL3 expression is more widely distributed (3,4). Although UCHL1 and UCHL3 are the most closely related UCH family members with about 53% identity, their biochemical properties differ in that UCHL1 binds monoubiquitin and UCHL3 shows dual specificity toward both ubiquitin (Ub) and NEDD8, a Ub-like molecule. In particular, UCHL3 functions as a Ub hydrolase involved in the processing of both Ub precursors and ubiquitinated substrates, generating free monomeric Ub. This is accomplished through the ability of UCHL3 to recognize and hydrolyze isopeptide bonds at the C-terminal glycine of either Ub or NEDD8 (5-7). Recent functional studies have identified UCH-L3 as a critical regulator of adipogenesis through its ability to promote IGF-IR and insulin receptor signaling (8). Furthermore, UCHL3 has been shown to promote deubiquitination, recycling, and cell surface expression of the epithelial sodium channel (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Uncoupling protein 1 (UCP1) is a mitochondrial inner membrane transport protein that is primarily expressed in brown adipose tissue (BAT). UCP1 dissipates the pH gradient resulting from oxidative phosphorylation, which uncouples ATP synthesis from oxidative phosphorylation and leads to the release of heat energy. As a result, UCP1 plays an important role in thermogenesis (reviewed in 1). Research studies indicate that subcutaneous white adipose depots in mice contain beige adipocytes that express low levels of UCP1 protein (2). Additional studies show possible differences in thermogenesis in individuals carrying specific polymorphisms in the corresponding UCP1 gene (3). Related studies link UCP1 to the possible development of obesity and type 2 diabetes (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Uncoupling protein 2 (UCP2) is a mitochondrial inner membrane transport protein that is expressed in a wide range of tissues (1). UCP2 inhibits mitochondrial glucose oxidation and promotes glycolysis in human pluripotent stem cells (hPSCs) (2). During early differentiation of hPSCs, the expression of UCP2 is repressed, which results in reduced glycolysis (2). This demonstrates a role for UCP2 in the metabolic reprogramming during differentiation of hPSCs (2). Overexpression of UCP2 in cancer cells stimulates oxidative phosphorylation in mitochondria and inhibits cell proliferation (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Uncoupling protein 3 (UCP3), a mitochondrial inner membrane transport protein, is highly expressed in skeletal muscle and activates glucose transport in muscle cells (2). UCP3 lowers the production of reactive oxygen species in mitochondria by reducing the mitochondrial inner membrane potential (3). UCP3 has been implicated in the protection against fat-induced insulin resistance in skeletal muscle (4) and fat gain induced by high-fat feeding (1).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1), also known as Inverted CCAAT box-binding protein of 90 kDa (ICBP90) and Nuclear Zinc Finger Protein NP95 (NP95), is a nuclear protein that was first discovered as a CCAAT box-binding protein that regulates the expression of the Topoisomerase IIα and Rb1 genes (1,2). Later studies have shown that UHRF1 is required for maintenance of CpG DNA methylation, the process of copying pre-existing methylation patterns onto the newly synthesized DNA strand after DNA replication (3-5). UHRF1 localizes primarily with highly methylated pericentromeric heterochromatin and is required for proper structure and function of these regions of the genome (6,7). However, UHRF1 also localizes to euchromatic regions of the genome and functions to negatively regulate the expression of a subset of tumor suppressor genes (2,8,9). The localization and repressive functions of UHRF1 are both mediated by several protein domains, including a ubiquitin-like domain (UBQ), Tudor domain, PHD domain, SET and RING finger-associated (SRA) domain, and a RING finger domain. The SRA domain of UHRF1 binds with high affinity to hemi-methylated DNA and functions to properly target the associated maintenance DNA methyltransferase DNMT1 protein to mediate faithful methylation of the newly synthesized DNA strand (3-5). Additional targeting of UHRF1 to heterochromatin is mediated by the Tudor domain, which binds specifically to tri-methylated lysine 9 of histone H3, a histone mark associated with pericentromeric heterochromatin (10-12). Targeting of UHRF1 to euchromatin is further mediated by the PHD domain, which binds specifically to un-methylated arginine 2 of histone H3, which is commonly associated with euchromatin (13). In addition to recruiting DNMT1, UHRF1 recruits the histone deacetylase 1 (HDAC1) protein to target loci, resulting in deacetylation of histones, and providing an additional mechanism for transcriptional repression (3). Taken together, these studies demonstrate that UHRF1 functions to link DNA methylation and histone modifications to the maintenance of repressive chromatin structures. These functions of UHRF1 are important for proper maintenance of cell growth and proliferation, as research studies have shown UHRF1 over-expression in a number of cancers (breast, lung, colon, and prostate cancer) is associated with increased proliferation and malignancy (9,14-16).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Two related serine/threonine kinases, UNC-51-like kinase 1 and 2 (ULK1, ULK2), were discovered as mammalian homologs of the C. elegans gene UNC-51 in which mutants exhibited abnormal axonal extension and growth (1-4). Both proteins are widely expressed and contain an amino-terminal kinase domain followed by a central proline/serine rich domain and a highly conserved carboxy-terminal domain. The roles of ULK1 and ULK2 in axon growth have been linked to studies showing that the kinases are localized to neuronal growth cones and are involved in endocytosis of critical growth factors, such as NGF (5). Yeast two-hybrid studies found ULK1/2 associated with modulators of the endocytic pathway, SynGAP and syntenin (6). Structural similarity of ULK1/2 has also been recognized with the yeast autophagy protein Atg1/Apg1 (7). Knockdown experiments using siRNA demonstrated that ULK1 is essential for autophagy (8), a catabolic process for the degradation of bulk cytoplasmic contents (9,10). It appears that Atg1/ULK1 can act as a convergence point for multiple signals that control autophagy (11), and can bind to several autophagy-related (Atg) proteins, regulating phosphorylation states and protein trafficking (12-16).

$305
100 µl
This Cell Signaling Technology antibody is conjugated to biotin under optimal conditions. The biotinylated antibody is expected to exhibit the same species cross-reactivity as the unconjugated ULK1 (D8H5) Rabbit mAb #8054.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Two related serine/threonine kinases, UNC-51-like kinase 1 and 2 (ULK1, ULK2), were discovered as mammalian homologs of the C. elegans gene UNC-51 in which mutants exhibited abnormal axonal extension and growth (1-4). Both proteins are widely expressed and contain an amino-terminal kinase domain followed by a central proline/serine rich domain and a highly conserved carboxy-terminal domain. The roles of ULK1 and ULK2 in axon growth have been linked to studies showing that the kinases are localized to neuronal growth cones and are involved in endocytosis of critical growth factors, such as NGF (5). Yeast two-hybrid studies found ULK1/2 associated with modulators of the endocytic pathway, SynGAP and syntenin (6). Structural similarity of ULK1/2 has also been recognized with the yeast autophagy protein Atg1/Apg1 (7). Knockdown experiments using siRNA demonstrated that ULK1 is essential for autophagy (8), a catabolic process for the degradation of bulk cytoplasmic contents (9,10). It appears that Atg1/ULK1 can act as a convergence point for multiple signals that control autophagy (11), and can bind to several autophagy-related (Atg) proteins, regulating phosphorylation states and protein trafficking (12-16).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: Two related serine/threonine kinases, UNC-51-like kinase 1 and 2 (ULK1, ULK2), were discovered as mammalian homologs of the C. elegans gene UNC-51 in which mutants exhibited abnormal axonal extension and growth (1-4). Both proteins are widely expressed and contain an amino-terminal kinase domain followed by a central proline/serine rich domain and a highly conserved carboxy-terminal domain. The roles of ULK1 and ULK2 in axon growth have been linked to studies showing that the kinases are localized to neuronal growth cones and are involved in endocytosis of critical growth factors, such as NGF (5). Yeast two-hybrid studies found ULK1/2 associated with modulators of the endocytic pathway, SynGAP and syntenin (6). Structural similarity of ULK1/2 has also been recognized with the yeast autophagy protein Atg1/Apg1 (7). Knockdown experiments using siRNA demonstrated that ULK1 is essential for autophagy (8), a catabolic process for the degradation of bulk cytoplasmic contents (9,10). It appears that Atg1/ULK1 can act as a convergence point for multiple signals that control autophagy (11), and can bind to several autophagy-related (Atg) proteins, regulating phosphorylation states and protein trafficking (12-16).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Netrin proteins belong to an evolutionarily conserved family of laminin-like molecules that are involved in axon guidance and vascular development. These secreted proteins can have opposing functions depending on specific receptor association. For example, deleted in colorectal cancer (DCC) family receptors typically mediate cellular attraction (1,2) while netrin bound to UNC5 family receptors induce cellular repulsion (2-4). The uncoordinated 5B homolog (UNC5B) is a transmembrane protein with extracellular Ig-like domains and an intracellular region containing a protein-binding death domain and a putative DCC interaction domain (2). Homodimers composed of DCC receptor proteins mediate axonal attraction responses, while UNC5B homodimers and UNC5B-DCC heterodimers promote cellular repulsion (2). The netrin receptor UNC5B mediates apoptosis in the absence of netrin through the activation of DAP kinase (5) and is involved in leukocyte migration inhibition (6). Expression of UNC5B correlates with bladder cancer stage and the receptor is a potential predictor of both bladder and colorectal cancer prognosis and possible disease recurrence (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The human urokinase-type plasminogen activator receptor (uPAR) is a 55-65 kDa, highly glycosylated, GPI-anchored cell surface receptor (the deglycosylated protein is 35 kDa) (1-3). It is a central player in the plasminogen activation pathway. uPAR binds with high affinity to a serine protease urokinase-type plasminogen activator (uPA) and converts plasminogen to its active form plasmin in a spatially restricted manner on the cell surface (4). Plasmin further carries out the activation of uPA, which is inhibited by serpins, such as plasminogen activator inhibitors (5). Therefore, uPAR plays a key role in regulating extracellular proteolysis. In addition, uPAR plays an important role in regulating cell proliferation, adhesion and mobility (6,7). Research studies have shown that overexpression of uPAR is found in various cancer cells and tissues (8,9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: The human urokinase-type plasminogen activator receptor (uPAR) is a 55-65 kDa, highly glycosylated, GPI-anchored cell surface receptor (the deglycosylated protein is 35 kDa) (1-3). It is a central player in the plasminogen activation pathway. uPAR binds with high affinity to a serine protease urokinase-type plasminogen activator (uPA) and converts plasminogen to its active form plasmin in a spatially restricted manner on the cell surface (4). Plasmin further carries out the activation of uPA, which is inhibited by serpins, such as plasminogen activator inhibitors (5). Therefore, uPAR plays a key role in regulating extracellular proteolysis. In addition, uPAR plays an important role in regulating cell proliferation, adhesion and mobility (6,7). Research studies have shown that overexpression of uPAR is found in various cancer cells and tissues (8,9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Upf1 was identified as an active component in nonsense-mediated decay (NMD), an mRNA surveillance mechanism in eukaryotic cells that degrades mRNAs containing premature termination codons (1). Upf1 was found to be an ATP-dependent RNA helicase in the cytoplasm (2) and was later shown to be a component of cytoplasmic P-bodies (3). Upf1 phosphorylation mediates the repression of translation that accompanies NMD, allowing mRNA accessibility to the NMD machinery (4). Two other active components of NMD, Upf2 and Upf3, were also identified and described as having perinuclear and nucleocytoplasmic localization, respectively (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Upf1 was identified as an active component in nonsense-mediated decay (NMD), an mRNA surveillance mechanism in eukaryotic cells that degrades mRNAs containing premature termination codons (1). Upf1 was found to be an ATP-dependent RNA helicase in the cytoplasm (2) and was later shown to be a component of cytoplasmic P-bodies (3). Upf1 phosphorylation mediates the repression of translation that accompanies NMD, allowing mRNA accessibility to the NMD machinery (4). Two other active components of NMD, Upf2 and Upf3, were also identified and described as having perinuclear and nucleocytoplasmic localization, respectively (5).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzymes (DUB) action (1,2). There are five DUB subfamilies including the USP, UCH, OTU, MJD, and JAMM enzymes. USP1 belongs to the USP subfamily and is regulated in a cell cycle dependent manner by both transcriptional and ubiquitin-proteosomal mechanisms (3). USP1 is a nuclear protein and localizes to chromatin where it is specifically associated with FANCD2. USP1 deubiquitinates monoubiquitinated FANCD2, which plays an important role in DNA damage repair and Chk1 protein stability (3,4). Another important target of USP1 is PCNA. USP1 deubiquitinates monoubiquitinated PCNA, thereby negatively regulating PCNA-mediated translesion synthesis (TLS) during DNA repair (5). USP1 interaction with UAF1, a WD40 repeat-containing protein, leads to formation of an activated USP1/UAF1 complex, which is required for the deubiquitinase activity of USP1 (6,7).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action (1,2). Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. USP10 possesses amino acid sequences that match the consensus cysteine and histidine boxes representative of the USP family of deubiquitinating enzymes. At the posttranslational level, USP10 appears to be regulated through both protein-protein interactions and phosphorylation. Indeed, interaction of USP10 with Ras-GAP SH3 domain binding protein (G3BP) has been found to inhibit its ability to catalyze the disassembly of ubiquitin chains (3). Furthermore, ATM-mediated phosphorylation of USP10 at Thr42 and Ser337 was shown to promote USP10 stabilization and redistribution from the cytoplasm to the nucleus, where it functions in p53 deubiquitination, stabilization, and activation in response to genotoxic stress (4). Recently, it was shown that USP10 works in concert with USP13 and Vps34 complexes. USP10, along with USP13, appears to deubiquitinate Vps34 complexes to regulate the levels of this class III PI3K. Beclin-1, another component of these complexes, functions to regulate the stability of USP13, which can deubiquitinate and stabilize the levels of USP10. Therefore, Beclin-1, can indirectly regulate p53 stability by controlling the DUB activity of USP10 (5). USP10 also functions in the endosomal compartment, where it has been shown to deubiquitinate CFTR in order to enhance its endocytic recycling and cell surface expression (6,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action (1,2). Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. Ubiquitin carboxyl-terminal hydrolase 13 (USP13; isopeptidase T-3) contains four ubiquitin-associated/translation elongation factor EF1B, amino terminal (UBA) domains and one ubiquitin-specific processing protease (UBP) domain. The UBP domain of USP13 contains a catalytic site, a zinc finger domain, and two UBA domains. Similar to other USP family members, USP13 contains cysteines and histidines that are likely involved in its catalytic mechanism. Studies show that USP13 plays a critical role in autophagy through the deubiquitination of target proteins such as BECN1 and USP10 (3). Research also suggests that USP13 is implicated in the pathogenesis of melanoma through its ability to regulate the ubiquitination status of MITF (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action (1,2). Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. In humans, there are three proteasomal DUBs: PSMD14 (POH1/RPN11), UCH37 (UCH-L5), and Ubiquitin-Specific Protease 14, which is also known as the 60 kDa subunit of tRNA-guanine transglycosylase (USP14/TGT60 kDa). USP14 is recruited to the proteasome through its reversible association with the PSMD2 (S2/hRPN1) subunit of the 19S regulatory particle. Whereas PSMD14 appears to promote substrate degradation (3,4), USP14 is thought to antagonize substrate degradation (5-8). While the underlying mechanism for the opposing roles of these two proteasomal DUBs is still uncertain, it is thought that USP14 removes ubiquitin from substrate upon docking of the substrate with the 26S proteasome. Furthermore, USP14 trims ubiquitin residues from the distal end of the polyubiquitin chain, thus decreasing the affinity of the chain for the ubiquitin receptors of the proteasome, and allowing for enhanced substrate stability (6,9,10). Studies have elucidated a physiologic role for USP14 in regulating synaptic activity in mammals (11). Research studies have shown that targeting this activity with small molecule inhibitors has potential benefits for the treatment of neurodegenerative diseases and cancer (5,12).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes (UBEs) and deubiquitinating enzymes (DUBs), respectively (1,2). DUBs are categorized into five subfamilies based on catalytic domain structure: USP, UCH, OTU, MJD, and JAMM. Ubiquitin carboxyl-terminal hydrolase 15 (USP15) is a USP subfamily deubiquitinating enzyme with similar domain structure to the paralogous DUBs, USP4, and USP11. The USP15 gene is amplified in glioblastoma and other solid tumors and its high expression correlates with a poor prognosis (3,4). Research studies demonstrate that USP15 is a positive regulator of oncogenic TGF-β signaling and that USP15 deubiquitinates monoubiquitinated R-SMADs to enhance target gene promoter binding (5). USP15 also promotes oncogenic TGF-β signaling by opposing SMURF2-mediated ubiquitination of the type I TGF-β receptor, which facilitates receptor stabilization (3,4). USP15 contributes to oncogenesis by negatively regulating T cell-mediated antitumor responses through the deubiquitination and stabilization of the E3 ubiquitin ligase MDM2. This observation supports USP15 as a potential target for cancer therapeutics (6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action. Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD and JAMM enzymes (1,2). USP18 (also known as UBP43) is a deubiquitinase best known for catalyzing the removal of ISG15, an interferon-regulated ubibiquitin-like protein, from conjugated proteins (3). Removal of ISG15 from target proteins by the USP18 peptidase maintains the critical cellular balance of ISG15-conjugated proteins important for normal development and brain function (4,5). Following induction by IFN or LPS (6), USP18 binds the INF receptor subunit IFNAR2 and inhibits signal transduction through the JAK-STAT pathway (7). USP18 regulation of IFN signaling inhibits IFN-mediated apoptosis and does not necessarily rely on USP18 peptidase activity (8). As the therapeutic use of recombinant IFN can lead to refractory IFN signaling and a less effective response, the combination of IFN treatment and regulation of USP18 expression may produce a more positive outcome (9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action (1,2). Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. The deubiquitinating enzyme ubiquitin-specific protease 8 (USP8/UBPy) is a cysteine protease belonging to the USP/UBP subfamily. Research studies have shown that USP8 is an essential growth-regulated enzyme indespensible for cell proliferation and survival (3,4). Indeed, conditional knock-out of murine USP8 was shown to promote a dramatic loss in expression of receptor tyrosine kinases, including EGFR, ErbB3, and c-Met (4). In agreement with these findings, USP8 inactivation leads to enhanced ubiquitination of ligand-activated EGFR (5,6). Furthermore, phosphorylation of USP8 at Ser680 results in its binding of 14-3-3, catalytic inactivation, and reduced EGFR deubiquitination (7). It appears as though USP8, in conjunction with components of the ESCRT-0 complex, plays an integral role in the early endosomal sorting machinery that functions to protect EGFR from lysosomal degradation (8,9).