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Product listing: UBE1L/UBA7 (D6U4S) Rabbit mAb, UniProt ID P41226 #61266 to UNC5B (D9M7Z) Rabbit mAb, UniProt ID Q8IZJ1 #13851

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Western Blotting

Background: Interferon-stimulated 15 kDa protein (ISG15), also known as ubiquitin cross-reactive protein (UCRP), is a member of the ubiquitin-like protein family and functions in various biological pathways from pregnancy to innate immune responses (1). Expression of ISG15 is stimulated by cellular exposure to type 1 interferons α and β, in addition to infection with viruses such as influenza B (2,3). After exposure to type I interferons, both lymphocytes and monocytes, in addition to some fibroblasts and epithelial cells, release ISG15 into culture medium (1,4). ISG15 has been shown to function as a cytokine, stimulating interferon γ secretion by monocytes and macrophages, proliferation of natural killer cells, and chemotactic responses in neutrophils (4,5). ISG15 has also been shown to function intracellularly, being covalently conjugated to other proteins by E1 (Ube1L), E2 (UbcH8) and E3 ligases via a multi-step process analogous to ubiquitination (6,7). ISG15 is removed from proteins by the ubiquitin processing protease Ubp43 (8). ISG15-protein conjugation (ISGylation) is induced by type 1 interferons, and target proteins include the serine protease inhibitor Serpin 2A, PLCγ1, ERK1/2, Jak1 and Stat1 (9,10). Unlike ubiquitination, ISGylation does not target proteins for degradation, rather ISGylation increases Jak1 and Stat1 activity, enhancing the cellular response to interferons (11).

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

Application Methods: Western Blotting

Background: Ubiquitin (Ub) is a conserved polypeptide that is covalently linked to many cellular proteins through the process of ubiquitination, which targets proteins for degradation by the 26S proteasome. Three enzymatic components are involved in the protein ubiquitination cascade. Ubiquitin is first activated by forming a thioester complex with an E1 ubiquitin-activating enzyme. Activated ubiquitin is subsequently transferred to an E2 ubiquitin-carrier protein, and then from the E2 to an E3 ubiquitin ligase for final delivery to the ε-amino group of the target protein lysine residue (1-3).The ubiquitin-conjugating enzyme E2 G2 (UBE2G2, UBC7) is a ubiquitously expressed E2 enzyme and critical component of the endoplasmic reticulum-associated degradation pathway (ERAD) (4). Research studies demonstrate that UBE2G2 forms homodimers and preassembles K48-linked poly-Ub chains at its active site (5-8). The association of Ub-charged UBE2G2 molecules with the ER-resident E3 ligase AMFR (gp78) is required for Ub chain transfer and efficient removal of misfolded or aggregated proteins through the ERAD pathway (9,10).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3 (1).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination is an important posttranslational modification that regulates protein function and fate (1). Ubiquitin (Ub) can be conjugated to target proteins in either monomeric or polymeric forms. There are several different lysine residues within Ub that can be used as conjugation sites for poly-Ub chain formation. Different poly-Ub linkages mediate different functions of the target protein ranging from alterations in protein function to degradation (2). UBE2N/Ubc13 is a ubiquitin-E2-conjugating enzyme that catalyzes K63-linked poly-Ub chain formation (1,2). UBE2N forms a heterodimer with MMS2 or Uev1A to exert its E2 ligase function. The UBE2N/MMS2 and UBE2N/Uev1A heterodimers catalyze different modes of target protein ubiquitination to mediate various signaling pathways (3-5) including: DNA damage and recombination, p53 and check point control, the cell cycle (6-10), immunoreceptor signaling (11,12), and endocytosis (13). Most recently, UBE2N was shown to play an important role in inflammatory signaling by promoting K63-linked ubiquitination and activation of IKK downstream of the IL-1β receptor (14). Furthermore, interaction of UBE2N with the Triad1 E3 protein-ubiquitin ligase was shown to play an important role in myelopoiesis (15).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3 (1).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3 (1).Ubiquitin conjugating-enzyme 2T (UBE2T) is an E2 family member responsible for the ATP-dependent ubiquitin tagging of target proteins for degradation. Research studies indicate that UBE2T plays an important role in the Fanconi anemia pathway and that UBE2T expression is required for normal DNA repair through this pathway. Interaction between UBE2T and FANCL appears to stimulate UBE2T auto monoubiquitination, leading to UBE2T inactivation and negative regulation of the Fanconi anemia pathway (2-4). Additional research details upregulation of UBE2T expression in breast cancer cells and certain lung carcinomas, suggesting a possible involvement in these malignancies (5,6).

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

Application Methods: Western Blotting

Background: UBE3A, also commonly referred to as E6AP (E6 Associated Protein), is an E3 ubiquitin protein ligase and founding member of the HECT (Homologous to the E6 Carboxyl Terminus) family of E3 ligases (1). UBE3A has been shown to be hijacked by the oncogenic E6 protein of high-risk human papillomaviruses (HPV16 and HPV18) that causes the ubiquitination activity of UBE3A to be inappropriately directed toward several specific cellular proteins, the most notable of which, with respect to carcinogenesis, is p53 (2). Although the DNA-repair enzyme, HHR23A (human homolog A of Rad23), was the first described E6-independent substrate of UBE3A, very few E6-independent targets of UBE3A have been identified. This continues to be an active area of research, particularly because mutations or disruption in expression of UBE3A in the brain are the cause of Angelman syndrome (AS), a severe form of mental retardation (3-6). Although UBE3A is expressed in most human tissues from both parental alleles, it is expressed from the maternal allele in subregions of the brain, with the paternal allele being epigenetically silenced. AS is caused by disruptions in expression of the materal UBE3A allele, generally by large chromosomal deletion, but also by point mutations within the UBE3A coding sequence. This strongly suggests that lack of ubiquitination of one or more UBE3A substrates in neuronal tissue is responsible for the AS phenotype (7). Indeed, a recent study identified several new neuronal substrates of UBE3A including Arc and Ephexin-5 (8). The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is rapidly upregulated after robust neuronal stimulation and promotes internalization of AMPA-type glutamate receptors (AMPARs), resulting in reduction in synaptic strength. UBE3A ubiquitinates Arc and promotes its degradation by the 26S proteasome, thus preventing AMPAR internalization (8). Disruption in neuronal UBE3A function leads to an increase in Arc expression and a decrease in AMPARs at excitatory synapses, which may contribute to the neurological symptoms of AS.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Ubiquitin is a conserved polypeptide unit that plays an important role in the ubiquitin-proteasome pathway. Ubiquitin can be covalently linked to many cellular proteins by the ubiquitination process, which targets proteins for degradation by the 26S proteasome. Three components are involved in the target 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 (1-3). The ubiquitin-proteasome pathway has been implicated in a wide range of normal biological processes and in disease-related abnormalities. Several proteins such as IκB, p53, cdc25A, and Bcl-2 have been shown to be targets for the ubiquitin-proteasome process as part of regulation of cell cycle progression, differentiation, cell stress response, and apoptosis (4-7).

$305
100 µl
This Cell Signaling Technology antibody is conjugated to the carbohydrate groups of horseradish peroxidase (HRP) via its amine groups. The HRP conjugated antibody is expected to exhibit the same species cross-reactivity as the unconjugated Ubiquitin (P4D1) Mouse mAb #3936.
APPLICATIONS
REACTIVITY
All Species Expected

Application Methods: Western Blotting

Background: Ubiquitin is a conserved polypeptide unit that plays an important role in the ubiquitin-proteasome pathway. Ubiquitin can be covalently linked to many cellular proteins by the ubiquitination process, which targets proteins for degradation by the 26S proteasome. Three components are involved in the target 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 (1-3). The ubiquitin-proteasome pathway has been implicated in a wide range of normal biological processes and in disease-related abnormalities. Several proteins such as IκB, p53, cdc25A, and Bcl-2 have been shown to be targets for the ubiquitin-proteasome process as part of regulation of cell cycle progression, differentiation, cell stress response, and apoptosis (4-7).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
All Species Expected

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Ubiquitin is a conserved polypeptide unit that plays an important role in the ubiquitin-proteasome pathway. Ubiquitin can be covalently linked to many cellular proteins by the ubiquitination process, which targets proteins for degradation by the 26S proteasome. Three components are involved in the target 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 (1-3). The ubiquitin-proteasome pathway has been implicated in a wide range of normal biological processes and in disease-related abnormalities. Several proteins such as IκB, p53, cdc25A, and Bcl-2 have been shown to be targets for the ubiquitin-proteasome process as part of regulation of cell cycle progression, differentiation, cell stress response, and apoptosis (4-7).

$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 H2A (Lys119) (D27C4) XP® Rabbit mAb #8240.
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 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).

$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).