Recombinant Human E3 Ubiquitin-Protein Ligase Huwe1 (HUWE1) Protein (His&Myc)

Name: Recombinant Human E3 Ubiquitin-Protein Ligase Huwe1 (HUWE1) Protein (His&Myc)
Brand: Beta LifeScience
SKU: BLC-07307P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human E3 Ubiquitin-Protein Ligase Huwe1 (HUWE1) Protein (His&Myc) is produced by our E.coli expression system. This is a protein fragment.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	Q7Z6Z7
Target Symbol	HUWE1
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-10His&C-Myc
Target Protein Sequence	LERLDEGLRKEDMAVHVRRDHVFEDSYRELHRKSPEEMKNRLYIVFEGEEGQDAGGLLREWYMIISREMFNPMYALFRTSPGDRVTYTINPSSHCNPNHLSYFKFVGRIVAKAVYDNRLLECYFTRSFYKHILGKSVRYTDMESEDYHFYQGLVYLLENDVSTLGYDLTFSTEVQEFGVCEVRDLKPNGANILVTEENKKEYVHLVCQMRMTGAIRKQLAAFLEGFYEIIPKRLISIFTEQELELLISGLPTIDIDDLKSNTEYHKYQSNSIQIQWFWRALRSFDQADRAKFLQFVTGTSKVPLQGFAALEGMNGIQKFQIHRDDRSTDRLPSAHTCFNQLDLPAYESFEKLRHMLLLAIQECSEGFGLA
Expression Range	4005-4374aa
Protein Length	Partial
Mol. Weight	50.7 kDa
Research Area	Cell Biology
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC. Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation. Mediates polyubiquitination of isoform 2 of PA2G4. Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1. Binds to an upstream initiator-like sequence in the preprodynorphin gene.
Subcellular Location	Cytoplasm. Nucleus. Mitochondrion.
Protein Families	UPL family, TOM1/PTR1 subfamily
Database References	HGNC: 30892 OMIM: 300697 KEGG: hsa:10075 STRING: 9606.ENSP00000262854 UniGene: Hs.136905
Associated Diseases	Mental retardation, X-linked, syndromic, Turner type (MRXST); Mental retardation, X-linked 17 (MRX17)
Tissue Specificity	Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas.

Gene Functions References

Ubiquitination modification through the coordinated action of PAQR3 with HUWE1 plays a crucial role in regulating the activity of hepatic PPARalpha in response to starvation. PMID: 29331071
HUWE1 missense variants may cause syndromic ID in both males and females. PMID: 29180823
HUWE1 overexpression could functionally suppress prostate carcinoma development both in vitro and in vivo, possibly by inverse regulation of c-Myc. PMID: 29966975
RBBP7 controls the stability of HUWE1.RBBP7 promotes HUWE1 ubiquitination. PMID: 29738775
The data supports an indispensable role for Mule in cardiac homeostasis through the regulation of mitochondrial function via maintenance of Pgc-1alpha and Pink1 expression and persistent negative regulation of c-Myc. PMID: 28148912
these results suggest that HUWE1 protein could contribute to preimplantation embryo development and dysregulated expression of HUWE1 could be related to poor embryo development and miscarriage in IVF clinic. PMID: 27901130
The authors show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. They also demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. PMID: 28193319
High HUWE1 expression is associated with Ovarian cancer. PMID: 28687618
HUWE1 is essential for genomic stability, by promoting replication of damaged DNA We show that HUWE1-knockout cells are unable to mitigate replication stress, resulting in replication defects and DNA breakage. PMID: 27146073
N-myc expression was upregulated in response to stress or following loss of Huwe1, which led to increased proliferation and stem-cell exhaustion. PMID: 27668798
The interaction with Huwe1 and polyubiquitylation were blocked by disruption of casein kinase 1 (CK1) activity, and mass spectrometry and mutational analysis identified serine 334 as an important phosphorylation site for Atoh1 ubiquitylation and subsequent degradation. PMID: 27542412
Elevated HECTH9 protein expression is associated with pathogenesis of hepatocellular carcinoma. PMID: 28205209
Mechanistic investigation revealed that HUWE1 can regulate p53 protein level through its stabilization. HUWE1 functions as a tumour suppressor in thyroid cancer progression, which may represent a novel therapeutic target for prevention or intervention of thyroid cancer. PMID: 27581931
We identified a HUWE1 mutation in an affected male with Juberg-Marsidi and Brooks syndromes from the original family reported by Juberg and Marsidi; it is evident the syndrome does not result from a mutation in ATRX as reported in the literature. Additionally, the data indicated that Juberg-Marsidi syndrome and Brooks syndromes are allelic having the same HUWE1 mutation. PMID: 27130160
Results reveal a pathway controlled by ATM, SIRT6, and SNF2H to block HUWE1, which stabilizes H2AX and induces its incorporation into chromatin only when cells are damaged. PMID: 26711340
miR-542-5p plays a critical role in the proliferation of osteosarcoma and targets HUWE1. PMID: 26498360
TNF activates Mule by inducing the dissociation of Mule from its inhibitor ARF. Inhibition of Mule phosphorylation by silencing Syk prevents this, thereby inhibiting Mule E3 ligase activity and TNF-induced JNK activation and cell death. PMID: 26212014
HUWE1 and NEDD4-1 are two E3 ligases that are fundamental enzymes in the post-translational regulation of ABCG1 and ABCG4 protein levels and cellular cholesterol export activity PMID: 26296893
Results show that ARF-BP1 was expressed at high levels in B-cell lymphoma cell lines and by regulating MYC and p53 transcriptional activity, ARF-BP1 is a critical determinant of the proliferation of B cell lymphomas. PMID: 22754359
Our findings highlight the importance of microduplications at Xp11.22 to ID, even in sporadic cases, and reveal new clinical and molecular insight into HUWE1 copy number gains. PMID: 25652354
we show that HUWE1 stimulates human lung cancer cell invasion through regulating TIAM1 stability. Finally, we demonstrate that HUWE1 and TIAM1 protein levels are inversely correlated in human lung carcinomas PMID: 25543140
Inhibition of HUWE1 stabilizes MIZ1 and induces global accumulation of MIZ1 on MYC-bound target genes. PMID: 25253726
analysis of ubiquitin-mediated proteolysis of DNA damage-inducible transcript 4 (DDIT4) by the E3 ligase HUWE1 PMID: 25147182
Results demonstrate that HUWE1 is a novel player involved in regulating ERK1/2 signal transmission through the Shoc2 scaffold complex. PMID: 25022756
Ubiquitin ligase HUWE1 regulates axon branching through the Wnt/beta-catenin pathway in a Drosophila model for intellectual disability. PMID: 24303071
Low Huwe1 expression is associated with medulloblastoma. PMID: 24960692
this study shows that MutYH is ubiquitinated in vitro and in vivo by the E3 ligase Mule between amino acids 475 and 535. PMID: 24443563
data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis PMID: 24342616
HUWE1 promotes BRCA1 ubiquitination. PMID: 24472556
Findings indicate p53-independent roles for MDM2 and HUWE1 in apoptosis and suggest the potential for therapy directed against MDM2 to overcome lapatinib resistance. PMID: 23652204
a critical regulatory mechanism of HDAC2 by Mule and suggest this pathway determines the cellular response to HDACs and DNA damage PMID: 22016339
HUWE1 and TRIP12 collaborate in degradation of ubiquitin-fusion proteins and misframed ubiquitin. PMID: 23209776
Increased dosage of HUWE1 causes nonsyndromic intellectual disability. PMID: 22840365
In PE, MULE preferentially targeted p53 for degradation, allowing accumulation of pro-apoptotic Mcl-1 isoforms. In IUGR, however, MULE targeted pro-survival Mcl-1, allowing p53 to accumulate and exert its apoptotic function. PMID: 22552282
the involvement of HUWE1 in the ubiquitination and proteasomal degradation of MyoD was described. PMID: 22277673
The E3 ligase Mule mediates the degradation of Pol lambda and the control of Pol lambda levels by Mule has functional consequences for the ability of mammalian cells to deal with 8-oxo-G lesions. PMID: 22203964
The present study reveals a novel regulation of RASSF1C and the potentially important role of RASSF1C in DNA damage responses via SCFbeta-TrCP and Mule. PMID: 21910689
Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site. PMID: 21613222
Studies indicate that ARF is induced in response to DNA damage and inhibits, by direct interaction, the E3 ubiquitin ligase Mule. PMID: 21726556
findings suggest that reduced Mule/Mcl-1 complex has a significant role in increasing the stability of Mcl-1 in breast cancer cells and increased resistance to apoptosis PMID: 21730980
Huwe1 interacted with HIV-1 Gag-Pol precursor protein through an IN domain PMID: 21167302
Arf-bp1 and Pam are novel regulators of circadian gene expression that target Rev-erb alpha for degradation PMID: 20534529
A structural element within the HUWE1 HECT domain modulates self-ubiquitination and substrate ubiquitination activities. PMID: 20007713
study modifies the current view of ARF-mediated p53 activation and reveals that ARF-BP1 is a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF PMID: 15989956
Mule is both required and sufficient for the polyubiquitination of Mcl-1; Mule is a unique BH3-containing E3 ubiquitin ligase apical to Bcl-2 family proteins during DNA damage-induced apoptosis PMID: 15989957
LASU1 is an E3 ligase that ubiquitinates Mcl-1 in vitro and is required for its proteasome-dependent degradation, the BH3 domain of LASU1 interactes with Mcl-1. PMID: 16213503
HectH9-mediated ubiquitination of Myc is required for transactivation of multiple target genes. PMID: 16269333
These findings demonstrate an important and conserved role for Huwe1 in regulating Cdc6 abundance after DNA damage. PMID: 17567951
An increased gene dosage of HSD17B10, HUWE1, or both contribute to the etiology of X-Linked Mental Retardation and suggest that point mutations in HUWE1 are associated with this disease too. PMID: 18252223
Huwe1 links destruction of N-Myc to the quiescent state that complements differentiation in the neural tissue PMID: 18488021

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