Recombinant Human E3 ubiquitin-protein ligase AMFR (AMFR)

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Code CSB-CF892337HU
Size $1620
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 85% as determined by SDS-PAGE.
Activity
Not Test
Target Names
AMFR
Uniprot No.
Research Area
Others
Alternative Names
(Autocrine motility factor receptor)(AMF receptor)(RING finger protein 45)(gp78)
Species
Homo sapiens (Human)
Source
in vitro E.coli expression system
Expression Region
1-643aa
Target Protein Sequence
MPLLFLERFPWPSLRTYTGLSGLALLGTIISAYRALSQPEAGPGEPDQLTASLQPEPPAPARPSAGGPRARDVAQYLLSDSLFVWVLVNTACCVLMLVAKLIQCIVFGPLRVSERQHLKDKFWNFIFYKFIFIFGVLNVQTVEEVVMWCLWFAGLVFLHLMVQLCKDRFEYLSFSPTTPMSSHGRVLSLLVAMLLSCCGLAAVCSITGYTHGMHTLAFMAAESLLVTVRTAHVILRYVIHLWDLNHEGTWEGKGTYVYYTDFVMELTLLSLDLMHHIHMLLFGNIWLSMASLVIFMQLRYLFHEVQRRIRRHKNYLRVVGNMEARFAVATPEELAVNNDDCAICWDSMQAARKLPCGHLFHNSCLRSWLEQDTSCPTCRMSLNIADNNRVREEHQGENLDENLVPVAAAEGRPRLNQHNHFFHFDGSRIASWLPSFSVEVMHTTNILGITQASNSQLNAMAHQIQEMFPQVPYHLVLQDLQLTRSVEITTDNILEGRIQVPFPTQRSDSIRPALNSPVERPSSDQEEGETSAQTERVPLDLSPRLEETLDFGEVEVEPSEVEDFEARGSRFSKSADERQRMLVQRKDELLQQARKRFLNKSSEDDAASESFLPSEGASSDPVTLRRRMLAAAAERRLQKQQTS
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
79.0 kDa
Protein Length
Full Length
Tag Info
N-terminal 10xHis-tagged
Form
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
3-7 business days
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4℃ for up to one week.
Datasheet & COA
Please contact us to get it.

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Target Background

Function
E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins, such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 and APOB for proteasomal degradation. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG1 complex at the ER membrane. In addition, interaction of AMFR with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced HMGCR ubiquitination. The ubiquitinated HMGCR is then released from the ER into the cytosol for subsequent destruction. In addition to ubiquitination on lysine residues, catalyzes ubiquitination on cysteine residues: together with INSIG1, mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid levels are low. Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols. Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation. Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor. In association with LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6.
Gene References into Functions
  1. There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. PMID: 28212872
  2. This is the first study to show that HSPA1L mediated HIF-1alpha stabilization. In addition, this is the first study to show that GP78 inactivation promotes cancer cell proliferation, migration and eventual tumor growth both in vivo and in vitro by increasing cellular prion protein. PMID: 28759037
  3. overexpression of gp78 or SVIP suppression may eliminate the toxic gain of function associated with polymerization of ZAAT, thus providing a potential new therapeutic approach to the treatment of alpha-1 antitrypsin deficiency PMID: 28301499
  4. Despite its interaction with gp78, Lnp does not seem to have a broad function in degradation of misfolded ER proteins. PMID: 27387505
  5. Further study discovered that the gp78 CUE domain works as a proofreading machine during the growth of K48-linked polyubiquitin chains to ensure the linkage specificity. Together, our studies uncover a novel mechanism underlying the linkage specificity determination of longer polyubiquitin chains. PMID: 27067047
  6. AMFR expression is significantly reduced in plasma from osteoporosis patients. PMID: 25689831
  7. Catalytic inactivation of MGRN1 results in elevated levels of GP78 and a consequential increase in the initiation of mitophagy. PMID: 26743086
  8. Authors conclude that the Hrd1 complex forms an essential retrotranslocation module that is evolutionarily conserved, but the mammalian ERAD system uses additional ubiquitin ligases to assist Hrd1 during retrotranslocation. PMID: 26424800
  9. Downregulation of AMFR induced cell cycle arrest at the G0/G1 phase, and increased apoptosis of the THP1 cells. PMID: 26136223
  10. The authors identify USP13 as a gp78-associated deubiquitinase that eliminates ubiquitin conjugates from Ubl4A to maintain the functionality of Bag6. PMID: 24424410
  11. Data show that autocrine motility factor receptor (AMFR) and NOTCH1 protein are the direct target genes of microRNA miR-139-5p in colorectal cancer (CRC). PMID: 25149074
  12. gp78 elongates polyubiquitin chains from the distal end through the cooperation of its G2BR and CUE domains. PMID: 25409783
  13. Our data uncovers a previously unknown functional link between gp78 and TRIM25 and provides mechanistic insight into gp78-mediated protein ubiquitylation. PMID: 24810856
  14. The ubiquitin ligase gp78, known for its role in protein quality control, is critical for unglycosylated PrP ubiquitylation and degradation. PMID: 24714645
  15. High AMFR expression is associated with invasion depth and lymph node metastasis in gastric cancer. PMID: 24568530
  16. DGAT2 is regulated by gp78-associated endoplasmic-reticulum-associated degradation at the post-translational level. PMID: 24820123
  17. gp78 is expressed specifically in human prostate cancer rather than normal prostate tissues, it could be a putative biomarker for prostate cancer diagnosis. PMID: 23666464
  18. data thus implicate two parallel pathways by which Gp78 regulates MAVS signaling PMID: 24285545
  19. gp78 is a ubiquitination machine where multiple E2-binding sites coordinately facilitate processive ubiquitination. PMID: 23942235
  20. A novel role for the endoplasmic reticulum-associated Gp78 ubiquitin ligase and the Mfn1 mitochondrial fusion factor in mitophagy. PMID: 23427266
  21. The GP78 CUE domain functions to both facilitate substrate binding and enable switching between adjacent ubiquitin molecules of a growing chain to enable processivity in ubiquitination. PMID: 23123110
  22. Delivery of ubiquitylated substrate to the central ER was regulated by ubiquitin chain elongation and opposing actions of gp78 CUE domain interactions and p97 recruitment. PMID: 22328510
  23. This review summarizes the structure and function of GP78, and its importance in both physiological and pathological processes.[review] PMID: 22812524
  24. cell surface expression of AMFR is associated with progression in Chronic lymphocytic leukemia PMID: 20574759
  25. identify two ER membrane proteins, SPFH2 and TMUB1, as associated proteins of gp78, a membrane-bound ubiquitin ligase that mediates sterol-accelerated ERAD of the cholesterol biosynthetic enzyme HMG-CoA reductase. PMID: 21343306
  26. AMFR pathway promotes invasion of esophageal squamous cell cancer cells PMID: 20504226
  27. KAI1 has a role in promotion of cell proliferation and mammary gland hyperplasia by the gp78 ubiquitin ligase PMID: 20089858
  28. These data demonstrate a role of the E3 ubiquitin ligases in CTA1 retro-translocation. PMID: 19864457
  29. The results support that gp78 is an E3 targeting CFTRDeltaF508 for degradation and Hrd1 inhibits CFTRDeltaF508 degradation by acting as an E3 for gp78. PMID: 19828134
  30. Gp78 promotes SOD1 and ataxin-3 degradation in endoplasmic reticulum. PMID: 19661182
  31. hippocampal expression of NLK and its receptor gp78 is associated with maze learning in rats. PMID: 11902125
  32. In a prospective study we have also analyzed AMF receptor protein expression in primary tumors of 54 skin melanoma patients using IHC PMID: 12067203
  33. demonstrate that GP78 is a bona fide E3 ligase in the apoB ER-associated degradation pathway PMID: 12670940
  34. Autocrine motility factor receptor may contribute to tumor progression and AMF-R gene expression can serve as a useful prognostic marker in non-small cell lung cancers (NSCLC). PMID: 12962414
  35. data provide evidence that the AMFR sequence coding for a seven-transmembrane domain E3 ubiquitin ligase codes for the gp78/AMFR protein recognized by the 3F3A mAb; the 3F3A mAb selectively recognizes a subpopulation of AMFR localized to an ER subdomain PMID: 15303277
  36. Results identify gp78 as the E3 that initiates sterol-accelerated degradation of reductase, and Insig-1 as a bridge between gp78/VCP and the reductase substrate. PMID: 16168377
  37. AMFR expression predicts an unfavourable surgical outcome in patients with stage I pulmonary adenocarcinomas PMID: 16184720
  38. gp78-mediated ubiquitylation is an early step in endoplasmic reticulum -associated degradation PMID: 16407162
  39. N-glyco side-chain of AMFR is a trigger and that interaction between the 117-C-terminal part of AMF and the extracellular core protein of AMFR is needed during AMF-AMFR interactions PMID: 16563432
  40. These data indicate that gp78 assumes multiple unique quality control roles over ATZ, including the facilitation of degradation and inhibition of aggregation of ATZ. PMID: 16979136
  41. Insig-1 sterol-regulated degradation is mediated by the membrane-bound ubiquitin ligase gp78 PMID: 17043353
  42. the receptor molecule for AMF/NLK/MF in leukemic differentiation is not gp78 PMID: 17071500
  43. Findings suggest a strong correlation between the expression of AMFR and RhoC and a correlation between them and invasion and metastasis of hepatocellular carcinoma. PMID: 17265125
  44. Ube2g2/gp78-mediated polyubiquitination involves preassembly of Lys 48-linked ubiquitin chains at the catalytic cysteine of Ube2g2 PMID: 17310145
  45. This study identifies Ufd1 as a cofactor of gp78, reveals an unappreciated function of Ufd1 in the ubiquitination reaction during endoplasmic reticulum -associated degradation, and illustrates that Ufd1 plays a critical role in cholesterol metabolism. PMID: 17681147
  46. SVIP is an endogenous inhibitor of ERAD that acts through regulating the assembly of the gp78-p97/VCP-Derlin1 complex. PMID: 17872946
  47. gp78 promotes sarcoma metastasis by targeting KAI1 for degradation PMID: 18037895
  48. both UBC7/gp78 and UbcH5a/CHIP may be involved in CYP3A4 ER-associated degradation, although their relative physiological contribution remains to be established PMID: 19103148
  49. The G2BR domain within the E3 gp78 binds selectively and with high affinity to the E2 Ube2g2. PMID: 19560420
  50. Hrd1 targets gp78 for proteasomal degradation independent of the ubiquitin ligase activity of gp78, without evidence of a reciprocal effect. PMID: 19835843

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Subcellular Location
Endoplasmic reticulum membrane; Multi-pass membrane protein.
Database Links

HGNC: 463

OMIM: 603243

KEGG: hsa:267

STRING: 9606.ENSP00000290649

UniGene: Hs.295137

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