Active, Human, Recombinant AREL1

E3 ligases

Product Code: TE3-065
Activity: Verified in Poly-ubiquitin Chain Synthesis Assay.
Verified Applications: In vitro, recombinant Apoptosis-resistant E3 ubiquitin-protein ligase 1 accepts activated ubiquitin from E2 conjugating enzymes UBE2D1 or UBE2L3, in a reaction that also requires Ubiquitin Activating Enzyme 1 (an E1). The charged E3 demonstrates strong autoubiquitylation in the absence of added substrates. Appropriate enzyme concentrations are specific to the application.
Purity: 95%
Concentration: 20 – 30 μM

For Research Use Only (RUO)

SDS-PAGE

2 μg UBA1 run on 4-12% SDS-PAGE gel under reducing conditions, then visualized with Colloidal Coomassie Blue Stain.
Formulation: 40 mM HEPES, 100 mM NaCl, 10% Glycerol, 1 mM EDTA, 1 mM TCEP, pH 7.6
Shipping: The product is shipped with dry ice or equivalent. Upon receipt, store it immediately at the temperature recommended below.
Storage and Stability: Use a manual defrost freezer and avoid repeated freeze-thaw cycles. Aliquot and store ≤ -70°C (stable for 24 months from date of receipt).

Additional Product Information

Protein Name: AREL1
UniProt #: O15033
Predicted Molecular Mass: 59 kDa
Protein Sequence: MGWSHPQFEKGSHHHHHHGSLEVLFQGPGSMSDQEAKPSTEDLGDKKEGEYIKLKVIGQDSSEIHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRIADNHTPKELGMEEEDVIEVYQEQTGGSETFQDKVNFFQRELRQVHMKRPHSKVTLKVSRHALLESSLKATRNFSISDWSKNFEVVFQDEEALDWGGPRREWFELICKALFDTTNQLFTRFSDNNQALVHPNPNRPAHLRLKMYEFAGRLVGKCLYESSLGGAYKQLVRARFTRSFLAQIIGLRMHYKYFETDDPEFYKSKVCFILNNDMSEMELVFAEEKYNKSGQLDKVVELMTGGAQTPVTNANKIFYLNLLAQYRLASQVKEEVEHFLKGLNELVPENLLAIFDENELELLMCGTGDISVSDFKAHAVVVGGSWHFREKVMRWFWTVVSSLTQEELARLLQFTTGSSQLPPGGFAALCPSFQIIAAPTHSTLPTAHTCFNQLCLPTYDSYEEVHRMLQLAISEGCEGFGML

Background Information and Alternate Names

Species & domain architecture. The 823-aa wild type AREL1 protein contains an N-terminal Filamin-like repeat, two WW motifs for substrate docking and a C-terminal HECT catalytic module (residues 436-823) with the active-site Cys790. High-resolution crystal data reveal a classic bilobed HECT fold capped by a unique β-hairpin that precisely positions the acceptor ubiquitin. UPS pathway role. Accepting ubiquitin from E2 enzyme UBE2L3, AREL1 transfers it to substrates, favoring Lys11/Lys33 linkages (UniProt). It deletes cytosolic IAP antagonists after mitochondrial outer-membrane permeabilization and suppresses necroptosis by degrading Metaxin-2. AREL1 also targets SOCS2, tuning cytokine responses in acute-lung-injury models. Relevance to TPD & disease biology. By dismantling pro-apoptotic signals, AREL1 may foster tumor survival; pharmacological inhibition could re-sensitize cancer cells or amplify TNF-induced necroptosis. Its bias toward non-canonical Lys33 chains offers a tractable system for probing novel ubiquitin topologies as degrader “handles.” Beyond oncology, modulation of AREL1-SOCS2 signaling represents a prospective anti-inflammatory angle. References Kim, J-B., et al. (2013) J Biol Chem 288(17):12014-21. PMID 23479728 Lear. T. B., et al., (2019) JCI Insight 4:e129110. PMID 31578312 Singh, S., et. al. (2019) J Biol Chem 2019 294:19934-19949. PMID 31732561 Jo, Y., et al. (2021) Exp Ther Med 2021 22:1195. PMID 34584540 Roberts, J. Z., et al., (2022) Cell Death Differ. 29:272-284. PMID 34912054
Alternate Names: AREL1 (gene AREL1; synonyms KIAA0317, FLR)