Literature summary extracted from

Shim, S.M.; Choi, H.R.; Sung, K.W.; Lee, Y.J.; Kim, S.T.; Kim, D.; Mun, S.R.; Hwang, J.; Cha-Molstad, H.; Ciechanover, A.; Kim, B.Y.; Kwon, Y.T.
The endoplasmic reticulum-residing chaperone BiP is short-lived and metabolized through N-terminal arginylation (2018), Sci. Signal., 11, eaan0630 .

Inhibitors

EC Number	Inhibitors	Comment	Organism	Structure
2.3.2.8	homocysteine-responsive endoplasmic reticlulum protein	i.e. HERP, a key inhibitor of the turnover and N-terminal arginylation of molecular chaperone BiP. HERP is a 43-kDa endoplasmic reticlulum (ER) membrane-integrated protein that is an essential component of ER-associated protein degradation	Homo sapiens

Localization

EC Number	Localization	Comment	Organism	GeneOntology No.	Textmining
2.3.2.8	endoplasmic reticulum	-	Homo sapiens	5783	-

Natural Substrates/ Products (Substrates)

EC Number	Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2.3.2.8	L-arginyl-tRNAArg + protein	Homo sapiens	-	tRNAArg + L-arginyl-[protein]	-	?

Organism

EC Number	Organism	UniProt	Comment	Textmining
2.3.2.8	Homo sapiens	O95260	-	-

Source Tissue

EC Number	Source Tissue	Comment	Organism	Textmining
2.3.2.8	HEK-293 cell	-	Homo sapiens	-
2.3.2.8	HeLa cell	-	Homo sapiens	-

Substrates and Products (Substrate)

EC Number	Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2.3.2.8	L-arginyl-tRNAArg + protein	-	Homo sapiens	tRNAArg + L-arginyl-[protein]	-	?

Synonyms

EC Number	Synonyms	Comment	Organism
2.3.2.8	arginyl-tRNA--protein transferase 1	UniProt	Homo sapiens
2.3.2.8	Ate1	-	Homo sapiens
2.3.2.8	ATE1-encoded R-transferase	-	Homo sapiens

General Information

EC Number	General Information	Comment	Organism
2.3.2.8	malfunction	knockdown of ATE1 does not significantly influence the mRNA expression of unfolded protein response (UPR) proteins, BiP, CHOP, and ATF4	Homo sapiens
2.3.2.8	metabolism	the molecular chaperone BiP (also known as GRP78) is short-lived under basal conditions and endoplasmic reticulum (ER) stress. The turnover of BiP is in part driven by its N-terminal arginylation (Nt-arginylation) by arginyltransferase ATE1, which generates an autophagic N-degron of the N-end rule pathway. ER stress elicits the formation of R-BiP, an effect that is increased when the proteasome is also inhibited. Nt-arginylation correlates with the cytosolic relocalization of BiP under the types of stress tested. The cytosolic relocalization of BiP does not require the functionality of the unfolded protein response or the Sec61- or Derlin1-containing translocon. A key inhibitor of the turnover and Nt-arginylation of BiP is HERP (homocysteine-responsive ER protein), a 43-kDa ER membrane-integrated protein that is an essential component of ER-associated protein degradation. Pharmacological inhibition of the ER-Golgi secretory pathway also suppressed R-BiP formation. Cytosolic R-BiP induced by ER stress and proteasomal inhibition is routed to autophagic vacuoles and possibly additional metabolic fates. These results suggest that Nt-arginylation is a posttranslational modification that modulates the function, localization, and metabolic fate of ER-resident proteins	Homo sapiens
2.3.2.8	physiological function	N-terminal arginylation (Nt-arginylation) is a posttranslational modification for which the amino acid L-Arg is conjugated to the Nt-Asp or Nt-Glu residues by ATE1-encoded R-transferases. Nt-arginylation is a posttranslational modification that modulates the function, localization, and metabolic fate of endoplasmic reticulum (ER)-resident proteins. A set of ER-residing molecular chaperones, such as BiP, calreticulin, and PDI, are N-terminally arginylated by enzyme ATE1. Nt-arginylation of BiP is induced in response to cytosolic double-stranded DNA, leading to the cytosolic accumulation of Nt-arginylated BiP, R-BiP. The Nt-Arg residue of R-BiP binds p62 (also known as SQSTM1 and Sequestosome-1) and subsequently is delivered to the autophagosomes for lysosomal degradation. Nt-arginylation mediates the cytosolic relocalization of BiP independently of the functionality of the ERAD core machinery	Homo sapiens

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Release 2023.1 (January 2023)