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IUBMB CommentsIn yeast this activity is catalysed by a dedicated enzyme that processes unfolded protein-bound Man8GlcNAc2 N-glycans within the endoplasmic reticulum to Man7GlcNAc2. The exposed alpha-1,6-linked mannose residue in the product enables the recognition by the YOS9 lectin, targeting the proteins for degradation. In mammalian cells this activity is part of the regular processing of N-glycosylated proteins, and is not associated with protein degradation. It is carried out by EC 3.2.1.113, Golgi mannosyl-oligosaccharide 1,2-alpha-mannosidase. The names of the isomers listed here are based on a nomenclature system proposed by Prien et al .
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Man8GlcNAc2 + H2O
Man7GlcNAc2 + D-mannose
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-
-
?
Man8GlcNAc2-[bovine ribonuclease B] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[bovine ribonuclease B] (isomer 7A1,2,3B3) + D-mannopyranose
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-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + H2O
Man7GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + D-mannopyranose
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
Man8GlcNAc2-[glucanosyl transferase Gas1p] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[glucanosyl transferase Gas1p] (isomer 7A1,2,3B3) + D-mannopyranose
Man8GlcNAc2-[protein] (isomer 8A1,2,3,B1,3) + H2O
?
-
-
-
-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
Man8GlcNAc2-[ricin A-chain-transmembrane-Leu2] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain-transmembrane-Leu2] + D-mannopyranose
Man8GlcNAc2-[ricin A-chain] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain] + D-mannopyranose
Manalpha(1-2)Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + H2O
Manalpha(1-2)Manalpha(1-3)[Manalpha(1-2)Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-6)]Manbeta(1-4)GlcNAcbeta(1-4)GlcNAc + D-mannose
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?
misfolded carboxypeptidase Y + H2O
?
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-
-
-
?
additional information
?
-
Man8GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + H2O
Man7GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + H2O
Man7GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
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-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[glucanosyl transferase Gas1p] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[glucanosyl transferase Gas1p] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[glucanosyl transferase Gas1p] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[glucanosyl transferase Gas1p] (isomer 7A1,2,3B3) + D-mannopyranose
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-
-
-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain-transmembrane-Leu2] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain-transmembrane-Leu2] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain] + D-mannopyranose
-
-
-
-
?
additional information
?
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the Htm1p exomannosidase activity requires processing of the N-glycan by glucosidase I, glucosidase II, and mannosidase I
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?
additional information
?
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the enzyme has no activity with an unglycosylated mutant form of the yeast alpha-mating pheromone, pro-alpha-factor. The enzyme has no alpha-mannosidase activity
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?
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Man8GlcNAc2-[bovine ribonuclease B] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[bovine ribonuclease B] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + H2O
Man7GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + D-mannopyranose
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
Man8GlcNAc2-[ricin A-chain-transmembrane-Leu2] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain-transmembrane-Leu2] + D-mannopyranose
Man8GlcNAc2-[ricin A-chain] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain] + D-mannopyranose
Man8GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + H2O
Man7GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + H2O
Man7GlcNAc2-[carboxypeptidase Y-transmembrane-Leu2] + D-mannopyranose
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-
?
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
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?
Man8GlcNAc2-[carboxypeptidase Y] + H2O
Man7GlcNAc2-[carboxypeptidase Y] + D-mannopyranose
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-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
-
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-
-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[protein] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[protein] (isomer 7A1,2,3B3) + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain-transmembrane-Leu2] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain-transmembrane-Leu2] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain-transmembrane-Leu2] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain] + D-mannopyranose
-
-
-
-
?
Man8GlcNAc2-[ricin A-chain] (isomer 8A1,2,3B1,3) + H2O
Man7GlcNAc2-[ricin A-chain] + D-mannopyranose
-
-
-
-
?
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physiological function
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Htm1 protein generates the N-glycan signal for glycoprotein degradation in the endoplasmic reticulum. Htm1p physically interacts with Pdi1p via its C-terminal domain
malfunction
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enzyme deletion causes retardation of the degradation of misfolded carboxypeptidase Y
malfunction
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enzyme deletion reduces the rate of degradation of mutant glycoproteins such as carboxypeptidase Y, ABC-transporter Pdr5-26p and oligosaccharyltransferase subunit Stt3-7p
metabolism
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a complex of the yeast protein disulfide isomerase Pdi1p and the enzyme Htm1p processes Man8GlcNAc2 carbohydrates bound to unfolded proteins, yielding Man7GlcNAc2. This glycan serves as a signal for HRD ligase-mediated glycoprotein disposal
metabolism
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the enzyme generates the N-glycan signal for glycoprotein degradation in the endoplasmic reticulum. The enzyme generates the Man7 GlcNAc2 oligosaccharide with a terminal alpha-1,6-linked mannosyl residue on degradation substrates. This oligosaccharide signal is decoded by the endoplasmic reticulum-localized lectin Yos9p that in conjunction with Hrd3p triggers the ubiquitin-proteasome-dependent hydrolysis of these glycoproteins. The exomannosidase activity of the enzyme requires processing of the N-glycan by glucosidase I, glucosidase II, and mannosidase I, resulting in a sequential order of specific N-glycan structures that reflect the folding status of the glycoprotein
metabolism
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the enzyme Htm1p marks misfolded glycoproteins by revealing a terminal alpha1,6-linked mannose that is recognized by Yos9p as the signal for degradation. Htm1p and Yos9p cooperate to enhance the specificity of the endoplasmic reticulum-associated degradation system
metabolism
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the enzyme is required for endoplasmic reticulum-associated degradation of glycoproteins
metabolism
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the enzyme is required for glycoprotein degradation but not involved in processing of N-linked oligosaccharides
metabolism
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a complex of the yeast protein disulfide isomerase Pdi1p and the enzyme Htm1p processes Man8GlcNAc2 carbohydrates bound to unfolded proteins, yielding Man7GlcNAc2. This glycan serves as a signal for HRD ligase-mediated glycoprotein disposal
-
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Clerc, S.; Hirsch, C.; Oggier, D.M.; Deprez, P.; Jakob, C.; Sommer, T.; Aebi, M.
Htm1 protein generates the N-glycan signal for glycoprotein degradation in the endoplasmic reticulum
J. Cell Biol.
184
159-172
2009
Saccharomyces cerevisiae
brenda
Jakob, C.; Bodmer, D.; Spirig, U.; Baettig, P.; Marcil, A.; Dignard, D.; Bergeron, J.; Thomas, D.; Aebi, M.
Htm1p, a mannosidase-like protein, is involved in glycoprotein degradation in yeast
EMBO Rep.
2
423-430
2001
Saccharomyces cerevisiae
brenda
Prien, J.; Ashline, D.; Lapadula, A.; Zhang, H.; Reinhold, V.
The high mannose glycans from bovine ribonuclease B isomer characterization by ion trap MS
J. Am. Soc. Mass Spectrom.
20
539-556
2009
unidentified
brenda
Nakatsukasa, K.; Nishikawa, S.; Hosokawa, N.; Nagata, K.; Endo, T.
Mnl1p, an alpha-mannosidase-like protein in yeast Saccharomyces cerevisiae, is required for endoplasmic reticulum-associated degradation of glycoproteins
J. Biol. Chem.
276
8635-8638
2001
Saccharomyces cerevisiae
brenda
Sakoh-Nakatogawa, M.; Nishikawa, S.; Endo, T.
Roles of protein-disulfide isomerase-mediated disulfide bond formation of yeast Mnl1p in endoplasmic reticulum-associated degradation
J. Biol. Chem.
284
11815-11825
2009
Saccharomyces cerevisiae, Saccharomyces cerevisiae W303-1A
brenda
Hosomi, A.; Tanabe, K.; Hirayama, H.; Kim, I.; Rao, H.; Suzuki, T.
Identification of an Htm1 (EDEM)-dependent, Mns1-independent endoplasmic reticulum-associated degradation (ERAD) pathway in Saccharomyces cerevisiae Application of a novel assay for glycoprotein ERAD
J. Biol. Chem.
285
24324-24334
2010
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
brenda
Chantret, I.; Kodali, V.; Lahmouich, C.; Harvey, D.; Moore, S.
Endoplasmic reticulum-associated degradation (ERAD) and free oligosaccharide generation in Saccharomyces cerevisiae
J. Biol. Chem.
286
41786-41800
2011
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4742
brenda
Clerc, S.; Hirsch, C.; Oggier, D.; Deprez, P.; Jakob, C.; Sommer, T.; Aebi, M.
Htm1 protein generates the N-glycan signal for glycoprotein degradation in the endoplasmic reticulum
J. Cell Biol.
184
159-172
2009
Saccharomyces cerevisiae
brenda
Quan, E.; Kamiya, Y.; Kamiya, D.; Denic, V.; Weibezahn, J.; Kato, K.; Weissman, J.
Defining the glycan destruction signal for endoplasmic reticulum-associated degradation
Mol. Cell.
32
870-877
2008
Saccharomyces cerevisiae
brenda
Gauss, R.; Kanehara, K.; Carvalho, P.; Ng, D.; Aebi, M.
A complex of Pdi1p and the mannosidase Htm1p initiates clearance of unfolded glycoproteins from the endoplasmic reticulum
Mol. Cell.
42
782-793
2011
Saccharomyces cerevisiae, Saccharomyces cerevisiae W303a
brenda