Gene Symbol: MAN1B1
Description: mannosidase alpha class 1B member 1
Alias: ERMAN1, ERManI, MANA-ER, MRT15, endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase, ER alpha 1,2-mannosidase, Man9GlcNAc2-specific processing alpha-mannosidase, endoplasmic Reticulum Class I alpha-mannosidase, endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase 1
Species: human
Products:     MAN1B1

Top Publications

  1. Vallee F, Karaveg K, Herscovics A, Moremen K, Howell P. Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases. J Biol Chem. 2000;275:41287-98 pubmed
    ..The structures also provide insight into the specificity of this class of enzymes and provide a blueprint for the future design of novel inhibitors that prevent degradation of misfolded proteins in genetic diseases. ..
  2. Cantu D, Nerinckx W, Reilly P. Theory and computation show that Asp463 is the catalytic proton donor in human endoplasmic reticulum alpha-(1-->2)-mannosidase I. Carbohydr Res. 2008;343:2235-42 pubmed publisher
  3. Groisman B, Shenkman M, Ron E, Lederkremer G. Mannose trimming is required for delivery of a glycoprotein from EDEM1 to XTP3-B and to late endoplasmic reticulum-associated degradation steps. J Biol Chem. 2011;286:1292-300 pubmed publisher
    ..We have shown before that ER mannosidase I (ERManI) is required for the trimming and concentrates together with the ERAD substrate and ERAD machinery in the ..
  4. Aikawa J, Takeda Y, Matsuo I, Ito Y. Trimming of glucosylated N-glycans by human ER ?1,2-mannosidase I. J Biochem. 2014;155:375-84 pubmed publisher
    ..cycle, glycoproteins are digested by ?-mannosidases in the ER, especially ?1,2-mannosidase I (ERManI)...
  5. Frenkel Z, Gregory W, Kornfeld S, Lederkremer G. Endoplasmic reticulum-associated degradation of mammalian glycoproteins involves sugar chain trimming to Man6-5GlcNAc2. J Biol Chem. 2003;278:34119-24 pubmed
    ..This could serve as a mechanism for removal of the glycoproteins from folding attempts catalyzed by cycles of reglucosylation and calnexin/calreticulin binding and result in targeting of these molecules for proteasomal degradation. ..
  6. Pan S, Cheng X, Sifers R. Golgi-situated endoplasmic reticulum ?-1, 2-mannosidase contributes to the retrieval of ERAD substrates through a direct interaction with ?-COP. Mol Biol Cell. 2013;24:1111-21 pubmed publisher
    Endoplasmic reticulum (ER) ?-1, 2-mannosidase (ERManI) contributes to ER-associated protein degradation (ERAD) by initiating the formation of degradation signals on misfolded N-linked glycoproteins...
  7. Caramelo J, Parodi A. Getting in and out from calnexin/calreticulin cycles. J Biol Chem. 2008;283:10221-5 pubmed publisher
  8. Avezov E, Frenkel Z, Ehrlich M, Herscovics A, Lederkremer G. Endoplasmic reticulum (ER) mannosidase I is compartmentalized and required for N-glycan trimming to Man5-6GlcNAc2 in glycoprotein ER-associated degradation. Mol Biol Cell. 2008;19:216-25 pubmed
    ..A possible candidate for this activity, ER mannosidase I (ERManI), accelerates the degradation of ERAD substrates when overexpressed...
  9. Hosokawa N, You Z, Tremblay L, Nagata K, Herscovics A. Stimulation of ERAD of misfolded null Hong Kong alpha1-antitrypsin by Golgi alpha1,2-mannosidases. Biochem Biophys Res Commun. 2007;362:626-32 pubmed
    ..Although transfected NHK is primarily localized in the ER, some NHK also co-localizes with Golgi markers, suggesting that mannose trimming by Golgi alpha1,2-mannosidases can also contribute to NHK degradation. ..

More Information


  1. Karaveg K, Siriwardena A, Tempel W, Liu Z, Glushka J, Wang B, et al. Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control. J Biol Chem. 2005;280:16197-207 pubmed
    ..A novel (3)H(4) conformation is proposed as the exploded transition state. ..
  2. Tremblay L, Herscovics A. Cloning and expression of a specific human alpha 1,2-mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis. Glycobiology. 1999;9:1073-8 pubmed
  3. Gonzalez D, Karaveg K, Vandersall Nairn A, Lal A, Moremen K. Identification, expression, and characterization of a cDNA encoding human endoplasmic reticulum mannosidase I, the enzyme that catalyzes the first mannose trimming step in mammalian Asn-linked oligosaccharide biosynthesis. J Biol Chem. 1999;274:21375-86 pubmed
    ..Enzyme reactions using a combination of human ER mannosidase I and recombinant Golgi mannosidase IA indicated that that these two enzymes are complementary in their cleavage of Man(9)GlcNAc(2) oligosaccharides to Man(5)GlcNAc(2). ..
  4. Hirao K, Natsuka Y, Tamura T, Wada I, Morito D, Natsuka S, et al. EDEM3, a soluble EDEM homolog, enhances glycoprotein endoplasmic reticulum-associated degradation and mannose trimming. J Biol Chem. 2006;281:9650-8 pubmed
    ..These results show that EDEM3 has alpha1,2-mannosidase activity in vivo, suggesting that the mechanism whereby EDEM3 accelerates glycoprotein ERAD is different from that of EDEM. ..
  5. Rafiq M, Kuss A, Puettmann L, Noor A, Ramiah A, Ali G, et al. Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. Am J Hum Genet. 2011;89:176-82 pubmed publisher
    ..Using a combination of next-generation sequencing and Sanger sequencing, we have identified mutations in the gene MAN1B1, encoding a mannosyl oligosaccharide, alpha 1,2-mannosidase...
  6. Pan S, Wang S, Utama B, Huang L, Blok N, Estes M, et al. Golgi localization of ERManI defines spatial separation of the mammalian glycoprotein quality control system. Mol Biol Cell. 2011;22:2810-22 pubmed publisher
    ..b>ERManI, a putative ER resident mannosidase, plays a rate-limiting role in generating a signal that targets misfolded N-..
  7. Hosokawa N, Tremblay L, You Z, Herscovics A, Wada I, Nagata K. Enhancement of endoplasmic reticulum (ER) degradation of misfolded Null Hong Kong alpha1-antitrypsin by human ER mannosidase I. J Biol Chem. 2003;278:26287-94 pubmed
  8. Wu Y, Swulius M, Moremen K, Sifers R. Elucidation of the molecular logic by which misfolded alpha 1-antitrypsin is preferentially selected for degradation. Proc Natl Acad Sci U S A. 2003;100:8229-34 pubmed
    ..Herein, we asked whether, and how, modification by endoplasmic reticulum mannosidase I (ERManI) contributes to the preferential selection of the misfolded AAT monomer for proteasomal degradation...
  9. Pan S, Huang L, McPherson J, Muzny D, Rouhani F, Brantly M, et al. Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency. Hepatology. 2009;50:275-81 pubmed publisher
    ..ER mannosidase I (ERManI) is a quality control factor that plays a critical role in the sorting and targeting of misfolded glycoproteins ..
  10. Balasubramanian M, Johnson D. MAN1B-CDG: Novel variants with a distinct phenotype and review of literature. Eur J Med Genet. 2019;62:109-114 pubmed publisher
    ..These patients were found to have three novel variants in MAN1B1 inherited from their healthy parents. Serum transferrin IEF showed a type 2 pattern...
  11. Wang H, Wu J, Gai J, Yang S, Ma Q, Ma H, et al. MAN1B1 is associated with poor prognosis and modulates proliferation and apoptosis in bladder cancer. Gene. 2018;679:314-319 pubmed publisher
    ..Here, our study aimed to explore the potentially biological function of MAN1B1 on BC...
  12. Lim S, Park S, Lee J, Kim S, Kim J, Min J, et al. Differential expression of microRNAs in recombinant Chinese hamster ovary cells treated with sodium butyrate using digital RNA counting. J Biotechnol. 2018;283:37-42 pubmed publisher
    ..e2f2, akt2, mtor, bcl-2, bim, p38α, and bmf) and five N-glycosylation-related target genes (neu1, b4galt3, gale, man1b1 and mgat4a) were selected by considering the effectiveness of NaBu on rCHO cell culture...
  13. Jin Z, Kitajima T, Dong W, Huang Y, Ren W, Guan F, et al. Genetic disruption of multiple α1,2-mannosidases generates mammalian cells producing recombinant proteins with high-mannose-type N-glycans. J Biol Chem. 2018;293:5572-5584 pubmed publisher
    ..complex-type glycans, we found that knocking out a gene encoding the endoplasmic reticulum mannosidase I (MAN1B1) in the double KO cells reduced most of the complex-type glycans...
  14. Abu Bakar N, Lefeber D, van Scherpenzeel M. Clinical glycomics for the diagnosis of congenital disorders of glycosylation. J Inherit Metab Dis. 2018;41:499-513 pubmed publisher the elucidation of previously unknown disorders of glycosylation, namely CCDC115-CDG, TMEM199-CDG, ATP6AP1-CDG, MAN1B1-CDG, and PGM1-CDG...
  15. Saldova R, Stöckmann H, O Flaherty R, Lefeber D, Jaeken J, Rudd P. N-Glycosylation of Serum IgG and Total Glycoproteins in MAN1B1 Deficiency. J Proteome Res. 2015;14:4402-12 pubmed publisher
    b>MAN1B1-CDG has recently been characterized as a type II congenital disorder of glycosylation (CDG), disrupting not only protein N-glycosylation but also general Golgi morphology...
  16. Hu S, Jiang L, Zou X, Yi W, Tian D. Hepatitis B virus upregulates host expression of ?-1,2-mannosidases via the PPAR? pathway. World J Gastroenterol. 2016;22:9534-9543 pubmed
    ..We measured the expression levels of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in cell lines HepG2.2.15, HepN10, HepAD38 and HepG2 by Western blot...
  17. Long E, Baker S, Oliveira V, Sawitzki B, Wood K. Alpha-1,2-mannosidase and hence N-glycosylation are required for regulatory T cell migration and allograft tolerance in mice. PLoS ONE. 2010;5:e8894 pubmed publisher
    ..Migration of Treg is central to their role in regulating in vivo immune responses and may require specific changes in N-glycosylation upon antigen encounter. ..
  18. Ondrušková N, Honzík T, Kytnarová J, Matoulek M, Zeman J, Hansíková H. Isoelectric Focusing of Serum Apolipoprotein C-III as a Sensitive Screening Method for the Detection of O-glycosylation Disturbances. Prague Med Rep. 2015;116:73-86 pubmed publisher
    ..Our results show that this method allows for a sensitive detection of ApoC-III O-glycosylation status, however this might be modulated by several factors (i.e. nutrition, medication) whose exact role remains to be determined. ..
  19. Joly P, Restier L, Bouchecareilh M, Lacan P, Cabet F, Chapuis Cellier C, et al. [DEFI-ALPHA cohort and POLYGEN DEFI-ALPHA clinical research hospital programme. A study about clinical, biological and genetics factors associated with the occurrence and the evolution of hepatic complications in children with alpha-1 antitrypsin def. Rev Mal Respir. 2015;32:759-67 pubmed publisher two complementary approaches: (i) the candidate genes strategy with the SERPINA1, CFTR (cystic fibrosis gene), MAN1B1 and SORL1 genes, these two latter being implied in the degradation of misfolding proteins; (ii) the whole exome ..
  20. van Scherpenzeel M, Steenbergen G, Morava E, Wevers R, Lefeber D. High-resolution mass spectrometry glycoprofiling of intact transferrin for diagnosis and subtype identification in the congenital disorders of glycosylation. Transl Res. 2015;166:639-649.e1 pubmed publisher
    ..SLC35A1-CDG], UDP-galactose transporter [SLC35A2-CDG] and mannosyl-oligosaccharide 1,2-alpha-mannosidase [MAN1B1-CDG]) resulted in characteristic diagnostic profiles...
  21. Herscovics A, Romero P, Tremblay L. The specificity of the yeast and human class I ER alpha 1,2-mannosidases involved in ER quality control is not as strict previously reported. Glycobiology. 2002;12:14G-15G pubmed
  22. Tremblay L, Campbell Dyke N, Herscovics A. Molecular cloning, chromosomal mapping and tissue-specific expression of a novel human alpha1,2-mannosidase gene involved in N-glycan maturation. Glycobiology. 1998;8:585-95 pubmed
    ..These results show that there are at least two Class I alpha1,2-mannosidases in the human and murine genomes with very distinct transcriptional regulation in different tissues. ..
  23. Benyair R, Ogen Shtern N, Mazkereth N, Shai B, Ehrlich M, Lederkremer G. Mammalian ER mannosidase I resides in quality control vesicles, where it encounters its glycoprotein substrates. Mol Biol Cell. 2015;26:172-84 pubmed publisher
    Endoplasmic reticulum α1,2 mannosidase I (ERManI), a central component of ER quality control and ER-associated degradation (ERAD), acts as a timer enzyme, modifying N-linked sugar chains of glycoproteins with time...
  24. Leonard C, Spellman M, Riddle L, Harris R, Thomas J, Gregory T. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990;265:10373-82 pubmed
  25. Doores K, Bonomelli C, Harvey D, Vasiljevic S, Dwek R, Burton D, et al. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci U S A. 2010;107:13800-5 pubmed publisher
    ..This study revises and extends our understanding of the glycan shield of HIV with implications for AIDS vaccine design. ..
  26. Blough H, Pauwels R, De Clercq E, Cogniaux J, Sprecher Goldberger S, Thiry L. Glycosylation inhibitors block the expression of LAV/HTLV-III (HIV) glycoproteins. Biochem Biophys Res Commun. 1986;141:33-8 pubmed
    ..The reverse transcriptase was not affected by the compounds. Glycosylation inhibitors may be considered for the chemotherapy of AIDS or AIDS-related complex, or chemoprophylaxis of HIV-positive individuals. ..
  27. Montefiori D, Robinson W, Mitchell W. Role of protein N-glycosylation in pathogenesis of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1988;85:9248-52 pubmed
    ..These results demonstrate that protein N-glycosylation is critical to the pathogenesis of HIV-1 at the levels of viral infectivity and cytopathicity but not at the level of virus replication or of host-cell infectibility. ..
  28. Beratis N, Kaperonis A, Eliopoulou M, Kourounis G, Tzingounis V. Increased activity of lysosomal enzymes in the peritoneal fluid of patients with gynecologic cancers and pelvic inflammatory disease. J Cancer Res Clin Oncol. 2005;131:371-6 pubmed
    ..003). The increased lysosomal enzyme activity in gynecologic cancers, without overlapping between patients and normal subjects or benign ovarian cyst fluid, indicates that such measurements might be applied for diagnostic purposes. ..
  29. Hart M, Saifuddin M, Spear G. Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. J Gen Virol. 2003;84:353-60 pubmed
    ..This study shows that specific alterations of the N-linked carbohydrates on HIV gp120/gp41 can enhance MBL-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL. ..
  30. Fenouillet E, Jones I, Powell B, Schmitt D, Kieny M, Gluckman J. Functional role of the glycan cluster of the human immunodeficiency virus type 1 transmembrane glycoprotein (gp41) ectodomain. J Virol. 1993;67:150-60 pubmed
  31. Zhou T, Frabutt D, Moremen K, Zheng Y. ERManI (Endoplasmic Reticulum Class I α-Mannosidase) Is Required for HIV-1 Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein Degradation Pathway. J Biol Chem. 2015;290:22184-92 pubmed publisher
    ..Here we investigated how the four ER-associated glycoside hydrolase family 47 (GH47) α-mannosidases, ERManI, and ER-degradation enhancing α-mannosidase-like (EDEM) proteins 1, 2, and 3, are involved in the Env ..
  32. Chappell S, Guetta Baranes T, Hadzic N, Stockley R, Kalsheker N. Polymorphism in the endoplasmic reticulum mannosidase I (MAN1B1) gene is not associated with liver disease in individuals homozygous for the Z variant of the alpha1-antitrypsin protease inhibitor (PiZZ individuals). Hepatology. 2009;50:1315; author reply 1315-6 pubmed publisher
  33. Pan S, Cheng X, Chen H, Castro P, Ittmann M, Hutson A, et al. ERManI is a target of miR-125b and promotes transformation phenotypes in hepatocellular carcinoma (HCC). PLoS ONE. 2013;8:e72829 pubmed publisher
    The MAN1B1 gene product, designated ER alpha-1, 2-mannosidase (ERManI), is an enzyme localized in the Golgi complex of mammalian cells...
  34. Bastaki F, Bizzari S, Hamici S, Nair P, Mohamed M, Saif F, et al. Single-center experience of N-linked Congenital Disorders of Glycosylation with a Summary of Molecularly Characterized Cases in Arabs. Ann Hum Genet. 2018;82:35-47 pubmed publisher
    ..In our sample of patients, five novel mutations were uncovered in the genes: MPDU1, PMM2, MAN1B1, and RFT1. In total, 9 mutations were harbored by the 10 patients in 7 genes...
  35. Papandreou M, Fenouillet E. Effect of various glycosidase treatments on the resistance of the HIV-1 envelope to degradation. FEBS Lett. 1997;406:191-5 pubmed
    ..Thus, partial deglycosylation increases Env sensitivity to proteases but only its total deglycosylation alters its stability. ..
  36. Bolmstedt A, Sjolander S, Hansen J, Akerblom L, Hemming A, Hu S, et al. Influence of N-linked glycans in V4-V5 region of human immunodeficiency virus type 1 glycoprotein gp160 on induction of a virus-neutralizing humoral response. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;12:213-20 pubmed
    ..These data indicated that elimination of the three N-linked glycans from gp160 resulted in an altered local antigenic conformation but did not uncover hidden neutralization epitopes, broadening the immune response. ..
  37. Jaeken J, Lefeber D, Matthijs G. Clinical utility gene card for: MAN1B1 defective congenital disorder of glycosylation. Eur J Hum Genet. 2016;24: pubmed publisher
  38. Xiang Y, Karaveg K, Moremen K. Substrate recognition and catalysis by GH47 α-mannosidases involved in Asn-linked glycan maturation in the mammalian secretory pathway. Proc Natl Acad Sci U S A. 2016;113:E7890-E7899 pubmed
    ..glycoside hydrolase family 47 (GH47) α-mannosidases, including endoplasmic reticulum (ER) α-mannosidase I (ERManI) and Golgi α-mannosidase IA (GMIA), are responsible for cleavage of terminal α1,2-linked mannose residues to ..
  39. Dedera D, Gu R, Ratner L. Role of asparagine-linked glycosylation in human immunodeficiency virus type 1 transmembrane envelope function. Virology. 1992;187:377-82 pubmed
  40. Aikawa J, Matsuo I, Ito Y. In vitro mannose trimming property of human ER ?-1,2 mannosidase I. Glycoconj J. 2012;29:35-45 pubmed publisher
    Endoplasmic reticulum ?-1,2 mannosidase I (ERManI) is an enzyme, which removes ?(1-2) linked mannoses from asparagine-linked oligosaccharides on glycoproteins in the endoplasmic reticulum (ER)...
  41. Hu H, Shioda T, Moriya C, Xin X, Hasan M, Miyake K, et al. Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface. J Virol. 1996;70:7462-70 pubmed
    ..Thus, the sialylation catalyzed by host cell pathways appeared to reduce the infectivity of human and nonhuman primate lentiviruses. Our results further suggested that desialylation would help increase the titers of HIV-based vectors. ..
  42. Stein B, Engleman E. Intracellular processing of the gp160 HIV-1 envelope precursor. Endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex. J Biol Chem. 1990;265:2640-9 pubmed
    ..Preliminary data also suggest that gp120 is post-translationally modified by sialylated O-linked oligosaccharides. ..
  43. Rymen D, Peanne R, Millón M, Race V, Sturiale L, Garozzo D, et al. MAN1B1 deficiency: an unexpected CDG-II. PLoS Genet. 2013;9:e1003989 pubmed publisher
    ..In the present study, exome sequencing was used to identify MAN1B1 as the culprit gene in an unsolved CDG-II patient. Subsequently, 6 additional cases with MAN1B1-CDG were found...
  44. Land A, Braakman I. Folding of the human immunodeficiency virus type 1 envelope glycoprotein in the endoplasmic reticulum. Biochimie. 2001;83:783-90 pubmed
    ..Here we present an overview of the present knowledge on the folding process of the heavily glycosylated human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein in the ER. ..
  45. van Scherpenzeel M, Timal S, Rymen D, Hoischen A, Wuhrer M, Hipgrave Ederveen A, et al. Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency. Brain. 2014;137:1030-8 pubmed publisher
    ..In a single patient with intellectual disability, whole-exome sequencing revealed MAN1B1 as congenital disorder of glycosylation type II candidate gene...