Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase

Details

Name

Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase

Synonyms

• 3.2.1.113
• ER alpha-1,2-mannosidase
• ER mannosidase 1
• ERMan1
• Man9GlcNAc2-specific-processing alpha-mannosidase
• Mannosidase alpha class 1B member 1

Gene Name

MAN1B1

Organism

Humans

Amino acid sequence

>lcl|BSEQ0019114|Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase
MAACEGRRSGALGSSQSDFLTPPVGGAPWAVATTVVMYPPPPPPPHRDFISVTLSFGENY
DNSKSWRRRSCWRKWKQLSRLQRNMILFLLAFLLFCGLLFYINLADHWKALAFRLEEEQK
MRPEIAGLKPANPPVLPAPQKADTDPENLPEISSQKTQRHIQRGPPHLQIRPPSQDLKDG
TQEEATKRQEAPVDPRPEGDPQRTVISWRGAVIEPEQGTELPSRRAEVPTKPPLPPARTQ
GTPVHLNYRQKGVIDVFLHAWKGYRKFAWGHDELKPVSRSFSEWFGLGLTLIDALDTMWI
LGLRKEFEEARKWVSKKLHFEKDVDVNLFESTIRILGGLLSAYHLSGDSLFLRKAEDFGN
RLMPAFRTPSKIPYSDVNIGTGVAHPPRWTSDSTVAEVTSIQLEFRELSRLTGDKKFQEA
VEKVTQHIHGLSGKKDGLVPMFINTHSGLFTHLGVFTLGARADSYYEYLLKQWIQGGKQE
TQLLEDYVEAIEGVRTHLLRHSEPSKLTFVGELAHGRFSAKMDHLVCFLPGTLALGVYHG
LPASHMELAQELMETCYQMNRQMETGLSPEIVHFNLYPQPGRRDVEVKPADRHNLLRPET
VESLFYLYRVTGDRKYQDWGWEILQSFSRFTRVPSGGYSSINNVQDPQKPEPRDKMESFF
LGETLKYLFLLFSDDPNLLSLDAYVFNTEAHPLPIWTPA

Number of residues

699

Molecular Weight

79579.18

Theoretical pI

7.8

GO Classification

Functions

calcium ion binding / mannosyl-oligosaccharide 1,2-alpha-mannosidase activity

Processes

cellular protein metabolic process / endoplasmic reticulum mannose trimming / ER-associated ubiquitin-dependent protein catabolic process / glycoprotein ERAD pathway / mannose trimming involved in glycoprotein ERAD pathway / N-glycan processing / oligosaccharide metabolic process / post-translational protein modification / protein alpha-1,2-demannosylation / protein folding / protein N-linked glycosylation / protein N-linked glycosylation via asparagine / trimming of terminal mannose on B branch

Components

endoplasmic reticulum / endoplasmic reticulum membrane / endoplasmic reticulum quality control compartment / extracellular vesicle / Golgi apparatus / integral component of membrane / membrane

General Function

Mannosyl-oligosaccharide 1,2-alpha-mannosidase activity

Specific Function

Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2).

Pfam Domain Function

• Glyco_hydro_47 (PF01532)

Transmembrane Regions

85-105

Cellular Location

Endoplasmic reticulum membrane

Gene sequence

>lcl|BSEQ0019115|Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1)
ATGGCTGCCTGCGAGGGCAGGAGAAGCGGAGCTCTCGGTTCCTCTCAGTCGGACTTCCTG
ACGCCGCCAGTGGGCGGGGCCCCTTGGGCCGTCGCCACCACTGTAGTCATGTACCCACCG
CCGCCGCCGCCGCCTCATCGGGACTTCATCTCGGTGACGCTGAGCTTTGGCGAGAACTAT
GACAACAGCAAGAGTTGGCGGCGGCGCTCGTGCTGGAGGAAATGGAAGCAACTGTCGAGA
TTGCAGCGGAATATGATTCTCTTCCTCCTTGCCTTTCTGCTTTTCTGTGGACTCCTCTTC
TACATCAACTTGGCTGACCATTGGAAAGCTCTGGCTTTCAGGCTAGAGGAAGAGCAGAAG
ATGAGGCCAGAAATTGCTGGGTTAAAACCAGCAAATCCACCCGTCTTACCAGCTCCTCAG
AAGGCGGACACCGACCCTGAGAACTTACCTGAGATTTCGTCACAGAAGACACAAAGACAC
ATCCAGCGGGGACCACCTCACCTGCAGATTAGACCCCCAAGCCAAGACCTGAAGGATGGG
ACCCAGGAGGAGGCCACAAAAAGGCAAGAAGCCCCTGTGGATCCCCGCCCGGAAGGAGAT
CCGCAGAGGACAGTCATCAGCTGGAGGGGAGCGGTGATCGAGCCTGAGCAGGGCACCGAG
CTCCCTTCAAGAAGAGCAGAAGTGCCCACCAAGCCTCCCCTGCCACCGGCCAGGACACAG
GGCACACCAGTGCATCTGAACTATCGCCAGAAGGGCGTGATTGACGTCTTCCTGCATGCA
TGGAAAGGATACCGCAAGTTTGCATGGGGCCATGACGAGCTGAAGCCTGTGTCCAGGTCC
TTCAGTGAGTGGTTTGGCCTCGGTCTCACACTGATCGACGCGCTGGACACCATGTGGATC
TTGGGTCTGAGGAAAGAATTTGAGGAAGCCAGGAAGTGGGTGTCGAAGAAGTTACACTTT
GAAAAGGACGTGGACGTCAACCTGTTTGAGAGCACGATCCGCATCCTGGGGGGGCTCCTG
AGTGCCTACCACCTGTCTGGGGACAGCCTCTTCCTGAGGAAAGCTGAGGATTTTGGAAAT
CGGCTAATGCCTGCCTTCAGAACACCATCCAAGATTCCTTACTCGGATGTGAACATCGGT
ACTGGAGTTGCCCACCCGCCACGGTGGACCTCCGACAGCACTGTGGCCGAGGTGACCAGC
ATTCAGCTGGAGTTCCGGGAGCTCTCCCGTCTCACAGGGGATAAGAAGTTTCAGGAGGCA
GTGGAGAAGGTGACACAGCACATCCACGGCCTGTCTGGGAAGAAGGATGGGCTGGTGCCC
ATGTTCATCAATACCCACAGTGGCCTCTTCACCCACCTGGGCGTATTCACGCTGGGCGCC
AGGGCCGACAGCTACTATGAGTACCTGCTGAAGCAGTGGATCCAGGGCGGGAAGCAGGAG
ACACAGCTGCTGGAAGACTACGTGGAAGCCATCGAGGGTGTCAGAACGCACCTGCTGCGG
CACTCCGAGCCCAGTAAGCTCACCTTTGTGGGGGAGCTTGCCCACGGCCGCTTCAGTGCC
AAGATGGACCACCTGGTGTGCTTCCTGCCAGGGACGCTGGCTCTGGGCGTCTACCACGGC
CTGCCCGCCAGCCACATGGAGCTGGCCCAGGAGCTCATGGAGACTTGTTACCAGATGAAC
CGGCAGATGGAGACGGGGCTGAGTCCCGAGATCGTGCACTTCAACCTTTACCCCCAGCCG
GGCCGTCGGGACGTGGAGGTCAAGCCAGCAGACAGGCACAACCTGCTGCGGCCAGAGACC
GTGGAGAGCCTGTTCTACCTGTACCGCGTCACAGGGGACCGCAAATACCAGGACTGGGGC
TGGGAGATTCTGCAGAGCTTCAGCCGATTCACACGGGTCCCCTCGGGTGGCTATTCTTCC
ATCAACAATGTCCAGGATCCTCAGAAGCCCGAGCCTAGGGACAAGATGGAGAGCTTCTTC
CTGGGGGAGACGCTCAAGTATCTGTTCTTGCTCTTCTCCGATGACCCAAACCTGCTCAGC
CTGGATGCCTACGTGTTCAACACCGAAGCCCACCCTCTGCCTATCTGGACCCCTGCCTAG

Chromosome Location

9

Locus

9q34

External Identifiers

Resource	Link
UniProtKB ID	Q9UKM7
UniProtKB Entry Name	MA1B1_HUMAN
GenBank Protein ID	6066222
GenBank Gene ID	AF148509
GenAtlas ID	MAN1B1
HGNC ID	HGNC:6823

General References

1. Tremblay LO, 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 Oct;9(10):1073-8. [Article]
2. Gonzalez DS, Karaveg K, Vandersall-Nairn AS, Lal A, Moremen KW: 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 Jul 23;274(30):21375-86. [Article]
3. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [Article]
4. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
6. Herscovics A, Romero PA, Tremblay LO: 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 Apr;12(4):14G-15G. [Article]
7. Avezov E, Frenkel Z, Ehrlich M, Herscovics A, Lederkremer GZ: 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 Jan;19(1):216-25. Epub 2007 Nov 14. [Article]
8. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
9. Vallee F, Karaveg K, Herscovics A, Moremen KW, Howell PL: Structural basis for catalysis and inhibition of N-glycan processing class I alpha 1,2-mannosidases. J Biol Chem. 2000 Dec 29;275(52):41287-98. [Article]
10. Karaveg K, Siriwardena A, Tempel W, Liu ZJ, Glushka J, Wang BC, Moremen KW: Mechanism of class 1 (glycosylhydrolase family 47) {alpha}-mannosidases involved in N-glycan processing and endoplasmic reticulum quality control. J Biol Chem. 2005 Apr 22;280(16):16197-207. Epub 2005 Feb 15. [Article]
11. Rafiq MA, Kuss AW, Puettmann L, Noor A, Ramiah A, Ali G, Hu H, Kerio NA, Xiang Y, Garshasbi M, Khan MA, Ishak GE, Weksberg R, Ullmann R, Tzschach A, Kahrizi K, Mahmood K, Naeem F, Ayub M, Moremen KW, Vincent JB, Ropers HH, Ansar M, Najmabadi H: Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. Am J Hum Genet. 2011 Jul 15;89(1):176-82. doi: 10.1016/j.ajhg.2011.06.006. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB01955	1,4-Butanediol	experimental	unknown		Details
DB02422	Methyl-2-S-(Alpha-D-Mannopyranosyl)-2-Thio-Alpha-D-Mannopyranoside	experimental	unknown		Details
DB02742	Kifunensine	experimental	unknown		Details
DB03206	Duvoglustat	investigational	unknown		Details