MAN2B1 mannosidase alpha class 2B member 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAN2B1provided by HGNC
Official Full Name: mannosidase alpha class 2B member 1provided by HGNC
Primary source: HGNC:HGNC:6826
See related: Ensembl:ENSG00000104774 MIM:609458; AllianceGenome:HGNC:6826
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MANB; LAMAN
Summary: This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
Expression: Ubiquitous expression in spleen (RPKM 48.9), appendix (RPKM 36.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.13

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (12646512..12666742, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (12771019..12791240, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (12757326..12777556, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A diagnosis can be established by measuring the activity of lysosomal alpha-mannosidase in leucocytes and screening for abnormal urinary excretion of mannose-rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations.
Title: Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: Report of seven new cases.
A novel heterozygous mutation (c.2013G>A; p.R638H) of MANBA was identified in patients with autosomal-dominant nystagmus. An additional mutation (c.2346T>A; p.L749H) in MANBA was found by screening patients with sporadic nystagmus.
Title: Lysosomal storage disease in the brain: mutations of the β-mannosidase gene identified in autosomal dominant nystagmus.
Our results indicate a correlation between the MAN2B1 genotypes and the cognitive function, upper limb coordination, balance, FVC% and the storage of oligosaccharides in CSF.
Title: Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation.
The results showed that the alpha-mannosidosis patient has compound heterozygous mutations in the MAN2B1 gene
Title: Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation.
MAN2B1 is targeted to the vacuole without passing through the Golgi complex.
Title: Traffic of human α-mannosidase in plant cells suggests the presence of a new endoplasmic reticulum-to-vacuole pathway without involving the Golgi complex.
A single nucleotide polymorphism in MAN2B, rs228614, is associated with risk for multiple sclerosis.
Title: MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis.
Observational study of gene-disease association. (HuGE Navigator)
Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
Expressed MAN2B1 and MAN2B2 in Drosophila S2 cells and functionally characterized them. MAN2B1 and MAN2B2 were significantly inhibited by the class II alpha-mannosidase inhibitors, swainsonine and mannostatin A.
Title: Human lysosomal alpha-mannosidases exhibit different inhibition and metal binding properties.
5 new mutations were found in the MAN2B1 gene: c.157G>T, c.562C>T, c.599A>T, c.293dupA, c.2402G>A (p.E53X, p.R188X, p.H200L, p.Y99VfsX61, p.G801D). p.H200L could involve the catalytic mechanism. p.G801D would affect correct folding.
Title: Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Deficiency of alpha-mannosidase MedGen: C0024748 OMIM: 248500 GeneReviews: Alpha-Mannosidosis	Compare labs

EBI GWAS Catalog

Description
Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Specific alterations of the N-linked carbohydrates on HIV-1 gp120 and gp41 by glucosidases and mannosidase inhibitors can enhance mannose-binding lectin (MBL)-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL	PubMed
	env	HIV-1 gp120 N-linked oligosaccharides are processed by manosidase I and II in the Golgi complex	PubMed
Envelope surface glycoprotein gp160, precursor	env	Oligosaccharide side-chains of HIV-1 gp160 are processed by glycosidase I and II, mannosidase I and II, acetylglucosaminyl transferase I and II, and fucosyl, galactosyl and sialyl transferases in both the endoplasmic reticulum and golgi apparatus	PubMed
Envelope transmembrane glycoprotein gp41	env	Mannose-containing, N-linked oligosaccharide side-chains of HIV-1 gp41 are involved in the initial stage of infection by HIV-1; glycosylation inhibitors block virus-cell and cell-cell fusion and release of the virions	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NIB1927 (e-PCR)
- UniSTS:15958

GDB:335318 (e-PCR)
- UniSTS:156597

WI-18725 (e-PCR)
- UniSTS:26861

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables alpha-mannosidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables carbohydrate binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in learning or memory	IEA Inferred from Electronic Annotation more info
involved_in mannose metabolic process	IEA Inferred from Electronic Annotation more info
involved_in oligosaccharide catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein deglycosylation	TAS Traceable Author Statement more info	PubMed
involved_in protein modification process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in azurophil granule lumen	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in lysosomal lumen	TAS Traceable Author Statement more info
is_active_in lysosome	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: lysosomal alpha-mannosidase

Names: lysosomal acid alpha-mannosidase; mannosidase alpha-B; mannosidase, alpha B, lysosomal

NP_000519.2

EC 3.2.1.24

NP_001166969.1

EC 3.2.1.24

XP_005259970.1

EC 3.2.1.24

XP_047294797.1

EC 3.2.1.24

XP_054177008.1

EC 3.2.1.24

XP_054177009.1

EC 3.2.1.24

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008318.1 RefSeqGene

Range

5036..25266

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000528.4 → NP_000519.2 lysosomal alpha-mannosidase isoform 1 precursor

See identical proteins and their annotated locations for NP_000519.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BC000736, DB237901

Consensus CDS

CCDS32919.1

UniProtKB/Swiss-Prot

G5E928, O00754, O15330, Q16680, Q93094, Q9BW13

UniProtKB/TrEMBL

A8K6A7

Related

ENSP00000395473.2, ENST00000456935.7

Conserved Domains (4) summary

PLN02701
Location:63 → 1000

PLN02701; alpha-mannosidase

cd10810
Location:63 → 341

GH38N_AMII_LAM_like; N-terminal catalytic domain of lysosomal alpha-mannosidase and similar proteins; glycoside hydrolase family 38 (GH38)

smart00872
Location:387 → 465

Alpha-mann_mid; Alpha mannosidase, middle domain

pfam07748
Location:510 → 1000

Glyco_hydro_38C; Glycosyl hydrolases family 38 C-terminal domain
NM_001173498.2 → NP_001166969.1 lysosomal alpha-mannosidase isoform 2 precursor

See identical proteins and their annotated locations for NP_001166969.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks a CAG copy at an splice site in the CDS, as compared to variant 1. The resulting isoform (2) lacks an internal Q, as compared to isoform 1.

Source sequence(s)

AK291572, BM982008, DB237901, U05572

Consensus CDS

CCDS54224.1

UniProtKB/TrEMBL

A8K6A7

Related

ENSP00000221363.4, ENST00000221363.9

Conserved Domains (4) summary

PLN02701
Location:63 → 999

PLN02701; alpha-mannosidase

cd10810
Location:63 → 341

GH38N_AMII_LAM_like; N-terminal catalytic domain of lysosomal alpha-mannosidase and similar proteins; glycoside hydrolase family 38 (GH38)

smart00872
Location:386 → 464

Alpha-mann_mid; Alpha mannosidase, middle domain

pfam07748
Location:509 → 999

Glyco_hydro_38C; Glycosyl hydrolases family 38 C-terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

12646512..12666742 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005259913.3 → XP_005259970.1 lysosomal alpha-mannosidase isoform X1

UniProtKB/TrEMBL

A8K6A7

Conserved Domains (4) summary

PLN02701
Location:63 → 1001

PLN02701; alpha-mannosidase

cd10810
Location:63 → 341

GH38N_AMII_LAM_like; N-terminal catalytic domain of lysosomal alpha-mannosidase and similar proteins; glycoside hydrolase family 38 (GH38)

smart00872
Location:388 → 466

Alpha-mann_mid; Alpha mannosidase, middle domain

pfam07748
Location:511 → 1001

Glyco_hydro_38C; Glycosyl hydrolases family 38 C-terminal domain
XM_047438841.1 → XP_047294797.1 lysosomal alpha-mannosidase isoform X2