Details for: MANEA

Gene ID: 79694

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: MANEA

Ensembl ID: ENSG00000172469

Description: mannosidase endo-alpha

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • plasma cell CL0000786
    CSI 4.69
    rCSI 6.15%
    PRS 96.22
  • pancreatic D cell CL0000173
    CSI 4.16
    rCSI 4.09%
    PRS 94.92
  • plasmablast CL0000980
    CSI 2.99
    rCSI 2.35%
    PRS 95.16
  • neural crest cell CL0011012
    CSI 2.98
    rCSI 2.35%
    PRS 89.1
  • renal alpha-intercalated cell CL0005011
    CSI 2.84
    rCSI 3.79%
    PRS 95.96
  • IgA plasma cell CL0000987
    CSI 2.78
    rCSI 2.85%
    PRS 94.39
  • stem cell CL0000034
    CSI 2.72
    rCSI 2.63%
    PRS 91.33
  • vascular leptomeningeal cell CL4023051
    CSI 2.57
    rCSI 4.51%
    PRS 91.85
  • fibroblast of lung CL0002553
    CSI 2.57
    rCSI 2.39%
    PRS 95.13
  • cerebral cortex endothelial cell CL1001602
    CSI 2.54
    rCSI 4.4%
    PRS 90.34
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.28
    rCSI 2.64%
    PRS 87.8
  • hepatocyte CL0000182
    CSI 2.16
    rCSI 3.86%
    PRS 92.4
  • periportal region hepatocyte CL0019026
    CSI 2.1
    rCSI 8.15%
    PRS 90.82
  • IgG plasma cell CL0000985
    CSI 1.98
    rCSI 2.37%
    PRS 95.95
  • lung pericyte CL0009089
    CSI 1.6
    rCSI 4.21%
    PRS 96.64
  • type B pancreatic cell CL0000169
    CSI 1.37
    rCSI 3.04%
    PRS 93.92
  • antibody secreting cell CL0000946
    CSI 0.99
    rCSI 4.38%
    PRS 99.08
  • podocyte CL0000653
    CSI 0.87
    rCSI 3.86%
    PRS 94.07
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.65
    rCSI 2.02%
    PRS 87.32

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [MANEA](/details-gene/79694) (mannosidase endo-alpha) is a protein-coding gene located on chromosome 6q16.1 that encodes the enzyme glycoprotein endo-alpha-1,2-mannosidase. This enzyme is a type II membrane protein primarily localized to the [Golgi apparatus](/details-cell/GO:0005794) ([Link](https://doi.org/10.1016/j.biochi.2004.11.004), [Link](https://doi.org/10.1093/glycob/cwi045)). Its principal function involves the trimming of N-linked glycans on newly synthesized glycoproteins, a critical step in protein maturation and quality control. Consistent with this role in post-translational modification, [MANEA](/details-gene/79694) shows high significance in professional secretory cells, such as [plasma cell](/details-cell/CL0000786)s and [pancreatic D cell](/details-cell/CL0000173), highlighting its importance in processes requiring high-volume protein processing and secretion. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [MANEA](/details-gene/79694) underscores its essential role in cells with a high capacity for protein synthesis and modification. The gene's highest significance is observed in terminally differentiated antibody-secreting cells, including [plasma cell](/details-cell/CL0000786) (CSI: 4.69), [plasmablast](/details-cell/CL0000980) (CSI: 2.99), [IgA plasma cell](/details-cell/CL0000987) (CSI: 2.78), and [IgG plasma cell](/details-cell/CL0000985) (CSI: 1.98). This suggests a crucial function in the maturation and glycosylation of immunoglobulins, a process known to influence antibody stability and effector function. Beyond the immune system, [MANEA](/details-gene/79694) is also a significant marker in other highly secretory or metabolically active cell types. Its high significance in [pancreatic D cell](/details-cell/CL0000173) (CSI: 4.16), which secretes somatostatin, and [hepatocyte](/details-cell/CL0000182)s (CSI: 2.16), which are central to the production of serum proteins, further supports its role in the general machinery of protein processing. The gene's expression in diverse cell types, including [neural crest cell](/details-cell/CL0011012) (CSI: 2.98), [fibroblast of lung](/details-cell/CL0002553) (CSI: 2.57), and [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 2.54), indicates its broad importance in maintaining the integrity of the secretory pathway across various tissues. ## Pathways and Molecular Function The function of [MANEA](/details-gene/79694) is primarily centered on N-glycan processing. Gene Ontology annotations confirm its role in [alpha-mannosidase activity](/details-cell/GO:0004559) and, more specifically, [glycoprotein endo-alpha-1,2-mannosidase activity](/details-cell/GO:0004569). Its localization is specified to the [Golgi apparatus](/details-cell/GO:0005794) and the [Golgi membrane](/details-cell/GO:0000139). This function is further contextualized by its involvement in key Reactome pathways. [MANEA](/details-gene/79694) is a component of the [Asparagine n-linked glycosylation](/details-pathway/R-HSA-446203) pathway, which is fundamental to [Post-translational protein modification](/details-pathway/R-HSA-597592). Specifically, it participates in [N-glycan trimming and elongation in the cis-golgi](/details-pathway/R-HSA-964739), an early and critical step in the maturation of glycoproteins following their transport from the endoplasmic reticulum. This enzymatic activity is integral to the broader process of [Metabolism of proteins](/details-pathway/R-HSA-392499) and is essential for producing correctly folded and functional proteins for secretion or cellular use. ## Research Directions The specific role of [MANEA](/details-gene/79694) in the context of cellular physiology and disease, particularly in cells with high secretory burdens, presents several avenues for future investigation. **Testable Hypotheses:** 1. Given its high significance in [plasma cell](/details-cell/CL0000786)s, dysregulation of [MANEA](/details-gene/79694) may alter the glycosylation patterns of secreted immunoglobulins, thereby impacting their half-life, antigen binding, or Fc-mediated effector functions in autoimmune diseases or multiple myeloma. 2. In [pancreatic D cell](/details-cell/CL0000173)s, a deficiency in [MANEA](/details-gene/79694) could impair the processing and secretion of somatostatin, potentially contributing to the dysregulation of insulin and glucagon release and impacting glucose homeostasis. **Proposed Experiment:** To test the first hypothesis, one could utilize a CRISPR-Cas9 system to knock out [MANEA](/details-gene/79694) in a human myeloma cell line that secretes a monoclonal antibody. The secreted antibodies from knockout and wild-type cells would be purified and their N-glycan profiles analyzed using mass spectrometry. Functional consequences could be assessed via in vitro assays measuring binding affinity to Fc gamma receptors (using surface plasmon resonance) and complement-dependent cytotoxicity (CDC) assays. **Therapeutic Potential:** As an intracellular enzyme located in the Golgi, [MANEA](/details-gene/79694) is a challenging target for traditional antibody-based therapies but may be amenable to small molecule inhibitors. In diseases characterized by aberrant protein glycosylation, such as certain cancers or congenital disorders of glycosylation, modulating [MANEA](/details-gene/79694) activity could be a potential therapeutic strategy. For instance, in cancers that rely on specific glycan structures for metastasis or immune evasion, inhibition of [MANEA](/details-gene/79694) could represent a novel approach to disrupt these pathological processes. However, because of its fundamental role in protein processing in many cell types, systemic inhibition could carry a high risk of toxicity, suggesting that targeted delivery systems or highly specific therapeutic contexts would be required.

Genular Protein ID: 962303915

Symbol: MANEA_HUMAN

Name: Glycoprotein endo-alpha-1,2-mannosidase

UniProtKB Accession Codes:

Q5SRI9 A6H8M6 Q5SRJ0 Q6MZV0 Q70JE9 Q7Z3V7 Q8WWX5 Q9H9D2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 12 Ensembl 3 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 9 PDBsum 9 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15760709

Title: Human endo-alpha1,2-mannosidase is a Golgi-resident type II membrane protein.

PubMed ID: 15760709

DOI: 10.1016/j.biochi.2004.11.004

PubMed ID: 15677381

Title: Intact alpha-1,2-endomannosidase is a typical type II membrane protein.

PubMed ID: 15677381

DOI: 10.1093/glycob/cwi045

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 462
  • Mass: 53671
  • Checksum: CB593CB9B3DAA056
  • Sequence:
    • MAKFRRRTCI ILALFILFIF SLMMGLKMLR PNTATFGAPF GLDLLPELHQ RTIHLGKNFD 
FQKSDRINSE TNTKNLKSVE ITMKPSKASE LNLDELPPLN NYLHVFYYSW YGNPQFDGKY 
IHWNHPVLEH WDPRIAKNYP QGRHNPPDDI GSSFYPELGS YSSRDPSVIE THMRQMRSAS 
IGVLALSWYP PDVNDENGEP TDNLVPTILD KAHKYNLKVT FHIEPYSNRD DQNMYKNVKY 
IIDKYGNHPA FYRYKTKTGN ALPMFYVYDS YITKPEKWAN LLTTSGSRSI RNSPYDGLFI 
ALLVEEKHKY DILQSGFDGI YTYFATNGFT YGSSHQNWAS LKLFCDKYNL IFIPSVGPGY 
IDTSIRPWNT QNTRNRINGK YYEIGLSAAL QTRPSLISIT SFNEWHEGTQ IEKAVPKRTS 
NTVYLDYRPH KPGLYLELTR KWSEKYSKER ATYALDRQLP VS