An official website of the United States government

MANF - mesencephalic astrocyte derived neurotrophic factor (human)

Gene
Symbol
Dates
  • Create:
    2016-09-14
  • Modify:
    2025-01-18
Description
The protein encoded by the MANF gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this protein is important in promoting the survival of dopaminergic neurons. The presence of polymorphisms in the N-terminal arginine-rich region, including a specific mutation that changes an ATG start codon to AGG, have been reported in a variety of solid tumors; however, these polymorphisms were later shown to exist in normal tissues and are thus no longer thought to be tumor-related. [provided by RefSeq, Apr 2014]
Enables sulfatide binding activity. Involved in regulation of response to endoplasmic reticulum stress. Located in endoplasmic reticulum lumen. Implicated in Parkinsonism; breast cancer; carcinoma (multiple); and pancreatic cancer.

1 Names and Identifiers

1.1 Synonyms

  • ARMET
  • ARP
  • DDDS
  • mesencephalic astrocyte-derived neurotrophic factor
  • arginine-rich, mutated in early stage tumors

1.2 Other Identifiers

1.2.1 HGNC ID

1.2.2 Ensembl ID

1.2.3 Alliance Gene ID

1.2.4 Bgee Gene ID

1.2.5 KEGG Gene

1.2.6 MIM Number

1.2.7 NCI Thesaurus Code

1.2.8 Open Targets ID

1.2.9 PharmGKB ID

1.2.10 Pharos Target

1.2.11 VEuPathDB ID

1.2.12 Wikidata

3 Proteins

3.1 Protein Function

Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PMID: 12794311). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons (By similarity). Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death (PMID: 18561914, PMID: 22637475, PMID: 29497057). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PMID: 22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PMID: 22637475). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PMID: 29497057). Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions (PMID: 29497057).

3.2 Protein 3D Structures

3.2.1 PDB Structures

3.2.2 NCBI Protein Structures

3.2.3 AlphaFold Structures

Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605

3.3 Protein Targets

4 BioAssays

4.1 RNAi BioAssays

5 Diseases and Phenotypes

5.1 KEGG Diseases

5.2 OMIM Phenotypes

5.3 MedGen Diseases

5.4 Gene-Disease Associations

6 Interactions and Pathways

6.1 Chemical-Gene Interactions

6.2 Interactions

7 Cell Lines

8 Expression

9 Target Development Level

10 Literature

10.1 Consolidated References

10.2 Gene-Chemical Co-Occurrences in Literature

10.3 Gene-Gene Co-Occurrences in Literature

10.4 Gene-Disease Co-Occurrences in Literature

11 Patents

11.1 Gene-Chemical Co-Occurrences in Patents

11.2 Gene-Gene Co-Occurrences in Patents

11.3 Gene-Disease Co-Occurrences in Patents

12 Classification

12.1 NCI Thesaurus Tree

12.2 Gene Ontology: Biological Process

12.3 Gene Ontology: Cellular Component

12.4 Gene Ontology: Molecular Function

13 Information Sources

  1. NCBI Gene
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  2. PubChem
  3. Alliance of Genome Resources
    LICENSE
    All annotations and data produced by Alliance members that are accessible from alliancegenome.org are distributed under a CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
    https://www.alliancegenome.org/privacy-warranty-licensing
  4. BioGRID
    LICENSE
    The MIT License (MIT); Copyright Mike Tyers Lab
    https://wiki.thebiogrid.org/doku.php/terms_and_conditions
  5. STRING: functional protein association networks
  6. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  7. Dependency Map (DepMap)
  8. HUGO Gene Nomenclature Committee (HGNC)
    LICENSE
    No restrictions are imposed on access to, or use of, the data provided by the HGNC, which are provided to enhance knowledge and encourage progress in the scientific community.
    https://www.genenames.org/about/
  9. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  10. NCBI Gene Expression Omnibus (GEO)
  11. NCBI MedGen
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  12. NCBI Structure
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  13. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  14. Online Mendelian Inheritance in Man (OMIM)
    LICENSE
    The OMIM database is made available to the general public subject to certain restrictions.
    https://omim.org/help/copyright
  15. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  16. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  17. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  18. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  19. Swiss Institute of Bioinformatics Bgee
    LICENSE
    Creative Commons Zero license (CC0)
    https://www.bgee.org/about/
  20. UniProt
    LICENSE
    We have chosen to apply the Creative Commons Attribution (CC BY 4.0, http://creativecommons.org/licenses/by/4.0/) License to all copyrightable parts of our databases.
    https://www.uniprot.org/help/license
  21. VEuPathDB: The Eukaryotic Pathogen, Vector and Host Informatics Resource
    LICENSE
    All data on VEuPathDB websites are provided freely for public use.
    https://veupathdb.org/veupathdb/app/static-content/about.html
  22. Wikidata
  23. Gene Ontology (GO)
    LICENSE
    Gene Ontology Consortium data and data products are licensed under the Creative Commons Attribution 4.0 Unported License (https://creativecommons.org/licenses/by/4.0/legalcode)
    http://geneontology.org/docs/go-citation-policy/
  24. AlphaFold DB
    LICENSE
    All of the data provided is freely available for both academic and commercial use under Creative Commons Attribution 4.0 (CC-BY 4.0) licence terms.
    https://alphafold.ebi.ac.uk/faq
CONTENTS