MANF

MANF
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KVD, 2KVE, 2W51
Identifiers
Aliases	MANF , ARMET, ARP, arginine-rich, mutated in early-stage tumors, arginine-rich protein, mesencephalic astrocyte-derived neurotrophic factor, mesencephalic astrocyte derived neurotrophic factor
External IDs	OMIM: 601916; MGI: 1922090; HomoloGene: 4383; GeneCards: MANF; OMA:MANF - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p21.2 Start 51,385,291 bp [1] End 51,389,397 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans beta cell body of pancreas right lobe of thyroid gland left lobe of thyroid gland mucosa of transverse colon anterior pituitary left testis right testis pericardium n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function growth factor activity RNA binding lipid binding sulfatide binding Cellular component nucleus extracellular region extracellular space endoplasmic reticulum cytosol endoplasmic reticulum lumen sarcoplasmic reticulum sarcoplasmic reticulum lumen Biological process response to unfolded protein platelet degranulation neuron projection development dopaminergic neuron differentiation regulation of signaling receptor activity regulation of response to endoplasmic reticulum stress signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7873 74840 Ensembl ENSG00000145050 ENSMUSG00000032575 UniProt P55145 Q9CXI5 RefSeq (mRNA) NM_006010 NM_029103 RefSeq (protein) NP_006001 n/a Location (UCSC) Chr 3: 51.39 – 51.39 Mb n/a PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Mesencephalic astrocyte-derived neurotrophic factor (MANF), Arginine-rich, mutated in early-stage tumors (ARMET), or arginine-rich protein (ARP) is a protein that in humans is encoded by the MANF housekeeping gene. ^{[4] [5]}

This gene encodes a highly conserved protein whose function is known. The protein was initially thought to be longer at the N-terminus and to contain an arginine-rich region but transcribed evidence indicates a smaller open reading frame that does not encode the arginine tract. The presence of a specific mutation changing the previously numbered codon 50 from ATG to AGG, or deletion of that codon, has been reported in a variety of solid tumors. With the protein size correction, this codon is now identified as the initiation codon. ^[5]

MANF has cytoprotective effects in neurons and pancreatic β cells, both in vitro (cell culture) and in vivo (animal models of neurodegeneration and diabetes). Specifically, it protects dopamine neurons from endoplasmic reticulum (ER) stress-induced death. It exerts this action by binding to ERN1, the unfolded protein response (UPR) sensor in the ER, which results in the attenuation of UPR. ^[6]

References

1. GRCh38: Ensembl release 89: ENSG00000145050 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Petrova P, Raibekas A, Pevsner J, Vigo N, Anafi M, Moore MK, Peaire AE, Shridhar V, Smith DI, Kelly J, Durocher Y, Commissiong JW (Jun 2003). "MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons". J Mol Neurosci. 20 (2): 173–88. doi:10.1385/JMN:20:2:173. PMID   12794311. S2CID   218459504.
5. "Entrez Gene: ARMET arginine-rich, mutated in early stage tumors".
6. Kovaleva V, Yu LY, Ivanova L, Shpironok O, Nam J, Eesmaa A, Kumpula EP, Sakson S, Toots U, Ustav M, Huiskonen JT, Voutilainen MH, Lindholm P, Karelson M, Saarma M (28 February 2023). "MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α". Cell Reports. 42 (2): 112066. doi: 10.1016/j.celrep.2023.112066 . PMID   36739529.

External links

• Human MANF genome location and MANF gene details page in the UCSC Genome Browser .

Further reading

• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID   12665801. S2CID   23783563.
• Lai MC, Kuo HW, Chang WC, Tarn WY (2003). "A novel splicing regulator shares a nuclear import pathway with SR proteins". EMBO J. 22 (6): 1359–69. doi:10.1093/emboj/cdg126. PMC   151058 . PMID   12628928.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Tanaka H, Shimada Y, Harada H, et al. (2000). "Polymorphic variation of the ARP gene on 3p21 in Japanese esophageal cancer patients". Oncol. Rep. 7 (3): 591–3. doi:10.3892/or.7.3.591. PMID   10767373.
• Shridhar V, Rivard S, Wang X, et al. (1997). "Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer". Oncogene. 14 (18): 2213–6. doi:10.1038/sj.onc.1201054. PMID   9174057. S2CID   21313298.
• Shridhar R, Shridhar V, Rivard S, et al. (1997). "Mutations in the arginine-rich protein gene, in lung, breast, and prostate cancers, and in squamous cell carcinoma of the head and neck". Cancer Res. 56 (24): 5576–8. PMID   8971156.
• Shridhar V, Rivard S, Shridhar R, et al. (1996). "A gene from human chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein and is mutated in renal cell carcinomas". Oncogene. 12 (9): 1931–9. PMID   8649854.