MANF explained

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.^{[1] [2]}

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.^[2]

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.^[3]

Further reading

• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Gevaert K, Goethals M, Martens L . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. . Nat. Biotechnol. . 21 . 5 . 566–9 . 2004 . 12665801 . 10.1038/nbt810 . 23783563 . etal.
• Lai MC, Kuo HW, Chang WC, Tarn WY . A novel splicing regulator shares a nuclear import pathway with SR proteins. . EMBO J. . 22 . 6 . 1359–69 . 2003 . 12628928 . 10.1093/emboj/cdg126 . 151058 .
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Tanaka H, Shimada Y, Harada H . Polymorphic variation of the ARP gene on 3p21 in Japanese esophageal cancer patients. . Oncol. Rep. . 7 . 3 . 591–3 . 2000 . 10767373 . 10.3892/or.7.3.591. etal.
• Shridhar V, Rivard S, Wang X . Mutations in the arginine-rich protein gene (ARP) in pancreatic cancer. . Oncogene . 14 . 18 . 2213–6 . 1997 . 9174057 . 10.1038/sj.onc.1201054 . etal. 21313298 .
• Shridhar R, Shridhar V, Rivard S . 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 . 1997 . 8971156 . etal.
• Shridhar V, Rivard S, Shridhar R . 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 . 1996 . 8649854 . etal.

Notes and References

1. Petrova P, Raibekas A, Pevsner J, Vigo N, Anafi M, Moore MK, Peaire AE, Shridhar V, Smith DI, Kelly J, Durocher Y, Commissiong JW . MANF: a new mesencephalic, astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons . J Mol Neurosci . 20 . 2 . 173–88 . Jun 2003 . 12794311 . 10.1385/JMN:20:2:173 . 218459504 .
2. Web site: Entrez Gene: ARMET arginine-rich, mutated in early stage tumors.
3. 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 . MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α. . Cell Reports . 28 February 2023 . 42 . 2 . 112066 . 10.1016/j.celrep.2023.112066 . 36739529. free .