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 MANFhousekeeping 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]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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. PMID12794311. S2CID218459504.
^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. PMID36739529.
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. PMID12665801. S2CID23783563.
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. PMID10767373.
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. PMID9174057. S2CID21313298.
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. PMID8971156.
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. PMID8649854.
