MANF

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]

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
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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]