Mesencephalic astrocyte-derived neurotrophic factor (MANF)

The protein contains 182 amino acids for an estimated molecular weight of 20700 Da.

 

Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PubMed: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 (PubMed:18561914, PubMed:22637475, PubMed:29497057). Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions (PubMed:22637475). Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia (PubMed:22637475). Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells (PubMed: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 (PubMed:29497057). (updated: May 23, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 89%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 601916

Arginine-rich protein mutated in early stage tumors; armet
Arginine-rich protein; arp
Mesencephalic astrocyte-derived neurotrophic factor; manf

CLONING

Shridhar et al. (1996) isolated a novel cDNA, which they designated ARP, from a gastric adenocarcinoma cDNA library. ARP encodes a deduced 234-amino acid that is arginine-rich. The ubiquitously expressed protein is highly conserved in evolution.

GENE STRUCTURE

Shridhar et al. (1996) determined that the ARP gene contains 4 exons. The nucleotide sequence at the 5-prime end of the mature transcript has an imperfect trinucleotide repeat (AGG/CGG) coding for arginine in 15 of 18 residues between amino acids 38 and 55.

MAPPING

Shridhar et al. (1996) identified the ARP gene on chromosome 3p21.1, a region that is frequently deleted in a variety of solid tumors.

MOLECULAR GENETICS

Shridhar et al. (1996, 1996) reported an ATG-to-AGG transversion in codon 50 of the ARP gene or deletion of codon 50 of the ARP gene in different tumor types including 10 of 21 sporadic renal cell carcinomas. Shridhar et al. (1997) observed the same mutations in 11 of 37 pancreatic tumors. Either of the changes abolishes a methionine residue and gives rise to an uninterrupted string of AGG trinucleotides in the ARP gene and arginines in its predicted protein product. The finding of 4 other nucleotide substitutions in codon 50 that replaced methionine with 4 different amino acids other than arginine suggested that loss of this methionine residue is critical to a carcinogenic role of this gene. Their finding of an AGG-to-AAG (arg-to-lys) mutation in the adjacent codon 51 in 2 tumors emphasized further the importance of this region. Other evidence (Shridhar et al., 1996) suggested that only a single copy of the ARP gene is mutated in the cancer cells, indicating its possible causal role as an oncogene. ... More on the omim web site

Subscribe to this protein entry history

May 26, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601916 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed