Methylthioribose-1-phosphate isomerase (MRI1)

The protein contains 369 amino acids for an estimated molecular weight of 39150 Da.

 

Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P). Independently from catalytic activity, promotes cell invasion in response to constitutive RhoA activation by promoting FAK tyrosine phosphorylation and stress fiber turnover. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  2. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  3. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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.

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

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs35098252
dbSNP:rs10402855

The reference OMIM entry for this protein is 615105

Methylthioribose-1-phosphate isomerase, s. cerevisiae, homolog of; mri1
Mediator of rhoa-dependent invasion; mrdi

DESCRIPTION

MRI1 functions both as an isomerase in the methionine salvage pathway and as a downstream target of RHOA (165390) that is required for cell migration (Kabuyama et al., 2009).

CLONING

By mass spectrometric analysis and peptide sequencing of proteins downregulated by a constitutively active RHOA mutant in metastatic melanoma cell lines, Kabuyama et al. (2009) identified MRI1, which they called MRDI. The deduced 369-amino acid protein shares significant similarity with a yeast isomerase that functions in the methionine salvage pathway. Immunofluorescence analysis revealed localization of MRD1 at cell protrusions and leading edge membranes in cultured human melanoma cells and transfected RPE cells. Western blot analysis detected 3 MRDI proteins, all of which showed an apparent molecular mass of 40 kD but different isoelectric points.

GENE FUNCTION

Kabuyama et al. (2009) found that RHOA induced expression of MRDI and that MRDI expression was elevated in metastatic melanoma cell lines. Knockdown of MRDI via RNA interference reduced cell migration in 3-dimensional gels, RHOA-dependent FAK (PTK2; 600758) autophosphorylation, and stress fiber turnover. MDRI also isomerized 5-methylribose 1-phosphate into 5-methylribulose 1-phosphate. Mutation of the critical catalytic residues cys168 and asp248 inhibited the isomerase activity of MRDI, but it did not alter the role of MRDI in RHOA signaling and cell invasion.

MAPPING

Hartz (2013) mapped the MRI1 gene to chromosome 19p13.2 based on an alignment of the MRI1 sequence (GenBank GENBANK GRCh37) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 615105 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).