Fermitin family homolog 3 (FERMT3)
The protein contains 667 amino acids for an estimated molecular weight of 75953 Da.
Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity).', 'Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. (updated: Nov. 22, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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Biological Process
Cell-matrix adhesion
Integrin activation
Integrin-mediated signaling pathway
Leukocyte cell-cell adhesion
Platelet aggregation
Platelet degranulation
Positive regulation of cell migration
Regulation of cell-cell adhesion mediated by integrin
Substrate adhesion-dependent cell spreading
The reference OMIM entry for this protein is 607901
Fermitin family (drosophila) homolog 3; fermt3
Unc112-related protein 2; urp2
Kindlin 3; kind3
Mig2b
DESCRIPTION
The FERMT3 gene encodes a protein involved in integrin activation; it is specifically expressed in hematopoietic cells (Moser et al., 2008). See also FERMT1 (607900), which is specific to epithelial cells, and FERMT2 (607746), which has more widespread expression.CLONING
Using microarray analysis of genes showing altered expression in several tumor tissues, followed by PCR of brain cDNA, Weinstein et al. (2003) cloned a full-length URP2 cDNA, encoding a protein with significant homology to the C. elegans protein Unc112. The deduced 663-amino acid protein has a calculated molecular mass of about 75.4 kD. They also cloned a variant that contains a 12-bp insertion from a leukocyte cDNA library. This variant encodes a 667-amino acid protein with a calculated molecular mass of almost 76 kD. In its C-terminal half, URP2 contains 2 FERM domains flanking a pleckstrin homology domain. URP2 shares 55.4% identity with MIG2 (607746) and 58.7% identity with URP1 (607900). All 3 proteins share weak but significant homology with talin-1 (186745) and talin-2 (607349). Northern blot analysis detected strong expression of a 2.7-kb URP2 transcript in thymus, spleen, and leukocytes, weaker expression in lung and placenta, and little to no expression in other tissues. By analyzing membrane proteins expressed in chronic lymphocytic leukemia, followed by database analysis, Boyd et al. (2003) identified MIG2B cDNAs. Quantitative RT-PCR showed hemopoietic tissue-specific MIG2B expression and increased MIG2B expression in B-cell malignancies. By SDS-PAGE, the apparent molecular mass of MIG2B was 60 kD.GENE STRUCTURE
Weinstein et al. (2003) determined that the URP2 gene contains 15 exons, spans about 20 kb, and is oriented in the telomere-to-centromere direction. The URP2 splice variant utilizes an alternative exon 10 acceptor site.MAPPING
By genomic sequence analysis, Weinstein et al. (2003) mapped the URP2 gene to chromosome 11q12.GENE FUNCTION
Using immunoblot analysis, Manevich-Mendelson et al. (2009) showed that KIND3-negative patients with leukocyte adhesion deficiency-3 (LAD3; 612840) who also lacked expression of CDGI (RAPGEF1; 600303) in resting T cells (seeMOLECULAR GENETICS
) acquired CDGI expression after T-cell activation. Inside-out (i.e., chemokine-mediated) activation with CXCL12 (600835) of normal and KIND3-negative cells resulted in normal CXCR4 (162643) expression but defective conformational activation of LFA1 (see ITGB2; 600065) and diminished transient and firm adhesiveness during a range of contact periods. In contrast, the intrinsic adhesiveness of VLA4 (see ITGA4; 192975) was largely conserved in KIND3-negative cells. Manevich-Mendelson et al. (2009) concluded that KIND3 is more critical to LFA1 than to VLA4 adhesiveness in human lymphocytes.MOLECULAR GENETICS
Integrins, the major adhesion receptors of leukocytes and platelets, bind poorly to their ligands but become active after 'inside-out' signaling through other membrane receptors. Hematopoietically derived cells from individuals with leukocyte adhesion deficiency-3 (LAD3; 612840) express beta-1 (ITGB1; 135630), beta-2 (ITGB2; 600065), and beta-3 (ITGB3; 173470) integrins, but defective inside-out signaling results in LAD1 (116920)-like immune deficiency and Glanzmann thrombasthenia (GT; 273800)-like bleeding problems. Svensson et al. (2009) noted that Pasvolsky et al. (2007) reported a C-to- ... More on the omim web site
Feb. 10, 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 607901 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed