Dematin (DMTN)
The protein contains 405 amino acids for an estimated molecular weight of 45514 Da.
Membrane-cytoskeleton-associated protein with F-actin-binding activity that induces F-actin bundles formation and stabilization. Its F-actin-bundling activity is reversibly regulated upon its phosphorylation by the cAMP-dependent protein kinase A (PKA). Binds to the erythrocyte membrane glucose transporter-1 SLC2A1/GLUT1, and hence stabilizes and attaches the spectrin-actin network to the erythrocytic plasma membrane. Plays a role in maintaining the functional integrity of PKA-activated erythrocyte shape and the membrane mechanical properties. Plays also a role as a modulator of actin dynamics in fibroblasts; acts as a negative regulator of the RhoA activation pathway. In platelets, functions as a regulator of internal calcium mobilization across the dense tubular system that affects platelet granule secretion pathways and aggregation. Also required for the formation of a diverse set of cell protrusions, such as filopodia and lamellipodia, necessary for platelet cell spreading, motility and migration. Acts as a tumor suppressor and inhibits malignant cell transformation. (updated: April 1, 2015)
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Actin filament bundle assembly
Actin filament capping
Actin filament reorganization
Calcium-mediated signaling using extracellular calcium source
Calcium-mediated signaling using intracellular calcium source
Cellular response to calcium ion
Cellular response to cAMP
Cytoskeleton organization
Erythrocyte development
Lamellipodium assembly
Negative regulation of cell-substrate adhesion
Negative regulation of focal adhesion assembly
Negative regulation of peptidyl-serine phosphorylation
Negative regulation of peptidyl-threonine phosphorylation
Negative regulation of peptidyl-tyrosine phosphorylation
Negative regulation of protein targeting to membrane
Negative regulation of substrate adhesion-dependent cell spreading
Positive regulation of blood coagulation
Positive regulation of fibroblast migration
Positive regulation of integrin-mediated signaling pathway
Positive regulation of platelet aggregation
Positive regulation of substrate adhesion-dependent cell spreading
Positive regulation of wound healing
Protein complex assembly
Protein secretion by platelet
Protein-containing complex assembly
Regulation of actin cytoskeleton organization
Regulation of cell shape
Regulation of filopodium assembly
Regulation of lamellipodium assembly
Transmembrane transport
Cellular Component
Actin cytoskeleton
Actin filament
Cell projection membrane
Cortical cytoskeleton
Cytoplasmic vesicle
Cytoplasmic, membrane-bounded vesicle
Cytosol
Endomembrane system
Perinuclear region of cytoplasm
Plasma membrane
Platelet dense tubular network membrane
Postsynaptic density
Spectrin-associated cytoskeleton
The reference OMIM entry for this protein is 125305
Erythrocyte membrane protein band 4.9; epb49
Dematin
DESCRIPTION
Dematin, or EPB49, is an actin-bundling protein originally identified in the erythroid membrane skeleton. Its actin-bundling activity is abolished upon phosphorylation by cAMP-dependent protein kinase and is restored after dephosphorylation (Rana et al., 1993).CLONING
Chishti et al. (1989) proposed the name dematin (from the Greek 'dema,' a bundle) for an actin-bundling protein identified in the human erythroid membrane skeleton. Rana et al. (1993) noted that dematin consists of 2 polypeptide chains of 48 and 52 kD that were identified as protein 4.9 on SDS-polyacrylamide gels. In solution, dematin exists as a trimer and bundles actin filaments in a phosphorylation-dependent manner. Rana et al. (1993) cloned dematin from a human reticulocyte cDNA library. The deduced 383-amino acid protein has a calculated molecular mass of 43 kD. Dematin has a polyglutamine motif that may constitute a nuclear localization signal, a PEST sequence, a C-terminal domain highly similar to the C-terminal headpiece domain of villin (VIL; 193040), and several putative phosphorylation sites. Northern blot analysis detected variable dematin expression in all tissues examined. Immunofluorescence microscopy revealed punctate dematin staining around the cell nucleus in cultured human erythroblasts. Although dematin is an actin-bundling protein of the erythroid membrane skeleton, it is abundantly expressed in human brain, heart, skeletal muscle, kidney, and lung. Azim et al. (1995) reported the primary structure of the 52-kD subunit of dematin, which differs from the 48-kD subunit by a 22-amino acid insertion within its headpiece domain. A unique feature of the insertion sequence of the 52-kD subunit is its homology to erythrocyte protein 4.2 (177070).GENE FUNCTION
Rana et al. (1993) confirmed that purified human dematin possessed actin-bundling activity in vitro. Protease treatment and microsequencing revealed that the C-terminal headpiece domain bound actin filaments, but it did not have actin-bundling activity. Azim et al. (1996) demonstrated that dematin and protein 4.2 bound ATP. Gilligan and Bennett (1993) provided a review.MAPPING
Using somatic cell hybrid panels and fluorescence in situ hybridization, Azim et al. (1995) localized the dematin gene to chromosome 8p21.1, a site distal to the locus of ankyrin (612641) at chromosome 8p11.2. Peters et al. (1995) demonstrated that the murine dematin gene, symbolized Epb4.9, maps to chromosome 14. They raised the possibility that dematin mutations may be involved in neurologic abnormalities in the mouse.ANIMAL MODEL
By using homologous recombination in mouse embryonic stem cells, Khanna et al. (2002) deleted the headpiece domain of dematin to evaluate its function in vivo. Dematin headpiece-null mice were viable and born at the expected mendelian ratio. Hematologic evaluation showed evidence of compensated anemia and spherocytosis in these mice, however. The headpiece-null erythrocytes were osmotically fragile, and displayed reduced deformability and filterability. In vitro, significantly greater membrane fragmentation of these erythrocytes was demonstrated. Biochemical characterization showed a weakened membrane skeleton evidenced by reduced association of spectrin and actin to the plasma membrane. Together, these results provided evidence for the physiologic significance of dematin and demonstrated a role for the headpiece domain in the mainten ... More on the omim web site
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for DMTN
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 125305 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed