Tropomodulin-1 (TMOD1)
The protein contains 359 amino acids for an estimated molecular weight of 40569 Da.
Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton. May play an important role in regulating the organization of actin filaments by preferentially binding to a specific tropomyosin isoform at its N-terminus. (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.
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Biological Process
Actin filament organization
Adult locomotory behavior
Lens fiber cell development
Muscle contraction
Muscle filament sliding
Myofibril assembly
Pointed-end actin filament capping
The reference OMIM entry for this protein is 190930
Tropomodulin; tmod
E-tropomodulin; etmod
CLONING
Sung et al. (1991, 1992) cloned the tropomodulin gene from human reticulocyte and fetal liver cDNA libraries. By Northern blot analysis, Sung et al. (1996) showed that the TMOD gene is expressed in major human tissues at different levels in the following order: heart and skeletal muscle much greater than in brain, lung, and pancreas, which is greater than in placenta, liver, and kidney. They pointed to structural similarities between tropomodulin and the 64-kD autoantigen in Graves disease (139080) and suggested that the 2 genes evolved from a common ancestral gene. Chu et al. (2000) noted that erythrocyte TMOD is a 359-amino acid globular protein. By RNA dot blot analysis, Conley et al. (2001) confirmed expression of ETMOD in almost every tissue tested, with highest abundance in fetal and adult heart and skeletal muscle.GENE FUNCTION
Human erythrocyte tropomodulin is a 43-kD tropomyosin-regulating protein (Gilligan and Bennett, 1993). It may modulate the association of tropomyosin with the spectrin-actin complex in the erythrocyte membrane skeleton, and thus the viscoelastic properties of erythrocytes. Tropomodulin is associated with the pointed end of the actin filaments (Fowler et al., 1993). Sung et al. (1996) stated that it binds specifically to the N terminus of tropomyosin and blocks the elongation and depolarization of tropomyosin-coated actin filaments. Conley (2001) found that both Tmod and Smlmod (LMOD1; 602715) cofractionated with tropomyosin in the Triton-insoluble cytoskeleton fraction of rabbit stomach smooth muscle, and both were solubilized by high salt. Immunofluorescent localization found Smlmod present along the length of actin filaments of rat intestinal smooth muscle, while Tmod stained in a punctate pattern distinct from that of actin filaments or the dense body marker, alpha-actinin (see 102575). Hypercontraction of rat intestinal smooth muscle with 10 mM Ca(2+) caused both Smlmod and Tmod to associate near alpha-actinin at the periphery of actin-rich contraction bands.GENE STRUCTURE
Using PCR methods to obtain TMOD genomic clones, Chu et al. (2000) determined that the TMOD gene contains 9 exons. Chu et al. (2000) suggested that the use of alternative promoters may account for tissue-specific expression and regulation.BIOCHEMICAL FEATURES
- Crystal Structure Rao et al. (2014) described the crystal structures of actin complexes with the unstructured amino-terminal and the leucine-rich repeat carboxy-terminal domains of TMOD. The structures and biochemical analysis of structure-inspired mutants showed that 1 TMOD molecule interacts with 3 actin subunits at the pointed end, while also contacting 2 tropomyosin (see TPM1, 191010) molecules on each side of the filament. Rao et al. (2014) found that TMOD achieves high-affinity binding through several discrete low-affinity interactions, which suggested a mechanism for controlled subunit exchange at the pointed end.MAPPING
Sung et al. (1991) mapped the TMOD gene to 9q22.2-q22.3 by in situ hybridization. By interspecific backcross linkage analysis, Pilz et al. (1995) mapped the Tmod gene to mouse chromosome 4, and White et al. (1995) used recombinant inbred strains to map the gene to a region within 1.0 cM of Mup1 (major urinary protein-1) on chromosome 4. Lench et al. (1996) created an EST- and STS-based YAC contig map of 9q22.3 and showed that it contains the following genes in this order (from centromere ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 190930 was added.