Tropomyosin alpha-1 chain (TPM1)
The protein contains 284 amino acids for an estimated molecular weight of 32709 Da.
Binds to actin filaments in muscle and non-muscle cells (PubMed:23170982). Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction (PubMed:23170982). Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. (updated: Jan. 31, 2018)
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.
- 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.
Biological Process
Actin filament organization
Cardiac muscle contraction
Cellular response to reactive oxygen species
Cytoskeleton organization
In utero embryonic development
Movement of cell or subcellular component
Muscle contraction
Muscle filament sliding
Negative regulation of cell migration
Negative regulation of vascular associated smooth muscle cell migration
Negative regulation of vascular associated smooth muscle cell proliferation
Positive regulation of ATPase activity
Positive regulation of cell adhesion
Positive regulation of heart rate by epinephrine
Positive regulation of stress fiber assembly
Regulation of cell shape
Regulation of heart contraction
Regulation of muscle contraction
Ruffle organization
Sarcomere organization
Ventricular cardiac muscle tissue morphogenesis
Wound healing
The reference OMIM entry for this protein is 115196
Cardiomyopathy, familial hypertrophic, 3; cmh3
A number sign (#) is used with this entry because of evidence that the form of familial hypertrophic cardiomyopathy linked to 15q2 is caused by mutation in the alpha-tropomyosin gene (TPM1; 191010). For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600).
MAPPING
By linkage analysis, Thierfelder et al. (1993) identified a form of familial hypertrophic cardiomyopathy that maps to 15q2. This was designated CMH3, CMH1 (192600) being the locus on chromosome 14 and CMH2 (115195) being the locus on chromosome 1. At least one more form of familial CMH is thought to exist because there are families that do not show linkage to any of these 3 locations. Although the gene for cardiac actin (ACTC; 102540) maps to 15q, it was excluded as a candidate gene on the basis of recombination with the CMH3 clinical phenotype (Thierfelder et al., 1993). Schleef et al. (1993) mapped the murine alpha-tropomyosin (TPM1; 191010) gene to a region that is syntenic to human chromosome 15. Because alpha-tropomyosin is an important component of muscle thin filaments, it became a candidate gene for CMH3.MOLECULAR GENETICS
In affected members of 2 families with hypertrophic cardiomyopathy mapping to the CMH3 locus on chromosome 15q2, Thierfelder et al. (1994) screened the candidate gene TPM1 and identified heterozygosity for 2 missense mutations, E180G (191010.0001) and D175N (191010.0002), respectively. Watkins et al. (1995) concluded that mutations in the TPM1 gene are a rare cause of CMH, accounting for approximately 3% of cases. These mutations, like those in the cardiac troponin T gene (TNNT2; 191045) that cause CMH2 (115195), are characterized by relatively mild and sometimes subclinical hypertrophy but a high incidence of sudden death. Genetic testing may therefore be especially important in this group. In a large Spanish American family with multiple members affected with hypertrophic cardiomyopathy, Karibe et al. (2001) identified a heterozygous missense mutation in the TPM1 gene (V95A; 191010.0003) that segregated with disease. The authors noted that this mutation was associated with the same mild degree of left ventricular hypertrophy as seen in some CMH1 families harboring specific mutations in MYH7 (160760.0010, 160760.0012, 160760.0001). Penetrance was estimated at 53% on the basis of an abnormal echocardiogram; however, 2 mutation carriers with normal echocardiograms and normal ECGs were only in their mid-thirties at the time of the study. Penetrance could not be accurately assessed by ECG, since 6 older mutation-negative family members had minor T-wave changes. Cumulative survival rates in this family were 73% +/- 10% at 40 years and 32% +/- 13% at 60 years. In a 36-year-old woman of Italian extraction with cardiomyopathy, in whom a transthoracic echocardiogram was consistent with a restrictive phenotype (RCM), Caleshu et al. (2011) sequenced the exons and exon-intron boundaries of 8 known cardiomyopathy-associated genes and identified homozygosity for a missense mutation (N279H) in the TPM1 gene. The patient's cardiac catheterization pattern was consistent with a restrictive phenotype, although the dip-plateau ('square-root sign') was absent. Her first-cousin parents were each heterozygous for the mutation. Her affected 75-year-old father had been diagnosed with hypertrophic cardiomyopathy at 42 years of age, and had a history of heart failure but was current ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 115196 was added.