Spectrin alpha chain, erythrocytic 1 (SPTA1)
The protein contains 2419 amino acids for an estimated molecular weight of 280014 Da.
Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane. (updated: March 4, 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 capping
Actin filament organization
Axon guidance
Endoplasmic reticulum to Golgi vesicle-mediated transport
Hemopoiesis
Lymphocyte homeostasis
MAPK cascade
Plasma membrane organization
Porphyrin-containing compound biosynthetic process
Positive regulation of protein binding
Positive regulation of T cell proliferation
Regulation of cell shape
The reference OMIM entry for this protein is 130600
Elliptocytosis 2; el2
Elliptocytosis, rhesus-unlinked type
A number sign (#) is used with this entry because of evidence that elliptocytosis-2 is caused by heterozygous mutation in the alpha-spectrin gene (SPTA1; 182860) on chromosome 1q23. For a general description and a discussion of genetic heterogeneity of elliptocytosis (HE), see EL1 (611804).
CLINICAL FEATURES
In some families with HE, spectrin is abnormally heat-sensitive (Lux and Wolfe, 1980). Coetzer and Zail (1981) studied spectrin in 4 cases of hereditary elliptocytosis and found an abnormality of tryptic digestion in 1. This patient was previously reported by Gomperts et al. (1973) as an instance of hemolytic anemia due to HE. Liu et al. (1982) examined erythrocytes from 18 patients with hereditary elliptocytosis. In 8 patients (referred to as type 1), spectrin was defective in dimer-dimer association as demonstrated in 2 ways. First, spectrin dimer was increased and tetramer decreased; spectrin dimer represented 15 to 33% of total spectrin compared with a normal range of 3 to 7%. Second, the equilibrium constants of spectrin dimer-dimer association was decreased in both solution and in situ in red cell membranes. In the other 10 patients (referred to as type 2), dimer-dimer association was normal. Membrane skeletons, produced from both types of elliptocytosis by Triton X-100 extraction of the red cell ghosts, were unstable when mechanically shaken. Spectrin tetramers but not dimers can crosslink actin. Evans et al. (1983) studied a family in which 3 sibs had severe transfusion-dependent, presumably homozygous elliptocytosis and both parents had asymptomatic elliptocytosis. Red cell membranes of all 3 sibs showed an excess of spectrin dimers over tetramers in spectrin extracts. Both parents showed an intermediate increase in spectrin dimers. In 7 black patients (from 5 unrelated families) with mild HE, Lecomte et al. (1985) found an abnormal thermal sensitivity and an important defect of spectrin dimer self-association. An excess of spectrin dimer and deficient dimer-to-tetramer conversion were demonstrated. Peptide patterns of crude spectrin showed a marked decrease in the 80-kD peptide (previously identified as the dimer-dimer interaction domain of the alpha chain) and a concomitant appearance of a novel 65-kD peptide. Anti-alpha-spectrin antibodies showed that the latter peptide was derived from the alpha chain. The patients were 3 unrelated adults, 2 children with hemolytic anemia, and the father of each child. Lawler et al. (1984, 1985) described a molecular defect in the alpha subunit of spectrin in a subset of patients with hereditary elliptocytosis; the self-association of alpha-beta heterodimers to form tetramers was defective. Abnormality of alpha spectrin was reported by Ravindranath and Johnson (1985) in a case of congenital hemolytic anemia. Lambert and Zail (1987) also found a variant of the alpha subunit. Two brothers with the poikilocytic variant of hereditary elliptocytosis were found to have a defect in spectrin dimer association and a decreased spectrin/band 3 ratio. The major abnormal tryptic peptides derived from the alpha-I domain had lower molecular weights and more basic isoelectric points than hitherto described. The propositus of Lambert and Zail (1987) was a black South African miner. In a 6-week-old black infant, Garbarz et al. (1986) found hemolytic anemia with red cell fragmentation, poikilocytosis, and elliptocytosis. Both parents and a brother of the propositus had compensated mild heredita ... More on the omim web siteFeb. 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 130600 was added.