LIM and SH3 domain protein 1 (LASP1)
The protein contains 261 amino acids for an estimated molecular weight of 29717 Da.
Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types (By similarity). (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.
- 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.
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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The reference OMIM entry for this protein is 602920
Lim and sh3 protein 1; lasp1
Mln50 lasp1/mll fusion gene, included
CLONING
By differential screening of cDNAs from breast cancer-derived metastatic axillary lymph nodes, Tomasetto et al. (1995) identified TRAF4 (602464) and 3 other novel genes that are overexpressed in breast cancer. They designated one of these genes, which mapped to chromosome 17q, MLN50. In breast cancer cell lines, overexpression of the 4-kb MLN50 mRNA was correlated with amplification of the gene and with amplification and overexpression of ERBB2 (164870), which maps to the same region. The authors suggested that the 2 genes belong to the same amplicon. Amplification of chromosomal region 17q11-q21 is one of the most common events occurring in human breast cancers (Tomasetto et al., 1995). Tomasetto et al. (1995) reported that the predicted 261-amino acid MLN50 protein contains an N-terminal LIM domain and a C-terminal SH3 domain. They renamed the protein LASP1, for 'LIM and SH3 protein.' Northern blot analysis revealed that LASP1 mRNA was expressed at a basal level in all normal tissues examined and overexpressed in 8% of primary breast cancers. In most of these cancers, LASP1 and ERBB2 were simultaneously overexpressed. Schreiber et al. (1998) isolated cDNAs encoding mouse Lasp1. They determined that both human and mouse LASP1 contain an actin-binding domain.MAPPING
Tomasetto et al. (1995) mapped the LASP1 gene to chromosome 17q11-q21.3 by radioactive in situ hybridization. Using in situ hybridization, Schreiber et al. (1998) mapped the mouse Lasp1 gene to the 11C-11D region of chromosome 11.GENE FUNCTION
By yeast 2-hybrid, truncation, and pull-down analyses, Li et al. (2004) found that an N-terminal motif of zyxin (ZYX; 602002) interacted with the C-terminal SH3 domains of LIM-nebulette (605491), nebulin (NEB; 161650), and LASP1, but not with the SH3 domains of other proteins examined. Zyxin, LIM-nebulette, and LASP1 colocalized at focal adhesions in transfected HeLa and HT1080 cells. Traenka et al. (2010) stated that LASP1 is frequently overexpressed in metastatic human breast cancer and ovarian cancer. Using expression profiling, quantitative real-time PCR, and immunohistochemical analysis, they found that LASP1 mRNA and protein were overexpressed in medulloblastomas and that LASP1 overexpression correlated with chromosome 17q gain, metastatic dissemination, and unfavorable outcome. LASP1 protein expression was strong in 2 of 5 recurrent medulloblastomas in which no LASP1 expression was detected in patient-matched primary tumors. In 2 adherent medulloblastoma cell lines, LASP1 expression was associated with focal adhesion contacts, with intense colocalization with filamentous actin. In an adherent/suspension medulloblastoma cell line with isochromosome 17q and abnormal neurofilament expression, LASP1 localization with filamentous actin was less definite but present at the leading edges of cells. Knockdown of LASP1 expression in all 3 medulloblastoma cell lines reduced cell proliferation and migratory potential and enhanced cell adhesion. Differential display analysis showed that knockdown of LASP1 resulted in upregulation of genes involved in cell adhesion and downregulation of genes involved in invasion and migration.CYTOGENETICS
- LASP1/MLL Fusion Gene The MLL gene (159555), located on chromosome 11q23, is frequently rearranged in acute leukemia. Strehl et al. (2003) identified a new MLL fusion partner on chromosome 17q in the case of an infant with AML-M4 (see 601626) and a t( ... 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 602920 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed