Alternative titles; symbols
HGNC Approved Gene Symbol: LIMS1
Cytogenetic location: 2q12.3 Genomic coordinates (GRCh38): 2:108,533,671-108,687,246 (from NCBI)
Rearden (1994) immunoscreened a human fetal liver expression library with an autoantibody from aged human red blood cells. Several of the clones obtained encoded a novel protein containing 5 LIM domains. The full-length LIMS1 cDNA sequence, assembled from RACE-PCR fragments, encodes a 325-amino acid polypeptide. Northern blotting revealed that the gene is expressed as a 4.6-kb mRNA in a variety of human tissues.
Fukuda et al. (2003) found that PINCH1 and integrin-linked kinase (ILK; 602366) are essential for prompt HeLa cell spreading and motility following passage, and that they are crucial for cell survival. While ILK depletion reduced AKT (see 164730) phosphorylation on ser473, PINCH1 depletion reduced AKT phosphorylation on both ser473 and thr308. PINCH1 also regulated ILK protein levels. Fukuda et al. (2003) concluded that PINCH1 is an obligate partner of ILK and both are indispensable for proper control of cell shape change, motility, and survival.
Bock-Marquette et al. (2004) demonstrated that the G-actin sequestering peptide thymosin beta-4 (300159) promoted myocardial and endothelial cell migration in the embryonic heart and retained this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin beta-4. Thymosin beta-4 formed a functional complex with PINCH1 and ILK, resulting in activation of the survival kinase AKT, also known as protein kinase B (164730). After coronary artery ligation in mice, thymosin beta-4 treatment resulted in upregulation of Ilk and Akt activity in the heart, enhanced early myocyte survival, and improved cardiac function. Bock-Marquette et al. (2004) concluded that thymosin beta-4 promotes cardiomyocyte migration, survival, and repair.
Chen et al. (2008) showed that several human cancer cell lines required PINCH1 for protection from apoptosis. PINCH1 mediated this protection by suppressing proapoptotic BIM (BCL2L11; 603827) both transcriptionally and posttranscriptionally. Depletion of PINCH1 from a fibrosarcoma cell line led to upregulation of BIM and translocation of BIM to mitochondria, resulting in activation of the intrinsic apoptosis pathway. PINCH1 downregulated BIM levels posttranscriptionally by promoting activating phosphorylation of SRC family kinases (see SRC; 190090) and ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948), leading to phosphorylation of BIM at ser69, a signal for BIM turnover.
The International Radiation Hybrid Mapping Consortium mapped the LIMS1 gene to chromosome 2 (WI-9344).
Steers et al. (2019) stated that the LIMS1 gene maps to chromosome 2q12.3.
In a 2-stage genetic association study of kidney allograft rejection, Steers et al. (2019) identified association with an intronic SNP in the LIMS1 gene, rs893403. They authors defined genomic collision as a specific donor-recipient genotype combination in which a recipient who was homozygous for a gene-intersecting deletion received a transplant from a nonhomozygous donor. In the discovery cohort, which included 705 recipients, Steers et al. (2019) found a significant association with allograft rejection at the LIMS1 locus represented by rs893403 (hazard ratio with the risk genotype vs nonrisk genotypes, 1.84; 95% confidence interval (CI) 1.35-2.50; p = 9.8 x 10(-5)). This effect was replicated under the genomic-collision model in 3 independent cohorts involving a total of 2,004 donor-recipient pairs (hazard ratio, 1.55; 95% CI 1.25-1.93; p = 6.5 x 10(-5)). In the combined analysis (discovery cohort plus replication cohorts), the risk genotype was associated with a higher risk of rejection than the nonrisk genotype (hazard ratio, 1.63; 95% CI 1.37-1.95; p = 4.7 x 10(-8)). In addition, Steers et al. (2019) identified a specific antibody response against LIMS1, a kidney-expressed protein encoded within the collision locus. The response involved predominantly IgG2 and IgG3 antibody subclasses.
Bock-Marquette, I., Saxena, A., White, M. D., DiMaio, J. M., Srivastava, D. Thymosin beta-4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 432: 466-472, 2004. [PubMed: 15565145] [Full Text: https://doi.org/10.1038/nature03000]
Chen, K., Tu, Y., Zhang, Z., Blair, H. C., Zhang, L., Wu, C. PINCH-1 regulates the ERK-Bim pathway and contributes to apoptosis resistance in cancer cells. J. Biol. Chem. 283: 2508-2517, 2008. [PubMed: 18063582] [Full Text: https://doi.org/10.1074/jbc.M707307200]
Fukuda, T., Chen, K., Shi, X., Wu, C. PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. J. Biol. Chem. 278: 51324-51333, 2003. [PubMed: 14551191] [Full Text: https://doi.org/10.1074/jbc.M309122200]
Rearden, A. A new LIM protein containing an autoepitope homologous to 'senescent cell antigen'. Biochem. Biophys. Res. Commun. 201: 1124-1131, 1994. Note: Erratum: Biochem. Biophys. Res. Commun. 282: 1074 only, 2001. [PubMed: 7517666] [Full Text: https://doi.org/10.1006/bbrc.1994.1822]
Steers, N. J., Li, Y., Drace, Z., D'Addario, J. A., Fischman, C., Liu, L., Xu, K., Na, Y.-J., Neugut, Y. D., Zhang, J. Y., Sterken, R., Balderes, O., Bradbury, D., and 32 others. Genomic mismatch at LIMS1 locus and kidney allograft rejection. New Eng. J. Med. 380: 1918-1928, 2019. [PubMed: 31091373] [Full Text: https://doi.org/10.1056/NEJMoa1803731]