Lck-interacting transmembrane adapter 1 (LIME1)
The protein contains 295 amino acids for an estimated molecular weight of 31288 Da.
Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. In absence of TCR signaling, may be involved in CD4-mediated inhibition of T-cell activation. Couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilization or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules. (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.
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs1151625 |
Biological Process
Adaptive immune response
B cell receptor signaling pathway
Regulation of I-kappaB kinase/NF-kappaB signaling
Regulation of MAP kinase activity
Regulation of NIK/NF-kappaB signaling
Regulation of phosphatidylinositol 3-kinase signaling
Regulation of release of sequestered calcium ion into cytosol
Regulation of transcription by RNA polymerase II
Spliceosomal complex disassembly
T cell receptor signaling pathway
The reference OMIM entry for this protein is 609809
Lck-interacting transmembrane adaptor 1; lime1
Lime
DESCRIPTION
LIME1 is a raft-associated transmembrane adaptor phosphoprotein that is preferentially expressed in hemopoietic cells, particularly T cells (Brdickova et al., 2003; Hur et al., 2003).CLONING
By searching databases for proteins with structural features characteristic of raft-targeted transmembrane adaptor proteins, Brdickova et al. (2003) identified LIME. The predicted 295-amino acid type III protein has a 4-amino acid extracellular peptide, a 23-amino acid transmembrane domain that is followed immediately by a potential palmitoylation motif (CxxC) and 2 arg residues, and a cytoplasmic domain with 5 potential tyrosine phosphorylation sites. RT-PCR analysis detected expression of LIME in liver, thymus, peripheral blood lymphocytes (PBLs), and other lymphoid tissues. Western blot analysis showed that, within PBLs, LIME was predominantly expressed in CD4 (186940) and CD8 (see 186910) T cells, and it was downmodulated after T-cell activation. Confocal microscopy, biosynthetic labeling, and Western blot analysis demonstrated membrane expression and association with lipid rafts. Using yeast 2-hybrid analysis with the SH2 and kinase domains of LCK (153390) as bait, Hur et al. (2003) cloned mouse Lime. They obtained the human sequence by database analysis. Northern blot analysis of mouse tissues revealed expression in spleen and lung, and Northern blot analysis of human tissues showed expression in spleen and PBLs. Western blot analysis detected an approximately 30-kD protein. Immunofluorescence microscopy showed that LIME localized to membrane rafts and was distributed within the immunologic synapse upon contact with antigen-presenting cells.GENE FUNCTION
Brdickova et al. (2003) found that engagement of CD4 or CD8 receptors induced tyrosine phosphorylation of LIME that was mediated by Src kinases, principally LCK or LYN (165120). They concluded that LIME is involved in the regulation of T-cell activation by coreceptors. Using Western blot analysis, Hur et al. (2003) demonstrated that LIME was involved in activation of the ERK (see 176948) and JNK (see 601158) pathways in T cells. Moreover, overexpression of LIME in T cells induced IL2 (147680) promoter activity. Hur et al. (2003) concluded that LIME is a raft-associated transmembrane adaptor protein that links T-cell receptor stimuli to downstream signaling pathways via associations with LCK.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the LIME1 gene to chromosome 20 (TMAP RH75350). ... 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 25, 2017: Additional information
No protein expression data in P. Mayeux work for LIME1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609809 was added.