Protein lin-7 homolog C (LIN7C)
The protein contains 197 amino acids for an estimated molecular weight of 21834 Da.
Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. (updated: June 17, 2020)
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.
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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Biological Process
Asymmetric protein localization
Exocytosis
Maintenance of epithelial cell apical/basal polarity
Morphogenesis of an epithelial sheet
Neurotransmitter secretion
Neurotransmitter transport
Protein localization to basolateral plasma membrane
Protein transport
The reference OMIM entry for this protein is 612332
Lin7, c. elegans, homolog of, c; lin7c
Vertebrate lin7 homolog 3; veli3
Mammalian lin7 homolog 3; mals3
CLONING
By searching EST databases for homologs of C. elegans Lin7, Butz et al. (1998) identified murine Lin7c, which they called Veli3. The deduced 197-amino acid Veli3 protein has a C-terminal PDZ domain. By Northern blot analysis, Jo et al. (1999) found that rat Lin7c, which they called Mals3, showed highest expression in kidney, followed by brain and liver. Weak expression was detected in thymus and heart, and no expression was detected in spleen. Mals3 had an apparent molecular mass of 25 kD by Western blot analysis. By immunohistochemistry and in situ hybridization using antibodies and cRNAs specific for mouse Mals1 (LIN7A; 603380), Mals2 (LIN7B; 612331), and Mals3, Misawa et al. (2001) showed that each Mals protein localized to distinct brain regions. The Mals proteins were predominantly expressed in both neuronal cell bodies and neuropil, and they were not detected in most nonneuronal cells in brain.GENE FUNCTION
Butz et al. (1998) identified a complex of 3 proteins in rat brain that had the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. The 3 proteins were Cask (300172), a protein related to membrane-associated guanylate kinases (MAGUKs); Mint1 (APBA1; 602414), a putative vesicular trafficking protein; and the Velis. Cask, Mint1, and the Velis formed a tight, salt-resistant complex. Butz et al. (1998) determined that the N-terminal domains of Cask, Mint1, and the Velis were involved in complex formation, leaving their C-terminal PDZ domains free to recruit adhesion molecules, receptors, and channels to the complex. Butz et al. (1998) proposed that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions. Jo et al. (1999) found that rat Mals proteins immunoprecipitated with Psd95 (DLG4; 602887) and NMDA receptor-2B (GRIN2B; 138252) from solubilized rat cerebral cortex membranes. Misawa et al. (2001) found that Mals1 -/- Mals2 -/- double-knockout mice appeared normal and showed normal excitatory synaptic activity in the CA1 region of the hippocampus. Mals3 expression was upregulated in most brain regions of the double-knockout mice, suggesting that Mals3 may compensate for loss of Mals1 and Mals2 expression. Aartsen et al. (2006) found that Mpp4 -/- mouse retinas showed downregulation of Psd95 and mislocalization of both Psd95 and Veli3 at the photoreceptor presynaptic membrane. They proposed that MPP4 may function as a recruitment factor to organize signal transducers at the photoreceptor synapse. Onda et al. (2007) found that the expression of LIN7C was downregulated in oral squamous cell carcinomas (OSCC; see 275355) compared with normal oral keratinocytes. Overexpression of LIN7C in OSCC cells resulted in a noninvasive phenotype with elevated beta-catenin (CTNNB1; 116806) expression. In immunodeficient mice, tumor cells expressing LIN7C showed reduced metastases. Onda et al. (2007) concluded that LIN7C in a tumor suppressor that functions in the beta-catenin signaling pathway.MAPPING
By genomic sequence analysis, Taylor et al. (2006) mapped the LIN7C gene to chromosome 11p14.1. ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for LIN7C
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 612332 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed