| Structural highlights
Function
[E41L3_HUMAN] Critical growth regulator in the pathogenesis of meningiomas. [CADM1_HUMAN] Mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Also mediates heterophilic cell-cell adhesion with CADM3 and PVRL3 in a Ca(2+)-independent manner. Acts as a tumor suppressor in non-small-cell lung cancer (NSCLC) cells. Interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM3 in vivo. May contribute to the less invasive phenotypes of lepidic growth tumor cells. In mast cells, may mediate attachment to and promote communication with nerves. CADM1, together with MITF, is essential for development and survival of mast cells in vivo. May act as a synaptic cell adhesion molecule that drives synapse assembly. May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons. May play diverse roles in the spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa.[1] [2] [3] [4] [5] [6] [UniProtKB:Q8R5M8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Perturbed cell-adhesion mechanisms are crucial for tumor invasion and metastasis. A cell-adhesion protein, Tumor Suppressor in Lung Cancer 1 (TSLC1), is inactivated in a majority of metastatic cancers. DAL-1 (differentially expressed in adenocarcinoma of the lung protein), another tumor suppressor, binds through its FERM domain to the TSLC1 C-terminal, 4.1 glycophorin C-like, cytoplasmic domain. However, the molecular basis for this interaction is unknown. Here, we describe the crystal structure of a complex between the DAL-1 FERM domain and a portion of the TSLC1 cytoplasmic domain. DAL-1 binds to TSLC1 through conserved residues in a well-defined hydrophobic pocket in the DAL-1 FERM domain's structural C-lobe. From the crystal structure, it is apparent that Tyr406 and Thr408 in the TSLC1 cytoplasmic domain form the most important interactions with DAL-1 and this was also confirmed by surface plasmon resonance studies. Our results refute earlier exon deletion experiments that indicated that glycophorin-C interacts with the alpha-lobe of 4.1 FERM domains.
Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding to differentially expressed in adenocarcinoma of the lung (DAL-1/4.1B).,Busam RD, Thorsell AG, Flores A, Hammarstrom M, Persson C, Obrink B, Hallberg BM J Biol Chem. 2010 Dec 3. PMID:21131357[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kuramochi M, Fukuhara H, Nobukuni T, Kanbe T, Maruyama T, Ghosh HP, Pletcher M, Isomura M, Onizuka M, Kitamura T, Sekiya T, Reeves RH, Murakami Y. TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer. Nat Genet. 2001 Apr;27(4):427-30. PMID:11279526 doi:10.1038/86934
- ↑ Yageta M, Kuramochi M, Masuda M, Fukami T, Fukuhara H, Maruyama T, Shibuya M, Murakami Y. Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer. Cancer Res. 2002 Sep 15;62(18):5129-33. PMID:12234973
- ↑ Masuda M, Yageta M, Fukuhara H, Kuramochi M, Maruyama T, Nomoto A, Murakami Y. The tumor suppressor protein TSLC1 is involved in cell-cell adhesion. J Biol Chem. 2002 Aug 23;277(34):31014-9. Epub 2002 Jun 5. PMID:12050160 doi:10.1074/jbc.M203620200
- ↑ Ito A, Okada M, Uchino K, Wakayama T, Koma Y, Iseki S, Tsubota N, Okita Y, Kitamura Y. Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioloalveolar carcinoma. Lab Invest. 2003 Aug;83(8):1175-83. PMID:12920246
- ↑ Boles KS, Barchet W, Diacovo T, Cella M, Colonna M. The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood. 2005 Aug 1;106(3):779-86. Epub 2005 Apr 5. PMID:15811952 doi:10.1182/blood-2005-02-0817
- ↑ Furuno T, Ito A, Koma Y, Watabe K, Yokozaki H, Bienenstock J, Nakanishi M, Kitamura Y. The spermatogenic Ig superfamily/synaptic cell adhesion molecule mast-cell adhesion molecule promotes interaction with nerves. J Immunol. 2005 Jun 1;174(11):6934-42. PMID:15905536
- ↑ Busam RD, Thorsell AG, Flores A, Hammarstrom M, Persson C, Obrink B, Hallberg BM. Structural basis of tumor suppressor in lung cancer 1 (TSLC1) binding to differentially expressed in adenocarcinoma of the lung (DAL-1/4.1B). J Biol Chem. 2010 Dec 3. PMID:21131357 doi:10.1074/jbc.M110.174011
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