Cell adhesion molecule 1

Cell adhesion molecule 1 is a protein that, in humans, is encoded by the CADM1 gene.[5][6]

CADM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3BIN, 4H5S
Identifiers
Aliases	CADM1, BL2, IGSF4, IGSF4A, NECL2, Necl-2, RA175, ST17, SYNCAM, TSLC1, sTSLC-1, sgIGSF, synCAM1, cell adhesion molecule 1
External IDs	OMIM: 605686 MGI: 1889272 HomoloGene: 8641 GeneCards: CADM1
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q23.3 Start 115,169,218 bp[1] End 115,504,957 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A5.3 Start 47,530,173 bp[2] End 47,858,115 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • PDZ domain binding • protein homodimerization activity • GO:0001948 protein binding • receptor binding • cell adhesion molecule binding Cellular component • integral component of membrane • membrane • intercellular junction • synapse • integral component of plasma membrane • cell junction • basolateral plasma membrane • cell membrane Biological process • cell differentiation • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules • activated T cell proliferation • immune system process • positive regulation of cytokine secretion • multicellular organism development • cell adhesion • spermatogenesis • adherens junction organization • T cell mediated cytotoxicity • homophilic cell adhesion via plasma membrane adhesion molecules • apoptotic process • susceptibility to natural killer cell mediated cytotoxicity • positive regulation of natural killer cell mediated cytotoxicity • detection of stimulus • cell recognition • GO:0022415 viral process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	23705	54725
Ensembl	ENSG00000182985	ENSMUSG00000032076
UniProt	Q9BY67	Q8R5M8
RefSeq (mRNA)	NM_001098517 NM_001301043 NM_001301044 NM_001301045 NM_014333	NM_001025600 NM_018770 NM_207675 NM_207676 NM_001310841
RefSeq (protein)	NP_001091987 NP_001287972 NP_001287973 NP_001287974 NP_055148	NP_001020771 NP_001297770 NP_061240 NP_997558 NP_997559
Location (UCSC)	Chr 11: 115.17 – 115.5 Mb	Chr 9: 47.53 – 47.86 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Model organisms

Cadm1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Rotarod	Normal
Non-Invasive Blood Pressure	Normal
Prepulse inhibition	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Brain histopathology	Normal
Salmonella infection	Normal[7]
Citrobacter infection	Normal[8]
All tests and analysis from[9]

Model organisms have been used in the study of CADM1 function. A conditional knockout mouse line, called Cadm1^tm1.2Brd[10] was generated.[11] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][12] Twenty six tests were carried out on homozygous mutant mice and one significant abnormality was observed: males were infertile.[9] Further analysis showed spermatogenesis had arrested in these mice.[11]

Interactions

Cell adhesion molecule 1 has been shown to interact with EPB41L3.[13]

Association studies

Genome-wide association studies identified an association between body mass index and two loci near the CADM1 and CADM2 gene.[14] Experimental results of another study showed that obese mice had an over expression of both CADM1 and CADM2 genes, and that loss of CADM1 protected mice from obesity, promoting a negative energy balance and weight loss.[15] Furthermore, a 2019 GWAS study revealed an association between Anorexia nervosa and CADM1.[16] In the brain, this genes mediate synaptic assembly, and mutations in CADM1 are also associated with Autistic spectrum disorder. [17]

See also

• Cell adhesion molecule

References

1. GRCh38: Ensembl release 89: ENSG00000182985 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032076 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Gomyo H, Arai Y, Tanigami A, Murakami Y, Hattori M, Hosoda F, Arai K, Aikawa Y, Tsuda H, Hirohashi S, Asakawa S, Shimizu N, Soeda E, Sakaki Y, Ohki M (Feb 2000). "A 2-Mb sequence-ready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2". Genomics. 62 (2): 139–46. doi:10.1006/geno.1999.6001. PMID 10610705.
6. "Entrez Gene: CADM1 cell adhesion molecule 1".
7. "Salmonella infection data for Cadm1". Wellcome Trust Sanger Institute.
8. "Citrobacter infection data for Cadm1". Wellcome Trust Sanger Institute.
9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
10. "Mouse Genome Informatics".
11. Van Der Weyden, L.; Arends, M. J.; Chausiaux, O. E.; Ellis, P. J.; Lange, U. C.; Surani, M. A.; Affara, N.; Murakami, Y.; Adams, D. J.; Bradley, A. (2006). "Loss of TSLC1 Causes Male Infertility Due to a Defect at the Spermatid Stage of Spermatogenesis". Molecular and Cellular Biology. 26 (9): 3595–3609. doi:10.1128/MCB.26.9.3595-3609.2006. PMC 1447413. PMID 16611999.
12. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
13. Yageta, Mika; Kuramochi Masami; Masuda Mari; Fukami Takeshi; Fukuhara Hiroshi; Maruyama Tomoko; Shibuya Masabumi; Murakami Yoshinori (Sep 2002). "Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer". Cancer Res. 62 (18): 5129–33. ISSN 0008-5472. PMID 12234973.
14. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al. (November 2010). "Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index". Nature Genetics. 42 (11): 937–48. doi:10.1038/ng.686. PMC 3014648. PMID 20935630.
15. Rathjen T, Yan X, Kononenko NL, Ku MC, Song K, Ferrarese L, et al. (August 2017). "Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1". Nature Neuroscience. 20 (8): 1096–1103. doi:10.1038/nn.4590. PMC 5533218. PMID 28628102.
16. Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JR, Gaspar HA, et al. (August 2019). "Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa". Nature Genetics. 51 (8): 1207–1214. doi:10.1038/s41588-019-0439-2. PMC 6779477. PMID 31308545.
17. Fujita E, Tanabe Y, Imhof BA, Momoi MY, Momoi T (December 2012). "A complex of synaptic adhesion molecule CADM1, a molecule related to autism spectrum disorder, with MUPP1 in the cerebellum". J Neurochem. 123 (5): 886–94. doi:10.1111/jnc.12022. PMID 22994563.

Further reading

• Watabe K, Ito A, Koma YI, Kitamura Y (2004). "IGSF4: a new intercellular adhesion molecule that is called by three names, TSLC1, SgIGSF and SynCAM, by virtue of its diverse function". Histol. Histopathol. 18 (4): 1321–9. PMID 12973698.
• Kuramochi M, Fukuhara H, Nobukuni T, et al. (2001). "TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer". Nat. Genet. 27 (4): 427–30. doi:10.1038/86934. hdl:2241/1028. PMID 11279526. S2CID 9773234.
• Masuda M, Yageta M, Fukuhara H, et al. (2002). "The tumor suppressor protein TSLC1 is involved in cell-cell adhesion". J. Biol. Chem. 277 (34): 31014–9. doi:10.1074/jbc.M203620200. PMID 12050160.
• Fukuhara H, Kuramochi M, Fukami T, et al. (2003). "Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer". Jpn. J. Cancer Res. 93 (6): 605–9. doi:10.1111/j.1349-7006.2002.tb01297.x. PMC 5927049. PMID 12079507.
• Allinen M, Peri L, Kujala S, et al. (2002). "Analysis of 11q21-24 loss of heterozygosity candidate target genes in breast cancer: indications of TSLC1 promoter hypermethylation". Genes Chromosomes Cancer. 34 (4): 384–9. doi:10.1002/gcc.10079. PMID 12112527. S2CID 396701.
• Biederer T, Sara Y, Mozhayeva M, et al. (2002). "SynCAM, a synaptic adhesion molecule that drives synapse assembly". Science. 297 (5586): 1525–31. Bibcode:2002Sci...297.1525B. doi:10.1126/science.1072356. PMID 12202822. S2CID 14529914.
• Yageta M, Kuramochi M, Masuda M, et al. (2002). "Direct association of TSLC1 and DAL-1, two distinct tumor suppressor proteins in lung cancer". Cancer Res. 62 (18): 5129–33. PMID 12234973.
• Jansen M, Fukushima N, Rosty C, et al. (2003). "Aberrant methylation of the 5' CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanlNs". Cancer Biol. Ther. 1 (3): 293–6. doi:10.4161/cbt.84. PMID 12432281.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Honda T, Tamura G, Waki T, et al. (2003). "Hypermethylation of the TSLC1 gene promoter in primary gastric cancers and gastric cancer cell lines". Jpn. J. Cancer Res. 93 (8): 857–60. doi:10.1111/j.1349-7006.2002.tb01329.x. PMC 5927103. PMID 12716461.
• Shingai T, Ikeda W, Kakunaga S, et al. (2003). "Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells". J. Biol. Chem. 278 (37): 35421–7. doi:10.1074/jbc.M305387200. PMID 12826663.
• Ito A, Okada M, Uchino K, et al. (2003). "Expression of the TSLC1 adhesion molecule in pulmonary epithelium and its down-regulation in pulmonary adenocarcinoma other than bronchioloalveolar carcinoma". Lab. Invest. 83 (8): 1175–83. doi:10.1097/01.LAB.0000081391.28136.80. PMID 12920246.
• Fukami T, Fukuhara H, Kuramochi M, et al. (2003). "Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines". Int. J. Cancer. 107 (1): 53–9. doi:10.1002/ijc.11348. PMID 12925956. S2CID 26363429.
• Uchino K, Ito A, Wakayama T, et al. (2003). "Clinical implication and prognostic significance of the tumor suppressor TSLC1 gene detected in adenocarcinoma of the lung". Cancer. 98 (5): 1002–7. doi:10.1002/cncr.11599. PMID 12942568. S2CID 35242800.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Fukuhara H, Masuda M, Yageta M, et al. (2003). "Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg". Oncogene. 22 (40): 6160–5. doi:10.1038/sj.onc.1206744. PMID 13679854.
• Ito T, Shimada Y, Hashimoto Y, et al. (2003). "Involvement of TSLC1 in progression of esophageal squamous cell carcinoma". Cancer Res. 63 (19): 6320–6. PMID 14559819.
• Mao X, Seidlitz E, Ghosh K, et al. (2004). "The cytoplasmic domain is critical to the tumor suppressor activity of TSLC1 in non-small cell lung cancer". Cancer Res. 63 (22): 7979–85. PMID 14633730.