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CADM4 (cell adhesion molecule 4)

Written2014-02Takeshi Ito, Yoshinori Murakami
Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_namesIGSF4C
immunoglobulin superfamily
Alias_symbol (synonym)TSLL2
Necl-4
SynCAM4
Other aliasNECL4
synCAM4
HGNC (Hugo) CADM4
LocusID (NCBI) 199731
Atlas_Id 46066
Location 19q13.31  [Link to chromosome band 19q13]
Location_base_pair Starts at 43622370 and ends at 43639839 bp from pter ( according to hg19-Feb_2009)  [Mapping CADM4.png]
Fusion genes
(updated 2016)
CADM4 (19q13.31) / RAB11FIP2 (10q26.11)CADM4 (19q13.31) / ZNF428 (19q13.31)ETHE1 (19q13.31) / CADM4 (19q13.31)

DNA/RNA

Description DNA contains 17470 bases composed of 9 coding exons.
Transcription 2176 bp mRNA transcribed in telomeric to centromeric orientation; 1164 bp open reading frame.

Protein

 
Description CADM4 encodes an immunoglobulin (Ig) superfamily cell adhesion molecule containing three Ig-like loops in their extracellular domain, a single transmembrane domain, and a short cytoplasmic domain with a protein 4.1-binding motif and a PDZ II-binding motif. The cytoplasmic domain is bound to the actin cytoskeleton through protein 4.1 such as 4.1B/DAL-1. CADM4 protein is 388 amino acids long and its molecular weight ranges from approximately 50 to 55 kDa dependent on N-glycosylation in the extracellular domain (deglycosylated form: 45 kDa).
Expression Brain, peripheral nerve, lung, large and small intestines, kidney, bladder, and prostate. Loss of expression is frequently observed in various cancers.
Localisation Cell membrane (type I transmembrane protein); Cell-cell contact site in epithelial tissues.
Function CADM4 forms homophilic cis-dimers on the cell surface and mediates Ca2+-independent cell-cell adhesion in a heterophilic manner with CADM2/Necl-3 or CADM3/Necl-1. CADM4 associates with 4.1B in the kidney.
Homology Pan troglodytes - CADM4; Canis lupus familiaris - CADM4; Bos taurus - CADM4; Mus musculus - Cadm4; Rattus norvegicus - Cadm4; Danio rerio - cadm4.

Mutations

Note No reports.

Implicated in

Note
  
Entity Prostate cancer
Oncogenesis CADM4 protein is lost or markedly reduced in nine of nine primary prostate cancers and two of four prostate cancer cell lines, PPC-1 and Du145, in comparison with that in normal human prostate. The tumorigenicity of PPC-1 was strongly suppressed by restoration of CADM4 expression without inducing significant cell death or growth inhibition in vitro, suggesting that the inactivation of CADM4 would be involved not in the direct cell growth but in the aberrant cell-cell contact in the prostate carcinogenesis.
  
  
Entity Renal clear cell carcinoma
Prognosis The expression of CADM4 is lost or markedly reduced in 70% of primary renal clear cell carcinoma (RCCC), where loss of CADM4 in RCCC correlates with vascular infiltration.
Oncogenesis CADM4 and its binding partner 4.1B are specifically expressed along the cell membrane in the proximal convoluted tubules, from which RCCC is derived. Approximately 80% of primary RCCC showed loss or marked reduction of either CADM4 or 4.1B, indicating that disruption of the CADM4-4.1B cascade is one of the most frequent events in RCCC. The CADM4 gene in human renal cell carcinoma cell 786-O was inactivated by promoter methylation, while restoration of CADM4 expression strongly suppressed subcutaneous tumor formation in nude mice by 786-O cells.
  
  
Entity Colorectal adenocarcinoma
Prognosis CADM4 expression is lost or reduced in 23% or 36% of colorectal adenocarcinoma, respectively. Loss or down-regulation of CADM4 is correlated with larger tumor size, mucinous tumor type, poorer differentiation, lymph node metastasis, and higher Dukes stage.
Oncogenesis Loss or down-regulation of CADM4 expression was positively correlated with low E-cadherin expression and high Ki-67 expression in colorectal adenocarcinoma. The restoration of CADM4 expression in LS174T human colon cancer cells suppressed cell growth, colony formation, motility, and tumorigenic capacity. These results suggest that CADM4 may be involved in the maintenance of epithelial structure and suppression of tumor growth.
  
  
Entity Breast cancer (ductal carcinoma)
Prognosis CADM4 expression was higher in ductal carcinoma in situ cases (82%) than invasive ductal adenocarcinoma cases (68%). Loss or reduced expression of CADM4 was significantly correlated with higher histological grade, overexpression of ErbB2 and absence of estrogen and/or progesterone receptors. CADM4 expression is associated with longer disease-free survival in stages I and II invasive ductal adenocarcinoma cases.
Oncogenesis Loss or reduced expression of CADM4 may play an important role in breast cancer invasiveness.
  

Bibliography

Bioinformatic characterization of the SynCAM family of immunoglobulin-like domain-containing adhesion molecules.
Biederer T.
Genomics. 2006 Jan;87(1):139-50. Epub 2005 Nov 28.
PMID 16311015
 
Isolation of the mouse Tsll1 and Tsll2 genes, orthologues of the human TSLC1-like genes 1 and 2 (TSLL1 and TSLL2).
Fukami T, Satoh H, Williams YN, Masuda M, Fukuhara H, Maruyama T, Yageta M, Kuramochi M, Takamoto S, Murakami Y.
Gene. 2003 Dec 24;323:11-8.
PMID 14659875
 
Isolation of the TSLL1 and TSLL2 genes, members of the tumor suppressor TSLC1 gene family encoding transmembrane proteins.
Fukuhara H, Kuramochi M, Nobukuni T, Fukami T, Saino M, Maruyama T, Nomura S, Sekiya T, Murakami Y.
Oncogene. 2001 Aug 30;20(38):5401-7.
PMID 11536053
 
Clinicopathological significance of CADM4 expression, and its correlation with expression of E-cadherin and Ki-67 in colorectal adenocarcinomas.
Jang SM, Han H, Jun YJ, Jang SH, Min KW, Sim J, Ahn HI, Lee KH, Jang KS, Paik SS.
J Clin Pathol. 2012 Oct;65(10):902-6. Epub 2012 Jun 20.
PMID 22718847
 
Clinicopathological significance of CADM4 expression in invasive ductal carcinoma of the breast.
Jang SM, Sim J, Han H, Ahn HI, Kim H, Yi K, Jun YJ, Rehman A, Chung MS, Jang K, Paik SS.
J Clin Pathol. 2013 Aug;66(8):681-6. doi: 10.1136/jclinpath-2012-201405. Epub 2013 Apr 4.
PMID 23559354
 
Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma.
Nagata M, Sakurai-Yageta M, Yamada D, Goto A, Ito A, Fukuhara H, Kume H, Morikawa T, Fukayama M, Homma Y, Murakami Y.
Int J Cancer. 2012 Mar 15;130(6):1329-37. doi: 10.1002/ijc.26160. Epub 2011 Jul 21.
PMID 21544807
 
The cell adhesion nectin-like molecules (Necl) 1 and 4 suppress the growth and tumorigenic ability of colon cancer cells.
Raveh S, Gavert N, Spiegel I, Ben-Ze'ev A.
J Cell Biochem. 2009 Sep 1;108(1):326-36. doi: 10.1002/jcb.22258.
PMID 19565570
 
A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and myelination.
Spiegel I, Adamsky K, Eshed Y, Milo R, Sabanay H, Sarig-Nadir O, Horresh I, Scherer SS, Rasband MN, Peles E.
Nat Neurosci. 2007 Jul;10(7):861-9. Epub 2007 Jun 3.
PMID 17558405
 
Cell adhesion and prostate tumor-suppressor activity of TSLL2/IGSF4C, an immunoglobulin superfamily molecule homologous to TSLC1/IGSF4.
Williams YN, Masuda M, Sakurai-Yageta M, Maruyama T, Shibuya M, Murakami Y.
Oncogene. 2006 Mar 9;25(10):1446-53.
PMID 16261159
 

Citation

This paper should be referenced as such :
T Ito, Y Murakami
CADM4 (cell adhesion molecule 4)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(10):709-710.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CADM4ID46066ch19q13.html


External links

Nomenclature
HGNC (Hugo)CADM4   30825
Cards
AtlasCADM4ID46066ch19q13
Entrez_Gene (NCBI)CADM4  199731  cell adhesion molecule 4
AliasesIGSF4C; NECL4; Necl-4; TSLL2; 
synCAM4
GeneCards (Weizmann)CADM4
Ensembl hg19 (Hinxton)ENSG00000105767 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000105767 [Gene_View]  chr19:43622370-43639839 [Contig_View]  CADM4 [Vega]
ICGC DataPortalENSG00000105767
TCGA cBioPortalCADM4
AceView (NCBI)CADM4
Genatlas (Paris)CADM4
WikiGenes199731
SOURCE (Princeton)CADM4
Genetics Home Reference (NIH)CADM4
Genomic and cartography
GoldenPath hg38 (UCSC)CADM4  -     chr19:43622370-43639839 -  19q13.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CADM4  -     19q13.31   [Description]    (hg19-Feb_2009)
EnsemblCADM4 - 19q13.31 [CytoView hg19]  CADM4 - 19q13.31 [CytoView hg38]
Mapping of homologs : NCBICADM4 [Mapview hg19]  CADM4 [Mapview hg38]
OMIM609744   
Gene and transcription
Genbank (Entrez)AF363368 AK313028 BC068457 BC113963 BC140326
RefSeq transcript (Entrez)NM_145296
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CADM4
Cluster EST : UnigeneHs.370984 [ NCBI ]
CGAP (NCI)Hs.370984
Alternative Splicing GalleryENSG00000105767
Gene ExpressionCADM4 [ NCBI-GEO ]   CADM4 [ EBI - ARRAY_EXPRESS ]   CADM4 [ SEEK ]   CADM4 [ MEM ]
Gene Expression Viewer (FireBrowse)CADM4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)199731
GTEX Portal (Tissue expression)CADM4
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8NFZ8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8NFZ8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8NFZ8
Splice isoforms : SwissVarQ8NFZ8
PhosPhoSitePlusQ8NFZ8
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)   
Domains : Interpro (EBI)Cadm4    CD80_C2-set    Ig-like_dom    Ig-like_fold    Ig_sub    Ig_sub2    Ig_V-set    Neurexin-like   
Domain families : Pfam (Sanger)C2-set_2 (PF08205)    V-set (PF07686)   
Domain families : Pfam (NCBI)pfam08205    pfam07686   
Domain families : Smart (EMBL)4.1m (SM00294)  IG (SM00409)  IGc2 (SM00408)  
Conserved Domain (NCBI)CADM4
DMDM Disease mutations199731
Blocks (Seattle)CADM4
SuperfamilyQ8NFZ8
Human Protein AtlasENSG00000105767
Peptide AtlasQ8NFZ8
HPRD17141
IPIIPI00176427   
Protein Interaction databases
DIP (DOE-UCLA)Q8NFZ8
IntAct (EBI)Q8NFZ8
FunCoupENSG00000105767
BioGRIDCADM4
STRING (EMBL)CADM4
ZODIACCADM4
Ontologies - Pathways
QuickGOQ8NFZ8
Ontology : AmiGOreceptor activity  receptor binding  integral component of plasma membrane  cell-cell adherens junction  homophilic cell adhesion via plasma membrane adhesion molecules  heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules  cell recognition  protein homodimerization activity  cell adhesion molecule binding  extracellular exosome  
Ontology : EGO-EBIreceptor activity  receptor binding  integral component of plasma membrane  cell-cell adherens junction  homophilic cell adhesion via plasma membrane adhesion molecules  heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules  cell recognition  protein homodimerization activity  cell adhesion molecule binding  extracellular exosome  
NDEx NetworkCADM4
Atlas of Cancer Signalling NetworkCADM4
Wikipedia pathwaysCADM4
Orthology - Evolution
OrthoDB199731
GeneTree (enSembl)ENSG00000105767
Phylogenetic Trees/Animal Genes : TreeFamCADM4
HOVERGENQ8NFZ8
HOGENOMQ8NFZ8
Homologs : HomoloGeneCADM4
Homology/Alignments : Family Browser (UCSC)CADM4
Gene fusions - Rearrangements
Fusion : MitelmanETHE1/CADM4 [19q13.31/19q13.31]  [t(19;19)(q13;q13)]  
Fusion: TCGAETHE1 19q13.31 CADM4 19q13.31 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCADM4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CADM4
dbVarCADM4
ClinVarCADM4
1000_GenomesCADM4 
Exome Variant ServerCADM4
ExAC (Exome Aggregation Consortium)CADM4 (select the gene name)
Genetic variants : HAPMAP199731
Genomic Variants (DGV)CADM4 [DGVbeta]
DECIPHERCADM4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCADM4 
Mutations
ICGC Data PortalCADM4 
TCGA Data PortalCADM4 
Broad Tumor PortalCADM4
OASIS PortalCADM4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCADM4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCADM4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CADM4
DgiDB (Drug Gene Interaction Database)CADM4
DoCM (Curated mutations)CADM4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CADM4 (select a term)
intoGenCADM4
NCG5 (London)CADM4
Cancer3DCADM4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM609744   
Orphanet
MedgenCADM4
Genetic Testing Registry CADM4
NextProtQ8NFZ8 [Medical]
TSGene199731
GENETestsCADM4
Target ValidationCADM4
Huge Navigator CADM4 [HugePedia]
snp3D : Map Gene to Disease199731
BioCentury BCIQCADM4
ClinGenCADM4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD199731
Chemical/Pharm GKB GenePA162380931
Clinical trialCADM4
Miscellaneous
canSAR (ICR)CADM4 (select the gene name)
Probes
Litterature
PubMed15 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCADM4
EVEXCADM4
GoPubMedCADM4
iHOPCADM4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Aug 1 17:22:12 CEST 2017

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