Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

L1CAM (L1 cell adhesion molecule)

Identity

Other namesCAML1
CD171
HSAS
HSAS1
MASA
MIC5
N-CAML1
S10
SPG1
HGNC (Hugo) L1CAM
LocusID (NCBI) 3897
Location Xq28
Location_base_pair Starts at 153126969 and ends at 153141500 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  Picture from Genetics Home Reference; Reviewed March 2008.

DNA/RNA

Description The L1CAM gene is 24,657 bp in length, consisting of 28 exons according to Ensembl and Entrez-gene.
Transcription There are 7 transcripts of the gene according to Ensembl.

Protein

 
  Protein domain structure (left) and cleavage sites (right) of L1CAM. NTF, 200 kDa N-terminal cleavage product; CTF1, 32 kDa C-terminal cleavage product; Ig, immunoglobulin like domain; FN, fibronectin like domain (From Fogel et al., 2003 and Maretzky et al., 2005).
Description L1CAM (L1) is a 200-220 kD glycoprotein and a member of the immunoglobulin superfamily. This type-1 transmembrane protein consists of six immunoglobulin like domains at the amino terminal end of the molecule followed by five fibronectin type III homologous repeats, a single transmembrane region and a short intracellular domain (Moos et al., 1988). Two splicing variants are known encoding for 1257 and 1253 amino acids proteins.
Expression Neural, hematopoietic and transformed epithelial cells.
Localisation Cell surface, extracellular matrix and nucleus (C-terminal fragment).
Function L1 plays a critical role in axon outgrowth and fasciculation, neuronal migration and survival, synaptic plasticity and regeneration after trauma (Maness et al., 2007). L1 can interact with itself (homophilic) but also with a variety of heterophilic ligands such as integrins, CD24, neurocan, neuropilin-1 and other members of the neural cell adhesion family. In many incidences the binding sites in the L1 molecule have been mapped. The RGD site in the sixth Ig domain supports α5β1, αvβ3,5 integrin-mediated cell binding and the first Ig domain can bind to the proteoglycan neurocan or the VEGF-R2-coreceptor neuropilin-1.
Beside its cell surface localization, L1CAM can also be cleaved by several proteases, i.e. the matrix metalloproteinases ADAM10 and ADAM17, metalloprotease PC5A proprotein convertase or by γ-secretases (Maretzky et al., 2005). Soluble L1CAM has been reported to be important for migration of neuronal as well as of tumor cells (Maretzky et al., 2005; Mechtersheimer et al., 2001), and several studies support a role for L1CAM in tumor growth (Arlt et al., 2006), tumor cell invasion, metastasis of melanoma, ovarial and colon cancer (Mechtersheimer et al., 2001; Gavert et al., 2005; Fogel et al., 2003) and chemoresistance (Sebens Müerköster et al., 2007; Stoeck et al., 2007).
L1 transiently activates pp60c-src, phosphoinositide 3-kinase (PI3 kinase), the VAV2 guanine nucleotide exchange factor, the RAC1 GTPase and p21-activated kinase (PAK1) in a pathway culminating in MEK and ERK activation.
Homology NrCAM/BRABO, CHL1, neurofascin; in invertebrates, neuroglian and sax-7.

Mutations

 
Germinal Numerous mutations in the L1CAM gene are known (De Angelis et al., 1999) accounting for X-linked neurological syndromes (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of a neuron-specific exon is thought to be functionally relevant.

Implicated in

Note Various cancers
Disease Overexpression of L1 has been reported in ovarian cancer, colon cancer, glioma, renal cell cancer, neuroblastoma, endometrial cancer, melanoma, pancreatic cancer. L1 expression promotes invasiveness of the tumor as well as chemoresistance. Thus, L1 expression is mainly found in the invasive front of coloretal cancer and blockade of L1 reduces tumor growth in mouse models. Blockade of L1 dimishes resistance of ovarian and pancreatic cancer towards anti-cancer drugs.
Prognosis In ovarian cancer, L1 expression associates with poor prognosis. Other L1 expressing tumor entities include those with extremely poor prognosis, i.e. pancreatic or renal cell cancer.
  
Entity Various diseases
Disease L1 mutations associate with X-linked mental retardation (=L1 syndrome: mental retardation, hydrocephalus, aphasia, spastic paraplegia, agenesis of corpus callosum, optic nerve atrophy), Hirschprung's disease and schizophrenia in some populations.
  

External links

Nomenclature
HGNC (Hugo)L1CAM   6470
Cards
AtlasL1CAMID44110chXq28
Entrez_Gene (NCBI)L1CAM  3897  L1 cell adhesion molecule
GeneCards (Weizmann)L1CAM
Ensembl (Hinxton)ENSG00000198910 [Gene_View]  chrX:153126969-153141500 [Contig_View]  L1CAM [Vega]
AceView (NCBI)L1CAM
Genatlas (Paris)L1CAM
WikiGenes3897
SOURCE (Princeton)NM_000425 NM_001143963 NM_001278116 NM_024003
Genomic and cartography
GoldenPath (UCSC)L1CAM  -  Xq28   chrX:153126969-153141500 -  Xq28   [Description]    (hg19-Feb_2009)
EnsemblL1CAM - Xq28 [CytoView]
Mapping of homologs : NCBIL1CAM [Mapview]
OMIM142623   303350   304100   307000   308840   
Gene and transcription
Genbank (Entrez)AB102653 AI361399 AK289754 AY927629 BC025843
RefSeq transcript (Entrez)NM_000425 NM_001143963 NM_001278116 NM_024003
RefSeq genomic (Entrez)AC_000155 NC_000023 NC_018934 NG_009645 NT_167198 NW_001842419 NW_003871103 NW_004929448
Consensus coding sequences : CCDS (NCBI)L1CAM
Cluster EST : UnigeneHs.522818 [ NCBI ]
CGAP (NCI)Hs.522818
Alternative Splicing : Fast-db (Paris)GSHG0032420
Alternative Splicing GalleryENSG00000198910
Gene ExpressionL1CAM [ NCBI-GEO ]     L1CAM [ SEEK ]   L1CAM [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP32004 (Uniprot)
NextProtP32004  [Medical]
With graphics : InterProP32004
Splice isoforms : SwissVarP32004 (Swissvar)
Domaine pattern : Prosite (Expaxy)FN3 (PS50853)    IG_LIKE (PS50835)   
Domains : Interpro (EBI)Fibronectin_type3    Ig-like_dom    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2    Neurofascin/L1/NrCAM_C   
Related proteins : CluSTrP32004
Domain families : Pfam (Sanger)Bravo_FIGEY (PF13882)    fn3 (PF00041)    I-set (PF07679)   
Domain families : Pfam (NCBI)pfam13882    pfam00041    pfam07679   
Domain families : Smart (EMBL)FN3 (SM00060)  IG (SM00409)  IGc2 (SM00408)  
DMDM Disease mutations3897
Blocks (Seattle)P32004
Human Protein AtlasENSG00000198910
Peptide AtlasP32004
HPRD02394
IPIIPI00871467   IPI00334532   IPI01013306   IPI01016031   IPI01011905   IPI00643864   IPI00646281   IPI00853275   IPI00853066   IPI00927501   IPI00927755   IPI00924481   
Protein Interaction databases
DIP (DOE-UCLA)P32004
IntAct (EBI)P32004
FunCoupENSG00000198910
BioGRIDL1CAM
InParanoidP32004
Interologous Interaction database P32004
IntegromeDBL1CAM
STRING (EMBL)L1CAM
Ontologies - Pathways
Ontology : AmiGOintegrin binding  plasma membrane  chemotaxis  cell adhesion  homophilic cell adhesion  heterophilic cell-cell adhesion  leukocyte cell-cell adhesion  cell surface receptor signaling pathway  nervous system development  axon guidance  blood coagulation  cell death  external side of plasma membrane  integral to membrane  positive regulation of cell-cell adhesion  cell-cell adhesion mediated by integrin  sialic acid binding  homotypic cell-cell adhesion  presynaptic membrane  identical protein binding  terminal bouton  protein self-association  positive regulation of calcium-mediated signaling  leukocyte migration  
Ontology : EGO-EBIintegrin binding  plasma membrane  chemotaxis  cell adhesion  homophilic cell adhesion  heterophilic cell-cell adhesion  leukocyte cell-cell adhesion  cell surface receptor signaling pathway  nervous system development  axon guidance  blood coagulation  cell death  external side of plasma membrane  integral to membrane  positive regulation of cell-cell adhesion  cell-cell adhesion mediated by integrin  sialic acid binding  homotypic cell-cell adhesion  presynaptic membrane  identical protein binding  terminal bouton  protein self-association  positive regulation of calcium-mediated signaling  leukocyte migration  
Pathways : KEGGAxon guidance    Cell adhesion molecules (CAMs)   
REACTOMEL1CAM
Protein Interaction DatabaseL1CAM
Wikipedia pathwaysL1CAM
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)L1CAM
SNP (GeneSNP Utah)L1CAM
SNP : HGBaseL1CAM
Genetic variants : HAPMAPL1CAM
1000_GenomesL1CAM 
ICGC programENSG00000198910 
Somatic Mutations in Cancer : COSMICL1CAM 
CONAN: Copy Number AnalysisL1CAM 
Mutations and Diseases : HGMDL1CAM
OMIM142623    303350    304100    307000    308840   
GENETestsL1CAM
Disease Genetic AssociationL1CAM
Huge Navigator L1CAM [HugePedia]  L1CAM [HugeCancerGEM]
Genomic VariantsL1CAM  L1CAM [DGVbeta]
Exome VariantL1CAM
dbVarL1CAM
ClinVarL1CAM
snp3D : Map Gene to Disease3897
General knowledge
Homologs : HomoloGeneL1CAM
Homology/Alignments : Family Browser (UCSC)L1CAM
Phylogenetic Trees/Animal Genes : TreeFamL1CAM
Chemical/Protein Interactions : CTD3897
Chemical/Pharm GKB GenePA30259
Clinical trialL1CAM
Cancer Resource (Charite)ENSG00000198910
Other databases
Probes
Litterature
PubMed195 Pubmed reference(s) in Entrez
CoreMineL1CAM
iHOPL1CAM

Bibliography

Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin.
Moos M, Tacke R, Scherer H, Teplow D, Fruh K, Schachner M.
Nature. 1988 Aug 25;334(6184):701-3.
PMID 3412448
 
Pathological missense mutations of neural cell adhesion molecule L1 affect homophilic and heterophilic binding activities.
De Angelis E, MacFarlane J, Du J-S, Yeo G, Hicks R, Rathjen FG, Kenwrick S, Brummendorf T.
EMBO J. 1999 Sep 1;18(17):4744-53.
PMID 10469653
 
Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins.
Mechtersheimer S, Gutwein P, Agmon-Levin N, Stoeck A, Oleszewski M, Riedle S, Postina R, Fahrenholz F, Fogel M, Lemmon V, Altevogt P.
J Cell Biol. 2001 Nov 12;155(4):661-73.
PMID 11706054
 
L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas.
Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, Edler L, Ben-Arie A, Huszar M, Altevogt P.
Lancet. 2003 Sep 13;362(9387):869-75.
PMID 13678974
 
L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers.
Gavert N, Conacci-Sorrell M, Gast D, Schneider A, Altevogt P, Brabletz T, Ben-Ze'ev A.
J Cell Biol. 2005 Feb 14;168(4):633-42.
PMID 15716380
 
L1 is sequentially processed by two differently activated metalloproteases and presenilin/gamma-secretase and regulates neural cell adhesion, cell migration, and neurite outgrowth.
Maretzky T, Schulte M, Ludwig A, Rose-John S, Blobel C, Hartmann D, Altevogt P, Saftig P, Reiss K.
Mol Cell Biol. 2005 Oct;25(20):9040-53.
PMID 16199880
 
Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment.
Arlt MJ, Novak-Hofer I, Gast D, Gschwend V, Moldenhauer G, Grunberg J, Honer M, Schubiger PA, Altevogt P, Kruger A.
Cancer Res. 2006 Jan 15;66(2):936-43.
PMID 16424028
 
Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration.
Maness PF, Schachner M.
Nat Neurosci. 2007 Jan;10(1):19-26. (REVIEW)
PMID 17189949
 
Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells.
Sebens Muerkoster S, Werbing V, Sipos B, Debus MA, Witt M, Grossmann M,Leisner D, Kotteritzsch J, Kappes H, Kloppel G, Altevogt P, Folsch UR, Schafer H.
Oncogene. 2007 Apr 26;26(19):2759-68.
PMID 17086212
 
L1-CAM in a membrane-bound or soluble form augments protection from apoptosis in ovarian carcinoma cells.
Stoeck A, Gast D, Sanderson MP, Issa Y, Gutwein P, Altevogt P.
Gynecol Oncol. 2007 Feb;104(2):461-9.
PMID 17030349
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written12-2008Heiner Schäfer, Susanne Sebens Müerköster
Laboratory of Molecular Gastroenterology, 1st Dept. of Medicine, UKSH Campus Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany

Citation

This paper should be referenced as such :
Schäfer H, Sebens Müerköster S . L1CAM (L1 cell adhesion molecule). Atlas Genet Cytogenet Oncol Haematol. December 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/L1CAMID44110chXq28.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/44612/1/12-2008-L1CAMID44110chXq28.pdf   [ Bibliographic record ]

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Apr 18 17:18:36 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.