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FLASH GENE

Symbol

L1CAM

contributors: mct/shn - updated : 17-01-2012

HGNC name	L1 cell adhesion molecule
HGNC id	6470

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_024003 27 - 5034 NP_076493 - 1253 - 2010 20543863 lacks a neuron-specific exon in the 3prime region NM_000425 27 polyA site 5046 NP_000416 140 1257 typical of low-REST neural cells 2010 20543863 L1-FL only isoform that can promote cell proliferation and tumour growth plays key roles in survival/migration, outgrowth/fasciculation/regeneration of axons, synaptic plasticity NM_001143963 26 splicing 5019 NP_001137435 - 1248 - 2010 20543863 lacking exon 27 and tyrosine based sorting motif

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain           nerve

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune dendritic cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six repeats of the Ig C2 domain
	five fibronectin FN, type III repeats
	a transmembrane, highly conserved cytoplasmic domain
	an intracellular domain L1 highly conserved
	RGD integrin binding site in the sixth Ig domain, important for nuclear signaling, and is a binding site for integrins

conjugated

GlycoP , PhosphoP

HOMOLOGY

interspecies	ortholog to L1cam, Mus musculus
	ortholog to L1cam, Rattus norvegicus
	ortholog to L1CAM, Pan troglodytes

Homologene

FAMILY

transmembrane molecule of the Ig superfamily

CATEGORY

adhesion , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
text	in neurons, L1CAM and CHL1 are mainly located in axonal membranes

basic FUNCTION	playing a role in nervous system development, neuronal migration and differentiation
	playing a role in in corticospinal tract development
	neural cell adhesion molecule that has been shown to help guide nascent axons to their targets (
	important for cell migration and axon outgrowth
	involved in IL-1&
	946;-mediated caspase inhibition in chemoresistant PDAC cells (
	implicated in the regulation of dendritic cells trafficking
	the soluble ectodomain of L1CAM promotes cell migration (, protects cells from apoptosis (, stimulates endothelial cell survival ( and acts as a proangiogenic factor
	involved in proliferation, invasion and metastasis both in vitro and in vivo (
	L1CAM cytoplasmic domain (L1CD) is involved in L1CAM trafficking, neurite branching, signaling, and interactions with the cytoskeleton (
	activating IL1B and increased IL1B levels were instrumental for sustained NFKB activation
	its ubiquitination might be involved in L1CAM-dependent functions in processes like cell migration and growth cone motility
	its trafficking is regulated by ubiquitin, providing a novel and additional mechanism regulating L1CAM presence at the cell surface
	regulates DNA damage checkpoint responses and radiosensitivity of Glioblastomas stem cells through nuclear translocation of L1CAM intracellular domain
	L1CAM and CHL1, are crucial for axonal guidance and maintenance of neural circuits
	in the adult brain, L1CAM and CHL1 continue to play important roles in maintenance and regeneration of neural circuits

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development , nervous system

text	a key player in the development of the nervous system, regulating cell–cell interactions, neuronal cell migration and the neurite outgrowth of Schwann cells and axons as well as neurite fasciculation and myelination (

PATHWAY

metabolism

signaling

kinase activity

a component

INTERACTION

DNA

RNA

small molecule

protein	440-kD ankyrinB (
	ezrin, AP2, ERM proteins (
	neuropilin-1 (
	Numb (
	alphavbeta3-integrin (
	RanBPM (
	fibroblast growth factor receptor 1, FGFR1 (
	NSG1 is a regulator of L1CAM sorting in somatodendritic endosomes
	EZR, TAFP2A
	can interact with itself (homophilic) and with heterophilic ligands such as integrins, CD24, neurocan, neuropilin-1 and other members of the neural cell adhesion family
	EGFR
	RGD-binding integrins (
	regulates expression of NBS1, a critical component of the MRE11-RAD50-NBS1 (MRN) complex that activates ataxia telangiectasia mutated (ATM) kinase and early checkpoint response
	REST control of L1CAM occurs by two mechanisms, transcription and alternative splicing v
	TGFB1-dependent L1CAM expression has an essential role in macrophage-induced apoptosis resistance and cell migration of human intestinal epithelial cells
	L1CAM and CHL1 are physiological substrates for BACE1 (pMID: 22692213)
	RABGEF1 regulates the endocytic trafficking pathway of ubiquitinated neural cell adhesion molecule L1CAM

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

HSAS , MASA , SPG1

related resource

L1CAM Mutation Web Page

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     contiguous gene syndrome encompassing AVPR2, in patients with congenital hydrocephalus and diabetes insipidus tumoral     --low   by hypomethylation at the L1CAM CpG islands might induce L1CAM aberrant expression and contribute to the acquisition of aggressive tumor behavior in colorectal cancer tumoral     --over   in pancreatic cancer constitutional     --over   in intestinal epithelial cells in tissues from inflammatory bowel disease (IBD) patients but not in normal colonic tissues

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology     offer novel therapeutic perspectives for the treatment of certain immunological disorders tumor     blockade of L1CAM binding to integrins abrogates L1CAM-induced tumour growth and reduces L1CAM-mediated chemoresistance cancer     a target for treatment of cancer with monoclonal antibodies

ANIMAL & CELL MODELS

	Cerebellar granule neurons expressing a deletion mutant of L1CAM lacking the cytoplasmic domain (hL1-1147) show a reduced branching of neurites (
	L1-6D mutant mice, homozygous for a deletion removing the sixth immunoglobulin-like domain of L1cam, seldom display hydrocephalus on the 129/Sv background, while the same L1-6D mutation produces severe hydrocephalus on the C57BL/6J background (
	L1cam knockout mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves (
	Enhanced expression of L1-CAM may contribute to the pain syndrome and perineural invasion and may correlate with poor overall survival in human pancreatic cancer (
	L1CD mutant lines that lack the ankyrin-binding region display normal brain morphology but the expression of L1 protein in the adult is dramatically reduced and they show defects in motor function (
	L1CAM expression leads to the activation of the nuclear factor (NF)-&
	954;B pathway, promoting cell proliferation in vitro and metastasis formation in vivo (