L1CAM
The protein encoded by this gene is an axonal glycoprotein belonging to the immunoglobulin supergene family. The ectodomain, consisting of several immunoglobulin-like domains and fibronectin-like repeats (type III), is linked via a single transmembrane sequence to a conserved cytoplasmic domain. This cell adhesion molecule plays an important role in nervous system development, including neuronal migration and differentiation. Mutations in the gene cause X-linked neurological syndromes known as CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia and hydrocephalus). Alternative splicing of this gene results in multiple transcript variants, some of which include an alternate exon that is considered to be specific to neurons.
Function
Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity.
Biological Process
Axon developmentManual Assertion Based On ExperimentIDA:UniProtKB
Axon guidanceManual Assertion Based On ExperimentIDA:UniProtKB
Cell adhesion1 PublicationNAS:ProtInc
Cell migrationManual Assertion Based On ExperimentIDA:UniProtKB
Cell-matrix adhesionManual Assertion Based On ExperimentIDA:UniProtKB
ChemotaxisManual Assertion Based On ExperimentTAS:BHF-UCL
Homophilic cell adhesion via plasma membrane adhesion moleculesManual Assertion Based On ExperimentIBA:GO_Central
Nervous system developmentManual Assertion Based On ExperimentTAS:ProtInc
Neuron projection developmentManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of axon extensionISS:UniProtKB
Synapse organizationManual Assertion Based On ExperimentIDA:UniProtKB
Cellular Location
Cell membrane
Cell projection, growth cone
Cell projection, axon
Cell projection, dendrite
Colocalized with SHTN1 in close apposition with actin filaments in filopodia and lamellipodia of axonalne growth cones of hippocampal neurons (By similarity).
In neurons, detected predominantly in axons and cell body, weak localization to dendrites (PubMed:20621658).
Involvement in disease
Hydrocephalus due to stenosis of the aqueduct of Sylvius (HSAS):
Hydrocephalus is a condition in which abnormal accumulation of cerebrospinal fluid in the brain causes increased intracranial pressure inside the skull. This is usually due to blockage of cerebrospinal fluid outflow in the brain ventricles or in the subarachnoid space at the base of the brain. In children is typically characterized by enlargement of the head, prominence of the forehead, brain atrophy, mental deterioration, and convulsions. In adults the syndrome includes incontinence, imbalance, and dementia. HSAS is characterized by mental retardation and enlarged brain ventricles.
Mental retardation, aphasia, shuffling gait, and adducted thumbs syndrome (MASA):
An X-linked recessive syndrome with a highly variable clinical spectrum. Main clinical features include spasticity and hyperreflexia of lower limbs, shuffling gait, mental retardation, aphasia and adducted thumbs. The features of spasticity have been referred to as complicated spastic paraplegia type 1 (SPG1). Some patients manifest corpus callosum hypoplasia and hydrocephalus. Inter- and intrafamilial variability is very wide, such that patients with hydrocephalus, MASA, SPG1, and agenesis of corpus callosum can be present within the same family.
Agenesis of the corpus callosum, X-linked, partial (ACCPX):
A syndrome characterized by partial corpus callosum agenesis, hypoplasia of inferior vermis and cerebellum, mental retardation, seizures and spasticity. Other features include microcephaly, unusual facies, and Hirschsprung disease in some patients.
Defects in L1CAM are associated with a wide phenotypic spectrum which varies from severe hydrocephalus and prenatal death (HSAS) to a milder phenotype (MASA). These variations may even occur within the same family. Due to the overlap of phenotypes between HSAS and MASA, many authors use the general concept of L1 syndrome which covers both ends of the spectrum.
Topology
Extracellular: 20-1120
Helical: 1121-1143
Cytoplasmic: 1144-1257
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Datasheet