L1CAM

Protein identityUniProt · HPA

UniProt accession

P32004

Gene

L1CAM

Ensembl

ENSG00000198910

Chromosome

X

Canonical length

1257 aa

Protein class

CD markers, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Plasma membrane

OverviewNCBI Gene

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. [provided by RefSeq, May 2013]

Canonical amino-acid sequenceUniProt

1257 residues, UniProt reviewed canonical sequence.

>P32004|L1CAM
     1  MVVALRYVWP LLLCSPCLLI QIPEEYEGHH VMEPPVITEQ SPRRLVVFPT DDISLKCEAS
    61  GKPEVQFRWT RDGVHFKPKE ELGVTVYQSP HSGSFTITGN NSNFAQRFQG IYRCFASNKL
   121  GTAMSHEIRL MAEGAPKWPK ETVKPVEVEE GESVVLPCNP PPSAEPLRIY WMNSKILHIK
   181  QDERVTMGQN GNLYFANVLT SDNHSDYICH AHFPGTRTII QKEPIDLRVK ATNSMIDRKP
   241  RLLFPTNSSS HLVALQGQPL VLECIAEGFP TPTIKWLRPS GPMPADRVTY QNHNKTLQLL
   301  KVGEEDDGEY RCLAENSLGS ARHAYYVTVE AAPYWLHKPQ SHLYGPGETA RLDCQVQGRP
   361  QPEVTWRING IPVEELAKDQ KYRIQRGALI LSNVQPSDTM VTQCEARNRH GLLLANAYIY
   421  VVQLPAKILT ADNQTYMAVQ GSTAYLLCKA FGAPVPSVQW LDEDGTTVLQ DERFFPYANG
   481  TLGIRDLQAN DTGRYFCLAA NDQNNVTIMA NLKVKDATQI TQGPRSTIEK KGSRVTFTCQ
   541  ASFDPSLQPS ITWRGDGRDL QELGDSDKYF IEDGRLVIHS LDYSDQGNYS CVASTELDVV
   601  ESRAQLLVVG SPGPVPRLVL SDLHLLTQSQ VRVSWSPAED HNAPIEKYDI EFEDKEMAPE
   661  KWYSLGKVPG NQTSTTLKLS PYVHYTFRVT AINKYGPGEP SPVSETVVTP EAAPEKNPVD
   721  VKGEGNETTN MVITWKPLRW MDWNAPQVQY RVQWRPQGTR GPWQEQIVSD PFLVVSNTST
   781  FVPYEIKVQA VNSQGKGPEP QVTIGYSGED YPQAIPELEG IEILNSSAVL VKWRPVDLAQ
   841  VKGHLRGYNV TYWREGSQRK HSKRHIHKDH VVVPANTTSV ILSGLRPYSS YHLEVQAFNG
   901  RGSGPASEFT FSTPEGVPGH PEALHLECQS NTSLLLRWQP PLSHNGVLTG YVLSYHPLDE
   961  GGKGQLSFNL RDPELRTHNL TDLSPHLRYR FQLQATTKEG PGEAIVREGG TMALSGISDF
  1021  GNISATAGEN YSVVSWVPKE GQCNFRFHIL FKALGEEKGG ASLSPQYVSY NQSSYTQWDL
  1081  QPDTDYEIHL FKERMFRHQM AVKTNGTGRV RLPPAGFATE GWFIGFVSAI ILLLLVLLIL
  1141  CFIKRSKGGK YSVKDKEDTQ VDSEARPMKD ETFGEYRSLE SDNEEKAFGS SQPSLNGDIK
  1201  PLGSDDSLAD YGGSVDVQFN EDGSFIGQYS GKKEKEAAGG NDSSGATSPI NPAVALE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against L1CAM can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

134 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about L1CAM.

Disease | AllUniProt

Conditions L1CAM is implicated in, by any mechanism.

• Hydrocephalus, congenital, X-linked (HYCX) MIM:307000
• MASA syndrome (MASA) MIM:303350
• Agenesis of the corpus callosum, X-linked, partial (ACCPX) MIM:304100

Disease | GeneticClinVar

204 pathogenic / likely-pathogenic of 1,535 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spastic paraplegia
• X-linked hydrocephalus syndrome
• MASA syndrome
• L1 syndrome
• X-linked complicated corpus callosum dysgenesis

ReferencesPubMed · IEDB

Publications for L1CAM from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.13

gnomAD pLI

1

gnomAD missense Z

2.84

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axon development
• axon guidance
• cell adhesion
• cell migration
• cell-matrix adhesion
• chemotaxis
• homophilic cell adhesion via plasma membrane adhesion molecules
• nervous system development
• neuron projection development
• positive regulation of axon extension
• synapse organization

Molecular functions

• axon guidance receptor activity
• protein domain specific binding

Cellular components

• axon
• axonal growth cone
• cell surface
• dendrite
• extracellular matrix
• focal adhesion
• neuronal cell body
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Neurofascin/L1/NrCAM, C-terminal domain
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Neural and epithelial cell adhesion domain-containing protein
• Fibronectin type III domain
• Immunoglobulin I-set domain
• Bravo-like intracellular region
• Immunoglobulin domain

KeywordsUniProt

• Cell adhesion
• Cell membrane
• Cell projection
• Developmental protein
• Differentiation
• Disulfide bond
• Glycoprotein
• Hereditary spastic paraplegia
• Hirschsprung disease
• Immunoglobulin domain
• Intellectual disability
• Membrane
• Neurodegeneration
• Neurogenesis
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of L1CAM in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SHTN1
• BSG