NCAM1

Protein identityUniProt · HPA

UniProt accession

P13591

Gene

NCAM1

Ensembl

ENSG00000149294

Chromosome

11

Canonical length

858 aa

Protein class

Cancer-related genes, CD markers, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Subcellular location

Plasma membrane,Cytosol

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene encodes a cell adhesion protein which is a member of the immunoglobulin superfamily. The encoded protein is involved in cell-to-cell interactions as well as cell-matrix interactions during development and differentiation. The encoded protein plays a role in the development of the nervous system by regulating neurogenesis, neurite outgrowth, and cell migration. This protein is also involved in the expansion of T lymphocytes, B lymphocytes and natural killer (NK) cells which play an important role in immune surveillance. This protein plays a role in signal transduction by interacting with fibroblast growth factor receptors, N-cadherin and other components of the extracellular matrix and by triggering signalling cascades involving FYN-focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K). One prominent isoform of this gene, cell surface molecule CD56, plays a role in several myeloproliferative disorders such as acute myeloid leukemia and differential expression of this gene is associated with differential disease progression. For example, increased expression of CD56 is correlated with lower survival in acute myeloid leukemia patients whereas increased severity of COVID-19 is correlated with decreased abundance of CD56-expressing NK cells in peripheral blood. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

858 residues, UniProt reviewed canonical sequence.

>P13591|NCAM1
     1  MLQTKDLIWT LFFLGTAVSL QVDIVPSQGE ISVGESKFFL CQVAGDAKDK DISWFSPNGE
    61  KLTPNQQRIS VVWNDDSSST LTIYNANIDD AGIYKCVVTG EDGSESEATV NVKIFQKLMF
   121  KNAPTPQEFR EGEDAVIVCD VVSSLPPTII WKHKGRDVIL KKDVRFIVLS NNYLQIRGIK
   181  KTDEGTYRCE GRILARGEIN FKDIQVIVNV PPTIQARQNI VNATANLGQS VTLVCDAEGF
   241  PEPTMSWTKD GEQIEQEEDD EKYIFSDDSS QLTIKKVDKN DEAEYICIAE NKAGEQDATI
   301  HLKVFAKPKI TYVENQTAME LEEQVTLTCE ASGDPIPSIT WRTSTRNISS EEKASWTRPE
   361  KQETLDGHMV VRSHARVSSL TLKSIQYTDA GEYICTASNT IGQDSQSMYL EVQYAPKLQG
   421  PVAVYTWEGN QVNITCEVFA YPSATISWFR DGQLLPSSNY SNIKIYNTPS ASYLEVTPDS
   481  ENDFGNYNCT AVNRIGQESL EFILVQADTP SSPSIDQVEP YSSTAQVQFD EPEATGGVPI
   541  LKYKAEWRAV GEEVWHSKWY DAKEASMEGI VTIVGLKPET TYAVRLAALN GKGLGEISAA
   601  SEFKTQPVQG EPSAPKLEGQ MGEDGNSIKV NLIKQDDGGS PIRHYLVRYR ALSSEWKPEI
   661  RLPSGSDHVM LKSLDWNAEY EVYVVAENQQ GKSKAAHFVF RTSAQPTAIP ANGSPTSGLS
   721  TGAIVGILIV IFVLLLVVVD ITCYFLNKCG LFMCIAVNLC GKAGPGAKGK DMEEGKAAFS
   781  KDESKEPIVE VRTEEERTPN HDGGKHTEPN ETTPLTEPEK GPVEAKPECQ ETETKPAPAE
   841  VKTVPNDATQ TKENESKA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NCAM1 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)

0.37

Highest tissue expression

187 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NCAM1.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 48 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• See cases

Disease | ImmuneIEDB

Conditions an epitope on NCAM1 was assayed in.

• human immunodeficiency virus infectious disease T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against NCAM1 are reported. Each links to that disease's full target list.

• Lupus Nephritis 3
• Schizophrenia 3

ReferencesPubMed · IEDB

Publications for NCAM1 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

0.19

gnomAD pLI

1

gnomAD missense Z

2.71

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• commissural neuron axon guidance
• epithelial to mesenchymal transition
• regulation of semaphorin-plexin signaling pathway

Molecular functions

• virus receptor activity

Cellular components

• cell surface
• cytosol
• external side of plasma membrane
• extracellular matrix
• extracellular region
• Golgi membrane
• membrane
• neuron projection
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Neural cell adhesion
• Immunoglobulin I-set
• Immunoglobulin-like fold
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Fibronectin type III domain
• Immunoglobulin I-set domain
• Immunoglobulin domain

KeywordsUniProt

• Cell adhesion
• Cell membrane
• Disulfide bond
• Glycoprotein
• GPI-anchor
• Host cell receptor for virus entry
• Host-virus interaction
• Immunoglobulin domain
• Lipoprotein
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NCAM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MDK
• C22orf39