Neural cell adhesion molecule

Neural cell adhesion molecule

(NCAM), also called CD56, is a
NCAM1
homophilic binding glycoprotein
expressed on the surface of neurons,
glia and skeletal muscle. Although
CD56 is often considered a marker
of neural lineage commitment due to
its discovery site, CD56 expression is
also found in, among others, the
hematopoietic system. Here, the
expression of CD56 is most
stringently associated with, but Available structures
certainly not limited to, natural killer
cells. CD56 has been detected on PDB Ortholog search: PDBe (https://www.ebi.ac.uk/pdbe/search
other lymphoid cells, including Results.html?display=both&term=P13595%20or%20P1359
gamma delta (γδ) Τ cells and 1%20or%20A0A0D9SF98) RCSB (http://www.rcsb.org/pdb/s
activated CD8+ T cells, as well as on earch/smartSubquery.do?smartSearchSubtype=UpAccessio
dendritic cells.[5] NCAM has been nIdQuery&accessionIdList=P13595,P13591,A0A0D9SF98)
implicated as having a role in cell–
List of PDB id codes
cell adhesion,[6] neurite outgrowth,
synaptic plasticity, and learning and
memory. 2E3V (https://www.rcsb.org/structure/2E3V), 2HAZ
(https://www.rcsb.org/structure/2HAZ), 2VKW (http
s://www.rcsb.org/structure/2VKW), 2VKX (https://ww
w.rcsb.org/structure/2VKX), 3MTR (https://www.rcsb.
Contents org/structure/3MTR), 5AEA (https://www.rcsb.org/str
ucture/5AEA)
Forms, domains and
homophilic binding
Identifiers
Minor exons
Aliases NCAM1 (https://www.genenames.org/data/gene-symbol-r
Posttranslational
eport/#!/hgnc_id/7656), CD56, MSK39, NCAM, neural
modification
cell adhesion molecule 1
Expression in normal cells
External OMIM: 116930 (https://omim.org/entry/116930) MGI:
Function IDs 97281 (http://www.informatics.jax.org/marker/MGI:97281)
Pathology HomoloGene: 40754 (https://www.ncbi.nlm.nih.gov/entre
Cancer z/query.fcgi?cmd=Retrieve&db=homologene&dopt=Homo
loGene&list_uids=40754) GeneCards: NCAM1 (https://w
Alzheimer's disease
ww.genecards.org/cgi-bin/carddisp.pl?gene=NCAM1)
Anti-NCAM therapy
Gene location (Human)
References
External links
Forms, domains and
homophilic binding
NCAM is a glycoprotein of
Immunoglobulin (Ig) superfamily. At
least 27 alternatively spliced NCAM Chr. Chromosome 11 (human)[1]
mRNAs are produced, giving a wide
diversity of NCAM isoforms.[7] The
three main isoforms of NCAM vary
only in their cytoplasmic domain:
Band 11q23.2 Start 112,961,247 bp[1]
NCAM-120kDa (GPI End 113,278,436 bp[1]
anchored)
NCAM-140kDa (short Gene location (Mouse)
cytoplasmic domain)
NCAM-180kDa (long
cytoplasmic domain)

The extracellular domain of NCAM

consists of five immunoglobulin-like
(Ig) domains followed by two Chr. Chromosome 9 (mouse)[2]
fibronectin type III (FNIII) domains.
The different domains of NCAM
have been shown to have different
roles, with the Ig domains being
involved in homophilic binding to Band 9 A5.3|9 26.83 cM Start 49,502,136 bp[2]
NCAM, and the FNIII domains End 49,798,925 bp[2]
being involved signalling leading to
neurite outgrowth. RNA expression pattern

Homophilic binding occurs between

NCAM molecules on opposing
surfaces (trans-) and NCAM
molecules on the same surface
(cis-)1. There is much controversy as
to how exactly NCAM homophilic
binding is arranged both in trans- and
cis-. Current models suggest trans-
homophilic binding occurs between
two NCAM molecules binding
antiparallel between all five Ig
domains or just IgI and IgII. cis-
homophilic binding is thought to
occur by interactions between both
IgI and IgII, and IgI and IgIII,
forming a higher order NCAM
multimer. Both cis- and trans-
NCAM homophilic binding have
been shown to be important in
NCAM “activation” leading to
More reference expression data (http://biogps.org/gene/4684/)
neurite outgrowth.

Minor exons
Another layer of complexity is
created by the insertion of other
"minor" exons in the NCAM
transcript. The two most notable are:
the VASE (VAriable domain
Spliced Exon) exon which is
thought to correlate with an
inhibition of the neurite
outgrowth promoting
properties of NCAM.
the MSD (Muscle Specific
Domain), which is thought to
play a positive role in
myoblast fusion.[8] In skeletal
muscle it is found in all three
NCAM isoforms, increasing
their MW, giving NCAM-125,
NCAM-145, and NCAM-185
isoforms, but is most
commonly found in the
NCAM-125 isoform.[8]
Posttranslational
modification
NCAM exhibits glycoforms as it can
be posttranslationally modified by the
addition of polysialic acid (PSA) to
the fifth Ig domain, which is thought
to abrogate its homophilic binding
properties and can lead to reduced
cell adhesion important in cell
migration and invasion. PSA has
been shown to be critical in learning
and memory. Removal of PSA from
NCAM by the enzyme
endoneuraminidase (EndoN) has
been shown to abolish long-term
potentiation (LTP) and long-term
depression (LTD).[9][10][11]
Expression in normal
cells
Gene ontology
Molecular • virus receptor activity (http://amigo.geneontology.or
function g/amigo/term/GO:0001618)
• identical protein binding (http://amigo.geneontology.
org/amigo/term/GO:0042802)
• Ras guanyl-nucleotide exchange factor activity (htt
p://amigo.geneontology.org/amigo/term/GO:0005088)
Cellular • integral component of membrane (http://amigo.gene
component ontology.org/amigo/term/GO:0016021)
• membrane (http://amigo.geneontology.org/amigo/ter
m/GO:0016020)
• Golgi membrane (http://amigo.geneontology.org/ami
go/term/GO:0000139)
• cell membrane (http://amigo.geneontology.org/amig
o/term/GO:0005886)
• extracellular region (http://amigo.geneontology.org/a
migo/term/GO:0005576)
• cell surface (http://amigo.geneontology.org/amigo/ter
m/GO:0009986)
• anchored component of membrane (http://amigo.ge
neontology.org/amigo/term/GO:0031225)
• extracellular exosome (http://amigo.geneontology.or
g/amigo/term/GO:0070062)
• external side of plasma membrane (http://amigo.gen
eontology.org/amigo/term/GO:0009897)
• cytosol (http://amigo.geneontology.org/amigo/term/G
O:0005829)
• extracellular matrix (http://amigo.geneontology.org/a
migo/term/GO:0031012)
• collagen-containing extracellular matrix (http://amig
o.geneontology.org/amigo/term/GO:0062023)
Biological • interferon-gamma-mediated signaling pathway (htt
process p://amigo.geneontology.org/amigo/term/GO:0060333)
• MAPK cascade (http://amigo.geneontology.org/amig
o/term/GO:0000165)
• axon guidance (http://amigo.geneontology.org/amig
o/term/GO:0007411)
• cell adhesion (http://amigo.geneontology.org/amigo/t
erm/GO:0007155)
• viral entry (http://amigo.geneontology.org/amigo/ter
m/GO:0046718)
• GO:0022415 viral process (http://amigo.geneontolog
y.org/amigo/term/GO:0016032,)
• regulation of molecular function (http://amigo.geneo
ntology.org/amigo/term/GO:0065009)
• commissural neuron axon guidance (http://amigo.ge
The neural cell adhesion molecule
NCAM1 appears on early embryonic
cells and is important in the
formation of cell collectives and their
boundaries at sites of morphogenesis.
Later in development, NCAM1
(CD56) expression is found on
various differentiated tissues and is a
major CAM mediating adhesion
among neurons and between neurons
and muscle.
Function
NCAM is thought to signal to induce
neurite outgrowth via the fibroblast
growth factor receptor (FGFR) and
act upon the p59Fyn signaling
pathway.
In nerves, NCAM1 regulates
homophilic (like-like) interactions
between neurons and between
neurons and muscle; it associates
with fibroblast growth factor receptor
(FGFR) and stimulates tyrosine
kinase activity of receptor to induce
neurite outgrowth. When neural crest
cells stop making N-CAM and N-
cadherin, and start displaying integrin
receptors, cells separate and migrate.
During hematopoiesis, CD56 is the
prototypic marker of NK cells, also
present on subset of CD4+ T cells
and CD8+ T cells.
In cell adhesion, CD56 contributes to
cell-cell adhesion or cell-matrix
adhesion during embryonic
development.
Pathology
In anatomic pathology, pathologists
make use of CD56
immunohistochemistry to recognize
certain tumors.
neontology.org/amigo/term/GO:0071679)
• regulation of semaphorin-plexin signaling pathway (h
ttp://amigo.geneontology.org/amigo/term/GO:200126
0)
• neuron projection development (http://amigo.geneon
tology.org/amigo/term/GO:0031175)
• regulation of synaptic plasticity (http://amigo.geneont
ology.org/amigo/term/GO:0048167)
Sources:Amigo (http://amigo.geneontology.org/) / QuickGO (https://
www.ebi.ac.uk/QuickGO/)
Orthologs
Species Human Mouse
Entrez
4684 (https://www.ncb 17967 (https://www.ncbi.
i.nlm.nih.gov/entrez/qu nlm.nih.gov/entrez/query.f
ery.fcgi?db=gene&cm cgi?db=gene&cmd=retrie
d=retrieve&dopt=defa ve&dopt=default&list_uid
ult&list_uids=4684&rn s=17967&rn=1)
=1)
Ensembl
ENSG00000149294 ENSMUSG00000039542
(http://www.ensembl.o (http://www.ensembl.org/
rg/Homo_sapiens/gen Mus_musculus/genevie
eview?gene=ENSG00 w?gene=ENSMUSG000
000149294;db=core) 00039542;db=core)
UniProt
P13591 (https://www.u P13595 (https://www.unip
niprot.org/uniprot/P13 rot.org/uniprot/P13595)
591)
RefSeq
(mRNA) NM_181351 (https://w NM_001081445 (https://
ww.ncbi.nlm.nih.gov/e www.ncbi.nlm.nih.gov/ent
ntrez/viewer.fcgi?val= rez/viewer.fcgi?val=NM_
NM_181351) 001081445)
NM_000615 (https://w NM_001113204 (https://
ww.ncbi.nlm.nih.gov/e www.ncbi.nlm.nih.gov/ent
ntrez/viewer.fcgi?val= rez/viewer.fcgi?val=NM_
NM_000615) 001113204)
NM_001076682 (http NM_010875 (https://ww
s://www.ncbi.nlm.nih.g w.ncbi.nlm.nih.gov/entre
ov/entrez/viewer.fcgi? z/viewer.fcgi?val=NM_01
val=NM_001076682) 0875)
NM_001242607 (http NM_001311065 (https://
s://www.ncbi.nlm.nih.g
ov/entrez/viewer.fcgi?
 Normal cells that stain
positively for CD56 include
NK cells, activated T cells,
the brain and cerebellum, and
neuroendocrine tissues.
Tumors that are CD56-
positive are myeloma,
myeloid leukemia,
neuroendocrine tumors,
Wilms' tumor, neuroblastoma,
extranodal NK/T-cell
lymphoma, nasal type,
pancreatic acinar cell
carcinoma,
pheochromocytoma,
paraganglioma, small cell
lung carcinoma, and the
Ewing's sarcoma family of
tumors.
Cancer
A member of the NCAM
superfamily, NCAM2 gene has been
observed progressively
downregulated in Human
papillomavirus-positive neoplastic
keratinocytes derived from uterine
cervical preneoplastic lesions at
different levels of malignancy.[12]
For this reason, NCAM2 is likely to
be associated with tumorigenesis and
may be a potential prognostic marker
for uterine cervical preneoplastic
lesions progression.[12]
val=NM_001242607) www.ncbi.nlm.nih.gov/ent
NM_001242608 (http rez/viewer.fcgi?val=NM_
s://www.ncbi.nlm.nih.g 001311065)
ov/entrez/viewer.fcgi?
val=NM_001242608)
RefSeq
(protein) NP_000606 (https://w NP_001074914 (https://w
ww.ncbi.nlm.nih.gov/e ww.ncbi.nlm.nih.gov/entr
ntrez/viewer.fcgi?val= ez/viewer.fcgi?val=NP_0
NP_000606) 01074914)
NP_001070150 (http NP_001106675 (https://w
s://www.ncbi.nlm.nih.g ww.ncbi.nlm.nih.gov/entr
ov/entrez/viewer.fcgi? ez/viewer.fcgi?val=NP_0
val=NP_001070150) 01106675)
NP_001229536 (http NP_001297994 (https://w
s://www.ncbi.nlm.nih.g ww.ncbi.nlm.nih.gov/entr
ov/entrez/viewer.fcgi? ez/viewer.fcgi?val=NP_0
val=NP_001229536) 01297994)
NP_001229537 (http NP_035005 (https://www.
s://www.ncbi.nlm.nih.g ncbi.nlm.nih.gov/entrez/vi
ov/entrez/viewer.fcgi? ewer.fcgi?val=NP_03500
val=NP_001229537) 5)
NP_851996 (https://w
ww.ncbi.nlm.nih.gov/e
ntrez/viewer.fcgi?val=
NP_851996)
Location Chr 11: 112.96 – 113.28 Chr 9: 49.5 – 49.8 Mb (http
(UCSC) Mb (https://genome.ucsc. s://genome.ucsc.edu/cgi-bin/
edu/cgi-bin/hgTracks?org hgTracks?org=Mouse&db=m
=Human&db=hg38&positi m0&position=chr9:49502136-
on=chr11:112961247-113 49798925)
278436)
PubMed [3] [4]

Alzheimer's disease search

Wikidata
NCAM2 is found in lower levels in
View/Edit Human View/Edit Mouse
hippocampal synapses of
Alzheimer's disease sufferers and is
found to be broken down by beta-amyloid[13]

Anti-NCAM therapy
NCAM has been used as a target molecule for experimental antibody-based immunotherapy. Successful radio-
immunolocalisation of metastases was demonstrated after giving injections of NCAM-binding 123J-UJ13a or
131J-UJ13a radio-immunoconjugates to children with neuroblastoma. Patients with small cell lung cancer
were treated with the anti-NCAM immunotoxine huN901-DM1 in two different clinical studies, revealing
acceptable toxicity and signs of clinical response.[14]
References
1. GRCh38: Ensembl release 89: ENSG00000149294 (http://May2017.archive.ensembl.org/Hom
o_sapiens/Gene/Summary?db=core;g=ENSG00000149294) - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039542 (http://May2017.archive.ensembl.org/
Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000039542) - Ensembl, May 2017
3. "Human PubMed Reference:" (https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&
LinkName=gene_pubmed&from_uid=4684). National Center for Biotechnology Information,
U.S. National Library of Medicine.
4. "Mouse PubMed Reference:" (https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&
LinkName=gene_pubmed&from_uid=17967). National Center for Biotechnology Information,
U.S. National Library of Medicine.
5. Van Acker HH, Capsomidis A, Smits EL, Van Tendeloo VF (2017). "CD56 in the Immune
System: More Than a Marker for Cytotoxicity?" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC
5522883). Frontiers in Immunology. 8: 892. doi:10.3389/fimmu.2017.00892 (https://doi.org/10.3
389%2Ffimmu.2017.00892). PMC 5522883 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC55
22883). PMID 28791027 (https://pubmed.ncbi.nlm.nih.gov/28791027).
6. Pathology Outlines (http://www.pathologyoutlines.com/cd5099.html#CD56)
7. Reyes AA, Small SJ, Akeson R (March 1991). "At least 27 alternatively spliced forms of the
neural cell adhesion molecule mRNA are expressed during rat heart development" (https://ww
w.ncbi.nlm.nih.gov/pmc/articles/PMC369464). Molecular and Cellular Biology. 11 (3): 1654–61.
doi:10.1128/mcb.11.3.1654 (https://doi.org/10.1128%2Fmcb.11.3.1654). PMC 369464 (https://w
ww.ncbi.nlm.nih.gov/pmc/articles/PMC369464). PMID 1996115 (https://pubmed.ncbi.nlm.nih.go
v/1996115).
8. Suzuki M, Angata K, Nakayama J, Fukuda M (December 2003). "Polysialic acid and mucin
type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion" (htt
ps://doi.org/10.1074/jbc.M308316200). The Journal of Biological Chemistry. 278 (49): 49459–
68. doi:10.1074/jbc.M308316200 (https://doi.org/10.1074%2Fjbc.M308316200).
PMID 13679364 (https://pubmed.ncbi.nlm.nih.gov/13679364).
9. Becker CG, Artola A, Gerardy-Schahn R, Becker T, Welzl H, Schachner M (July 1996). "The
polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning
and hippocampal long-term potentiation". Journal of Neuroscience Research. 45 (2): 143–52.
doi:10.1002/(SICI)1097-4547(19960715)45:2<143::AID-JNR6>3.0.CO;2-A (https://doi.org/10.1
002%2F%28SICI%291097-4547%2819960715%2945%3A2%3C143%3A%3AAID-JNR6%3E
3.0.CO%3B2-A). PMID 8843031 (https://pubmed.ncbi.nlm.nih.gov/8843031).
10. Stoenica L, Senkov O, Gerardy-Schahn R, Weinhold B, Schachner M, Dityatev A (May 2006).
"In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion
molecule NCAM or its polysialic acid". The European Journal of Neuroscience. 23 (9): 2255–
64. doi:10.1111/j.1460-9568.2006.04771.x (https://doi.org/10.1111%2Fj.1460-9568.2006.0477
1.x). PMID 16706834 (https://pubmed.ncbi.nlm.nih.gov/16706834).
11. Senkov O, Sun M, Weinhold B, Gerardy-Schahn R, Schachner M, Dityatev A (October 2006).
"Polysialylated neural cell adhesion molecule is involved in induction of long-term potentiation
and memory acquisition and consolidation in a fear-conditioning paradigm" (https://doi.org/10.1
523/JNEUROSCI.0878-06.2006). The Journal of Neuroscience. 26 (42): 10888–109898.
doi:10.1523/JNEUROSCI.0878-06.2006 (https://doi.org/10.1523%2FJNEUROSCI.0878-06.20
06). PMID 17050727 (https://pubmed.ncbi.nlm.nih.gov/17050727).
12. Rotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, Magri E, Selvatici R, Torresani S,
Marci R, Garutti P, Negrini M, Tognon M, Martini F (April 2015). "Gene expression changes in
progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic
keratinocytes". J Cell Physiol. 230 (4): 802–812. doi:10.1002/jcp.24808 (https://doi.org/10.100
2%2Fjcp.24808). PMID 25205602 (https://pubmed.ncbi.nlm.nih.gov/25205602).
13. Leshchyns'ka I, Liew HT, Shepherd C, Halliday GM, Stevens CH, Ke YD, Ittner LM, Sytnyk V
(November 2015). "Aβ-dependent reduction of NCAM2-mediated synaptic adhesion
contributes to synapse loss in Alzheimer's disease" (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC4674770). Nature Communications. 6: 8836. doi:10.1038/ncomms9836 (https://doi.org/10.
1038%2Fncomms9836). PMC 4674770 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46747
70). PMID 26611261 (https://pubmed.ncbi.nlm.nih.gov/26611261).
14. Jensen M, Berthold F (December 2007). "Targeting the neural cell adhesion molecule in
cancer". Cancer Letters. 258 (1): 9–21. doi:10.1016/j.canlet.2007.09.004 (https://doi.org/10.101
6%2Fj.canlet.2007.09.004). PMID 17949897 (https://pubmed.ncbi.nlm.nih.gov/17949897).

External links
Neural+Cell+Adhesion+Molecule (https://meshb.nlm.nih.gov/record/ui?name=Neural%20Cel
l%20Adhesion%20Molecule) at the US National Library of Medicine Medical Subject Headings
(MeSH)

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