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FLASH GENE

Symbol

NCAM1

contributors: mct - updated : 26-11-2014

HGNC name	neural cell adhesion molecule 1
HGNC id	7656

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

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       specific Reproductive female system uterus     lowly   male system testis     lowly Urinary kidney nephron     highly Homo sapiens Fetal   kidney renal medulla     highly Homo sapiens Fetal Visual eye retina     lowly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Homo sapiens Nervous neuron Homo sapiens Visual Muller cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	five immunoglobulin-like (Ig) extracellular domains
	two fibronectin type III-like domains
	an intracellular domain of NCAM (residues 975–1105) is a binding partner of dynein
	a conserved C-terminal motif that may signal via myosin light chain kinase to regulate myosin-driven synaptic vesicle trafficking at the presynaptic terminal

HOMOLOGY

interspecies	homolog to rattus Ncam1 (95.22 pc)
	homolog to murine Ncam1 (91.14 pc)

Homologene

FAMILY	immunoglobulin superfamily
	immunoglobulin C-2 type family
	neural cell adhesion molecule signature

CATEGORY

adhesion

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,lysosome
text	endocytosed and subsequently recycled to the plasma membrane, whereas only a minor fraction was degraded in lysosomes

basic FUNCTION	involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites
	major polysialyl acid -carrying glycoprotein
	promotes assembly of the spectrin-based postsynaptic signaling complex, which is required for activity-associated, long-lasting changes in synaptic strength
	plays an important role during neural development and in the adult brain
	plays an important role during neural development and in the adult brain, whereby most functions of NCAM1 have been ascribed to its unique polysialic acid (PSA) modification
	membrane-bound cell recognition molecule that exerts important functions in normal neurodevelopment including cell migration, neurite outgrowth, axon fasciculation, and synaptic plasticity
	role of NCAM1 in promoting insulin signaling and adipocyte differentiation of adult stem cells (pMID: 21730021)
	exhibits a regulatory function in pathological angiogenesis in oxygen induced retinopathy
	homeostatic regulation of NCAM1 polysialylation is critical for correct synaptic targeting
	vital function of NCAM in MSCs migration and differentiation thus raising the possibility of manipulating NCAM expression to enhance homing and therapeutic potential of MSCs in cellular therapy
	NCAM1 activates PAK1 to drive actin polymerization to promote neuronal differentiation
	cell adhesion molecule that has been widely implicated in axonal outgrowth, guidance and fasciculation
	implicated in different neurodevelopmental processes and in synaptic plasticity in adult brain

CELLULAR PROCESS	cell life, differentiation
	cell communication

PHYSIOLOGICAL PROCESS

development , nervous system

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	with GFRA1 to downregulate NCAM-mediated cell adhesion
	binding to FGFR1 and FGFR2
	associates with the postsynaptic spectrin-based scaffold, cross-linking NCAM1 with the N-methyl-d-aspartate (NMDA) receptor and Ca2+/calmodulin-dependent protein kinase II alpha (CAMK2A)
	directly interacts with the intracellular domain of the receptor-like protein tyrosine phosphatase PTPRA, a known activator of FYN
	interacting with GAP43 (play pivotal roles in neuronal development and plasticity and possess inter-dependent functions)
	GDNF-induced neurite outgrowth via NCAM1 differs from NCAM1-induced neurite outgrowth by being independent of NCAM1 polysialylation)
	directly binds to NTRK2 and KCNJ9
	co-localization of NCAM1 and FGFR2 in early vertebrate development with intracellular signaling pathways present to enable a cellular response
	NCAM1 regulates RIC8A membrane localization and potentiates beta-adrenergic response
	UCHL1 is a novel interaction partner of both NCAM1 isoforms (NCAM140, NCAM180) that regulates their ubiquitination and intracellular trafficking
	NCAM1 interacts with PAK1 in growth cones of neurons
	NTRK2 and NCAM1 are downstream targets of NEUROD1 that contribute to the actions of NEUROD1 in neuroendocrine lung
	dynein-NCAM180 interaction might have a role in regulating microtubule dynamics and enhancing cell-cell interactions in these cells
	dynein-NCAM1 interaction might have a functional role at synapses

cell & other

REGULATION

Other

ubiquitylated, endocytosed and recycled in neurons

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   is one of the factors associated with or possibly responsible for disease progression in multiple sclerosis constitutional       gain of function plays a pivotal role in the pathogenesis of ischemic cardiomyopathy (ICM) and may be a target for future immunotherapeutic strategies in the treatment of this common and often fatal disease constitutional     --over   of CHRNG, CHRND, NCAM1, RUNX1 associated with neuromuscular junction denervation in ageing tumoral     --over   in follicular adenoma (FA), and nonneoplastic thyroid lesions

Susceptibility

to neural tube defects to alcohol dependence to left ventricular wall thickness and relative wall thickness in hypertensive families

Variant & Polymorphism SNP , other	SNP associated to neural tube defects
	variant of exon12/intron 13 increasing risk of alcohol dependence
	variant in NCAM1 associated with left ventricular wall thickness and relative wall thickness in hypertensive families

Candidate gene
Marker	expression of NCAM1 is an unfavorable prognostic marker for acute promyelocytic leukemia with higher initial white blood cell counts
Therapy target
	System Type Disorder Pubmed miscelleaneous urinary chronic kidney disease ability to influence an endogenous regenerative response via NCAM1 targeting may lead to novel therapeutics for renal diseases

ANIMAL & CELL MODELS

bone marrow-derived MSCs from Ncam deficient mice exhibit defective migratory ability and significantly impaired adipogenic and osteogenic differentiation potential