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FLASH GENE

Symbol

CADM1

contributors: mct/pgu - updated : 23-08-2015

HGNC name	cell adhesion molecule 1
HGNC id	5951

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	11q23.3      Physical location : 115.044.345 - 115.375.241
Synonym name	synaptic cell adhesion molecule
	tumor supressor in lung cancer (see ST3)
	immunoglobulin superfamily, member 4
	nectin-like molecule 2
	spermatogenic immunoglobulin superfamily
Synonym symbol(s)	ST17, TSLC1, BL2, NECL2, SYNCAM, SYNCAM1, RA175, BL2, ST17, IGSF4, IGSF4A, Necl-2, MGC51880, MGC149785, sgIGSF

DNA

TYPE	functioning gene
STRUCTURE	330.90 kb     10 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D11S144 - D11S4501 - D11S145 - D11S4517 - D11S1256 - D11S4111 /CADM1 - D11S4502 - D11S4484 - D11S1885 - D11S4500 - D11S4507 - qter

regionally located

situated in a common loss of heterozygosity region (see IGBF4)

RNA

TRANSCRIPTS	type	messenger

text

same ORF

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_014333 10 splicing 4324 NP_055148 - 442 - 2009 19854157 also called IGSF4L NM_001098517 9 - 4240 NP_001091987 - 414 - 2009 19854157 also called IGSF4S CADM1 SP4 - - - - - - 2013 23620770 key receptor mediating mast cells adhesion to airway smooth muscle cells and lung fibroblasts

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart       highly Endocrine pancreas islet of Langerhans     highly Nervous brain       highly Homo sapiens Reproductive male system testis     highly Homo sapiens Respiratory lung       highly Homo sapiens Skin/Tegument skin appendages hair bulb   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Nervous neuron Reproductive spermatid Reproductive spermatocyte Skin/Tegument hair follicle cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, perinatal

Text	expressed in the late embryonic and early postnatal brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal signal peptide
	three Ig-C2-like domains
	a transmembrane segment (TM1)
	cytoplasmic domain with a binding motif to the protein 4.1 family of molecules
	cytoplasmic domain with a type II PSD95/Dlg/ZO-1 (PDZ)-binding motif (BM) for associating with other intracellular proteins
	a C-terminal transmembrane domain, and an intracellular type II PDZ binding domain and band 4.1 binding domain
	extracellular domain of CADM1 undergoing homophilic or heterophilic interaction with CADM3, PVRL3, and CRTAM (class-I MHC-restricted T cell-associated molecule)

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to murine Igsf4

intraspecies

homolog to NCAM1,NCAM2

Homologene

FAMILY	immunoglobulin superfamily
	nectin family

CATEGORY

adhesion

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
text	integral membrane protein, localized to both sides of the synaptic cleft

basic FUNCTION	potentially involved in cell-surface recognition during synapse assembly
	involved in the suppression of lung tumor formation and metastasis
	playing an important role in normal cell-cell interaction
	a central effector gene for controlling the biologic aggressiveness of the tumor and that it is an essential biomarker for predicting patient prognosis
	plays an important role in meningioma pathogenesis
	functions as a glioma tumor suppressor
	may be playing a role in normal spermatogenesis
	synaptic cell adhesion molecule sufficient for promoting the formation of presynaptic terminals and inducing the functional synapse
	mediates nerve-mast cell attachment and communication through homophilic binding
	may be involved in hormone secretion from islet cell tumors
	involved in regulating epidermal stem cell quiescence and location
	selectively involved in endothelial cell migration, suggesting a role in endothelial barrier repair
	tumor suppressor, involved in cell adhesion and preferentially inactivated in invasive cancer
	involved in the formation of epithelia-like cell structure with EPB41L3 and MPP2, while loss of its function could cause morphological transformation of cancer cells
	plays an important role in the formation of the epithelial cell structure with mature cell adhesion
	CADM1 complex may play a key role in the formation of the epithelia-like cell structure, whereas inactivation of the components of the complex would be a key step in malignant progression of cancer
	negatively regulates the morphological complexity of migrating growth cones
	acts in developing neurons to shape migrating growth cones and contributes to the adhesive differentiation of their axo-dendritic contacts
	contributes to ERBB4 receptor-mediated control of female sexual development
	self-assembles laterally via its extracellular, membrane-proximal immunoglobulin (Ig) domains 2 and 3
	function for CADM1 in suppressing metastasis by sensitizing tumor cells to immune surveillance mechanisms
	promotes the formation of presynaptic terminals and induces functional synapses in the central nervous system

CELLULAR PROCESS

cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

forms a tripartite protein complex with EPB41L3 and MPP1, MPP2, MPP3

INTERACTION

DNA

RNA

small molecule

protein	intracellular PDZ-domain proteins
	associating with MPP3(interaction dependent on the presence of a PDZ-binding motif at the carboxyl terminus of TSLC1)
	associates with an actin-binding protein, EPB41L3, and a scaffold protein, membrane protein palmitoylated 3 MPP3, MPP2, MPP1
	recruits NMDA receptors via protein EPB41L3
	interaction with PTK2 (PTK2 is a binding partner and effector in shaping growth cones)
	interacting with TIAM1 (cytoplasmic domain of CADM1 directly interacted with the PDZ domain of Tiam1 and induced formation of lamellipodia through Rac activation in HTLV-I-transformed cell lines as well as adult T-cell leukemia cell lines)
	EPB41L3 binds to CADM1 through conserved residues in a well defined hydrophobic pocket in the structural C-lobe of the EPB41L3 FERM domain
	ADAM10 mediates endogenous CADM1 shedding
	triggers a retrograde signal regulating active zone composition via CADM1
	interacts with ERBB4 and regulates the development of excitatory synapses via the regulation of ERBB4 activity in GABAergic neurons
	interaction of CADM1 with ERBB3 inhibits the NRG1-induced ERBB3/ERBB2 signaling in epithelial cells
	CDH2 promotes neurite branching and it is required for three synaptic organizers, NLGN1, leucine-rich repeat transmembrane protein 2 (LRRTM2), and CADM1 to stimulate presynaptic differentiation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOH     in breast cancer, neuroblastoma, non small cell lung cancer, hepatocellular, nasopharyngeal and pancreatic carcinomas tumoral       loss of function by promoter hypermethylation in non small cell lung cancer, hepatocellular carcinoma, pancreatic carcinoma, and prostate tumor tumoral     --low   in lung adenocarcinoma associated with lower patient survival, supporting its role as a tumor suppressor and in esophageal squamous cell carcinoma with a poor prognosis tumoral       loss of function by hypermethylation in premalignant cervical intraepithelial neoplasia by infection with high-risk human papillomavirus (HPV) types, in progression tumoral     --low   in meningioma, associated with decreased survival, and in the atypical meningiomas constitutional       loss of function causes male infertility tumoral     --low   in metastatic lymph node nasopharyngeal carcinoma tumoral     --over   frequent overexpression in lung adenocarcinoma tumoral     --over   resulted in reduced proliferation and increased levels of CASK and CDH1 at the leading edge of healing wounds tumoral     --low   frequently observed in various cancers, including non-small cell lung cancer (NSCLC) especially in their invasive lesions tumoral     --low   is a critical event in neuroblastoma pathogenesis resulting in tumour progression and unfavourable patient outcome tumoral     --low   by hypermethylation in squamous cell carcinomas (SCCs)of uterine cervix tumoral     --over   in adult T-cell leukemia-lymphoma (ATL) cells

Susceptibility

to Autism Spectrum Disorder (ASD)

Variant & Polymorphism other	mutationslocated in the third immunoglobulin (Ig3) domain essential for homophilic or heterophilic transactive interaction associated to Autism Spectrum Disorder (likely these mutations cause the loss of function, resulting in the impaired synaptogenesis, which is closely associated with the pathogenesis of ASD)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Cadm1-knock out (KO) mice exhibit smaller cerebella with decreased number of synapse of Purkinje cells and some ASD-like symptoms, including impaired ultrasonic vocalization
	epidermal overexpression of Cadm1 in transgenic mice led to increased autoimmune alopecia susceptibility relative to nontransgenic littermate controls