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ADAM23 (ADAM metallopeptidase domain 23)

Written2014-09Erico T Costa, Anamaria A Camargo
Ludwig Institute for Cancer Research - at Hospital Sirio-Libanes, Sao Paulo - SP - Brazil
This article is an update of :
2007-07Marilia de Freitas Calmon, Paula Rahal
Laboratory of Genomics studies - Sao Paulo State University _ Departament of Biology _ Sao Jose do Rio Preto- SP- Brazil

Abstract ADAM23 belongs to the ADAM (A Disintegrin And Metalloproteinase domain) family of proteins. Members of this family present a common structural organization including metalloprotease, disintegrin, cystein-rich, epidermal growth factor-like, transmembrane and cytoplasmatic domains and are structurally related to snake venom disintegrins. ADAM23 has close similarity to ADAM11 and ADAM22; is highly expressed in the CNS, and is crucial for normal brain development. Mice homozygous for an insertional mutation that inactivates the gene are smaller than normal littermates, show delayed lung development, are lethal by postnatal day 14, and display severe tremor and ataxia. ADAM23 does not present metalloprotease activity and probably plays its biological role through the disintegrin domain. ADAM23 is involved in cell-cell adhesion and communication and cell-matrix modulation. The ADAM23 gene is frequently silenced by DNA promoter methylation in different types of solid cancers and epigenetic inactivation is associated with cancer progression, increased tumor cell mobility and reduced tumor cell proliferation.

Keywords ADAM family, cell-cell adhesion, cell migration, invasion, proliferation, differentiation, metastasis

(Note : for Links provided by Atlas : click)


Alias (NCBI)MDC3
HGNC (Hugo) ADAM23
HGNC Alias symbMDC3
HGNC Previous namea disintegrin and metalloproteinase domain 23
LocusID (NCBI) 8745
Atlas_Id 44041
Location 2q33.3  [Link to chromosome band 2q33]
Location_base_pair Starts at 206443532 and ends at 206621127 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping ADAM23.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ADAM23 (2q33.3)::ADAM23 (2q33.3)ADAM23 (2q33.3)::CERKL (2q31.3)ADAM23 (2q33.3)::PLPP1 (5q11.2)
ADAM23 (2q33.3)::SGO2 (2q33.1)


  Genomic structure of ADAM23 human gene composed of 27 coding exons. Black boxes represent constitutive exons present in all splicing isoforms. Colored boxes represent alternatively spliced exons.
Description DNA contains 177488 bp composed of 27 coding exons (26 reported by RefSeq sequences).
Transcription 6236 bp mRNA transcribed (RefSeq NM_003812.3) in centromeric to telomeric orientation; 2499 bp open reading frame. There are three alternative splicing isoforms of the human ADAM23 gene: ADAM23-alpha (chosen as the 'canonical' sequence), ADAM23-beta and ADAM23-gamma. These splicing isoforms are generated by the mutually exclusive use or skipping of the exons 25 and/or 26, both of which coding for transmembrane domains with different aminoacid compositions. The ADAM23 proteins encoded by the alpha and beta splicing isoforms are anchored to the membrane by different transmembrane domains (encoded by exon 26 in the isoform alpha and by exon 25 in the isoform beta) and are predicted to have distinct membrane subdomain localizations. ADAM23-gamma is generated by exon skipping of exons 25 and 26 and therefore lacks the transmembrane domain and is predicted to be either a cytoplasmatic or a secreted isoform of the ADAM23 protein. ADAM23 mRNA is detected at high or medium expression levels in brain, testis and heart muscle (The Human Protein Atlas, ENSG00000114948).
Pseudogene No pseudogenes reported.


  Domain structure of ADAM23. Its deduced amino acid sequence lacks essential residues conserved in metalloproteinases (adapted from Cal et al., 2000).
Description ADAM23 is a non-catalytically active member of ADAM family and exhibits all the conserved protein domains, including: an N-terminal signal, a pro-domain, a metalloprotease and a disintegrin domains, a cysteine-rich region, an EGF-like domain, a transmembrane and a short cytoplasmic domains. Within the metalloprotease domain, ADAM23 lacks the conserved zinc-binding sequence HEXXHXXGXXH, which is critical for the proteinase activity. Interacts with LGI1, LGI3 and LGI4 (leucine-rich glioma inactivated family), alphav-beta3 integrins and PrPc proteins.
Size: 832 amino acid; 92 kDa predicted (RefSeq NP_003803).
Expression Detected at medium/high expression levels in 46 of 82 analyzed normal tissue types, including: brain, testis, lung, breast, colon, pancreas and kidney (according to The Human Protein Atlas).
Localisation Cell membrane; single-pass type I membrane protein (isoform ADAM23-alpha and ADAM23-beta). Secreted protein (predicted for ADAM23-gama isoform).
  Immunohistochemistry staining of ADAM23 protein in normal colon and normal breast tissues was carried out using the polyclonal antibody anti-ADAM23 (HPA012130, Sigma) (photograph courtesy of Dra. Gabriela F Barnabe from Ludwig Institute for Cancer Research - SP - Brazil).
Function ADAM23 was originally described to promote neuroblastoma and astrocytoma cell-cell adhesion via direct interaction with alphavbeta3 integrin. Following reports showed that the interaction between ADAM23 and alphavbeta3 integrin inhibits cell-matrix adhesion and negatively modulates alphavbeta3 activation during metastatic progression. Silencing of the ADAM23 gene promotes cell cycle arrest and terminal differentiation in P19 mice embryonic carcinoma cells and, in MDA-MB435 and SK-Mel37 tumor cell lines, promotes tumor cell migration and invasion and inhibits tumor cell proliferation.
Homology H. sapiens: ADAM23, P. troglodytes: ADAM23, C. lupus: LOC607871, M. musculus: ADAM23, R. novergicus: ADAM23, G. gallus: LOC424099.


Note No mutations have been reported for ADAM23 gene.
Epigenetics Epigenetic silencing of the ADAM23 have been frequently reported in different types of solid tumors.
Germinal No germline mutations have been reported for the ADAM23 gene (OMIM603710).
Somatic No somatic point mutations and CNVs have been reported.

Implicated in

Entity Breast carcinoma
Note ADAM23 expression is downregulated by promoter hypermethylation during breast cancer progression and hypermethylation was significantly associated with a higher incidence of distant metastasis and reduced overall survival. Recently, ADAM23 epigenetic silencing during tumor progression was shown to generate genetic and functional heterogeneity in invasive breast tumors. ADAM23-intratumoral heterogeneity (ADAM23-ITH) was observed in topographically distinct areas of undifferentiated breast invasive ductal carcinomas, with invasive components being frequently composed by mosaic clusters of ADAM23-positive tumor cells coexisting in close proximity with ADAM23-silenced cells. Most importantly, it was demonstrated that ADAM23-ITH promotes tumor growth and metastasis by establishing a crosstalk between ADAM23-positives and ADAM23-negatives tumor cells in which ADAM23-negative cells promote tumor growth and metastasis by enhancing the proliferation and invasion of adjacent ADAM23-positive cells through the production of the ADAM23-ligant LGI4 (leucine-rich glioma Inactivated gene 4) and pro-migratory levels of nitric oxide (NO).
Entity Lung carcinoma
Note ADAM23 protein levels is lower in non-small-cell lung carcinoma (NSCLC) compared to corresponding normal tissues and benign pulmonary lesions, and a decrease in ADAM23 protein expression was observed during NSCLC progression. Hypermethylation of ADAM23 promoter region was observed in 40% of NSCLC but in only 7.6% of the adjacent normal tissues.
Entity Gastric tumors
Note ADAM23 promoter hypermethylation is frequently observed in gastric dysplasia (90%) and gastric tumors (29-55%) but is rarely observed in normal mucosa (9%). The frequency of ADAM23 methylation is higher in metastatic lesions compared to paired primary tumors. Homozygous loss of ADAM23 was also reported for gastric tumors but at a lower frequency (~3%).
Entity Pancreatic tumors
Note ADAM23 promoter methylation was detected in 7 out of 24 (29%) primary invasive pancreatic ductal adenocarcinomas.
Entity Head and neck cancer
Note ADAM23 promoter hypermethylation was detected in 18 out of 43 head and neck tumors (42%) and a significant association between ADAM23 hypermethylation and advanced stages (T3-T4) was observed larynx tumors.
Entity Multiple myeloma
Note ADAM23 mRNA expression is absent in normal bone marrow plasma cells, but is aberrantly expressed in 2/131 (1,5%) patients with newly diagnosed multiple myeloma. In two independent cohorts of patients with primary multiple myeloma, 24 out of 557 patients (4%) showed increased levels of ADAM23 mRNA expression, which was significantly associated with poor overall survival.


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This paper should be referenced as such :
Costa ET, Camargo AA
ADAM23 (ADAM metallopeptidase domain 23);
Atlas Genet Cytogenet Oncol Haematol. in press
Free journal version : [ pdf ]   [ DOI ]
History of this paper:
Marilia, de Freitas C ; Rahal, P. ADAM23 (ADAM metallopeptidase domain 23). Atlas Genet Cytogenet Oncol Haematol. 2008;12(1):17-19.

External links


HGNC (Hugo)ADAM23   202
Entrez_Gene (NCBI)ADAM23    ADAM metallopeptidase domain 23
AliasesMDC-3; MDC3
GeneCards (Weizmann)ADAM23
Ensembl hg19 (Hinxton)ENSG00000114948 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000114948 [Gene_View]  ENSG00000114948 [Sequence]  chr2:206443532-206621127 [Contig_View]  ADAM23 [Vega]
ICGC DataPortalENSG00000114948
TCGA cBioPortalADAM23
AceView (NCBI)ADAM23
Genatlas (Paris)ADAM23
SOURCE (Princeton)ADAM23
Genetics Home Reference (NIH)ADAM23
Genomic and cartography
GoldenPath hg38 (UCSC)ADAM23  -     chr2:206443532-206621127 +  2q33.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ADAM23  -     2q33.3   [Description]    (hg19-Feb_2009)
GoldenPathADAM23 - 2q33.3 [CytoView hg19]  ADAM23 - 2q33.3 [CytoView hg38]
Genome Data Viewer NCBIADAM23 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB009672 AF052115 AJ005580 AK091800 AK129906
RefSeq transcript (Entrez)NM_003812
Consensus coding sequences : CCDS (NCBI)ADAM23
Gene ExpressionADAM23 [ NCBI-GEO ]   ADAM23 [ EBI - ARRAY_EXPRESS ]   ADAM23 [ SEEK ]   ADAM23 [ MEM ]
Gene Expression Viewer (FireBrowse)ADAM23 [ Firebrowse - Broad ]
GenevisibleExpression of ADAM23 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8745
GTEX Portal (Tissue expression)ADAM23
Human Protein AtlasENSG00000114948-ADAM23 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO75077   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO75077  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO75077
Domaine pattern : Prosite (Expaxy)ADAM_MEPRO (PS50215)    DISINTEGRIN_2 (PS50214)    EGF_1 (PS00022)    EGF_3 (PS50026)   
Domains : Interpro (EBI)ADAM_Cys-rich    Disintegrin_dom    Disintegrin_dom_sf    EGF-like_dom    MetalloPept_cat_dom_sf    Peptidase_M12B    Peptidase_M12B_N    Reprolysin_adamalysin   
Domain families : Pfam (Sanger)ADAM_CR (PF08516)    Disintegrin (PF00200)    Pep_M12B_propep (PF01562)    Reprolysin (PF01421)   
Domain families : Pfam (NCBI)pfam08516    pfam00200    pfam01562    pfam01421   
Domain families : Smart (EMBL)ACR (SM00608)  DISIN (SM00050)  
Conserved Domain (NCBI)ADAM23
AlphaFold pdb e-kbO75077   
Human Protein Atlas [tissue]ENSG00000114948-ADAM23 [tissue]
Protein Interaction databases
IntAct (EBI)O75077
Ontologies - Pathways
Ontology : AmiGOmetalloendopeptidase activity  integrin binding  protein binding  extracellular region  plasma membrane  integral component of plasma membrane  proteolysis  cell adhesion  central nervous system development  metallopeptidase activity  glutamatergic synapse  integral component of presynaptic membrane  cellular response to leukemia inhibitory factor  
Ontology : EGO-EBImetalloendopeptidase activity  integrin binding  protein binding  extracellular region  plasma membrane  integral component of plasma membrane  proteolysis  cell adhesion  central nervous system development  metallopeptidase activity  glutamatergic synapse  integral component of presynaptic membrane  cellular response to leukemia inhibitory factor  
REACTOMEO75077 [protein]
REACTOME PathwaysR-HSA-5682910 [pathway]   
NDEx NetworkADAM23
Atlas of Cancer Signalling NetworkADAM23
Wikipedia pathwaysADAM23
Orthology - Evolution
GeneTree (enSembl)ENSG00000114948
Phylogenetic Trees/Animal Genes : TreeFamADAM23
Homologs : HomoloGeneADAM23
Homology/Alignments : Family Browser (UCSC)ADAM23
Gene fusions - Rearrangements
Fusion : MitelmanADAM23::CERKL [2q33.3/2q31.3]  
Fusion : MitelmanADAM23::PPAP2A [2q33.3/5q11.2]  
Fusion : MitelmanADAM23::SGOL2 [2q33.3/2q33.1]  
Fusion : QuiverADAM23
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerADAM23 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ADAM23
Exome Variant ServerADAM23
GNOMAD BrowserENSG00000114948
Varsome BrowserADAM23
ACMGADAM23 variants
Genomic Variants (DGV)ADAM23 [DGVbeta]
DECIPHERADAM23 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisADAM23 
ICGC Data PortalADAM23 
TCGA Data PortalADAM23 
Broad Tumor PortalADAM23
OASIS PortalADAM23 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICADAM23  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DADAM23
Mutations and Diseases : HGMDADAM23
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)ADAM23
DoCM (Curated mutations)ADAM23
CIViC (Clinical Interpretations of Variants in Cancer)ADAM23
NCG (London)ADAM23
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry ADAM23
NextProtO75077 [Medical]
Target ValidationADAM23
Huge Navigator ADAM23 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDADAM23
Pharm GKB GenePA24519
Clinical trialADAM23
DataMed IndexADAM23
PubMed36 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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