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ADAM23 (ADAM metallopeptidase domain 23)

Identity

Other namesMDC3
Hugo ADAM23
Location 2q33

DNA/RNA

 
  DNA of ADAM23 gene composed of 26 coding exons.
Description DNA contains 174312 bp composed of 26 coding exons.
Transcription 3059 bp mRNA transcribed in centromeric to telomeric orientation; 2499 bp open reading frame. There are two isoforms of human ADAM23 (ADAM23alpha), i.e. ADAM23beta and ADAM23gamma. ADAM23beta is consistent with ADAM23alpha in domain structure except for a different transmembrane domain. ADAM23gamma, without transmembrane domain, is predicted to be a secreted form of ADAM23. ADAM23gamma is formed by skipping both exons enconding transmembrane domain in RNA splicing.
Pseudogene No pseudogenes reported.

Protein

 
  Domain structure of ADAM23. Its deduced amino acid sequence lacks essential residues conserved in metalloproteinases (Cal S. et al., 2000).
Description 832amino acid protein including a hydrophobic transmembrane domain and eight potential N-linked glycosylation sites. This protein has multiple domain structures including a pro-, a metalloproteinase-like, a desintegrin-like, a cysteine-rich, an epidermal growth factor-like, a transmembrane and a cytoplasmatic domain. Within the metalloproteinase-like domain, ADAM23 lacks HEXXHXXGXXH active-site amino acids for zinc-binding, which is critical for the proteinase activity. So, the metalloproteinase domain is inactive, suggesting that it is exclusively involved in cell adhesion processes rather than in protease-mediated events.
Expression Highly expressed in the brain and weakly expressed in the heart. In the brain, expressed prominently in the amygdala, caudate nucleus, hypothalamus, thalamus, cerebral cortex and occipital pole.
Localisation Cell membrane; single-pass type I membrane protein (Potential). Isoform Gamma: Secreted protein.
Function May play a role in cell-cell and cell-matrix interactions. This is a non-catalytic metalloprotease-like protein.
Homology H. sapiens: ADAM23
P.troglodytes: ADAM23
C.lupus: LOC607871
M.musculus: ADAM23
R.novergicus: ADAM23
G.gallus: LOC424099

Mutations

Note There are one SNP on exon 1 in the amino acid position 1 with function start codon and two SNPs on exon 23 in the amino acid position 695 with functions synonymous and contig reference.

Implicated in

Entity gastric tumors.
Note Hypermethylation of the promoter region of ADAM 23 gene, along with decreased expression, occurs in primary gastric tumors compared with noncancerous gastric tissue.
Prognosis Not determined.
Cytogenetics Not determined.
Hybrid/Mutated Gene Not determined.
Oncogenesis Loss of ADAM23, which is likely to play an important role regard to cell-cell and cell- extracellular matrix interactions in gastric tissue as well, might be essential for the progression of gastric cancer.
  
Entity breast tumors.
Note Hypermethylation of the promoter region of ADAM23 gene, along with decreased expression, occurs in primary breast tumors and primary breast tumors with a more advanced grade have higher degree of methylation.
Cytogenetics Not determined.
Hybrid/Mutated Gene Not determined.
Oncogenesis Primary breast tumors with a more advanced grade have a higher degree of methylation, suggesting that the adhesion molecule ADAM23 may be downregulated during the progression of breast cancer.
  
Entity Head and neck cancer.
Note Hypermethylation of the promoter region of ADAM23 gene, along with decreased expression, occurs in Head and neck cancer and the frequency of hypermethylation of ADAM23 gene is higher in primary head and neck tumors with a more advanced grade
Cytogenetics Not determined.
Hybrid/Mutated Gene Not determined.
Oncogenesis Hypermethylation of the ADAM23 gene could lead to tumor progression, because the neoplastic cells would lose the contact inhibition. As a consequence, these cells would proliferate in an uncontrolled manner; once the proliferation of most cancer cells is no longer sensitive to density-dependent inhibition, a permissive environment for cell proliferation is created.
  

External links

Nomenclature
HugoADAM23
GDBADAM23
Entrez_GeneADAM23  8745  ADAM metallopeptidase domain 23
Cards
AtlasADAM23ID44041ch2q33
GeneCardsADAM23
EnsemblADAM23 [Search_View]   ENSG00000114948 [Gene_View]
GenatlasADAM23
GeneLynxADAM23
eGenomeADAM23
euGene8745
Genomic and cartography
GoldenPathADAM23  -  2q33   chr2:207016613-207190922 +  2q33   [Description]    (hg18-Mar_2006)
EnsemblADAM23 - 2q33 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneADAM23
Gene and transcription
GenbankAB009672 [ ENTREZ ]
GenbankAJ005580 [ ENTREZ ]
GenbankAK129906 [ ENTREZ ]
GenbankBC132763 [ ENTREZ ]
GenbankBC132765 [ ENTREZ ]
RefSeqNM_003812 [ SRS ]    NM_003812 [ ENTREZ ]
RefSeqAC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeqNC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeqNT_005403 [ SRS ]    NT_005403 [ ENTREZ ]
RefSeqNW_921618 [ SRS ]    NW_921618 [ ENTREZ ]
AceViewADAM23 AceView - NCBI
UnigeneHs.591643 [ SRS ]    Hs.591643 [ NCBI ]     HS591643 [ spliceNest ]
Fast-db14658 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtO75077 [ SRS]    O75077 [ EXPASY ]     O75077 [ INTERPRO ]
PrositePS50215 ADAM_MEPRO [ SRS ]    PS50215 ADAM_MEPRO [ Expasy ]
PrositePS00427 DISINTEGRIN_1 [ SRS ]    PS00427 DISINTEGRIN_1 [ Expasy ]
PrositePS50214 DISINTEGRIN_2 [ SRS ]    PS50214 DISINTEGRIN_2 [ Expasy ]
PrositePS00022 EGF_1 [ SRS ]    PS00022 EGF_1 [ Expasy ]
PrositePS01186 EGF_2 [ SRS ]    PS01186 EGF_2 [ Expasy ]
PrositePS50026 EGF_3 [ SRS ]    PS50026 EGF_3 [ Expasy ]
InterproIPR006586 ADAM_cysteine [ SRS ]    IPR006586 ADAM_cysteine [ EBI ]
InterproIPR001762 Blood-coag_inhib_Disintegrin [ SRS ]    IPR001762 Blood-coag_inhib_Disintegrin [ EBI ]
InterproIPR006210 EGF [ SRS ]    IPR006210 EGF [ EBI ]
InterproIPR000742 EGF_3 [ SRS ]    IPR000742 EGF_3 [ EBI ]
InterproIPR013111 EGF_extracell [ SRS ]    IPR013111 EGF_extracell [ EBI ]
InterproIPR013032 EGF_like_reg_CS [ SRS ]    IPR013032 EGF_like_reg_CS [ EBI ]
InterproIPR001590 Peptidase_M12B [ SRS ]    IPR001590 Peptidase_M12B [ EBI ]
InterproIPR002870 Peptidase_M12B_N [ SRS ]    IPR002870 Peptidase_M12B_N [ EBI ]
CluSTrO75077
PfamPF08516 ADAM_CR [ SRS ]    PF08516 ADAM_CR [ Sanger ]    pfam08516 [ NCBI-CDD ]
PfamPF00200 Disintegrin [ SRS ]    PF00200 Disintegrin [ Sanger ]    pfam00200 [ NCBI-CDD ]
PfamPF07974 EGF_2 [ SRS ]    PF07974 EGF_2 [ Sanger ]    pfam07974 [ NCBI-CDD ]
PfamPF01562 Pep_M12B_propep [ SRS ]    PF01562 Pep_M12B_propep [ Sanger ]    pfam01562 [ NCBI-CDD ]
PfamPF01421 Reprolysin [ SRS ]    PF01421 Reprolysin [ Sanger ]    pfam01421 [ NCBI-CDD ]
SmartSM00608 ACR [EMBL]
SmartSM00050 DISIN [EMBL]
SmartSM00181 EGF [EMBL]
ProdomPD000664 Disintegrin[INRA-Toulouse]
ProdomO75077 ADA23_HUMAN [ Domain structure ]   O75077 ADA23_HUMAN  [ sequences sharing at least 1 domain ]
BlocksO75077
HPRD04752
Protein Interaction databases
DIPO75077
IntActO75077
Polymorphism : SNP, mutations, diseases
OMIM603710    [ map ]   
GENECLINICS603710
SNPADAM23 [dbSNP-NCBI]  
SNPNM_003812 [SNP-NCI]  
SNPADAM23 [GeneSNPs - Utah]  ADAM23] [HGBASE - SRS]
HAPMAPADAM23 [HAPMAP]  
COSMICADAM23 [Somatic mutation (COSMIC-CGP-Sanger)]  
HGMDADAM23
General knowledge
Family BrowserADAM23 [UCSC Family Browser]
SOURCENM_003812
SMDHs.591643
SAGEHs.591643
GOmetalloendopeptidase activity [Amigo]  metalloendopeptidase activity
GOintegrin binding [Amigo]  integrin binding
GOprotein binding [Amigo]  protein binding
GOextracellular region [Amigo]  extracellular region
GOplasma membrane [Amigo]  plasma membrane
GOintegral to plasma membrane [Amigo]  integral to plasma membrane
GOproteolysis [Amigo]  proteolysis
GOcell adhesion [Amigo]  cell adhesion
GOcentral nervous system development [Amigo]  central nervous system development
GOzinc ion binding [Amigo]  zinc ion binding
PubGeneADAM23
TreeFamADAM23
CTD8745 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeADAM23 Related clones (RZPD - Berlin)
PubMed
PubMed11 Pubmed reference(s) in LocusLink

Bibliography

Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain.
Sagane K, Ohya Y, Hasegawa Y, Tanaka I
The Biochemical journal. 1998 ; 334 ( Pt 1) : 93-98.
PMID 9693107
 
The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries.
Poindexter K, Nelson N, DuBose RF, Black RA, Cerretti DP
Gene. 1999 ; 237 (1) : 61-70.
PMID 10524237
 
ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism.
Cal S, Freije JM, Lˆ„pez JM, Takada Y, Lˆ„pez-Otˆ‚n C
Molecular biology of the cell. 2000 ; 11 (4) : 1457-1469.
PMID 10749942
 
Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors.
Costa FF, Verbisck NV, Salim AC, Ierardi DF, Pires LC, Sasahara RM, Sogayar MC, Zanata SM, Mackay A, O'Hare M, Soares F, Simpson AJ, Camargo AA
Oncogene. 2004 ; 23 (7) : 1481-1488.
PMID 14661055
 
Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains.
Sun YP, Deng KJ, Wang F, Zhang J, Huang X, Qiao S, Zhao S
Gene. 2004 ; 325 : 171-178.
PMID 14697522
 
ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation.
Takada H, Imoto I, Tsuda H, Nakanishi Y, Ichikura T, Mochizuki H, Mitsufuji S, Hosoda F, Hirohashi S, Ohki M, Inazawa J
Oncogene. 2005 ; 24 (54) : 8051-8060.
PMID 16103878
 
Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer.
Calmon MF, Colombo J, Carvalho F, Souza FP, Filho JF, Fukuyama EE, Camargo AA, Caballero OL, Tajara EH, Cordeiro JA, Rahal P
Cancer genetics and cytogenetics. 2007 ; 173 (1) : 31-37.
PMID 17284367
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2007Calmon Marilia de Freitas, Paula Rahal
Laboratory of Genomics studies - Sao Paulo State University ­ Departament of Biology ­ Sao Jose do Rio Preto- SP- Brasil.

Citation

This paper should be referenced as such :
Marilia de Freitas C, Rahal P . ADAM23 (ADAM metallopeptidase domain 23). Atlas Genet Cytogenet Oncol Haematol. July 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/ADAM23ID44041ch2q33.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:21:29 2008


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