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CD9 (CD9 molecule)

Written2009-08Laure Humbert, Mario Chevrette
The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada

(Note : for Links provided by Atlas : click)

Identity

Other alias5H9
BA2
P24
GIG2
MIC3
MRP-1
BTCC-1
DRAP-27
TSPAN29
LocusID (NCBI) 928
Atlas_Id 995
Location 12p13.31  [Link to chromosome band 12p13]
Location_base_pair Starts at and ends at bp from pter
Local_order The CD9 gene is located between the VWF and the ATP5J2P5 genes.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
C12orf4 (12p13.32) / CD9 (12p13.31)CD9 (12p13.31) / ANO2 (12p13.31)CD9 (12p13.31) / CD9 (12p13.31)
CD9 (12p13.31) / IQCE (7p22.3)CD9 (12p13.31) / NBPF14 (1q21.2)CD9 (12p13.31) / PPP3CA (4q24)
CDKN1A (6p21.2) / CD9 (12p13.31)CSRP1 (1q32.1) / CD9 (12p13.31)MKL1 (22q13.1) / CD9 (12p13.31)

DNA/RNA

 
  Genomic organisation of the CD9 gene on chromosome 12.
Description The gene spans 38 kb of DNA, including a 10 kb intron separating the first two exons. CD9 encodes 8 exons, ranging from 63 to 109 base pairs. The coding sequence is highly conserved between species. The promoter contains neither TATA nor CAAT boxes, but does contain several consensus sequences for the binding of transcription factors (GATA, ETS, E2F, NF-kB, AP2) as well as three putative Sp1 binding sites.
Transcription The CD9 transcribed RNA has 1246 bases, of which 684 bases (from 112 (Met) to 795 (Val)) encode the protein.
Pseudogene None.

Protein

 
  Structure of the CD9 protein.
Description CD9 is a member of the transmembrane 4 superfamily, also called the tetraspanin family. As other tetraspanins, CD9 is a cell-surface protein containing four hydrophobic transmembrane domains (indicated in green) and two extracellular domains (illustrated in violet). CD9 consists of 228 amino acids and weighs 24-27 kDa. CD9 contains four small and highly conserved hydrophobic transmembrane domains (24-27 amino acids); a small N-terminal (11 amino acids) and a C-terminal cytoplasmic (7 amino acids) tails, and a very small intracellular domain (4 amino acids). The remaining part of the protein is composed of two extracellular domains (also called loops; a small one of 20 amino acids and a large one of 83 amino acids). Two disulfide bonds, generated by four well-conserved cysteine residues (C), stabilize the large extracellular domain. CD9 also contains a tetraspanin signature (amino acids 65-89) and a CCG motif (amino acids 152 to 154), but lacks other motifs found on other tetraspanins (DW, PxSc3, Gc4).
Expression CD9 is expressed by a variety of hematopoietic and epithelial cells. It is transiently expressed during development of spinal motoneurons and other fetal nervous system sites, as well as in hematopoietic development. CD9 is glycosylated (the glycosylation site is in the first extracellular loop unlike most glycosylated tetraspanins where the site is located in the second extracellular loop) and acylated. CD9 is also phosphorylated on tyrosine following B-cell activation.
CD9 is up-regulated on activated B and T lymphocytes.
Localisation In normal cells, CD9 localizes mainly in the membranes while in cancer cells the protein may also be detected throughout the cytoplasm.
Function CD9 can interact or form complexes with many other proteins, including other tetraspanins, integrins, EWI molecules, TGF-a, diphtheria toxin receptor, receptor tyrosine kinase, pregnancy specific glycoproteins, and proteins of the immune system such as MHC class II molecules and members of the Ig superfamily. Moreover, probably because of its localization in the cell membrane, CD9 is involved in platelet activation and aggregation, as well as in cell adhesion, spreading, cell motility and tumor metastasis. CD9 also regulates paranodal junction formation, and is required for gamete fusion. Furthermore, CD9 promotes muscle cell fusion and supports myotube maintenance.
Homology Although there are variations in the amino acid sequence in the extracellular loops, the CD9 protein sequence is very well conserved between species (90% between human, mice and rat). CD9 share also some homologies with other tetraspanins, particularly in the transmembrane domains.

Mutations

Note Although no genomic CD9 mutation has been reported, in prostate cancer, there is mention of cDNA mutation compatible with an RNA editing mechanism. So far, CD9 has never been implicated in gene fusion that could result in a modified protein.

Implicated in

Note
  
Entity Various cancers
Note Decreased expression of the CD9 protein has been associated with many types of cancer.
Disease - Expressed in 90% of non-T cell acute lymphoblastic leukemia cells and in 50% of chronic lymphocytic leukemia and acute myeloblastic leukemia.
- Expression inversely correlated with metastatic potential of melanoma.
- Expression suppresses motility and metastasis of carcinoma cells.
- Reduction of expression correlated with poor prognosis in breast, lung and colon carcinomas.
  

Bibliography

Molecular cloning of the CD9 antigen. A new family of cell surface proteins.
Boucheix C, Benoit P, Frachet P, Billard M, Worthington RE, Gagnon J, Uzan G.
J Biol Chem. 1991 Jan 5;266(1):117-22.
PMID 1840589
 
Differential display cloning identifies motility-related protein (MRP1/CD9) as highly expressed in primary compared to metastatic human colon carcinoma cells.
Cajot JF, Sordat I, Silvestre T, Sordat B.
Cancer Res. 1997 Jul 1;57(13):2593-7.
PMID 9205061
 
The tetraspanin CD9 influences the adhesion, spreading, and pericellular fibronectin matrix assembly of Chinese hamster ovary cells on human plasma fibronectin.
Cook GA, Wilkinson DA, Crossno JT Jr, Raghow R, Jennings LK.
Exp Cell Res. 1999 Sep 15;251(2):356-71.
PMID 10471321
 
Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.
Higashiyama M, Taki T, Ieki Y, Adachi M, Huang CL, Koh T, Kodama K, Doi O, Miyake M.
Cancer Res. 1995 Dec 15;55(24):6040-4.
PMID 8521390
 
CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82.
Horvath G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E.
J Biol Chem. 1998 Nov 13;273(46):30537-43.
PMID 9804823
 
Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA.
Ikeyama S, Koyama M, Yamaoko M, Sasada R, Miyake M.
J Exp Med. 1993 May 1;177(5):1231-7.
PMID 8478605
 
Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation.
Ishibashi T, Ding L, Ikenaka K, Inoue Y, Miyado K, Mekada E, Baba H.
J Neurosci. 2004 Jan 7;24(1):96-102.
PMID 14715942
 
Structural organization and interactions of transmembrane domains in tetraspanin proteins.
Kovalenko OV, Metcalf DG, DeGrado WF, Hemler ME.
BMC Struct Biol. 2005 Jun 28;5:11.
PMID 15985154
 
Transcriptional regulation of the human CD9 gene: characterization of the 5'-flanking region.
Le Naour F, Prenant M, Francastel C, Rubinstein E, Uzan G, Boucheix C.
Oncogene. 1996 Aug 1;13(3):481-6.
PMID 8760289
 
The tetraspanin superfamily: molecular facilitators.
Maecker HT, Todd SC, Levy S.
FASEB J. 1997 May;11(6):428-42. (REVIEW)
PMID 9194523
 
Requirement of CD9 on the egg plasma membrane for fertilization.
Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, Ryu F, Suzuki K, Kosai K, Inoue K, Ogura A, Okabe M, Mekada E.
Science. 2000 Jan 14;287(5451):321-4.
PMID 10634791
 
Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer.
Miyake M, Nakano K, Itoi SI, Koh T, Taki T.
Cancer Res. 1996 Mar 15;56(6):1244-9.
PMID 8640807
 
Mechanisms of the mAb ALB6(CD9) induced human platelet activation: comparison with thrombin.
Rendu F, Boucheix C, Lebret M, Bourdeau N, Benoit P, Maclouf J, Soria C, Levy-Toledano S.
Biochem Biophys Res Commun. 1987 Aug 14;146(3):1397-404.
PMID 3039999
 
Organization of the human CD9 gene.
Rubinstein E, Benoit P, Billard M, Plaisance S, Prenant M, Uzan G, Boucheix C.
Genomics. 1993 Apr;16(1):132-8.
PMID 8486348
 
The functional glycoprotein CD9 is variably acylated: localization of the variably acylated region to a membrane-associated peptide containing the binding site for the agonistic monoclonal antibody 50H.19.
Seehafer JG, Tang SC, Slupsky JR, Shaw AR.
Biochim Biophys Acta. 1988 Dec 2;957(3):399-410.
PMID 3058210
 
Structure of the tetraspanin main extracellular domain. A partially conserved fold with a structurally variable domain insertion.
Seigneuret M, Delaguillaumie A, Lagaudriere-Gesbert C, Conjeaud H.
J Biol Chem. 2001 Oct 26;276(43):40055-64. Epub 2001 Aug 1.
PMID 11483611
 
Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation.
Shaw AR, Domanska A, Mak A, Gilchrist A, Dobler K, Visser L, Poppema S, Fliegel L, Letarte M, Willett BJ.
J Biol Chem. 1995 Oct 13;270(41):24092-9.
PMID 7592610
 
Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma.
Si Z, Hersey P.
Int J Cancer. 1993 Apr 22;54(1):37-43.
PMID 8478146
 
Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance.
Tachibana I, Hemler ME.
J Cell Biol. 1999 Aug 23;146(4):893-904.
PMID 10459022
 
Distribution of CD9 in the developing and mature rat nervous system.
Tole S, Patterson PH.
Dev Dyn. 1993 Jun;197(2):94-106.
PMID 8219357
 
Down-regulation of CD9 expression during prostate carcinoma progression is associated with CD9 mRNA modifications.
Wang JC, Begin LR, Berube NG, Chevalier S, Aprikian AG, Gourdeau H, Chevrette M.
Clin Cancer Res. 2007 Apr 15;13(8):2354-61. Epub 2007 Apr 3.
PMID 17406028
 

Citation

This paper should be referenced as such :
Humbert, L ; Chevrette, M
CD9 (CD9 molecule)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(7):630-632.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CD9ID995ch12p13.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]
  Lung: Translocations in Small Cell Carcinoma
inv(12)(p13p13) C12orf4/CD9
t(4;12)(q24;p13) CD9/PPP3CA
t(6;12)(p21;p13) CDKN1A/CD9
t(7;12)(p22;p13) CD9/IQCE
CD9/ANO2 (12p13)
t(12;12)(p13;q13) CD9/ARHGEF25


External links

Nomenclature
Cards
AtlasCD9ID995ch12p13.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)928
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:31:16 CEST 2018

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