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Gene Section
Mini Review
CD9 (CD9 molecule)
Laure Humbert, Mario Chevrette
The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada
(LH, MC)
Published in Atlas Database: August 2009
Online updated version : http://AtlasGeneticsOncology.org/Genes/CD9ID995ch12p13.html
DOI: 10.4267/2042/44793
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Pseudogene
Identity
None.
Other names: 5H9; BA2; P24; GIG2; MIC3; MRP-1;
BTCC-1; DRAP-27; TSPAN29
HGNC (Hugo): CD9
Location: 12p13.31
Local order: The CD9 gene is located between the
VWF and the ATP5J2P5 genes.
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
DNA/RNA
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, NFkB, 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.
Genomic organisation of the CD9 gene on chromosome 12.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(7)
630
CD9 (CD9 molecule)
Humbert L, Chevrette M
Structure of the CD9 protein.
other motifs found on other tetraspanins (DW, PxSc3,
Gc4).
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.
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.
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.
Localisation
In normal cells, CD9 localizes mainly in the
membranes while in cancer cells the protein may also
be detected throughout the cytoplasm.
Implicated in
Function
Various cancers
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.
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.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(7)
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CD9 (CD9 molecule)
Humbert L, Chevrette M
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This article should be referenced as such:
Le Naour F, Prenant M, Francastel C, Rubinstein E, Uzan G,
Boucheix C. Transcriptional regulation of the human CD9
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(7)
Humbert L, Chevrette M. CD9 (CD9 molecule). Atlas Genet
Cytogenet Oncol Haematol. 2010; 14(7):630-632.
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