CD9 (CD9 molecule)

2009-08-01   Laure Humbert , Mario Chevrette 

The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada




Atlas Image
Genomic organisation of the CD9 gene on chromosome 12.


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.


The CD9 transcribed RNA has 1246 bases, of which 684 bases (from 112 (Met) to 795 (Val)) encode the protein.




Atlas Image
Structure of the CD9 protein.


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).


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.


In normal cells, CD9 localizes mainly in the membranes while in cancer cells the protein may also be detected throughout the cytoplasm.


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.


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.



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

Entity name
Various cancers
Decreased expression of the CD9 protein has been associated with many types of cancer.
- 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.


Pubmed IDLast YearTitleAuthors
18405891991Molecular cloning of the CD9 antigen. A new family of cell surface proteins.Boucheix C et al
92050611997Differential display cloning identifies motility-related protein (MRP1/CD9) as highly expressed in primary compared to metastatic human colon carcinoma cells.Cajot JF et al
104713211999The tetraspanin CD9 influences the adhesion, spreading, and pericellular fibronectin matrix assembly of Chinese hamster ovary cells on human plasma fibronectin.Cook GA et al
85213901995Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.Higashiyama M et al
98048231998CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82.Horváth G et al
84786051993Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA.Ikeyama S et al
147159422004Tetraspanin protein CD9 is a novel paranodal component regulating paranodal junctional formation.Ishibashi T et al
159851542005Structural organization and interactions of transmembrane domains in tetraspanin proteins.Kovalenko OV et al
87602891996Transcriptional regulation of the human CD9 gene: characterization of the 5'-flanking region.Le Naour F et al
91945231997The tetraspanin superfamily: molecular facilitators.Maecker HT et al
106347912000Requirement of CD9 on the egg plasma membrane for fertilization.Miyado K et al
86408071996Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer.Miyake M et al
30399991987Mechanisms of the mAb ALB6(CD9) induced human platelet activation: comparison with thrombin.Rendu F et al
84863481993Organization of the human CD9 gene.Rubinstein E et al
30582101988The 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 et al
114836112001Structure of the tetraspanin main extracellular domain. A partially conserved fold with a structurally variable domain insertion.Seigneuret M et al
75926101995Ectopic 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 et al
84781461993Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma.Si Z et al
104590221999Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance.Tachibana I et al
82193571993Distribution of CD9 in the developing and mature rat nervous system.Tole S et al
174060282007Down-regulation of CD9 expression during prostate carcinoma progression is associated with CD9 mRNA modifications.Wang JC et al

Other Information

Locus ID:

NCBI: 928
MIM: 143030
HGNC: 1709
Ensembl: ENSG00000010278


dbSNP: 928
ClinVar: 928
TCGA: ENSG00000010278


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Hematopoietic cell lineageKEGGko04640
Hematopoietic cell lineageKEGGhsa04640
Infectious diseaseREACTOMER-HSA-5663205
Uptake and actions of bacterial toxinsREACTOMER-HSA-5339562
Uptake and function of diphtheria toxinREACTOMER-HSA-5336415
Sperm:Oocyte Membrane BindingREACTOMER-HSA-1300652
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
Response to elevated platelet cytosolic Ca2+REACTOMER-HSA-76005
Platelet degranulationREACTOMER-HSA-114608

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
175222072007Human immunodeficiency virus type 1 assembly, budding, and cell-cell spread in T cells take place in tetraspanin-enriched plasma membrane domains.101
155911172005Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation.72
170156972006Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion.68
119591202002Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation.66
187109262008Single-molecule analysis of CD9 dynamics and partitioning reveals multiple modes of interaction in the tetraspanin web.57
194580022009Formation of syncytia is repressed by tetraspanins in human immunodeficiency virus type 1-producing cells.49
176447582007A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9.43
189811202008Tetraspanins regulate ADAM10-mediated cleavage of TNF-alpha and epidermal growth factor.36
159851542005Structural organization and interactions of transmembrane domains in tetraspanin proteins.35
185089212008DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151.35


Laure Humbert ; Mario Chevrette

CD9 (CD9 molecule)

Atlas Genet Cytogenet Oncol Haematol. 2009-08-01

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