CD82 (CD82 molecule)

2009-06-01   Yanhui H Zhang , Mekel M Richardson , Feng Zhang , Xin A Zhang 

Vascular Biology, Cancer Centers, Departments of Medicine, Molecular Science, University of Tennessee Health Science Center, Memphis TN 38163, USA


Atlas Image



We do notice that, in literature, there is one more splicing variant with functional importance (Lee et al., 2003). In this variant, the 84bp exon that encodes the amino acids 215-242 of CD82/kAI1 protein is selectively deleted. However, the chromosome location and exon numbers of this splicing variant described in the publication are not consistent with those for the other two splicing variants herein. There is no gene accession number be assigned to this slicing variant. Thus, this variant is not presented in the following diagram.
Atlas Image
NM_002231 encodes the longer isoform, i.e., CD82 wild type; NM_001024844 encodes a shorter isoform, which lacks exon 6.


Gene type: protein coding.
Gene size: 54.2 kb.
Two splicing variants in addition to wild type (NM_002231 or CD82 wild type consists of 10 exons; NM_001024844 or the splicing variant lacking exon 6 and the splicing variant likely lacking exon 8 consist of 9 exons).


Transcript length: NM_002231 is 1715 bp; NM_001024844 is 1640 bp; and the splicing variant likely lacking exon 8 is 1631 bp.


Atlas Image
CD82 is a 4-transmembrane glycoprotein and belongs to the tetraspanin superfamily. This family of proteins is characterized by the conservation of several motifs located within the extracellular and transmembrane domains. CD82 undergoes two types of post-translational modifications: glycosylation at its large extracellular loop and palmitoylation at the cysteine residues in or near cytoplasmic domains.


Size: 267 amino acids.
Because of the glycosylation, the molecular weight of CD82 proteins ranges between 30-90 kDa depending on tissue and cell types.


CD82 is ubiquitously expressed in various human tissues such as epithelium and endothelium. CD82 expression is frequently diminished or lost in invasive and metastatic solid-tumor tissues.


CD82 is found in the plasma membrane, endosomes, lysosomes, and exosomes.


In relation to cancer, CD82 function is to inhibit tumor invasion and suppresses tumor metastasis. Palmitoylation is essential for CD82 function as well as the presence of three polar residues, NQE, located within its transmembrane domains. CD82 associates with other transmembrane proteins such as tetraspanins, integrins, Ig superfamily members, and growth factor receptors and intracellular signaling proteins to regulate membrane microdomain organization, vesicular trafficking, and transmembrane signaling.


Mouse and other human tetraspanins.



Currently there is no report for the disease-related or biologically significant mutation for CD82 gene (See HGMD).

Implicated in

Entity name
Prostate cancer, breast cancer, pancreatic cancer, gastric cancer, bladder cancer, ovarian cancers, non-small-cell lung carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and other solid tumors.
Invasion and metastasis suppression.
CD82 is expressed in many normal tissues such as epithelia. In invasive or metastatic cancers, CD82 expression is typically reduced or lost. In most of the solid tumors studied so far, CD82 expression is inversely correlated with the invasive and metastatic abilities of malignant tumors.
The metastasis-suppressive effect of CD82 can be observed in the animal studies of cancer metastasis by re-introducing CD82 expression in various metastatic cancer cell lines such as prostate cancer AT6.1, prostate cancer LNCaP, fibroblastoma HT1080, melanoma MDA-MB-435, breast cancer LCC6, liver cancer MHCC97-H, and lung cancer LLC lines.
The observations of CD82-mediated suppression of cancer metastasis in animal models are supported by a variety of clinical studies on the human cancers from prostate, breast, ovary, colon, lung, stomach, liver, and other organs.
CD82 attenuates the signaling from integrins and growth factor receptors such as epidermal growth factor receptor and c-Met. CD82 also reorganizes the membrane micordomains including tetraspanin webs and lipid rafts. The interaction of CD82 and its counter-receptor DARC inhibits tumor cell proliferation and induces senescence.
The lower or no expression of CD82 in the tumors from prostate, breast, colon, stomach, bladder, lung, liver, pancreas, ovary, and other organs predicts the poor clinical outcome. Conversely, the expression of CD82 wild type proteins in solid tumors reflects the less invasiveness and low metastatic potential of the tumors.


Pubmed IDLast YearTitleAuthors
86204881996Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.Adachi M et al
168621542006Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression.Bandyopadhyay S et al
191163622009Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis.Bari R et al
91264781997Genomic organization of the human KAI1 metastasis-suppressor gene.Dong JT et al
77543741995KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2.Dong JT et al
88131311996Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss.Dong JT et al
98282101998KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma.Guo XZ et al
15969071992Localization of metastasis suppressor gene(s) for prostatic cancer to the short arm of human chromosome 11.Ichikawa T et al
156180092005KAI1 tetraspanin and metastasis suppressor.Jackson P et al
92549001997Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic loss in advanced human prostate cancer.Kawana Y et al
158299682005Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes.Kim JH et al
146125202003Expression of a splice variant of KAI1, a tumor metastasis suppressor gene, influences tumor invasion and progression.Lee JH et al
112791412001Novel NEMO/IkappaB kinase and NF-kappa B target genes at the pre-B to immature B cell transition.Li J et al
108734022000Frequent down-regulation and lack of mutation of the KAI1 metastasis suppressor gene in epithelial ovarian carcinoma.Liu FS et al
162600832006KAI1/CD82, a tumor metastasis suppressor.Liu WM et al
97367321998The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53.Mashimo T et al
188223722009Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses metastasis.Miranti CK et al
103270611999A novel molecular staging protocol for non-small cell lung cancer.Miyake M et al
109643242000Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma.Miyazaki T et al
109853912000Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1.Odintsova E et al
183059552008Down-regulation of the metastasis suppressor protein KAI1/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma.Protzel C et al
112122672001Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53.Shinohara T et al
192424142009Learning therapeutic lessons from metastasis suppressor proteins.Smith SC et al
163312632006Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases.Sridhar SC et al
105513261999Down-regulation of KAI1 messenger RNA expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma.Tagawa K et al
172152492007Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse.Todeschini AR et al
162715112005CD82 metastasis suppressor gene: a potential target for new therapeutics?Tonoli H et al
180378952007The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation.Tsai YC et al
89092321996Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.Ueda T et al
118959162002High prevalence of decreased expression of KAI1 metastasis suppressor in human oral carcinogenesis.Uzawa K et al
96713931998Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines.White A et al
194979832009CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts.Xu C et al
114313712001Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells.Yang X et al
98157821997Loss of KAI1 messenger RNA expression in both high-grade and invasive human bladder cancers.Yu Y et al
127387932003Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration.Zhang XA et al
154922702004The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity.Zhou B et al

Other Information

Locus ID:

NCBI: 3732
MIM: 600623
HGNC: 6210
Ensembl: ENSG00000085117


dbSNP: 3732
ClinVar: 3732
TCGA: ENSG00000085117


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
p53 signaling pathwayKEGGko04115
p53 signaling pathwayKEGGhsa04115

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
180378952007The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation.73
172152492007Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse.51
155926842005Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases.46
214546132011KAI1 gene is engaged in NDRG1 gene-mediated metastasis suppression through the ATF3-NFkappaB complex in human prostate cancer.37
189811202008Tetraspanins regulate ADAM10-mediated cleavage of TNF-alpha and epidermal growth factor.36
154545692004Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation.35
182725012008Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway.32
127502952003EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells.31
145763492003Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR.31
201449922010Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling.29


Yanhui H Zhang ; Mekel M Richardson ; Feng Zhang ; Xin A Zhang

CD82 (CD82 molecule)

Atlas Genet Cytogenet Oncol Haematol. 2009-06-01

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