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CD82 (CD82 molecule)

Identity

Other names4F9
C33
GR15
IA4
KAI1
R2
SAR2
ST6
TSPAN27
Tetraspanin-27
Tspan-27
HGNC (Hugo) CD82
LocusID (NCBI) 3732
Location 11p11.2
Location_base_pair Starts at 44587141 and ends at 44641315 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order LOC729793---LOC729798---ALX4---LOC646535---CD82---TSPAN18---TP53I11---LOC100131432---PRDM11---CHST1
 

DNA/RNA

Note 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.
 
  NM_002231 encodes the longer isoform, i.e., CD82 wild type; NM_001024844 encodes a shorter isoform, which lacks exon 6.
Description 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).
Transcription Transcript length: NM_002231 is 1715 bp; NM_001024844 is 1640 bp; and the splicing variant likely lacking exon 8 is 1631 bp.

Protein

 
  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.
Description 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.
Expression 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.
Localisation CD82 is found in the plasma membrane, endosomes, lysosomes, and exosomes.
Function 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.
Homology Mouse and other human tetraspanins.

Mutations

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

Implicated in

Entity 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.
Note 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.
Prognosis 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.
  

External links

Nomenclature
HGNC (Hugo)CD82   6210
Cards
AtlasCD82ID41045ch11p11
Entrez_Gene (NCBI)CD82  3732  CD82 molecule
GeneCards (Weizmann)CD82
Ensembl (Hinxton) [Gene_View]  chr11:44587141-44641315 [Contig_View]  CD82 [Vega]
AceView (NCBI)CD82
Genatlas (Paris)CD82
WikiGenes3732
SOURCE (Princeton)NM_001024844 NM_002231
Genomic and cartography
GoldenPath (UCSC)CD82  -  11p11.2   chr11:44587141-44641315 +  11p11.2   [Description]    (hg19-Feb_2009)
EnsemblCD82 - 11p11.2 [CytoView]
Mapping of homologs : NCBICD82 [Mapview]
OMIM176807   600623   
Gene and transcription
Genbank (Entrez)AK225410 AK225708 AK312677 AY303776 BC000726
RefSeq transcript (Entrez)NM_001024844 NM_002231
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_023234 NT_009237 NW_001838022 NW_004929378
Consensus coding sequences : CCDS (NCBI)CD82
Cluster EST : UnigeneHs.527778 [ NCBI ]
CGAP (NCI)Hs.527778
Alternative Splicing : Fast-db (Paris)GSHG0004778
Gene ExpressionCD82 [ NCBI-GEO ]     CD82 [ SEEK ]   CD82 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP27701 (Uniprot)
NextProtP27701  [Medical]
With graphics : InterProP27701
Splice isoforms : SwissVarP27701 (Swissvar)
Domaine pattern : Prosite (Expaxy)TM4_1 (PS00421)   
Domains : Interpro (EBI)Tetraspanin    Tetraspanin/Peripherin    Tetraspanin_CS    Tetraspanin_EC2   
Related proteins : CluSTrP27701
Domain families : Pfam (Sanger)Tetraspannin (PF00335)   
Domain families : Pfam (NCBI)pfam00335   
DMDM Disease mutations3732
Blocks (Seattle)P27701
Peptide AtlasP27701
HPRD09004
IPIIPI00020446   IPI00979298   IPI00385291   IPI00980770   IPI00979984   IPI00982092   IPI00981036   IPI00979212   IPI00977277   IPI00982573   
Protein Interaction databases
DIP (DOE-UCLA)P27701
IntAct (EBI)P27701
BioGRIDCD82
IntegromeDBCD82
STRING (EMBL)CD82
Ontologies - Pathways
QuickGOP27701
Ontology : AmiGOprotein binding  plasma membrane  integral component of plasma membrane  extracellular vesicular exosome  
Ontology : EGO-EBIprotein binding  plasma membrane  integral component of plasma membrane  extracellular vesicular exosome  
Pathways : KEGGp53 signaling pathway   
Protein Interaction DatabaseCD82
Wikipedia pathwaysCD82
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)CD82
SNP (GeneSNP Utah)CD82
SNP : HGBaseCD82
Genetic variants : HAPMAPCD82
1000_GenomesCD82 
CONAN: Copy Number AnalysisCD82 
Somatic Mutations in Cancer : COSMICCD82 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)11:44587141-44641315
Mutations and Diseases : HGMDCD82
OMIM176807    600623   
MedgenCD82
GENETestsCD82
Disease Genetic AssociationCD82
Huge Navigator CD82 [HugePedia]  CD82 [HugeCancerGEM]
Genomic VariantsCD82  CD82 [DGVbeta]
Exome VariantCD82
dbVarCD82
ClinVarCD82
snp3D : Map Gene to Disease3732
General knowledge
Homologs : HomoloGeneCD82
Homology/Alignments : Family Browser (UCSC)CD82
Phylogenetic Trees/Animal Genes : TreeFamCD82
Chemical/Protein Interactions : CTD3732
Chemical/Pharm GKB GenePA142672155
Clinical trialCD82
Other databases
Probes
Litterature
PubMed145 Pubmed reference(s) in Entrez
CoreMineCD82
GoPubMedCD82
iHOPCD82

Bibliography

Genetic factors and suppression of metastatic ability of prostatic cancer.
Ichikawa T, Ichikawa Y, Isaacs JT.
Cancer Res. 1991 Jul 15;51(14):3788-92.
PMID 2065333
 
Localization of metastasis suppressor gene(s) for prostatic cancer to the short arm of human chromosome 11.
Ichikawa T, Ichikawa Y, Dong J, Hawkins AL, Griffin CA, Isaacs WB, Oshimura M, Barrett JC, Isaacs JT.
Cancer Res. 1992 Jun 15;52(12):3486-90.
PMID 1596907
 
KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2.
Dong JT, Lamb PW, Rinker-Schaeffer CW, Vukanovic J, Ichikawa T, Isaacs JT, Barrett JC.
Science. 1995 May 12;268(5212):884-6.
PMID 7754374
 
Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.
Adachi M, Taki T, Ieki Y, Huang CL, Higashiyama M, Miyake M.
Cancer Res. 1996 Apr 15;56(8):1751-5.
PMID 8620488
 
Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss.
Dong JT, Suzuki H, Pin SS, Bova GS, Schalken JA, Isaacs WB, Barrett JC, Isaacs JT.
Cancer Res. 1996 Oct 1;56(19):4387-90.
PMID 8813131
 
Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer.
Ueda T, Ichikawa T, Tamaru J, Mikata A, Akakura K, Akimoto S, Imai T, Yoshie O, Shiraishi T, Yatani R, Ito H, Shimazaki J.
Am J Pathol. 1996 Nov;149(5):1435-40.
PMID 8909232
 
Genomic organization of the human KAI1 metastasis-suppressor gene.
Dong JT, Isaacs WB, Barrett JC, Isaacs JT.
Genomics. 1997 Apr 1;41(1):25-32.
PMID 9126478
 
Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic loss in advanced human prostate cancer.
Kawana Y, Komiya A, Ueda T, Nihei N, Kuramochi H, Suzuki H, Yatani R, Imai T, Dong JT, Imai T, Yoshie O, Barrett JC, Isaacs JT, Shimazaki J, Ito H, Ichikawa T.
Prostate. 1997 Aug 1;32(3):205-13.
PMID 9254900
 
Loss of KAI1 messenger RNA expression in both high-grade and invasive human bladder cancers.
Yu Y, Yang JL, Markovic B, Jackson P, Yardley G, Barrett J, Russell PJ.
Clin Cancer Res. 1997 Jul;3(7):1045-9.
PMID 9815782
 
KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma.
Guo XZ, Friess H, Di Mola FF, Heinicke JM, Abou-Shady M, Graber HU, Baer HU, Zimmermann A, Korc M, Buchler MW.
Hepatology. 1998 Dec;28(6):1481-8.
PMID 9828210
 
The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53.
Mashimo T, Watabe M, Hirota S, Hosobe S, Miura K, Tegtmeyer PJ, Rinker-Shaeffer CW, Watabe K.
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11307-11.
PMID 9736732
 
Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines.
White A, Lamb PW, Barrett JC.
Oncogene. 1998 Jun 18;16(24):3143-9.
PMID 9671393
 
A novel molecular staging protocol for non-small cell lung cancer.
Miyake M, Adachi M, Huang C, Higashiyama M, Kodama K, Taki T.
Oncogene. 1999 Apr 8;18(14):2397-404.
PMID 10327061
 
Down-regulation of KAI1 messenger RNA expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma.
Tagawa K, Arihiro K, Takeshima Y, Hiyama E, Yamasaki M, Inai K.
Jpn J Cancer Res. 1999 Sep;90(9):970-6.
PMID 10551326
 
Methylation of a CpG island within the promoter region of the KAI1 metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines.
Jackson P, Millar D, Kingsley E, Yardley G, Ow K, Clark S, Russell PJ.
Cancer Lett. 2000 Sep 1;157(2):169-76.
PMID 10936677
 
Frequent down-regulation and lack of mutation of the KAI1 metastasis suppressor gene in epithelial ovarian carcinoma.
Liu FS, Dong JT, Chen JT, Hsieh YT, Ho ES, Hung MJ.
Gynecol Oncol. 2000 Jul;78(1):10-5.
PMID 10873402
 
Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma.
Miyazaki T, Kato H, Shitara Y, Yoshikawa M, Tajima K, Masuda N, Shouji H, Tsukada K, Nakajima T, Kuwano H.
Cancer. 2000 Sep 1;89(5):955-62.
PMID 10964324
 
Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1.
Odintsova E, Sugiura T, Berditchevski F.
Curr Biol. 2000 Aug 24;10(16):1009-12.
PMID 10985391
 
Novel NEMO/IkappaB kinase and NF-kappa B target genes at the pre-B to immature B cell transition.
Li J, Peet GW, Balzarano D, Li X, Massa P, Barton RW, Marcu KB.
J Biol Chem. 2001 May 25;276(21):18579-90. Epub 2001 Feb 21.
PMID 11279141
 
Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53.
Shinohara T, Miki T, Nishimura N, Nokihara H, Hamada H, Mukaida N, Sone S.
Cancer Res. 2001 Jan 15;61(2):673-8.
PMID 11212267
 
Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells.
Yang X, Wei LL, Tang C, Slack R, Mueller S, Lippman ME.
Cancer Res. 2001 Jul 1;61(13):5284-8.
PMID 11431371
 
High prevalence of decreased expression of KAI1 metastasis suppressor in human oral carcinogenesis.
Uzawa K, Ono K, Suzuki H, Tanaka C, Yakushiji T, Yamamoto N, Yokoe H, Tanzawa H.
Clin Cancer Res. 2002 Mar;8(3):828-35.
PMID 11895916
 
Expression of a splice variant of KAI1, a tumor metastasis suppressor gene, influences tumor invasion and progression.
Lee JH, Seo YW, Park SR, Kim YJ, Kim KK.
Cancer Res. 2003 Nov 1;63(21):7247-55.
PMID 14612520
 
Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration.
Zhang XA, He B, Zhou B, Liu L.
J Biol Chem. 2003 Jul 18;278(29):27319-28. Epub 2003 May 8.
PMID 12738793
 
The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity.
Zhou B, Liu L, Reddivari M, Zhang XA.
Cancer Res. 2004 Oct 15;64(20):7455-63.
PMID 15492270
 
KAI1 tetraspanin and metastasis suppressor.
Jackson P, Marreiros A, Russell PJ.
Int J Biochem Cell Biol. 2005 Mar;37(3):530-4.
PMID 15618009
 
Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes.
Kim JH, Kim B, Cai L, Choi HJ, Ohgi KA, Tran C, Chen C, Chung CH, Huber O, Rose DW, Sawyers CL, Rosenfeld MG, Baek SH.
Nature. 2005 Apr 14;434(7035):921-6.
PMID 15829968
 
CD82 metastasis suppressor gene: a potential target for new therapeutics?
Tonoli H, Barrett JC.
Trends Mol Med. 2005 Dec;11(12):563-70. Epub 2005 Nov 3. (REVIEW)
PMID 16271511
 
Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression.
Bandyopadhyay S, Zhan R, Chaudhuri A, Watabe M, Pai SK, Hirota S, Hosobe S, Tsukada T, Miura K, Takano Y, Saito K, Pauza ME, Hayashi S, Wang Y, Mohinta S, Mashimo T, Iiizumi M, Furuta E, Watabe K.
Nat Med. 2006 Aug;12(8):933-8. Epub 2006 Jul 23.
PMID 16862154
 
KAI1/CD82, a tumor metastasis suppressor.
Liu WM, Zhang XA.
Cancer Lett. 2006 Aug 28;240(2):183-94. Epub 2005 Nov 2. (REVIEW)
PMID 16260083
 
Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases.
Sridhar SC, Miranti CK.
Oncogene. 2006 Apr 13;25(16):2367-78.
PMID 16331263
 
Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse.
Todeschini AR, Dos Santos JN, Handa K, Hakomori SI.
J Biol Chem. 2007 Mar 16;282(11):8123-33. Epub 2007 Jan 10.
PMID 17215249
 
The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation.
Tsai YC, Mendoza A, Mariano JM, Zhou M, Kostova Z, Chen B, Veenstra T, Hewitt SM, Helman LJ, Khanna C, Weissman AM.
Nat Med. 2007 Dec;13(12):1504-9. Epub 2007 Nov 25.
PMID 18037895
 
Down-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, Kakies C, Kleist B, Poetsch M, Giebel J.
Virchows Arch. 2008 Apr;452(4):369-75. Epub 2008 Feb 28.
PMID 18305955
 
Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis.
Bari R, Zhang YH, Zhang F, Wang NX, Stipp CS, Zheng JJ, Zhang XA.
Am J Pathol. 2009 Feb;174(2):647-60. Epub 2008 Dec 30.
PMID 19116362
 
Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses metastasis.
Miranti CK.
Cell Signal. 2009 Feb;21(2):196-211. Epub 2008 Sep 11. (REVIEW)
PMID 18822372
 
Learning therapeutic lessons from metastasis suppressor proteins.
Smith SC, Theodorescu D.
Nat Rev Cancer. 2009 Apr;9(4):253-64. Epub 2009 Feb 26. (REVIEW)
PMID 19242414
 
CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts.
Xu C, Zhang YH, Thangavel M, Richardson MM, Liu L, Zhou B, Zheng Y, Ostrom RS, Zhang XA.
FASEB J. 2009 Jun 4.
PMID 19497983
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written06-2009Yanhui H Zhang, Mekel M Richardson, Feng Zhang, Xin A Zhang
Vascular Biology and Cancer Centers and Departments of Medicine and Molecular Science, University of Tennessee Health Science Center, Memphis TN 38163, USA

Citation

This paper should be referenced as such :
Zhang, YH ; Richardson, MM ; Zhang, F ; Zhang, XA
CD82 (CD82 molecule)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(5):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/CD82ID41045ch11p11.html

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indexed on : Sat Nov 8 16:56:48 CET 2014

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