Full text data of CD82
CD82
(KAI1, SAR2, ST6, TSPAN27)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
CD82 antigen (C33 antigen; IA4; Inducible membrane protein R2; Metastasis suppressor Kangai-1; Suppressor of tumorigenicity 6 protein; Tetraspanin-27; Tspan-27; CD82)
CD82 antigen (C33 antigen; IA4; Inducible membrane protein R2; Metastasis suppressor Kangai-1; Suppressor of tumorigenicity 6 protein; Tetraspanin-27; Tspan-27; CD82)
UniProt
P27701
ID CD82_HUMAN Reviewed; 267 AA.
AC P27701; D3DQN6; E9PC70; Q7Z2D4; Q7Z5N2;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1992, sequence version 1.
DT 22-JAN-2014, entry version 115.
DE RecName: Full=CD82 antigen;
DE AltName: Full=C33 antigen;
DE AltName: Full=IA4;
DE AltName: Full=Inducible membrane protein R2;
DE AltName: Full=Metastasis suppressor Kangai-1;
DE AltName: Full=Suppressor of tumorigenicity 6 protein;
DE AltName: Full=Tetraspanin-27;
DE Short=Tspan-27;
DE AltName: CD_antigen=CD82;
GN Name=CD82; Synonyms=KAI1, SAR2, ST6, TSPAN27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=1842498; DOI=10.1002/eji.1830210219;
RA Gaugitsch H.W., Hofer E., Huber N.E., Schnabl E., Baumruker T.;
RT "A new superfamily of lymphoid and melanoma cell proteins with
RT extensive homology to Schistosoma mansoni antigen Sm23.";
RL Eur. J. Immunol. 21:377-383(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1401919;
RA Imai T., Fukudome K., Takagi S., Nagira M., Furuse M., Fukuhara N.,
RA Nishimura M., Hinuma Y., Yoshie O.;
RT "C33 antigen recognized by monoclonal antibodies inhibitory to human T
RT cell leukemia virus type 1-induced syncytium formation is a member of
RT a new family of transmembrane proteins including CD9, CD37, CD53, and
RT CD63.";
RL J. Immunol. 149:2879-2886(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7754374; DOI=10.1126/science.7754374;
RA Dong J.T., Barrett J.C.;
RT "KAI1, a metastasis suppressor gene for prostate cancer on human
RT chromosome 11p11.2.";
RL Science 268:884-886(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-241.
RA Zhou G., Li S., Li H., Shen C., Li M., Xiao W., Lin L., Yang S.;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9126478; DOI=10.1006/geno.1997.4618;
RA Dong J.T., Isaacs W.B., Barrett J.C., Isaacs J.T.;
RT "Genomic organization of the human KAI1 metastasis-suppressor gene.";
RL Genomics 41:25-32(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-241.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP VAL-241.
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH IGSF8.
RX PubMed=12750295;
RA Zhang X.A., Lane W.S., Charrin S., Rubinstein E., Liu L.;
RT "EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and
RT inhibits the migration of prostate cancer cells.";
RL Cancer Res. 63:2665-2674(2003).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-129, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-129 AND ASN-198, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
CC -!- FUNCTION: Associates with CD4 or CD8 and delivers costimulatory
CC signals for the TCR/CD3 pathway.
CC -!- SUBUNIT: Interacts directly with IGSF8.
CC -!- INTERACTION:
CC Q8TAA9:VANGL1; NbExp=6; IntAct=EBI-682379, EBI-682393;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P27701-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P27701-2; Sequence=VSP_045656;
CC -!- TISSUE SPECIFICITY: Lymphoid specific.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CD82ID41045ch11p11.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X53795; CAA37804.1; -; mRNA.
DR EMBL; S48196; AAB23825.1; -; mRNA.
DR EMBL; U20770; AAC50133.1; -; mRNA.
DR EMBL; AY303776; AAP76181.1; -; mRNA.
DR EMBL; U67274; AAC51205.1; -; Genomic_DNA.
DR EMBL; U67268; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67269; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67270; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67271; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67272; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67273; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; CR542255; CAG47051.1; -; mRNA.
DR EMBL; AC010768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68063.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68064.1; -; Genomic_DNA.
DR EMBL; BC000726; AAH00726.1; -; mRNA.
DR EMBL; BC001821; AAH01821.1; -; mRNA.
DR PIR; I38942; A46493.
DR RefSeq; NP_001020015.1; NM_001024844.1.
DR RefSeq; NP_002222.1; NM_002231.3.
DR UniGene; Hs.527778; -.
DR ProteinModelPortal; P27701; -.
DR IntAct; P27701; 2.
DR MINT; MINT-1432537; -.
DR STRING; 9606.ENSP00000227155; -.
DR PhosphoSite; P27701; -.
DR DMDM; 131775; -.
DR PaxDb; P27701; -.
DR PRIDE; P27701; -.
DR DNASU; 3732; -.
DR Ensembl; ENST00000227155; ENSP00000227155; ENSG00000085117.
DR Ensembl; ENST00000342935; ENSP00000339686; ENSG00000085117.
DR GeneID; 3732; -.
DR KEGG; hsa:3732; -.
DR UCSC; uc001myc.3; human.
DR CTD; 3732; -.
DR GeneCards; GC11P044586; -.
DR HGNC; HGNC:6210; CD82.
DR HPA; CAB002508; -.
DR HPA; HPA028900; -.
DR MIM; 600623; gene.
DR neXtProt; NX_P27701; -.
DR PharmGKB; PA142672155; -.
DR eggNOG; NOG259116; -.
DR HOGENOM; HOG000230651; -.
DR HOVERGEN; HBG002324; -.
DR InParanoid; P27701; -.
DR KO; K06509; -.
DR OMA; VTYPCSC; -.
DR PhylomeDB; P27701; -.
DR ChiTaRS; CD82; human.
DR GeneWiki; CD82_(gene); -.
DR GenomeRNAi; 3732; -.
DR NextBio; 14607; -.
DR PRO; PR:P27701; -.
DR ArrayExpress; P27701; -.
DR Bgee; P27701; -.
DR CleanEx; HS_CD82; -.
DR Genevestigator; P27701; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR InterPro; IPR000301; Tetraspanin.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR018503; Tetraspanin_CS.
DR InterPro; IPR008952; Tetraspanin_EC2.
DR Pfam; PF00335; Tetraspannin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR PRINTS; PR00259; TMFOUR.
DR SUPFAM; SSF48652; SSF48652; 1.
DR PROSITE; PS00421; TM4_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Glycoprotein; Membrane;
KW Polymorphism; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1 267 CD82 antigen.
FT /FTId=PRO_0000219226.
FT TOPO_DOM 1 11 Cytoplasmic (Potential).
FT TRANSMEM 12 32 Helical; (Potential).
FT TOPO_DOM 33 53 Extracellular (Potential).
FT TRANSMEM 54 72 Helical; (Potential).
FT TOPO_DOM 73 83 Cytoplasmic (Potential).
FT TRANSMEM 84 110 Helical; (Potential).
FT TOPO_DOM 111 228 Extracellular (Potential).
FT TRANSMEM 229 250 Helical; (Potential).
FT TOPO_DOM 251 267 Cytoplasmic (Potential).
FT CARBOHYD 129 129 N-linked (GlcNAc...).
FT CARBOHYD 157 157 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 198 198 N-linked (GlcNAc...).
FT VAR_SEQ 88 112 Missing (in isoform 2).
FT /FTId=VSP_045656.
FT VARIANT 241 241 I -> V (in dbSNP:rs1139971).
FT /FTId=VAR_052326.
FT CONFLICT 124 124 L -> P (in Ref. 4; AAP76181).
FT CONFLICT 240 241 II -> MV (in Ref. 2; AAB23825).
SQ SEQUENCE 267 AA; 29626 MW; FC379855BD1CABDE CRC64;
MGSACIKVTK YFLFLFNLIF FILGAVILGF GVWILADKSS FISVLQTSSS SLRMGAYVFI
GVGAVTMLMG FLGCIGAVNE VRCLLGLYFA FLLLILIAQV TAGALFYFNM GKLKQEMGGI
VTELIRDYNS SREDSLQDAW DYVQAQVKCC GWVSFYNWTD NAELMNRPEV TYPCSCEVKG
EEDNSLSVRK GFCEAPGNRT QSGNHPEDWP VYQEGCMEKV QAWLQENLGI ILGVGVGVAI
IELLGMVLSI CLCRHVHSED YSKVPKY
//
ID CD82_HUMAN Reviewed; 267 AA.
AC P27701; D3DQN6; E9PC70; Q7Z2D4; Q7Z5N2;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1992, sequence version 1.
DT 22-JAN-2014, entry version 115.
DE RecName: Full=CD82 antigen;
DE AltName: Full=C33 antigen;
DE AltName: Full=IA4;
DE AltName: Full=Inducible membrane protein R2;
DE AltName: Full=Metastasis suppressor Kangai-1;
DE AltName: Full=Suppressor of tumorigenicity 6 protein;
DE AltName: Full=Tetraspanin-27;
DE Short=Tspan-27;
DE AltName: CD_antigen=CD82;
GN Name=CD82; Synonyms=KAI1, SAR2, ST6, TSPAN27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=1842498; DOI=10.1002/eji.1830210219;
RA Gaugitsch H.W., Hofer E., Huber N.E., Schnabl E., Baumruker T.;
RT "A new superfamily of lymphoid and melanoma cell proteins with
RT extensive homology to Schistosoma mansoni antigen Sm23.";
RL Eur. J. Immunol. 21:377-383(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1401919;
RA Imai T., Fukudome K., Takagi S., Nagira M., Furuse M., Fukuhara N.,
RA Nishimura M., Hinuma Y., Yoshie O.;
RT "C33 antigen recognized by monoclonal antibodies inhibitory to human T
RT cell leukemia virus type 1-induced syncytium formation is a member of
RT a new family of transmembrane proteins including CD9, CD37, CD53, and
RT CD63.";
RL J. Immunol. 149:2879-2886(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7754374; DOI=10.1126/science.7754374;
RA Dong J.T., Barrett J.C.;
RT "KAI1, a metastasis suppressor gene for prostate cancer on human
RT chromosome 11p11.2.";
RL Science 268:884-886(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-241.
RA Zhou G., Li S., Li H., Shen C., Li M., Xiao W., Lin L., Yang S.;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9126478; DOI=10.1006/geno.1997.4618;
RA Dong J.T., Isaacs W.B., Barrett J.C., Isaacs J.T.;
RT "Genomic organization of the human KAI1 metastasis-suppressor gene.";
RL Genomics 41:25-32(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-241.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP VAL-241.
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH IGSF8.
RX PubMed=12750295;
RA Zhang X.A., Lane W.S., Charrin S., Rubinstein E., Liu L.;
RT "EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and
RT inhibits the migration of prostate cancer cells.";
RL Cancer Res. 63:2665-2674(2003).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-129, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-129 AND ASN-198, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-
RT linked cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
CC -!- FUNCTION: Associates with CD4 or CD8 and delivers costimulatory
CC signals for the TCR/CD3 pathway.
CC -!- SUBUNIT: Interacts directly with IGSF8.
CC -!- INTERACTION:
CC Q8TAA9:VANGL1; NbExp=6; IntAct=EBI-682379, EBI-682393;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P27701-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P27701-2; Sequence=VSP_045656;
CC -!- TISSUE SPECIFICITY: Lymphoid specific.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CD82ID41045ch11p11.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X53795; CAA37804.1; -; mRNA.
DR EMBL; S48196; AAB23825.1; -; mRNA.
DR EMBL; U20770; AAC50133.1; -; mRNA.
DR EMBL; AY303776; AAP76181.1; -; mRNA.
DR EMBL; U67274; AAC51205.1; -; Genomic_DNA.
DR EMBL; U67268; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67269; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67270; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67271; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67272; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; U67273; AAC51205.1; JOINED; Genomic_DNA.
DR EMBL; CR542255; CAG47051.1; -; mRNA.
DR EMBL; AC010768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68063.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68064.1; -; Genomic_DNA.
DR EMBL; BC000726; AAH00726.1; -; mRNA.
DR EMBL; BC001821; AAH01821.1; -; mRNA.
DR PIR; I38942; A46493.
DR RefSeq; NP_001020015.1; NM_001024844.1.
DR RefSeq; NP_002222.1; NM_002231.3.
DR UniGene; Hs.527778; -.
DR ProteinModelPortal; P27701; -.
DR IntAct; P27701; 2.
DR MINT; MINT-1432537; -.
DR STRING; 9606.ENSP00000227155; -.
DR PhosphoSite; P27701; -.
DR DMDM; 131775; -.
DR PaxDb; P27701; -.
DR PRIDE; P27701; -.
DR DNASU; 3732; -.
DR Ensembl; ENST00000227155; ENSP00000227155; ENSG00000085117.
DR Ensembl; ENST00000342935; ENSP00000339686; ENSG00000085117.
DR GeneID; 3732; -.
DR KEGG; hsa:3732; -.
DR UCSC; uc001myc.3; human.
DR CTD; 3732; -.
DR GeneCards; GC11P044586; -.
DR HGNC; HGNC:6210; CD82.
DR HPA; CAB002508; -.
DR HPA; HPA028900; -.
DR MIM; 600623; gene.
DR neXtProt; NX_P27701; -.
DR PharmGKB; PA142672155; -.
DR eggNOG; NOG259116; -.
DR HOGENOM; HOG000230651; -.
DR HOVERGEN; HBG002324; -.
DR InParanoid; P27701; -.
DR KO; K06509; -.
DR OMA; VTYPCSC; -.
DR PhylomeDB; P27701; -.
DR ChiTaRS; CD82; human.
DR GeneWiki; CD82_(gene); -.
DR GenomeRNAi; 3732; -.
DR NextBio; 14607; -.
DR PRO; PR:P27701; -.
DR ArrayExpress; P27701; -.
DR Bgee; P27701; -.
DR CleanEx; HS_CD82; -.
DR Genevestigator; P27701; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR InterPro; IPR000301; Tetraspanin.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR018503; Tetraspanin_CS.
DR InterPro; IPR008952; Tetraspanin_EC2.
DR Pfam; PF00335; Tetraspannin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR PRINTS; PR00259; TMFOUR.
DR SUPFAM; SSF48652; SSF48652; 1.
DR PROSITE; PS00421; TM4_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Glycoprotein; Membrane;
KW Polymorphism; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1 267 CD82 antigen.
FT /FTId=PRO_0000219226.
FT TOPO_DOM 1 11 Cytoplasmic (Potential).
FT TRANSMEM 12 32 Helical; (Potential).
FT TOPO_DOM 33 53 Extracellular (Potential).
FT TRANSMEM 54 72 Helical; (Potential).
FT TOPO_DOM 73 83 Cytoplasmic (Potential).
FT TRANSMEM 84 110 Helical; (Potential).
FT TOPO_DOM 111 228 Extracellular (Potential).
FT TRANSMEM 229 250 Helical; (Potential).
FT TOPO_DOM 251 267 Cytoplasmic (Potential).
FT CARBOHYD 129 129 N-linked (GlcNAc...).
FT CARBOHYD 157 157 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 198 198 N-linked (GlcNAc...).
FT VAR_SEQ 88 112 Missing (in isoform 2).
FT /FTId=VSP_045656.
FT VARIANT 241 241 I -> V (in dbSNP:rs1139971).
FT /FTId=VAR_052326.
FT CONFLICT 124 124 L -> P (in Ref. 4; AAP76181).
FT CONFLICT 240 241 II -> MV (in Ref. 2; AAB23825).
SQ SEQUENCE 267 AA; 29626 MW; FC379855BD1CABDE CRC64;
MGSACIKVTK YFLFLFNLIF FILGAVILGF GVWILADKSS FISVLQTSSS SLRMGAYVFI
GVGAVTMLMG FLGCIGAVNE VRCLLGLYFA FLLLILIAQV TAGALFYFNM GKLKQEMGGI
VTELIRDYNS SREDSLQDAW DYVQAQVKCC GWVSFYNWTD NAELMNRPEV TYPCSCEVKG
EEDNSLSVRK GFCEAPGNRT QSGNHPEDWP VYQEGCMEKV QAWLQENLGI ILGVGVGVAI
IELLGMVLSI CLCRHVHSED YSKVPKY
//
MIM
600623
*RECORD*
*FIELD* NO
600623
*FIELD* TI
*600623 CD82 ANTIGEN; CD82
;;KANGAI 1; KAI1;;
PROSTATE CANCER ANTIMETASTASIS GENE KAI1;;
read moreLEUKOCYTE SURFACE ANTIGEN R2; SAR2;;
SUPPRESSOR OF TUMORIGENICITY 6; ST6;;
R2 LEUKOCYTE ANTIGEN
*FIELD* TX
CLONING
Ichikawa et al. (1991) demonstrated by somatic cell hybridization of
highly metastatic and nonmetastatic rat prostate cancer cells that the
resultant hybrids were nonmetastatic if all of the parental chromosomes
were retained. Somatic hybrid segregants that underwent nonrandom
chromosomal loss reexpressed high metastatic ability. These results
demonstrated the existence of gene(s), the expression of which can
suppress metastatic ability of prostate cancer cells. To identify the
location of homologous gene(s) in the human, Ichikawa et al. (1992)
introduced specific human chromosomes into highly metastatic rat
prostatic cells by use of microcell-mediated chromosome transfer.
Introduction of human chromosome 11 resulted in suppression of
metastatic ability without suppression of the in vivo growth rate or
tumorigenicity of the hybrid cells. Spontaneous deletion of portions of
human chromosome 11 in some of the clones delineated the minimal portion
of human chromosome 11 capable of suppressing prostate cancer
metastases: 11p13-p11.2, not including the Wilms tumor-1 locus (607102).
Dong et al. (1995) isolated the metastasis suppressor gene on 11p11.2 by
PCR methods and designated it KAI1 for 'kang ai' (Chinese for
anticancer). Expression of this gene was reduced in human cell lines
derived from metastatic prostate tumors. KAI1 specifies a protein of 267
amino acids, with 4 hydrophobic and presumably transmembrane domains and
1 large extracellular hydrophilic domain with 3 potential
N-glycosylation sites. KAI1 is evolutionarily conserved, is expressed in
many human tissues, and encodes a member of a structurally distinct
family of leukocyte surface glycoproteins. Decreased expression of this
gene may be involved in the malignant progression of prostate and other
cancers. The gene has also been referred to as ST6. Sequence comparisons
showed that KAI1 is likely the human homolog of the mouse leukocyte
surface antigen R2, which in turn is similar to CD37 (151523) and CD53
(151525). It appears to be upregulated in activated T cells, i.e., it is
an 'activation antigen' of T cells.
Guo et al. (1998) analyzed KAI1 mRNA expression in normal liver and in
metastatic and nonmetastatic hepatocellular carcinoma (HCC) cells.
Significantly lower KAI1 mRNA levels were found in metastatic HCC cells.
Miyazaki et al. (2000) demonstrated immunohistochemically that the
expression of KAI1 protein appears to be correlated with lymph node
metastasis in esophageal squamous cell carcinoma (ESCC). None of 22
patients studied with ESCC showed mutation of the KAI1 gene by PCR-SSCP.
GENE FUNCTION
As noted, KAI1 is capable of inhibiting the metastatic process in
experimental animals. The expression of the KAI1 gene is also
downregulated during tumor progression of prostate, breast, lung,
bladder, and pancreatic cancers in humans, and this downregulation
appears to be at the level of transcription or posttranscription.
Mashimo et al. (1998) found that the tumor suppressor gene p53 (TP53;
191170) can directly activate the KAI1 gene by interacting with the
5-prime upstream region. The p53 responding region is located
approximately 860 bases upstream of the transcriptional initiation site,
and contains a typical tandem repeat of the p53 consensus binding
sequence. Mutations of this sequence abolish the responsiveness to p53
and also the ability to bind to p53 protein. Immunohistochemical
analysis of 177 samples of human prostate tumors showed that the
expression of the KAI1 gene correlated strongly with that of the p53
gene and that the loss of these 2 markers resulted in poor survival of
patients. The data indicated a direct relationship between p53 and KAI1
genes and suggested that the loss of p53 function, which is commonly
observed in many types of cancer, leads to downregulation of the KAI1
gene, which may result in progression of metastases.
Baek et al. (2002) demonstrated that interleukin-1-beta (IL1B; 147720)
causes nuclear export of a specific NCOR (600849) corepressor complex,
resulting in derepression of a specific subset of nuclear factor-kappa-B
(NFKB; see 164011)-regulated genes. These genes are exemplified by the
tetraspanin KAI1, which regulates membrane receptor function. Nuclear
export of the NCOR/TAB2 (605101)/HDAC3 (605166) complex by IL1B is
temporally linked to selective recruitment of a TIP60 (601409)
coactivator complex. KAI1 is also directly activated by a ternary
complex, dependent on the acetyltransferase activity of TIP60, that
consists of the presenilin-dependent C-terminal cleavage product of the
beta amyloid precursor protein (APP; 104760), FE65 (602709), and TIP60,
identifying a specific in vivo gene target of an APP-dependent
transcription complex in the brain.
Kim et al. (2005) reported that the downregulation of the metastasis
suppressor gene KAI1 in prostate cancer cells involves the inhibitory
actions of beta-catenin (116806), along with a reptin (TIP48; 604788)
chromatin remodeling complex. This inhibitory function of
beta-catenin-reptin requires both increased beta-catenin expression and
recruitment of histone deacetylase activity. The coordinated actions of
beta-catenin-reptin components that mediate the repressive state serve
to antagonize a TIP60 coactivator complex that is required for
activation; the balance of these opposing complexes controls the
expression of KAI1 and metastatic potential. The molecular mechanisms
underlying the antagonistic regulation of beta-catenin-reptin and the
TIP60 coactivator complexes for the metastasis suppressor gene, KAI1,
are likely to be prototypic of a selective downregulation strategy for
many genes, including a subset of NF-kappa-B (see 164011) target genes.
Using a cell invasion assays, Jee et al. (2006) found CD82
overexpression reduced the invasiveness of a human nonsmall cell lung
carcinoma cell line. RT-PCR and Western blot analyses showed elevated
MMP9 (120361) mRNA and protein; however, gel zymography revealed reduced
MMP9 enzymatic activity that could be attributed to elevated TIMP1
(305370) levels. Jee et al. (2006) concluded that CD82 overexpression
can suppress tumor invasiveness and metastatic potential by inducing
MMP9 inactivation via upregulation of TIMP1.
Using a yeast 2-hybrid screen, Bandyopadhyay et al. (2006) identified an
endothelial cell-surface protein, DARC (613665), as an interacting
partner of KAI1. They demonstrated that cancer cells expressing KAI1
attach to vascular endothelial cells through direct interaction between
KAI1 and DARC, leading to inhibition of tumor cell proliferation and
induction of senescence by modulating the expression of TBX2 (600747)
and CDKN1A (116899). In DARC knockout mice, the metastasis-suppression
activity of KAI1 was significantly compromised, whereas KAI1 completely
abrogated pulmonary metastasis in wildtype and heterozygous littermates.
Bandyopadhyay et al. (2006) concluded that DARC is essential for the
function of KAI1 as a suppressor of metastasis.
GP78 (AMFR; 603243) is an E3 ubiquitin ligase that is integral to
endoplasmic reticulum-associated degradation of diverse substrates. Tsai
et al. (2007) found that GP78 had a causal role in metastasis of an
aggressive human sarcoma and that its prometastatic activity required
its E3 activity. Furthermore, GP78 associated with and targeted KAI1 for
degradation. Suppression of GP78 increased KAI1 abundance and reduced
the metastatic potential of tumor cells, an effect that was largely
blocked by concomitant suppression of KAI1. Tsai et al. (2007) confirmed
an inverse relationship between GP78 and KAI1 in human sarcoma tissue by
microarray analysis.
GENE STRUCTURE
Dong et al. (1997) reported that the KAI1 gene is contained within 80 kb
of DNA. They identified 10 exons; however, 800 nucleotides of the
3-prime untranslated region were not characterized. Among KAI1 and
several other members of the 'transmembrane 4 superfamily,' the
locations of the splice sites relative to the structural domains of the
encoded protein are conserved.
MAPPING
By study of human/rodent somatic cell hybrids, Virtaneva et al. (1993)
demonstrated that the R2 gene (CD82) is located on 11p12.
*FIELD* RF
1. Baek, S. H.; Ohgi, K. A.; Rose, D. W.; Koo, E. H.; Glass, C. K.;
Rosenfeld, M. G.: Exchange of N-CoR corepressor and Tip60 coactivator
complexes links gene expression by NF-kappa-B and beta-amyloid precursor
protein. Cell 110: 55-67, 2002.
2. Bandyopadhyay, S.; Zhan, R.; Chaudhuri, A.; Watabe, M.; Pai, S.
K.; Hirota, S.; Hosobe, S.; Tsukara, T.; Miura, K.; Takano, Y.; Saito,
K.; Pauza, M. E.; Hayashi, S.; Wang, Y.; Mohinta, S.; Mashimo, T.;
Iiizumi, M.; Furuta, E.; Watabe, K.: Interaction of KAI1 on tumor
cells with DARC on vascular endothelium leads to metastasis suppression. Nature
Med. 12: 933-938, 2006.
3. Dong, J.-T.; Isaacs, W. B.; Barrett, J. C.; Isaacs, J. T.: Genomic
organization of the human KAI1 metastasis-suppressor gene. Genomics 41:
25-32, 1997.
4. Dong, J.-T.; Lamb, P. W.; Rinker-Schaeffer, C. W.; Vukanovic, J.;
Ichikawa, T.; Isaacs, J. T.; Barrett, J. C.: KAI1, a metastasis suppressor
gene for prostate cancer on human chromosome 11p11.2. Science 268:
884-886, 1995.
5. Guo, X.-Z.; Friess, H.; Di Mola, F. F.; Heinicke, J.-M.; Abou-Shady,
M.; Graber, H. U.; Baer, H. U.; Zimmermann, A.; Korc, M.; Buchler,
M. W.: KAI1, a new metastasis suppressor gene, is reduced in metastatic
hepatocellular carcinoma. Hepatology 28: 1481-1488, 1998.
6. Ichikawa, T.; Ichikawa, Y.; Dong, J.; Hawkins, A. L.; Griffin,
C. A.; Isaacs, W. B.; Oshimura, M.; Barrett, J. C.; Isaacs, J. T.
: Localization of metastasis suppressor gene(s) for prostatic cancer
to the short arm of human chromosome 11. Cancer Res. 52: 3486-3490,
1992.
7. Ichikawa, T.; Ichikawa, Y.; Isaacs, J. T.: Genetic factors and
suppression of metastatic ability of prostatic cancer. Cancer Res. 51:
3788-3792, 1991.
8. Jee, B. K.; Park, K. M.; Surendran, S.; Lee, W. K.; Han, C. W.;
Kim, Y. S.; Lim, Y.: KAI1/CD82 suppresses tumor invasion by MMP9
inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma
cell line. Biochem. Biophys. Res. Commun. 342: 655-661, 2006.
9. Kim, J. H.; Kim, B.; Cai, L.; Choi, H. J.; Ohgi, K. A.; Tran, C.;
Chen, C.; Chung, C. H.; Huber, O.; Rose, D. W.; Sawyers, C. L.; Rosenfeld,
M. G.; Baek, S. H.: Transcriptional regulation of a metastasis suppressor
gene by Tip60 and beta-catenin complexes. Nature 434: 921-926, 2005.
10. Mashimo, T.; Watabe, M.; Hirota, S.; Hosobe, S.; Miura, K.; Tegtmeyer,
P. J.; Rinker-Shaeffer, C. W.; Watabe, K.: The expression of the
KAI1 gene, a tumor metastasis suppressor, is directly activated by
p53. Proc. Nat. Acad. Sci. 95: 11307-11311, 1998.
11. Miyazaki, T.; Kato, H.; Shitara, Y.; Yoshikawa, M.; Tajima, K.;
Masuda, N.; Shouji, H.; Tsukada, K.; Nakajima, T.; Kuwano, H.: Mutation
and expression of the metastasis suppressor gene KAI1 in esophageal
squamous cell carcinoma. Cancer 89: 955-962, 2000.
12. Tsai, Y. C.; Mendoza, A.; Mariano, J. M.; Zhou, M.; Kostova, Z.;
Chen, B.; Veenstra, T.; Hewitt, S. M.; Helman, L. J.; Khanna, C.;
Weissman, A. M.: The ubiquitin ligase gp78 promotes sarcoma metastasis
by targeting KAI1 for degradation. Nature Med. 13: 1504-1509, 2007.
13. Virtaneva, K. I.; Angelisova, P.; Baumruker, T.; Horejsi, V.;
Nevanlinna, H.; Schroder, J.: The genes for CD37, CD53, and R2, all
members of a novel gene family, are located on different chromosomes. Immunogenetics 37:
461-465, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 1/25/2008
Marla J. F. O'Neill - updated: 8/18/2006
Patricia A. Hartz - updated: 8/9/2006
Ada Hamosh - updated: 9/19/2005
Stylianos E. Antonarakis - updated: 7/29/2002
Victor A. McKusick - updated: 10/27/2000
Victor A. McKusick - updated: 3/15/1999
Victor A. McKusick - updated: 10/5/1998
Rebekah S. Rasooly - updated: 5/15/1998
Alan F. Scott - updated: 2/7/1996
*FIELD* CD
Victor A. McKusick: 8/23/1995
*FIELD* ED
mgross: 12/21/2010
mgross: 1/28/2008
terry: 1/25/2008
carol: 7/26/2007
wwang: 8/28/2006
terry: 8/18/2006
wwang: 8/10/2006
terry: 8/9/2006
carol: 2/21/2006
alopez: 1/19/2006
alopez: 9/20/2005
terry: 9/19/2005
terry: 3/16/2005
ckniffin: 8/26/2002
mgross: 7/29/2002
mcapotos: 11/7/2000
mcapotos: 11/2/2000
terry: 10/27/2000
alopez: 8/19/1999
terry: 3/15/1999
carol: 10/9/1998
terry: 10/5/1998
psherman: 5/15/1998
terry: 4/17/1996
mark: 2/7/1996
joanna: 2/7/1996
mimadm: 11/3/1995
mark: 8/23/1995
*RECORD*
*FIELD* NO
600623
*FIELD* TI
*600623 CD82 ANTIGEN; CD82
;;KANGAI 1; KAI1;;
PROSTATE CANCER ANTIMETASTASIS GENE KAI1;;
read moreLEUKOCYTE SURFACE ANTIGEN R2; SAR2;;
SUPPRESSOR OF TUMORIGENICITY 6; ST6;;
R2 LEUKOCYTE ANTIGEN
*FIELD* TX
CLONING
Ichikawa et al. (1991) demonstrated by somatic cell hybridization of
highly metastatic and nonmetastatic rat prostate cancer cells that the
resultant hybrids were nonmetastatic if all of the parental chromosomes
were retained. Somatic hybrid segregants that underwent nonrandom
chromosomal loss reexpressed high metastatic ability. These results
demonstrated the existence of gene(s), the expression of which can
suppress metastatic ability of prostate cancer cells. To identify the
location of homologous gene(s) in the human, Ichikawa et al. (1992)
introduced specific human chromosomes into highly metastatic rat
prostatic cells by use of microcell-mediated chromosome transfer.
Introduction of human chromosome 11 resulted in suppression of
metastatic ability without suppression of the in vivo growth rate or
tumorigenicity of the hybrid cells. Spontaneous deletion of portions of
human chromosome 11 in some of the clones delineated the minimal portion
of human chromosome 11 capable of suppressing prostate cancer
metastases: 11p13-p11.2, not including the Wilms tumor-1 locus (607102).
Dong et al. (1995) isolated the metastasis suppressor gene on 11p11.2 by
PCR methods and designated it KAI1 for 'kang ai' (Chinese for
anticancer). Expression of this gene was reduced in human cell lines
derived from metastatic prostate tumors. KAI1 specifies a protein of 267
amino acids, with 4 hydrophobic and presumably transmembrane domains and
1 large extracellular hydrophilic domain with 3 potential
N-glycosylation sites. KAI1 is evolutionarily conserved, is expressed in
many human tissues, and encodes a member of a structurally distinct
family of leukocyte surface glycoproteins. Decreased expression of this
gene may be involved in the malignant progression of prostate and other
cancers. The gene has also been referred to as ST6. Sequence comparisons
showed that KAI1 is likely the human homolog of the mouse leukocyte
surface antigen R2, which in turn is similar to CD37 (151523) and CD53
(151525). It appears to be upregulated in activated T cells, i.e., it is
an 'activation antigen' of T cells.
Guo et al. (1998) analyzed KAI1 mRNA expression in normal liver and in
metastatic and nonmetastatic hepatocellular carcinoma (HCC) cells.
Significantly lower KAI1 mRNA levels were found in metastatic HCC cells.
Miyazaki et al. (2000) demonstrated immunohistochemically that the
expression of KAI1 protein appears to be correlated with lymph node
metastasis in esophageal squamous cell carcinoma (ESCC). None of 22
patients studied with ESCC showed mutation of the KAI1 gene by PCR-SSCP.
GENE FUNCTION
As noted, KAI1 is capable of inhibiting the metastatic process in
experimental animals. The expression of the KAI1 gene is also
downregulated during tumor progression of prostate, breast, lung,
bladder, and pancreatic cancers in humans, and this downregulation
appears to be at the level of transcription or posttranscription.
Mashimo et al. (1998) found that the tumor suppressor gene p53 (TP53;
191170) can directly activate the KAI1 gene by interacting with the
5-prime upstream region. The p53 responding region is located
approximately 860 bases upstream of the transcriptional initiation site,
and contains a typical tandem repeat of the p53 consensus binding
sequence. Mutations of this sequence abolish the responsiveness to p53
and also the ability to bind to p53 protein. Immunohistochemical
analysis of 177 samples of human prostate tumors showed that the
expression of the KAI1 gene correlated strongly with that of the p53
gene and that the loss of these 2 markers resulted in poor survival of
patients. The data indicated a direct relationship between p53 and KAI1
genes and suggested that the loss of p53 function, which is commonly
observed in many types of cancer, leads to downregulation of the KAI1
gene, which may result in progression of metastases.
Baek et al. (2002) demonstrated that interleukin-1-beta (IL1B; 147720)
causes nuclear export of a specific NCOR (600849) corepressor complex,
resulting in derepression of a specific subset of nuclear factor-kappa-B
(NFKB; see 164011)-regulated genes. These genes are exemplified by the
tetraspanin KAI1, which regulates membrane receptor function. Nuclear
export of the NCOR/TAB2 (605101)/HDAC3 (605166) complex by IL1B is
temporally linked to selective recruitment of a TIP60 (601409)
coactivator complex. KAI1 is also directly activated by a ternary
complex, dependent on the acetyltransferase activity of TIP60, that
consists of the presenilin-dependent C-terminal cleavage product of the
beta amyloid precursor protein (APP; 104760), FE65 (602709), and TIP60,
identifying a specific in vivo gene target of an APP-dependent
transcription complex in the brain.
Kim et al. (2005) reported that the downregulation of the metastasis
suppressor gene KAI1 in prostate cancer cells involves the inhibitory
actions of beta-catenin (116806), along with a reptin (TIP48; 604788)
chromatin remodeling complex. This inhibitory function of
beta-catenin-reptin requires both increased beta-catenin expression and
recruitment of histone deacetylase activity. The coordinated actions of
beta-catenin-reptin components that mediate the repressive state serve
to antagonize a TIP60 coactivator complex that is required for
activation; the balance of these opposing complexes controls the
expression of KAI1 and metastatic potential. The molecular mechanisms
underlying the antagonistic regulation of beta-catenin-reptin and the
TIP60 coactivator complexes for the metastasis suppressor gene, KAI1,
are likely to be prototypic of a selective downregulation strategy for
many genes, including a subset of NF-kappa-B (see 164011) target genes.
Using a cell invasion assays, Jee et al. (2006) found CD82
overexpression reduced the invasiveness of a human nonsmall cell lung
carcinoma cell line. RT-PCR and Western blot analyses showed elevated
MMP9 (120361) mRNA and protein; however, gel zymography revealed reduced
MMP9 enzymatic activity that could be attributed to elevated TIMP1
(305370) levels. Jee et al. (2006) concluded that CD82 overexpression
can suppress tumor invasiveness and metastatic potential by inducing
MMP9 inactivation via upregulation of TIMP1.
Using a yeast 2-hybrid screen, Bandyopadhyay et al. (2006) identified an
endothelial cell-surface protein, DARC (613665), as an interacting
partner of KAI1. They demonstrated that cancer cells expressing KAI1
attach to vascular endothelial cells through direct interaction between
KAI1 and DARC, leading to inhibition of tumor cell proliferation and
induction of senescence by modulating the expression of TBX2 (600747)
and CDKN1A (116899). In DARC knockout mice, the metastasis-suppression
activity of KAI1 was significantly compromised, whereas KAI1 completely
abrogated pulmonary metastasis in wildtype and heterozygous littermates.
Bandyopadhyay et al. (2006) concluded that DARC is essential for the
function of KAI1 as a suppressor of metastasis.
GP78 (AMFR; 603243) is an E3 ubiquitin ligase that is integral to
endoplasmic reticulum-associated degradation of diverse substrates. Tsai
et al. (2007) found that GP78 had a causal role in metastasis of an
aggressive human sarcoma and that its prometastatic activity required
its E3 activity. Furthermore, GP78 associated with and targeted KAI1 for
degradation. Suppression of GP78 increased KAI1 abundance and reduced
the metastatic potential of tumor cells, an effect that was largely
blocked by concomitant suppression of KAI1. Tsai et al. (2007) confirmed
an inverse relationship between GP78 and KAI1 in human sarcoma tissue by
microarray analysis.
GENE STRUCTURE
Dong et al. (1997) reported that the KAI1 gene is contained within 80 kb
of DNA. They identified 10 exons; however, 800 nucleotides of the
3-prime untranslated region were not characterized. Among KAI1 and
several other members of the 'transmembrane 4 superfamily,' the
locations of the splice sites relative to the structural domains of the
encoded protein are conserved.
MAPPING
By study of human/rodent somatic cell hybrids, Virtaneva et al. (1993)
demonstrated that the R2 gene (CD82) is located on 11p12.
*FIELD* RF
1. Baek, S. H.; Ohgi, K. A.; Rose, D. W.; Koo, E. H.; Glass, C. K.;
Rosenfeld, M. G.: Exchange of N-CoR corepressor and Tip60 coactivator
complexes links gene expression by NF-kappa-B and beta-amyloid precursor
protein. Cell 110: 55-67, 2002.
2. Bandyopadhyay, S.; Zhan, R.; Chaudhuri, A.; Watabe, M.; Pai, S.
K.; Hirota, S.; Hosobe, S.; Tsukara, T.; Miura, K.; Takano, Y.; Saito,
K.; Pauza, M. E.; Hayashi, S.; Wang, Y.; Mohinta, S.; Mashimo, T.;
Iiizumi, M.; Furuta, E.; Watabe, K.: Interaction of KAI1 on tumor
cells with DARC on vascular endothelium leads to metastasis suppression. Nature
Med. 12: 933-938, 2006.
3. Dong, J.-T.; Isaacs, W. B.; Barrett, J. C.; Isaacs, J. T.: Genomic
organization of the human KAI1 metastasis-suppressor gene. Genomics 41:
25-32, 1997.
4. Dong, J.-T.; Lamb, P. W.; Rinker-Schaeffer, C. W.; Vukanovic, J.;
Ichikawa, T.; Isaacs, J. T.; Barrett, J. C.: KAI1, a metastasis suppressor
gene for prostate cancer on human chromosome 11p11.2. Science 268:
884-886, 1995.
5. Guo, X.-Z.; Friess, H.; Di Mola, F. F.; Heinicke, J.-M.; Abou-Shady,
M.; Graber, H. U.; Baer, H. U.; Zimmermann, A.; Korc, M.; Buchler,
M. W.: KAI1, a new metastasis suppressor gene, is reduced in metastatic
hepatocellular carcinoma. Hepatology 28: 1481-1488, 1998.
6. Ichikawa, T.; Ichikawa, Y.; Dong, J.; Hawkins, A. L.; Griffin,
C. A.; Isaacs, W. B.; Oshimura, M.; Barrett, J. C.; Isaacs, J. T.
: Localization of metastasis suppressor gene(s) for prostatic cancer
to the short arm of human chromosome 11. Cancer Res. 52: 3486-3490,
1992.
7. Ichikawa, T.; Ichikawa, Y.; Isaacs, J. T.: Genetic factors and
suppression of metastatic ability of prostatic cancer. Cancer Res. 51:
3788-3792, 1991.
8. Jee, B. K.; Park, K. M.; Surendran, S.; Lee, W. K.; Han, C. W.;
Kim, Y. S.; Lim, Y.: KAI1/CD82 suppresses tumor invasion by MMP9
inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma
cell line. Biochem. Biophys. Res. Commun. 342: 655-661, 2006.
9. Kim, J. H.; Kim, B.; Cai, L.; Choi, H. J.; Ohgi, K. A.; Tran, C.;
Chen, C.; Chung, C. H.; Huber, O.; Rose, D. W.; Sawyers, C. L.; Rosenfeld,
M. G.; Baek, S. H.: Transcriptional regulation of a metastasis suppressor
gene by Tip60 and beta-catenin complexes. Nature 434: 921-926, 2005.
10. Mashimo, T.; Watabe, M.; Hirota, S.; Hosobe, S.; Miura, K.; Tegtmeyer,
P. J.; Rinker-Shaeffer, C. W.; Watabe, K.: The expression of the
KAI1 gene, a tumor metastasis suppressor, is directly activated by
p53. Proc. Nat. Acad. Sci. 95: 11307-11311, 1998.
11. Miyazaki, T.; Kato, H.; Shitara, Y.; Yoshikawa, M.; Tajima, K.;
Masuda, N.; Shouji, H.; Tsukada, K.; Nakajima, T.; Kuwano, H.: Mutation
and expression of the metastasis suppressor gene KAI1 in esophageal
squamous cell carcinoma. Cancer 89: 955-962, 2000.
12. Tsai, Y. C.; Mendoza, A.; Mariano, J. M.; Zhou, M.; Kostova, Z.;
Chen, B.; Veenstra, T.; Hewitt, S. M.; Helman, L. J.; Khanna, C.;
Weissman, A. M.: The ubiquitin ligase gp78 promotes sarcoma metastasis
by targeting KAI1 for degradation. Nature Med. 13: 1504-1509, 2007.
13. Virtaneva, K. I.; Angelisova, P.; Baumruker, T.; Horejsi, V.;
Nevanlinna, H.; Schroder, J.: The genes for CD37, CD53, and R2, all
members of a novel gene family, are located on different chromosomes. Immunogenetics 37:
461-465, 1993.
*FIELD* CN
Patricia A. Hartz - updated: 1/25/2008
Marla J. F. O'Neill - updated: 8/18/2006
Patricia A. Hartz - updated: 8/9/2006
Ada Hamosh - updated: 9/19/2005
Stylianos E. Antonarakis - updated: 7/29/2002
Victor A. McKusick - updated: 10/27/2000
Victor A. McKusick - updated: 3/15/1999
Victor A. McKusick - updated: 10/5/1998
Rebekah S. Rasooly - updated: 5/15/1998
Alan F. Scott - updated: 2/7/1996
*FIELD* CD
Victor A. McKusick: 8/23/1995
*FIELD* ED
mgross: 12/21/2010
mgross: 1/28/2008
terry: 1/25/2008
carol: 7/26/2007
wwang: 8/28/2006
terry: 8/18/2006
wwang: 8/10/2006
terry: 8/9/2006
carol: 2/21/2006
alopez: 1/19/2006
alopez: 9/20/2005
terry: 9/19/2005
terry: 3/16/2005
ckniffin: 8/26/2002
mgross: 7/29/2002
mcapotos: 11/7/2000
mcapotos: 11/2/2000
terry: 10/27/2000
alopez: 8/19/1999
terry: 3/15/1999
carol: 10/9/1998
terry: 10/5/1998
psherman: 5/15/1998
terry: 4/17/1996
mark: 2/7/1996
joanna: 2/7/1996
mimadm: 11/3/1995
mark: 8/23/1995