Associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway. (updated: March 4, 2015)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
Total structural coverage: 66%
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The reference OMIM entry for this protein is 600623
Cd82 antigen; cd82
Kangai 1; kai1
Prostate cancer antimetastasis gene kai1
Leukocyte surface antigen r2; sar2
Suppressor of tumorigenicity 6; st6
R2 leukocyte antigen
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 tha ...
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Subscribe to this protein entry history
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600623 was added.