Disease relevance of KIR2DS4

• In this study, we show that KIR2DS4 is able to also interact with a non-class I MHC protein expressed on melanoma cell lines and on a primary melanoma [1].
• In the human paired box-containing (PAX) gene family, only two members, PAX-3 and PAX-6, which are associated with Waardenburg's syndrome and aniridia, respectively have been mapped to human chromosomes [2].
• Induction of apoptosis in rhabdomyosarcoma cells through down-regulation of PAX proteins [3].
• A collection of 23 medulloblastomas was analyzed for expression of the developmental control genes of the PAX and EN gene families by RNase protection and in situ hybridization [4].
• Identification and epitope enhancement of a PAX-FKHR fusion protein breakpoint epitope in alveolar rhabdomyosarcoma cells created by a tumorigenic chromosomal translocation inducing CTL capable of lysing human tumors [5].

Psychiatry related information on KIR2DS4

• Paired box (PAX) genes play a critical role in human development and disease [6].

High impact information on KIR2DS4

• The chromosomal location of all cloned PAX genes was determined by analysis of somatic cell hybrids and (except PAX-4) by fluorescence in situ hybridization to metaphase chromosomes [2].
• Mutation of the identified binding site eliminates PAX protein binding in vitro and renders the promoter inactive in cells [7].
• CpG islands associated with many other homeobox genes, such as SIX, LHX, PAX, DLX, and Engrailed, were highly methylated as well [8].
• Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1) [9].
• These data suggest that the PAX3/FKHR fusion gene and wild-type PAX genes play a causative role in the formation of RMS and presumably other tumor types, possibly by suppressing the apoptotic program that would normally eliminate these cells [3].

Chemical compound and disease context of KIR2DS4

• Substitution of a basic amino acid for asparagine at residue 47, conserved in all known murine Pax and human PAX genes, appears to have a more drastic effect on the phenotype than missense, frameshift and deletion mutations of PAX3 that cause Waardenburg syndrome type 1 [10].

Biological context of KIR2DS4

• The genes KIR3DL1, KIR2DS4 and KIR2DL3 were present on 31, 32 and 15 different B haplotypes, respectively, and 64, 65 and 40 of the total B haplotypes, respectively [11].
• The method was designed around the specific amplification of exons 4-5 of the KIR2DS4 gene [12].
• We observed eleven different genotypes and four KIR2DS4 alleles in the population, with the KIR2DS4*00101 having the highest frequency, 0.576, and also confirmed the new KIR2DS4*007 allele [12].
• Furthermore, cell line DNA and families from the 13th International Histocompatibility Workshop, in addition to local families, have also been allele typed at the KIR2DS4 locus [13].
• Haplotype definition included subtyping for the expressed and nonexpressed KIR2DL5 variants, for two alleles of pseudogene 3DP1, and for two alleles of 2DS4, including a novel 2DS4 allele, KIR1D [14].

Anatomical context of KIR2DS4

• This subset may express killer cell Ig-like receptor two-domain short tail number 4 (KIR2DS4), as suggested by staining with various mAb [15].
• Hypothetical soluble KIR2DS4 natural killer cell receptor molecule does not associate with successful ageing in the Irish [16].
• Importantly, p13 was inducibly tyrosine phosphorylated upon cross-linking of NKAT8, which strongly suggests that the associated p13 provides KAR with appropriate cytoplasmic structure to couple with tyrosine kinase-mediated signaling effectors [17].
• Mutations in transcription factors such as HOX and PAX and members of the transforming growth factor-beta superfamily cause disorders associated with abnormal mesenchymal condensation, whereas defects in the transcription factor SOX-9 lead to abnormalities in chondrocyte differentiation [18].
• Very frequent PAX gene expression was identified in tumor cell lines, including lymphoma, breast, ovarian, lung, and colon cancer [19].

Associations of KIR2DS4 with chemical compounds

• Similar to p50 molecules, the KKA3-encoded molecules are characterized by two extracellular immunoglobulin-like domains, by the presence of a lysine in the transmembrane region and a short (39 amino acids) cytoplasmic tail which does not contain immune receptor tyrosine-based activation motifs (ITAM)-like sequences [20].
• In this review, we discuss the basic aspects of PAX gene structure and function and how mutations of PAX2 might interfere with structure of the developing nephron [21].

Other interactions of KIR2DS4

• The binding of KIR2DS4-Ig to HLA-Cw4 is weaker than that of killer cell Ig-like receptor two-domain long tail number 1 (KIR2DL1)-Ig fusion protein; however, such weak recognition is capable of inhibiting lysis by an NK transfectant expressing a chimeric molecule of KIR2DS4 fused to the transmembrane and cytoplasmic portion of KIR2DL1 [15].
• In this report, we demonstrate that recognition of HLA-Cw3 by the p50 KAR, NKAT8, can potentiate the cytotoxic response of appropriate NK cell clones [17].
• A polymerase chain reaction sequence-specific oligonucleotide probe typing method identifying and distinguishing alleles of the KIR2DS4 gene has been established [13].

Analytical, diagnostic and therapeutic context of KIR2DS4

• While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA [22].
• To test to what extent PAX-FKHR determine class and behavior of ARMS, we used oligonucleotide microarray expression profiling on 139 primary rhabdomyosarcoma tumors and an in vitro model [23].
• Since no one has investigated the expression of the isoforms of PAX 3 in the neuroectodermal tumors melanoma and small cell lung cancer (SCLC), we have carried out a comprehensive screening for the expression of the isoforms PAX 3a-e using RT-PCR in human melanoma cell lines, primary human ocular and secondary cutaneous melanomas [24].
• We report the cloning, partial sequence analysis, and spatiotemporal expression of the chicken Pax-1 (chPax-1) and Pax-9 (chPax-9) gene, two closely related members of the paired box-containing (PAX) gene family [25].
• Among specimens with informative results for both FISH and RT-PCR or standard karyotyping, PAX/FKHR classification results were concordant in 94.6% (53/56) [26].

References