Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P16104 (H2AX)
 3,930 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ARCN1, KIAA0638, TREH, DDX6, BLR1, BCL9L, UPK2, DLNB13, DLNB14, RPS25, SBDN, G6PT1, HYOU1, VPS11, HMBS, H2AFX, DPAGT1, KIAA0285, MIZF, ABCG4, NOD9, PDZK2, CBL, MCAM, RNF26, C1QTNF5, MFRP, USP2, THY1, and PVRL1 genes are located within the commonly deleted region of neuroblastoma at human chromosome 11q23.3. Here, we characterized the KIAA0638 gene within the 11q23.3 region by using bioinformatics. Because human KIAA0638 gene was homologous to human LL5B gene encoding LL5beta protein, KIAA0638 was designated LL5A gene encoding LL5alpha protein. LL5A isoform 1 (FLJ00141 type) consists of exons 1-12, 14-21 and 23, while LL5A isoform 2 (KIAA0638 type) consists of exon 1-23. LL5A isoform 1 was the major transcript among LL5A isoforms generated due to alternative splicing. Nucleotide sequence of mouse Ll5a cDNA was determined by assembling CB522359 EST and 5'-truncated mKIAA0638 cDNA. Human LL5alpha isoform 2 showed 94.4 and 35.9% total-amino-acid identity with mouse Ll5alpha and human LL5beta, respectively. LL5alpha proteins consist of Forkhead associated (FHA) domain, bipartite nuclear localization signal (NLS), Chromosome segregation ATPases (SMC) domain, and Pleckstrin homology (PH) domain. LL5alpha proteins were homologous to PtdIns(3,4,5)P3 sensor protein LL5beta in the SMC and PH domains, and were also homologous to KIF1A, KIF1B, KIF13A, KIF13B, KIF14, and SNX23 proteins in the FHA domain. LL5alpha protein might be a transducer of PtdIns(3,4,5)P3 levels to the intracellular trafficking system.
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PMID:Identification and characterization of human LL5A gene and mouse Ll5a gene in silico. 1453 93

The isolation of the NBS1 gene revealed the molecular mechanisms of DSB repair. In response to DNA damage, histone H2AX in the vicinity of DSBs is phosphorylated by ATM. NBS1 then targets the MRE11/RAD50 complex to the sites of DSBs through interaction of the FHA/BRCT domain with gamma-H2AX. NBSI complex binds to damaged-DNA directly, and HR repair is initiated. To collaborate DSB repair, ATM also regulates cell cycle checkpoints at GI, G2, and intra-S phases via phosphorylation of SMC, CHK2 and FANCD2. The phosphorylation of these proteins require NBS1 complex. Thus, NBSI has at least two important roles in genome maintenance, as a DNA repair protein in HR pathway and as a signal modifier in intra-S phase checkpoints. NBSI is also known to be involved in maintenance of telomores, which have DSB-like structures and defects here can cause telomcric fusion. Therefore, NBS1 should be a multi-functional protein for the maintenance of genomic integrity. Further studies on NBS1 will provide insights into the mechanisms of DNA damage response and the network of these factors involved in genomic stability.
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PMID:Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex. 1547 93

The isolation of the NBS1 gene revealed the molecular mechanisms of DSB repair. In response to DNA damage, histone H2AX in the vicinity of DSBs is phosphorylated by ATM. NBS1 then targets the MRE11/RAD50 complex to the sites of DSBs through interaction of the FHA/BRCT domain with gamma-H2AX. NBS1 complex binds to damaged-DNA directly, and HR repair is initiated. To collaborate DSB repair, ATM also regulates cell cycle checkpoints at G1, G2, and intra-S phases via phosphorylation of SMC, CHK2 and FANCD2. The phosphorylation of these proteins require NBS1 complex. Thus, NBS1 has at least two important roles in genome maintenance, as a DNA repair protein in HR pathway and as a signal modifier in intra-S phase checkpoints. NBS1 is also known to be involved in maintenance of telomeres, which have DSB-like structures and defects here can cause telomeric fusion. Therefore, NBS1 should be a multifunctional protein for the maintenance of genomic integrity. Further studies on NBS1 will provide insights into the mechanisms of DNA damage response and the network of these factors involved in genomic stability.
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PMID:Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex. 1549 28