4htp: Difference between revisions

<StructureSection load='4htp' size='340' side='right' caption='[[4htp]], [[Resolution|resolution]] 2.25&Aring;' scene=''>

<table><tr><td colspan='2'>[[4htp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTP FirstGlance]. <br>

</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LIG4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4htp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htp OCA], [http://pdbe.org/4htp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4htp RCSB], [http://www.ebi.ac.uk/pdbsum/4htp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4htp ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Defects in LIG4 are the cause of LIG4 syndrome (LIG4S) [MIM:[http://omim.org/entry/606593 606593]]. This disease is characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.<ref>PMID:11779494</ref>  Defects in LIG4 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:[http://omim.org/entry/602450 602450]]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity. [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Severe combined immunodeficiency, alymphocytotic type;Omenn syndrome. Defects in DCLRE1C are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:[http://omim.org/entry/602450 602450]]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.<ref>PMID:11336668</ref> <ref>PMID:12406895</ref> <ref>PMID:12921762</ref> <ref>PMID:12592555</ref> <ref>PMID:12569164</ref>  Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:[http://omim.org/entry/602450 602450]]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan-speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.<ref>PMID:12055248</ref>  Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:[http://omim.org/entry/603554 603554]]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T-cell receptor (TCR) repertoire. They also generally lack B-lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).  

[[http://www.uniprot.org/uniprot/DNLI4_HUMAN DNLI4_HUMAN]] Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.<ref>PMID:9809069</ref> <ref>PMID:10854421</ref> [[http://www.uniprot.org/uniprot/DCR1C_HUMAN DCR1C_HUMAN]] Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ.<ref>PMID:11336668</ref> <ref>PMID:12055248</ref> <ref>PMID:11955432</ref> <ref>PMID:15071507</ref> <ref>PMID:15468306</ref> <ref>PMID:14744996</ref> <ref>PMID:15574326</ref> <ref>PMID:15574327</ref> <ref>PMID:15456891</ref> <ref>PMID:15811628</ref> <ref>PMID:15936993</ref> 

*[[DNA ligase|DNA ligase]]

[[Category: Human]]

[[Category: Aggarwal, A K]]

[[Category: Ioannes, P E.De]]

[[Category: Artemi]]

[[Category: Ligase-hydrolase complex]]