InnateDB Protein
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IDBP-367103.5
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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DCLRE1C
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Protein Name
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DNA cross-link repair 1C
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Synonyms
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000413180
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InnateDB Gene
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IDBG-56338 (DCLRE1C)
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Protein Structure
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Function |
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. {ECO:0000269PubMed:11336668, ECO:0000269PubMed:11955432, ECO:0000269PubMed:12055248, ECO:0000269PubMed:14744996, ECO:0000269PubMed:15071507, ECO:0000269PubMed:15456891, ECO:0000269PubMed:15468306, ECO:0000269PubMed:15574326, ECO:0000269PubMed:15574327, ECO:0000269PubMed:15811628, ECO:0000269PubMed:15936993}.
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Subcellular Localization |
Nucleus {ECO:0000269PubMed:12055248, ECO:0000269PubMed:15071507}.
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Disease Associations |
Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]: A form of severe combined immunodeficiency, 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 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. {ECO:0000269PubMed:11336668, ECO:0000269PubMed:12406895, ECO:0000269PubMed:12569164, ECO:0000269PubMed:12592555, ECO:0000269PubMed:12921762}. Note=The disease is caused by mutations affecting the gene represented in this entry.Severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:602450]: A variety of SCID with sensitivity to ionizing radiation. A founder mutation has been detected in Athabascan- speaking native Americans, being inherited as an autosomal recessive trait. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID. {ECO:0000269PubMed:12055248}. Note=The disease is caused by mutations affecting the gene represented in this entry.Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. {ECO:0000269PubMed:15731174}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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Tissue Specificity |
Ubiquitously expressed, with highest levels in the kidney, lung, pancreas and placenta (at the mRNA level). Expression is not increased in thymus or bone marrow, sites of V(D)J recombination. {ECO:0000269PubMed:11336668}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
20
[view]
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Protein-Protein |
17
[view]
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Protein-DNA |
3
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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InterPro |
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
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PhosphoSite |
PhosphoSite-Q96SD1
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TrEMBL |
X6RJV5
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UniProt Splice Variant |
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Entrez Gene |
64421
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UniGene |
Hs.737284
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RefSeq |
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HUGO |
HGNC:17642
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OMIM |
605988
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CCDS |
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HPRD |
05817
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IMGT |
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EMBL |
AC069544
AL360083
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GenPept |
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