Artemis 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. 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). 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. Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA). 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. Defects in DCLRE1C are a cause of Omenn syndrome (OS). 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+). Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage; Deoxyribonuclease; EC 3.1.-.-
Chromosomal Location of Human Ortholog: 2|2 A1
Cellular Component:  Golgi apparatus; nonhomologous end joining complex; nuclear chromosome, telomeric region; nucleoplasm; nucleus
Molecular Function:  5'-3' exodeoxyribonuclease activity; 5'-3' exonuclease activity; damaged DNA binding; endonuclease activity; exonuclease activity; hydrolase activity; nuclease activity; single-stranded DNA endodeoxyribonuclease activity
Biological Process:  adaptive immune response; B cell differentiation; cellular response to DNA damage stimulus; chromosome organization; DNA recombination; DNA repair; double-strand break repair; double-strand break repair via nonhomologous end joining; immune system process; interstrand cross-link repair; protection from non-homologous end joining at telomere; response to ionizing radiation; telomere maintenance; V(D)J recombination
Reference #:  Q8K4J0 (UniProtKB)
Alt. Names/Synonyms: 9930121L06Rik; AI661365; Art; artemis; Dclre1c; DCR1C; DNA cross-link repair 1A, PSO2 homolog; DNA cross-link repair 1C protein; DNA cross-link repair 1C, PSO2 homolog (S. cerevisiae); mArt; MGC123409; OTTMUSP00000011550; OTTMUSP00000011552; Protein artemis; SNM1-like protein; Snm1l
Gene Symbols: Dclre1c
Molecular weight: 78,834 Da
Basal Isoelectric point: 5.72  Predict pI for various phosphorylation states
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Artemis

Protein Structure Not Found.


Cross-references to other databases:  STRING  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene