Human Gene DCLRE1C (ENST00000378278.7) from GENCODE V44
Description: Homo sapiens DNA cross-link repair 1C (DCLRE1C), transcript variant b, mRNA. (from RefSeq NM_022487) RefSeq Summary (NM_001033855): This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The encoded protein has single-strand-specific 5'-3' exonuclease activity; it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins. The protein also functions in the regulation of the cell cycle in response to DNA damage. Mutations in this gene can cause Athabascan-type severe combined immunodeficiency (SCIDA) and Omenn syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]. Gencode Transcript: ENST00000378278.7 Gencode Gene: ENSG00000152457.19 Transcript (Including UTRs) Position: hg38 chr10:14,904,613-14,954,096 Size: 49,484 Total Exon Count: 14 Strand: - Coding Region Position: hg38 chr10:14,908,408-14,954,010 Size: 45,603 Coding Exon Count: 14
ID:DCR1C_HUMAN DESCRIPTION: RecName: Full=Protein artemis; EC=3.1.-.-; AltName: Full=DNA cross-link repair 1C protein; AltName: Full=Protein A-SCID; AltName: Full=SNM1 homolog C; Short=hSNM1C; AltName: Full=SNM1-like protein; 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. SUBUNIT: Interacts with ATM, BRCA1, PRKDC and TP53BP1. Also exhibits ATM- and phosphorylation-dependent interaction with the MRN complex, composed of MRE11A/MRE11, RAD50, and NBN. SUBCELLULAR LOCATION: Nucleus. 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. PTM: Phosphorylation on undefined residues by PRKDC may stimulate endonucleolytic activity on 5' and 3' hairpins and overhangs. PRKDC must remain present, even after phosphorylation, for efficient hairpin opening. Also phosphorylated by ATM in response to ionizing radiation (IR) and by ATR in response to ultraviolet (UV) radiation. DISEASE: 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: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. DISEASE: Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM: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. DISEASE: Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM: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+). SIMILARITY: Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family. SEQUENCE CAUTION: Sequence=CAI40018.1; Type=Erroneous gene model prediction; Sequence=CAI40019.1; Type=Erroneous gene model prediction; Sequence=CAI40021.1; Type=Erroneous gene model prediction; Sequence=CAI40023.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=DCLRE1Cbase; Note=DCLRE1C mutation db; URL="http://bioinf.uta.fi/DCLRE1Cbase/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/DCLRE1C"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/dclre1c/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF07522 - DNA repair metallo-beta-lactamase
ModBase Predicted Comparative 3D Structure on Q96SD1
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC022254 - Homo sapiens DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae), mRNA (cDNA clone MGC:22216 IMAGE:4272155), complete cds. KJ903077 - Synthetic construct Homo sapiens clone ccsbBroadEn_12471 DCLRE1C gene, encodes complete protein. KR711183 - Synthetic construct Homo sapiens clone CCSBHm_00021006 DCLRE1C (DCLRE1C) mRNA, encodes complete protein. KR711184 - Synthetic construct Homo sapiens clone CCSBHm_00021008 DCLRE1C (DCLRE1C) mRNA, encodes complete protein. KR711185 - Synthetic construct Homo sapiens clone CCSBHm_00021009 DCLRE1C (DCLRE1C) mRNA, encodes complete protein. AK021422 - Homo sapiens cDNA FLJ11360 fis, clone HEMBA1000231. BC108276 - Homo sapiens DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae), mRNA (cDNA clone IMAGE:4538406), with apparent retained intron. AF395747 - Homo sapiens Athabascan SCID transcript variant 1 (SCIDA) mRNA, complete cds; alternatively spliced. AF395748 - Homo sapiens Athabascan SCID transcript variant 2 (SCIDA) mRNA, complete cds; alternatively spliced. AF395749 - Homo sapiens Athabascan SCID transcript variant 3 (SCIDA) mRNA, complete cds; alternatively spliced. AF395750 - Homo sapiens Athabascan SCID transcript variant 4 (SCIDA) mRNA, complete cds; alternatively spliced. AF395751 - Homo sapiens Athabascan SCID transcript variant 5 (SCIDA) mRNA, complete cds; alternatively spliced. AF395752 - Homo sapiens Athabascan SCID transcript variant 6 (SCIDA) mRNA, complete cds; alternatively spliced. AJ296101 - Homo sapiens mRNA for artemis. BC009185 - Homo sapiens DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae), mRNA (cDNA clone MGC:15064 IMAGE:3945623), complete cds. BX648858 - Homo sapiens mRNA; cDNA DKFZp686F04233 (from clone DKFZp686F04233). AK022922 - Homo sapiens cDNA FLJ12860 fis, clone NT2RP2003559, highly similar to Artemis protein (EC 3.1.-.-). AK290598 - Homo sapiens cDNA FLJ77068 complete cds, highly similar to Homo sapiens DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae) (DCLRE1C), transcript variant c, mRNA. AK307912 - Homo sapiens cDNA, FLJ97860. CU692508 - Synthetic construct Homo sapiens gateway clone IMAGE:100022255 5' read DCLRE1C mRNA. BC067233 - Homo sapiens cDNA clone IMAGE:4333081, partial cds. JD489237 - Sequence 470261 from Patent EP1572962. JD499762 - Sequence 480786 from Patent EP1572962. JD561714 - Sequence 542738 from Patent EP1572962. JD093166 - Sequence 74190 from Patent EP1572962. JD184250 - Sequence 165274 from Patent EP1572962. JD066850 - Sequence 47874 from Patent EP1572962. JD176577 - Sequence 157601 from Patent EP1572962. JD531887 - Sequence 512911 from Patent EP1572962. JD232056 - Sequence 213080 from Patent EP1572962. JD401848 - Sequence 382872 from Patent EP1572962. JD323088 - Sequence 304112 from Patent EP1572962. JD307205 - Sequence 288229 from Patent EP1572962. JD435051 - Sequence 416075 from Patent EP1572962. JD529803 - Sequence 510827 from Patent EP1572962. JD557568 - Sequence 538592 from Patent EP1572962. JD430533 - Sequence 411557 from Patent EP1572962. JD401847 - Sequence 382871 from Patent EP1572962. JD401846 - Sequence 382870 from Patent EP1572962. JD135737 - Sequence 116761 from Patent EP1572962. JD249868 - Sequence 230892 from Patent EP1572962. JD322179 - Sequence 303203 from Patent EP1572962. JD381548 - Sequence 362572 from Patent EP1572962. JD189747 - Sequence 170771 from Patent EP1572962. JD229984 - Sequence 211008 from Patent EP1572962. JD281947 - Sequence 262971 from Patent EP1572962. JD162342 - Sequence 143366 from Patent EP1572962. JD061165 - Sequence 42189 from Patent EP1572962. JD174814 - Sequence 155838 from Patent EP1572962. JD265464 - Sequence 246488 from Patent EP1572962. JD088008 - Sequence 69032 from Patent EP1572962. JD377454 - Sequence 358478 from Patent EP1572962. JD442734 - Sequence 423758 from Patent EP1572962. JD180340 - Sequence 161364 from Patent EP1572962. JD457109 - Sequence 438133 from Patent EP1572962. JD335304 - Sequence 316328 from Patent EP1572962. JD335305 - Sequence 316329 from Patent EP1572962. JD442914 - Sequence 423938 from Patent EP1572962. JD442915 - Sequence 423939 from Patent EP1572962. JD532223 - Sequence 513247 from Patent EP1572962. JD558740 - Sequence 539764 from Patent EP1572962. JD532222 - Sequence 513246 from Patent EP1572962. JD558739 - Sequence 539763 from Patent EP1572962. JD430922 - Sequence 411946 from Patent EP1572962. JD326911 - Sequence 307935 from Patent EP1572962. JD388068 - Sequence 369092 from Patent EP1572962. JD335303 - Sequence 316327 from Patent EP1572962. JD178636 - Sequence 159660 from Patent EP1572962. JD471550 - Sequence 452574 from Patent EP1572962. JD223408 - Sequence 204432 from Patent EP1572962. BC000863 - Homo sapiens, Similar to hypothetical protein FLJ11360, clone IMAGE:3459836, mRNA, partial cds. AK093757 - Homo sapiens cDNA FLJ36438 fis, clone THYMU2012113, highly similar to Artemis protein (EC 3.1.-.-). JD522152 - Sequence 503176 from Patent EP1572962. JD556242 - Sequence 537266 from Patent EP1572962. JD340808 - Sequence 321832 from Patent EP1572962. JD443007 - Sequence 424031 from Patent EP1572962. JD558812 - Sequence 539836 from Patent EP1572962. JD430996 - Sequence 412020 from Patent EP1572962. JD291806 - Sequence 272830 from Patent EP1572962. JD498393 - Sequence 479417 from Patent EP1572962. JD197865 - Sequence 178889 from Patent EP1572962. JD212490 - Sequence 193514 from Patent EP1572962. KJ894555 - Synthetic construct Homo sapiens clone ccsbBroadEn_03949 DCLRE1C gene, encodes complete protein. AF088055 - Homo sapiens full length insert cDNA clone ZD65E09. CU679259 - Synthetic construct Homo sapiens gateway clone IMAGE:100022485 5' read DCLRE1C mRNA. JD499826 - Sequence 480850 from Patent EP1572962. JD043668 - Sequence 24692 from Patent EP1572962. JD129465 - Sequence 110489 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03450 - Non-homologous end-joining hsa05340 - Primary immunodeficiency
Reactome (by CSHL, EBI, and GO)
Protein Q96SD1 (Reactome details) participates in the following event(s):
R-HSA-5686924 DCLRE1C binds PRKDC:XRCC5:XRCC6 at DNA DSBs R-HSA-5686704 Activated ATM phosphorylates DCLRE1C R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM R-HSA-5693604 XRCC4:LIG4 ligates DNA DSB ends during NHEJ R-HSA-5687183 PRKDC phosphorylates DCLRE1C at DNA DSBs R-HSA-5693533 DCLRE1C (ARTEMIS) processes DNA DSB ends R-HSA-5693574 XRCC4:LIG4, NHEJ1 and POLL or POLM bind DNA DSBs in NHEJ R-HSA-5693578 TDP1 and TDP2 process unligatable DSB ends R-HSA-5687360 POLL or POLM extends aligned DNA DSB ends to fill gaps R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-73894 DNA Repair
US Server
