Human Gene DCLRE1C (ENST00000378289.8) Description and Page Index
  Description: Homo sapiens DNA cross-link repair 1C (DCLRE1C), transcript variant m, non-coding RNA. (from RefSeq NR_146960)
RefSeq Summary (NR_146960): 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]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803611.272921.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END##
Gencode Transcript: ENST00000378289.8
Gencode Gene: ENSG00000152457.18
Transcript (Including UTRs)
   Position: hg38 chr10:14,897,359-14,954,432 Size: 57,074 Total Exon Count: 14 Strand: -
Coding Region
   Position: hg38 chr10:14,899,164-14,954,010 Size: 54,847 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:14,897,359-14,954,432)mRNA (may differ from genome)Protein (434 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
Stanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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/";

-  MalaCards Disease Associations
  MalaCards Gene Search: DCLRE1C
Diseases sorted by gene-association score: severe combined immunodeficiency, athabascan type* (1650), omenn syndrome* (1214), malignant histiocytosis* (231), severe combined immunodeficiency (47), artemis deficiency (27), conjunctival degeneration (11), lig4 syndrome (8), ataxia-telangiectasia (8), combined t cell and b cell immunodeficiency (7), pinguecula (6), primary immunodeficiency disease (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 4.88 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 78.65 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -188.00422-0.445 Picture PostScript Text
3' UTR -392.601805-0.218 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001279 - Beta-lactamas-like
IPR011084 - DRMBL

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000014 single-stranded DNA endodeoxyribonuclease activity
GO:0003684 damaged DNA binding
GO:0004518 nuclease activity
GO:0004519 endonuclease activity
GO:0004527 exonuclease activity
GO:0005515 protein binding
GO:0008409 5'-3' exonuclease activity
GO:0016787 hydrolase activity
GO:0035312 5'-3' exodeoxyribonuclease activity

Biological Process:
GO:0000723 telomere maintenance
GO:0002250 adaptive immune response
GO:0002376 immune system process
GO:0006281 DNA repair
GO:0006302 double-strand break repair
GO:0006303 double-strand break repair via nonhomologous end joining
GO:0006310 DNA recombination
GO:0006974 cellular response to DNA damage stimulus
GO:0010212 response to ionizing radiation
GO:0030183 B cell differentiation
GO:0031848 protection from non-homologous end joining at telomere
GO:0033151 V(D)J recombination
GO:0036297 interstrand cross-link repair
GO:0051276 chromosome organization
GO:0090305 nucleic acid phosphodiester bond hydrolysis

Cellular Component:
GO:0000784 nuclear chromosome, telomeric region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005794 Golgi apparatus
GO:0070419 nonhomologous end joining complex


-  Descriptions from all associated GenBank mRNAs
  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.
CU675796 - Synthetic construct Homo sapiens gateway clone IMAGE:100019054 3' read SUV39H2 mRNA.
AK093757 - Homo sapiens cDNA FLJ36438 fis, clone THYMU2012113, highly similar to Artemis protein (EC 3.1.-.-).
KJ894555 - Synthetic construct Homo sapiens clone ccsbBroadEn_03949 DCLRE1C gene, encodes complete protein.
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

-  Other Names for This Gene
  Alternate Gene Symbols: ARTEMIS, ASCID, D3DRT6, DCR1C_HUMAN, NR_146960, Q1HCL2, Q5JSR4, Q5JSR5, Q5JSR7, Q5JSR8, Q5JSR9, Q5JSS0, Q5JSS7, Q6PK14, Q8N101, Q8N132, Q8TBW9, Q96SD1, Q9BVW9, Q9HAM4, SCIDA, SNM1C, uc010qbx.1, uc010qbx.2, uc010qbx.3, uc010qbx.4
UCSC ID: uc010qbx.4
RefSeq Accession: NR_146960
Protein: Q96SD1 (aka DCR1C_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.