ID:EXO1_HUMAN DESCRIPTION: RecName: Full=Exonuclease 1; Short=hExo1; EC=3.1.-.-; AltName: Full=Exonuclease I; Short=hExoI; FUNCTION: 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch- containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis. COFACTOR: Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding (By similarity). SUBUNIT: Interacts with the MLH1-PMS2 heterodimer via MLH1. Interacts with MSH3. Interacts with the MSH2-MSH6 heterodimer via MSH2, and this interaction may increase the processivity of the 5'->3' exonuclease activity. Interacts with PCNA, and this interaction may both stimulate the cryptic 3'->5' exonuclease activity and suppress the 5'->3' exonuclease activity. Interacts with WRN, and this interaction stimulates both the 5'->3' exonuclease activity and cleavage of 5'-overhanging flap structures. Interacts with RECQL/RECQ1, and this interaction stimulates cleavage of 5'-overhanging flap structures. SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with PCNA to discrete nuclear foci in S-phase. TISSUE SPECIFICITY: Highly expressed in bone marrow, testis and thymus. Expressed at lower levels in colon, lymph nodes, ovary, placenta, prostate, small intestine, spleen and stomach. DEVELOPMENTAL STAGE: Highly expressed in fetal liver and at lower levels in fetal brain, heart, kidney, spleen and thymus. PTM: Phosphorylated upon DNA damage and in response to agents stalling DNA replication, probably by ATM or ATR. Phosphorylation at Ser-454, Thr-621 and Ser-714 is induced upon DNA-damage caused by treatment with hydroxyurea (HU) but not upon IR treatment. The HU-induced EXO1 triple phosphorylation facilitates destabilisation/degradation of the protein. POLYMORPHISM: Most naturally occurring variants in this protein are not associated with familial disposition to hereditary non- polyposis colorectal cancer (HNPCC). Furthermore, germline deletions involving this locus are not associated with clinically manifested colorectal tumors. SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily. SEQUENCE CAUTION: Sequence=AAC33874.1; Type=Frameshift; Positions=793; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/exo1/";
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.
ModBase Predicted Comparative 3D Structure on Q9UQ84
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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.
AK291291 - Homo sapiens cDNA FLJ76659 complete cds, highly similar to Homo sapiens exonuclease 1 (EXO1), transcript variant 2, mRNA. BC007491 - Homo sapiens exonuclease 1, mRNA (cDNA clone MGC:1908 IMAGE:2967734), complete cds. JD484064 - Sequence 465088 from Patent EP1572962. JD058412 - Sequence 39436 from Patent EP1572962. JD485519 - Sequence 466543 from Patent EP1572962. JD376657 - Sequence 357681 from Patent EP1572962. AF042282 - Homo sapiens Hex1 (HEX1) mRNA, complete cds. AF091740 - Homo sapiens exonuclease 1a (EXO1a) mRNA, complete cds. AF060479 - Homo sapiens exonuclease I (EXO1) mRNA, complete cds. AF084974 - Homo sapiens exonuclease I (EXOI) mRNA, complete cds. JD555584 - Sequence 536608 from Patent EP1572962. JD507697 - Sequence 488721 from Patent EP1572962. JD331672 - Sequence 312696 from Patent EP1572962. JD528898 - Sequence 509922 from Patent EP1572962. EU176754 - Synthetic construct Homo sapiens clone IMAGE:100011531; FLH191845.01L; RZPDo839E12255D exonuclease 1 (EXO1) gene, encodes complete protein. DQ893032 - Synthetic construct clone IMAGE:100005662; FLH191846.01X; RZPDo839H0777D exonuclease 1 (EXO1) gene, encodes complete protein. AB590178 - Synthetic construct DNA, clone: pFN21AE1492, Homo sapiens EXO1 gene for exonuclease 1, without stop codon, in Flexi system. KJ904622 - Synthetic construct Homo sapiens clone ccsbBroadEn_14016 EXO1-like gene, encodes complete protein. AL080139 - Homo sapiens mRNA; cDNA DKFZp434L013 (from clone DKFZp434L013). JD349848 - Sequence 330872 from Patent EP1572962. JD093304 - Sequence 74328 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9UQ84 (Reactome details) participates in the following event(s):
R-HSA-5358545 EXO1 interacts with MSH2:MSH3 (MutSbeta) and MLH1:PMS2 (MutLalpha) R-HSA-5358597 EXO1 interacts with MSH2:MSH6 (MutSalpha) and MLH1:PMS2 (MutLalpha) R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment R-HSA-5686410 BLM mediates dissolution of double Holliday junction R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5693589 D-loop dissociation and strand annealing R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament R-HSA-5685838 CX3 complex binds D-loop structures R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) R-HSA-5358508 Mismatch Repair R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-73894 DNA Repair R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693537 Resolution of D-Loop Structures R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-5693538 Homology Directed Repair R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-69473 G2/M DNA damage checkpoint R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-69481 G2/M Checkpoints R-HSA-5633007 Regulation of TP53 Activity R-HSA-69620 Cell Cycle Checkpoints R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-1640170 Cell Cycle R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
