| IED ID | IndEnz0002004315 |
| Enzyme Type ID | protease004315 |
| Protein Name |
Exonuclease 3'-5' domain-containing protein 2 EC 3.1.11.1 3'-5' exoribonuclease EXD2 EC 3.1.13.- Exonuclease 3'-5' domain-like-containing protein 2 |
| Gene Name | EXD2 C14orf114 EXDL2 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MSRQNLVALTVTTLLGVAVGGFVLWKGIQRRRRSKTSPVTQQPQQKVLGSRELPPPEDDQLHSSAPRSSWKERILKAKVVTVSQEAEWDQIEPLLRSELEDFPVLGIDCEWVNLEGKASPLSLLQMASPSGLCVLVRLPKLICGGKTLPRTLLDILADGTILKVGVGCSEDASKLLQDYGLVVRGCLDLRYLAMRQRNNLLCNGLSLKSLAETVLNFPLDKSLLLRCSNWDAETLTEDQVIYAARDAQISVALFLHLLGYPFSRNSPGEKNDDHSSWRKVLEKCQGVVDIPFRSKGMSRLGEEVNGEATESQQKPRNKKSKMDGMVPGNHQGRDPRKHKRKPLGVGYSARKSPLYDNCFLHAPDGQPLCTCDRRKAQWYLDKGIGELVSEEPFVVKLRFEPAGRPESPGDYYLMVKENLCVVCGKRDSYIRKNVIPHEYRKHFPIEMKDHNSHDVLLLCTSCHAISNYYDNHLKQQLAKEFQAPIGSEEGLRLLEDPERRQVRSGARALLNAESLPTQRKEELLQALREFYNTDVVTEEMLQEAASLETRISNENYVPHGLKVVQCHSQGGLRSLMQLESRWRQHFLDSMQPKHLPQQWSVDHNHQKLLRKFGEDLPIQLS |
| Enzyme Length | 621 |
| Uniprot Accession Number | Q9NVH0 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates.; EC=3.1.11.1; Evidence={ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:31127291}; |
| DNA Binding | |
| EC Number | 3.1.11.1; 3.1.13.- |
| Enzyme Function | FUNCTION: Exonuclease that has both 3'-5' exoribonuclease and exodeoxyribonuclease activities, depending on the divalent metal cation used as cofactor (PubMed:29335528, PubMed:31127291). In presence of Mg(2+), only shows 3'-5' exoribonuclease activity, while it shows both exoribonuclease and exodeoxyribonuclease activities in presence of Mn(2+) (PubMed:29335528, PubMed:31127291). Acts as an exoribonuclease in mitochondrion, possibly by regulating ATP production and mitochondrial translation (PubMed:29335528). Also involved in the response to DNA damage (PubMed:26807646, PubMed:31255466). Acts as 3'-5' exodeoxyribonuclease for double-strand breaks resection and efficient homologous recombination (PubMed:20603073, PubMed:26807646). Plays a key role in controlling the initial steps of chromosomal break repair, it is recruited to chromatin in a damage-dependent manner and functionally interacts with the MRN complex to accelerate resection through its 3'-5' exonuclease activity, which efficiently processes double-stranded DNA substrates containing nicks (PubMed:26807646). Also involved in response to replicative stress: recruited to stalled forks and is required to stabilize and restart stalled replication forks by restraining excessive fork regression, thereby suppressing their degradation (PubMed:31255466). {ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:29335528, ECO:0000269|PubMed:31127291, ECO:0000269|PubMed:31255466}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Beta strand (8); Chain (1); Compositional bias (2); Domain (1); Frameshift (1); Helix (10); Metal binding (4); Mutagenesis (6); Natural variant (2); Region (2); Sequence conflict (1); Topological domain (2); Transmembrane (1); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Chromosome;DNA damage;DNA repair;Exonuclease;Hydrolase;Magnesium;Manganese;Membrane;Metal-binding;Mitochondrion;Mitochondrion outer membrane;Nuclease;Nucleus;Reference proteome;Transmembrane;Transmembrane helix |
| Interact With | Q99708 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000269|PubMed:29599527, ECO:0000269|PubMed:31127291}; Single-pass membrane protein {ECO:0000255, ECO:0000269|PubMed:31127291}. Mitochondrion matrix {ECO:0000269|PubMed:29335528}. Nucleus {ECO:0000269|PubMed:26807646}. Chromosome {ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:31255466}. Note=Mainly localizes to the mitochondrial outer membrane (PubMed:29599527, PubMed:31127291). May translocate to the nucleus in response to DNA damage; however mechanism that explain nuclear localization are unknown and require experimental evidences (PubMed:26807646). Recruited to replication forks following replication stress (PubMed:31255466). {ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:29599527, ECO:0000269|PubMed:31127291, ECO:0000269|PubMed:31255466}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (8) |
| Cross Reference PDB | 6K17; 6K18; 6K19; 6K1A; 6K1B; 6K1C; 6K1D; 6K1E; |
| Mapped Pubmed ID | 25609649; |
| Motif | |
| Gene Encoded By | |
| Mass | 70,353 |
| Kinetics | |
| Metal Binding | METAL 108; /note="Divalent metal cation 1; catalytic"; /evidence="ECO:0000269|PubMed:31127291, ECO:0007744|PDB:6K18, ECO:0007744|PDB:6K1A, ECO:0007744|PDB:6K1B, ECO:0007744|PDB:6K1D, ECO:0007744|PDB:6K1E"; METAL 108; /note="Divalent metal cation 2; catalytic"; /evidence="ECO:0000269|PubMed:31127291, ECO:0007744|PDB:6K19, ECO:0007744|PDB:6K1A, ECO:0007744|PDB:6K1B, ECO:0007744|PDB:6K1C, ECO:0007744|PDB:6K1D, ECO:0007744|PDB:6K1E"; METAL 110; /note="Divalent metal cation 1; catalytic"; /evidence="ECO:0000269|PubMed:31127291, ECO:0007744|PDB:6K18, ECO:0007744|PDB:6K1A, ECO:0007744|PDB:6K1B, ECO:0007744|PDB:6K1D, ECO:0007744|PDB:6K1E"; METAL 246; /note="Divalent metal cation 1; catalytic"; /evidence="ECO:0000269|PubMed:31127291, ECO:0007744|PDB:6K18, ECO:0007744|PDB:6K1A, ECO:0007744|PDB:6K1B, ECO:0007744|PDB:6K1D, ECO:0007744|PDB:6K1E" |
| Rhea ID | |
| Cross Reference Brenda |