| IED ID | IndEnz0002006429 |
| Enzyme Type ID | protease006429 |
| Protein Name |
Abasic site processing protein HMCES Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein ES cell-specific 5hmC-binding protein Peptidase HMCES EC 3.4.-.- SRAP domain-containing protein 1 |
| Gene Name | HMCES C3orf37 DC12 SRAPD1 |
| 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 | MCGRTSCHLPRDVLTRACAYQDRRGQQRLPEWRDPDKYCPSYNKSPQSNSPVLLSRLHFEKDADSSERIIAPMRWGLVPSWFKESDPSKLQFNTTNCRSDTVMEKRSFKVPLGKGRRCVVLADGFYEWQRCQGTNQRQPYFIYFPQIKTEKSGSIGAADSPENWEKVWDNWRLLTMAGIFDCWEPPEGGDVLYSYTIITVDSCKGLSDIHHRMPAILDGEEAVSKWLDFGEVSTQEALKLIHPTENITFHAVSSVVNNSRNNTPECLAPVDLVVKKELRASGSSQRMLQWLATKSPKKEDSKTPQKEESDVPQWSSQFLQKSPLPTKRGTAGLLEQWLKREKEEEPVAKRPYSQ |
| Enzyme Length | 354 |
| Uniprot Accession Number | Q96FZ2 |
| Absorption | |
| Active Site | ACT_SITE 2; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:31235913, ECO:0000305|PubMed:30554877" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.-.- |
| Enzyme Function | FUNCTION: Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites (PubMed:30554877, PubMed:31235915, PubMed:31235913). Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue (PubMed:30554877, PubMed:31235913). The HMCES DNA-protein cross-link is then degraded by the proteasome (PubMed:30554877). Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks (PubMed:30554877). Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (PubMed:31235915, PubMed:31806351). Also involved in class switch recombination (CSR) in B-cells independently of the formation of a DNA-protein cross-link: acts by binding and protecting ssDNA overhangs to promote DNA double-strand break repair through the microhomology-mediated alternative-end-joining (Alt-EJ) pathway (By similarity). Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity). {ECO:0000250|UniProtKB:Q8R1M0, ECO:0000269|PubMed:30554877, ECO:0000269|PubMed:31235913, ECO:0000269|PubMed:31235915, ECO:0000269|PubMed:31806351}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Beta strand (13); Chain (1); Compositional bias (3); Cross-link (7); Frameshift (1); Helix (12); Initiator methionine (1); Modified residue (4); Motif (1); Mutagenesis (6); Region (1); Sequence conflict (1); Site (2); Turn (3) |
| Keywords | 3D-structure;Autocatalytic cleavage;Chromosome;Covalent protein-DNA linkage;DNA damage;DNA-binding;Hydrolase;Isopeptide bond;Phosphoprotein;Protease;Reference proteome;Ubl conjugation |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:30554877}. Note=Recruited to chromatin following DNA damage (PubMed:30554877). Localizes to replication forks (PubMed:30554877). {ECO:0000269|PubMed:30554877}. |
| Modified Residue | MOD_RES 2; /note=Thiazolidine linkage to a ring-opened DNA abasic site; /evidence=ECO:0000269|PubMed:31235913; MOD_RES 160; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 295; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163; MOD_RES 322; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: Ubiquitinated; the covalent HMCES DNA-protein cross-link is ubiquitinated, leading to its degradation by the proteasome. {ECO:0000269|PubMed:30554877}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 5KO9; 6OE7; 6OEA; 6OEB; 6OOV; |
| Mapped Pubmed ID | 23602568; 23902751; 24267889; 24387984; 24679604; 25471351; 25827305; 26356709; 26496610; 31992357; 32307824; 32492421; 32663791; 33203436; 33788831; |
| Motif | MOTIF 332..338; /note=PIP-box; /evidence=ECO:0000269|PubMed:30554877 |
| Gene Encoded By | |
| Mass | 40,575 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |