| IED ID | IndEnz0002004317 |
| Enzyme Type ID | protease004317 |
| Protein Name |
Serine protease FAM111A EC 3.4.21.- |
| Gene Name | FAM111A KIAA1895 |
| 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 | MSCKKQRSRKHSVNEKCNMKIEHYFSPVSKEQQNNCSTSLMRMESRGDPRATTNTQAQRFHSPKKNPEDQTMPQNRTIYVTLKVNHRRNQDMKLKLTHSENSSLYMALNTLQAVRKEIETHQGQEMLVRGTEGIKEYINLGMPLSCFPEGGQVVITFSQSKSKQKEDNHIFGRQDKASTECVKFYIHAIGIGKCKRRIVKCGKLHKKGRKLCVYAFKGETIKDALCKDGRFLSFLENDDWKLIENNDTILESTQPVDELEGRYFQVEVEKRMVPSAAASQNPESEKRNTCVLREQIVAQYPSLKRESEKIIENFKKKMKVKNGETLFELHRTTFGKVTKNSSSIKVVKLLVRLSDSVGYLFWDSATTGYATCFVFKGLFILTCRHVIDSIVGDGIEPSKWATIIGQCVRVTFGYEELKDKETNYFFVEPWFEIHNEELDYAVLKLKENGQQVPMELYNGITPVPLSGLIHIIGHPYGEKKQIDACAVIPQGQRAKKCQERVQSKKAESPEYVHMYTQRSFQKIVHNPDVITYDTEFFFGASGSPVFDSKGSLVAMHAAGFAYTYQNETRSIIEFGSTMESILLDIKQRHKPWYEEVFVNQQDVEMMSDEDL |
| Enzyme Length | 611 |
| Uniprot Accession Number | Q96PZ2 |
| Absorption | |
| Active Site | ACT_SITE 385; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P06681; ACT_SITE 439; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P06681; ACT_SITE 541; /note=Charge relay system; /evidence=ECO:0000305|PubMed:32165630 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.21.- |
| Enzyme Function | FUNCTION: Single-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:32165630). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:32165630). Protects replication fork from stalling by removing DPCs, such as covalently trapped topoisomerase 1 (TOP1) adducts on DNA lesion, or poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors (PubMed:32165630). Required for PCNA loading on replication sites (PubMed:24561620). Promotes S-phase entry and DNA synthesis (PubMed:24561620). {ECO:0000269|PubMed:24561620, ECO:0000269|PubMed:32165630}.; FUNCTION: (Microbial infection) May directly function at replication forks, explaining why Simian virus 40 (SV40) interacts with FAM111A to overcome host range restriction. {ECO:0000269|PubMed:23093934}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Cross-link (3); Erroneous initiation (2); Modified residue (1); Motif (1); Mutagenesis (4); Natural variant (6); Region (2); Sequence conflict (1); Site (1) |
| Keywords | Autocatalytic cleavage;Chromosome;Cytoplasm;DNA damage;DNA repair;DNA replication;DNA-binding;Disease variant;Dwarfism;Host-virus interaction;Hydrolase;Isopeptide bond;Nucleus;Phosphoprotein;Protease;Reference proteome;Ubl conjugation |
| Interact With | |
| Induction | INDUCTION: Regulated in a cell cycle dependent manner with the lowest expression during G0 or the quiescent phase and with peak expression during G2/M phase (at protein level). {ECO:0000269|PubMed:23093934}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23093934, ECO:0000269|PubMed:24561620}. Chromosome {ECO:0000269|PubMed:24561620}. Cytoplasm {ECO:0000269|PubMed:23093934}. Note=Mainly localizes to nucleus: colocalizes with PCNA on replication sites. {ECO:0000269|PubMed:24561620}. |
| Modified Residue | MOD_RES 26; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification | PTM: Autocatalytically cleaved; activating the protein (PubMed:32165630). Autocatalytic cleavage takes place in trans (PubMed:32165630). {ECO:0000269|PubMed:32165630}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 20711500; 26496610; |
| Motif | MOTIF 16..28; /note=PIP-box; /evidence=ECO:0000269|PubMed:24561620 |
| Gene Encoded By | |
| Mass | 70,196 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |