Protein: Serine protease FAM111A (EC 3.4.21.-) (Q96PZ2)
Organism: Homo sapiens (Human)
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. 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. 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. Required for PCNA loading on replication sites. Promotes S-phase entry and DNA synthesis.
Subcellular location: Nucleus {ECO:0000269|PubMed:23093934, ECO:0000269|PubMed:24561620, ECO:0000269|PubMed:37607234}. Chromosome {ECO:0000269|PubMed:24561620}. Cytoplasm {ECO:0000269|PubMed:23093934, ECO:0000269|PubMed:37607234}. Note=Mainly localizes to nucleus: colocalizes with PCNA on replication sites. {ECO:0000269|PubMed:24561620}.
Sequence: MSCKKQRSRKHSVNEKCNMKIEHYFSPVSKEQQNNCSTSLMRMESRGDPRATTNTQAQRFHSPKKNPEDQTMPQNRTIYVTLKVNHRRNQDMKLKLTHSENSSLYMALNTLQAVRKEIETHQGQEMLVRGTEGIKEYINLGMPLSCFPEGGQVVITFSQSKSKQKEDNHIFGRQDKASTECVKFYIHAIGIGKCKRRIVKCGKLHKKGRKLCVYAFKGETIKDALCKDGRFLSFLENDDWKLIENNDTILESTQPVDELEGRYFQVEVEKRMVPSAAASQNPESEKRNTCVLREQIVAQYPSLKRESEKIIENFKKKMKVKNGETLFELHRTTFGKVTKNSSSIKVVKLLVRLSDSVGYLFWDSATTGYATCFVFKGLFILTCRHVIDSIVGDGIEPSKWATIIGQCVRVTFGYEELKDKETNYFFVEPWFEIHNEELDYAVLKLKENGQQVPMELYNGITPVPLSGLIHIIGHPYGEKKQIDACAVIPQGQRAKKCQERVQSKKAESPEYVHMYTQRSFQKIVHNPDVITYDTEFFFGASGSPVFDSKGSLVAMHAAGFAYTYQNETRSIIEFGSTMESILLDIKQRHKPWYEEVFVNQQDVEMMSDEDL
InterPro domains: - IPR043504: Peptidase S1, PA clan, chymotrypsin-like fold (homologous_superfamily) [464-585]
- IPR009003: Peptidase S1, PA clan (homologous_superfamily) [329-603]
Interaction partners: - Tubulin-specific chaperone E
- Tubulin-specific chaperone E
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0017171 (serine hydrolase activity), GO:0008233 (peptidase activity), GO:0008236 (serine-type peptidase activity), GO:0004175 (endopeptidase activity), GO:0004252 (serine-type endopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0071704 (organic substance metabolic process), GO:0048523 (negative regulation of cellular process), GO:0009056 (catabolic process), GO:0044238 (primary metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0009894 (regulation of catabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0044248 (cellular catabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009895 (negative regulation of catabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:1901575 (organic substance catabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0034655 (nucleobase-containing compound catabolic process), GO:0009057 (macromolecule catabolic process), GO:0044270 (cellular nitrogen compound catabolic process), GO:0090304 (nucleic acid metabolic process), GO:0044265 (cellular macromolecule catabolic process), GO:0031330 (negative regulation of cellular catabolic process), GO:0019439 (aromatic compound catabolic process), GO:1901361 (organic cyclic compound catabolic process), GO:0046700 (heterocycle catabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0031329 (regulation of cellular catabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010629 (negative regulation of gene expression), GO:0010468 (regulation of gene expression), GO:0016070 (RNA metabolic process), GO:0006402 (mRNA catabolic process), GO:0006401 (RNA catabolic process), GO:1902369 (negative regulation of RNA catabolic process), GO:0016071 (mRNA metabolic process), GO:0000956 (nuclear-transcribed mRNA catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)