| IED ID | IndEnz0002013384 |
| Enzyme Type ID | protease013384 |
| Protein Name |
YTH domain-containing family protein 3 DF3 |
| Gene Name | YTHDF3 |
| 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 | MSATSVDQRPKGQGNKVSVQNGSIHQKDAVNDDDFEPYLSSQTNQSNSYPPMSDPYMPSYYAPSIGFPYSLGEAAWSTAGDQPMPYLTTYGQMSNGEHHYIPDGVFSQPGALGNTPPFLGQHGFNFFPGNADFSTWGTSGSQGQSTQSSAYSSSYGYPPSSLGRAITDGQAGFGNDTLSKVPGISSIEQGMTGLKIGGDLTAAVTKTVGTALSSSGMTSIATNSVPPVSSAAPKPTSWAAIARKPAKPQPKLKPKGNVGIGGSAVPPPPIKHNMNIGTWDEKGSVVKAPPTQPVLPPQTIIQQPQPLIQPPPLVQSQLPQQQPQPPQPQQQQGPQPQAQPHQVQPQQQQLQNRWVAPRNRGAGFNQNNGAGSENFGLGVVPVSASPSSVEVHPVLEKLKAINNYNPKDFDWNLKNGRVFIIKSYSEDDIHRSIKYSIWCSTEHGNKRLDAAYRSLNGKGPLYLLFSVNGSGHFCGVAEMKSVVDYNAYAGVWSQDKWKGKFEVKWIFVKDVPNNQLRHIRLENNDNKPVTNSRDTQEVPLEKAKQVLKIIATFKHTTSIFDDFAHYEKRQEEEEAMRRERNRNKQ |
| Enzyme Length | 585 |
| Uniprot Accession Number | Q7Z739 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 428; /note="N6-methyladenosine residue"; /evidence="ECO:0000250|UniProtKB:Q9Y5A9"; BINDING 468; /note="N6-methyladenosine residue"; /evidence="ECO:0000250|UniProtKB:Q9Y5A9"; BINDING 492; /note="N6-methyladenosine residue"; /evidence="ECO:0000269|PubMed:33073985, ECO:0007744|PDB:6ZOT"; BINDING 497; /note="N6-methyladenosine residue"; /evidence="ECO:0000269|PubMed:33073985, ECO:0007744|PDB:6ZOT" |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28106072, PubMed:28106076, PubMed:28281539, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:28106072, PubMed:28281539, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3 (PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:28106076, PubMed:32492408). Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs (By similarity). Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification (By similarity). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (PubMed:28106072). Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (PubMed:28281539). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31388144, PubMed:31292544, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation (PubMed:32194978). {ECO:0000250|UniProtKB:Q8BYK6, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:28106076, ECO:0000269|PubMed:28281539, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:32194978, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: Has some antiviral activity against HIV-1 virus: incorporated into HIV-1 particles in a nucleocapsid-dependent manner and reduces viral infectivity in the next cycle of infection (PubMed:32053707). May interfere with this early step of the viral life cycle by binding to N6-methyladenosine (m6A) modified sites on the HIV-1 RNA genome (PubMed:32053707). {ECO:0000269|PubMed:32053707}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (6); Binding site (4); Chain (1); Compositional bias (4); Domain (1); Helix (8); Initiator methionine (1); Modified residue (2); Region (5); Sequence conflict (3); Site (3); Turn (2) |
| Keywords | 3D-structure;Acetylation;Cytoplasm;Direct protein sequencing;Host-virus interaction;Phosphoprotein;RNA-binding;Reference proteome |
| Interact With | Q9UNN5; P04591 |
| Induction | INDUCTION: Following heat shock stress. {ECO:0000269|PubMed:26458103}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:32492408, ECO:0000305|PubMed:28106072}. Cytoplasm, P-body {ECO:0000269|PubMed:32492408}. Cytoplasm, Stress granule {ECO:0000269|PubMed:32451507}. |
| Modified Residue | MOD_RES 2; /note="N-acetylserine"; /evidence="ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378"; MOD_RES 23; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231" |
| Post Translational Modification | PTM: (Microbial infection) Proteolytically cleaved by HIV-1 protease when incorporated into HIV-1 particles in a nucleocapsid-dependent-manner. Cleavage by HIV-1 protease probably ensures optimal infectivity of the mature virion. {ECO:0000269|PubMed:32053707}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 6ZOT; |
| Mapped Pubmed ID | 20463905; 20711500; 22190034; 23902751; 24705354; 26496610; 26638075; 27371828; 30866959; 32905781; 33125861; 33849973; 34190193; 34497675; |
| Motif | |
| Gene Encoded By | |
| Mass | 63,861 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |