Q7Z739 · YTHD3_HUMAN
- ProteinYTH domain-containing family protein 3
- GeneYTHDF3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids585 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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:31292544, PubMed:31388144, 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).
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:31292544, PubMed:31388144, 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).
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).
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).
Features
Showing features for site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 157-158 | (Microbial infection) Cleavage; by HIV-1 protease | ||||
Sequence: YP | ||||||
Binding site | 422-424 | N6-methyladenosine 5'-phosphate residue (UniProtKB | ChEBI) of RNA (UniProtKB | ChEBI) | ||||
Sequence: KSY | ||||||
Binding site | 428 | N6-methyladenosine 5'-phosphate residue (UniProtKB | ChEBI) of RNA (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 438-439 | N6-methyladenosine 5'-phosphate residue (UniProtKB | ChEBI) of RNA (UniProtKB | ChEBI) | ||||
Sequence: WC | ||||||
Binding site | 468 | N6-methyladenosine 5'-phosphate residue (UniProtKB | ChEBI) of RNA (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 492 | N6-methyladenosine 5'-phosphate residue (UniProtKB | ChEBI) of RNA (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 497 | N6-methyladenosine 5'-phosphate residue (UniProtKB | ChEBI) of RNA (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Site | 538-539 | (Microbial infection) Cleavage; by HIV-1 protease | ||||
Sequence: VP | ||||||
Site | 570-571 | (Microbial infection) Cleavage; by HIV-1 protease | ||||
Sequence: QE |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoplasmic stress granule | |
Cellular Component | cytosol | |
Cellular Component | P-body | |
Molecular Function | mRNA binding | |
Molecular Function | N6-methyladenosine-containing RNA reader activity | |
Molecular Function | ribosome binding | |
Molecular Function | RNA binding | |
Biological Process | mRNA destabilization | |
Biological Process | negative regulation of type I interferon-mediated signaling pathway | |
Biological Process | organelle assembly | |
Biological Process | positive regulation of translation | |
Biological Process | positive regulation of translational initiation | |
Biological Process | regulation of mRNA stability | |
Biological Process | regulation of trophoblast cell migration | |
Biological Process | stress granule assembly |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameYTH domain-containing family protein 3
- Short namesDF3
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ7Z739
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 587 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, modified residue (large scale data), chain.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Chain | PRO_0000230991 | 2-585 | UniProt | YTH domain-containing family protein 3 | |||
Sequence: SATSVDQRPKGQGNKVSVQNGSIHQKDAVNDDDFEPYLSSQTNQSNSYPPMSDPYMPSYYAPSIGFPYSLGEAAWSTAGDQPMPYLTTYGQMSNGEHHYIPDGVFSQPGALGNTPPFLGQHGFNFFPGNADFSTWGTSGSQGQSTQSSAYSSSYGYPPSSLGRAITDGQAGFGNDTLSKVPGISSIEQGMTGLKIGGDLTAAVTKTVGTALSSSGMTSIATNSVPPVSSAAPKPTSWAAIARKPAKPQPKLKPKGNVGIGGSAVPPPPIKHNMNIGTWDEKGSVVKAPPTQPVLPPQTIIQQPQPLIQPPPLVQSQLPQQQPQPPQPQQQQGPQPQAQPHQVQPQQQQLQNRWVAPRNRGAGFNQNNGAGSENFGLGVVPVSASPSSVEVHPVLEKLKAINNYNPKDFDWNLKNGRVFIIKSYSEDDIHRSIKYSIWCSTEHGNKRLDAAYRSLNGKGPLYLLFSVNGSGHFCGVAEMKSVVDYNAYAGVWSQDKWKGKFEVKWIFVKDVPNNQLRHIRLENNDNKPVTNSRDTQEVPLEKAKQVLKIIATFKHTTSIFDDFAHYEKRQEEEEAMRRERNRNKQ | |||||||
Modified residue (large scale data) | 5 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 23 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 23 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 186 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 383 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 385 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 425 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 558 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
(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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Following heat shock stress.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with CNOT1; promoting recruitment of the CCR4-NOT complex (PubMed:32492408).
Interacts with YTHDF1 (PubMed:28106072).
Interacts with YTHDF2 (PubMed:28106072).
Interacts with PAN3 (By similarity).
Interacts with YTHDF1 (PubMed:28106072).
Interacts with YTHDF2 (PubMed:28106072).
Interacts with PAN3 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q7Z739 | FAF1 Q9UNN5 | 3 | EBI-2849837, EBI-718246 | |
XENO | Q7Z739 | gag PRO_0000038596 P04591 | 2 | EBI-2849837, EBI-6179727 | |
BINARY | Q7Z739 | YTHDF1 Q9BYJ9 | 3 | EBI-2849837, EBI-1051237 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-26 | Polar residues | ||||
Sequence: MSATSVDQRPKGQGNKVSVQNGSIHQ | ||||||
Region | 1-52 | Disordered | ||||
Sequence: MSATSVDQRPKGQGNKVSVQNGSIHQKDAVNDDDFEPYLSSQTNQSNSYPPM | ||||||
Compositional bias | 36-52 | Polar residues | ||||
Sequence: EPYLSSQTNQSNSYPPM | ||||||
Region | 243-277 | Disordered | ||||
Sequence: RKPAKPQPKLKPKGNVGIGGSAVPPPPIKHNMNIG | ||||||
Compositional bias | 304-333 | Pro residues | ||||
Sequence: PQPLIQPPPLVQSQLPQQQPQPPQPQQQQG | ||||||
Region | 304-351 | Disordered | ||||
Sequence: PQPLIQPPPLVQSQLPQQQPQPPQPQQQQGPQPQAQPHQVQPQQQQLQ | ||||||
Compositional bias | 334-351 | Polar residues | ||||
Sequence: PQPQAQPHQVQPQQQQLQ | ||||||
Domain | 416-550 | YTH | ||||
Sequence: GRVFIIKSYSEDDIHRSIKYSIWCSTEHGNKRLDAAYRSLNGKGPLYLLFSVNGSGHFCGVAEMKSVVDYNAYAGVWSQDKWKGKFEVKWIFVKDVPNNQLRHIRLENNDNKPVTNSRDTQEVPLEKAKQVLKII |
Domain
The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues (PubMed:31292544).
This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons (PubMed:31292544).
This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons (PubMed:31292544).
Sequence similarities
Belongs to the YTHDF family. YTHDF3 subfamily.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length585
- Mass (Da)63,861
- Last updated2003-10-01 v1
- ChecksumC7021FE48DEA441E
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A024R7W5 | A0A024R7W5_HUMAN | YTHDF3 | 534 | ||
S4R373 | S4R373_HUMAN | YTHDF3 | 52 | ||
A0A087X0C3 | A0A087X0C3_HUMAN | YTHDF3 | 41 | ||
A0A087X0U5 | A0A087X0U5_HUMAN | YTHDF3 | 119 | ||
A0A087X0Q1 | A0A087X0Q1_HUMAN | YTHDF3 | 583 | ||
A0A087WU40 | A0A087WU40_HUMAN | YTHDF3 | 86 | ||
A0A087WU63 | A0A087WU63_HUMAN | YTHDF3 | 102 | ||
A0A087WWB0 | A0A087WWB0_HUMAN | YTHDF3 | 111 | ||
A0A087WY31 | A0A087WY31_HUMAN | YTHDF3 | 588 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-26 | Polar residues | ||||
Sequence: MSATSVDQRPKGQGNKVSVQNGSIHQ | ||||||
Compositional bias | 36-52 | Polar residues | ||||
Sequence: EPYLSSQTNQSNSYPPM | ||||||
Sequence conflict | 139 | in Ref. 2; CAH56224 | ||||
Sequence: S → R | ||||||
Compositional bias | 304-333 | Pro residues | ||||
Sequence: PQPLIQPPPLVQSQLPQQQPQPPQPQQQQG | ||||||
Compositional bias | 334-351 | Polar residues | ||||
Sequence: PQPQAQPHQVQPQQQQLQ | ||||||
Sequence conflict | 381 | in Ref. 2; CAH56224 | ||||
Sequence: P → S | ||||||
Sequence conflict | 532 | in Ref. 2; CAH56480 | ||||
Sequence: S → P |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK127574 EMBL· GenBank· DDBJ | BAG54526.1 EMBL· GenBank· DDBJ | mRNA | ||
AL832005 EMBL· GenBank· DDBJ | CAH56224.1 EMBL· GenBank· DDBJ | mRNA | ||
BX537996 EMBL· GenBank· DDBJ | CAH56480.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471068 EMBL· GenBank· DDBJ | EAW86867.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC052970 EMBL· GenBank· DDBJ | AAH52970.1 EMBL· GenBank· DDBJ | mRNA |