YTHD3_PONAB
ID YTHD3_PONAB Reviewed; 585 AA.
AC Q5RFL8;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=YTH domain-containing family protein 3 {ECO:0000305};
GN Name=YTHDF3 {ECO:0000250|UniProtKB:Q7Z739};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Specifically recognizes and binds N6-methyladenosine (m6A)-
CC containing RNAs, and regulates their stability. M6A is a modification
CC present at internal sites of mRNAs and some non-coding RNAs and plays a
CC role in mRNA stability and processing. Acts as a regulator of mRNA
CC stability by promoting degradation of m6A-containing mRNAs via
CC interaction with the CCR4-NOT complex or PAN3. The YTHDF paralogs
CC (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act
CC redundantly to mediate mRNA degradation and cellular differentiation
CC (By similarity). Acts as a negative regulator of type I interferon
CC response by down-regulating interferon-stimulated genes (ISGs)
CC expression: acts by binding to FOXO3 mRNAs. Binds to FOXO3 mRNAs
CC independently of METTL3-mediated m6A modification (By similarity). Can
CC also act as a regulator of mRNA stability in cooperation with YTHDF2 by
CC binding to m6A-containing mRNA and promoting their degradation.
CC Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs
CC are generated through back-splicing of pre-mRNAs, a non-canonical
CC splicing process promoted by dsRNA structures across circularizing
CC exons. Promotes formation of phase-separated membraneless compartments,
CC such as P-bodies or stress granules, by undergoing liquid-liquid phase
CC separation upon binding to mRNAs containing multiple m6A-modified
CC residues: polymethylated mRNAs act as a multivalent scaffold for the
CC binding of YTHDF proteins, juxtaposing their disordered regions and
CC thereby leading to phase separation. The resulting mRNA-YTHDF complexes
CC then partition into different endogenous phase-separated membraneless
CC compartments, such as P-bodies, stress granules or neuronal RNA
CC granules. May also recognize and bind N1-methyladenosine (m1A)-
CC containing mRNAs: inhibits trophoblast invasion by binding to m1A-
CC methylated transcripts of IGF1R, promoting their degradation (By
CC similarity). {ECO:0000250|UniProtKB:Q7Z739,
CC ECO:0000250|UniProtKB:Q8BYK6}.
CC -!- SUBUNIT: Interacts with CNOT1; promoting recruitment of the CCR4-NOT
CC complex. Interacts with YTHDF1. Interacts with YTHDF2 (By similarity).
CC Interacts with PAN3 (By similarity). {ECO:0000250|UniProtKB:Q7Z739,
CC ECO:0000250|UniProtKB:Q8BYK6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q7Z739}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q7Z739}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q7Z739}.
CC -!- DOMAIN: The disordered regions have the ability to interact with each
CC other and to 'phase separate' into liquid droplets within the cytosol
CC following binding to mRNAs containing multiple m6A-modified residues.
CC This leads to the partition of m6A-containing mRNAs into membraneless
CC compartments, where mRNAs may be stored, degraded or used to transport
CC mRNAs to dendritic arbors in neurons. {ECO:0000250|UniProtKB:Q7Z739}.
CC -!- SIMILARITY: Belongs to the YTHDF family. YTHDF3 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR857137; CAH89439.1; -; mRNA.
DR RefSeq; NP_001124613.1; NM_001131141.1.
DR AlphaFoldDB; Q5RFL8; -.
DR SMR; Q5RFL8; -.
DR Ensembl; ENSPPYT00000021724; ENSPPYP00000020890; ENSPPYG00000018626.
DR GeneID; 100171450; -.
DR KEGG; pon:100171450; -.
DR CTD; 253943; -.
DR eggNOG; KOG1901; Eukaryota.
DR GeneTree; ENSGT00940000158777; -.
DR InParanoid; Q5RFL8; -.
DR OrthoDB; 1523251at2759; -.
DR Proteomes; UP000001595; Chromosome 8.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; ISS:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0070925; P:organelle assembly; ISS:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB.
DR GO; GO:1901163; P:regulation of trophoblast cell migration; ISS:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; ISS:UniProtKB.
DR InterPro; IPR007275; YTH_domain.
DR InterPro; IPR045168; YTH_prot.
DR PANTHER; PTHR12357; PTHR12357; 1.
DR Pfam; PF04146; YTH; 1.
DR PROSITE; PS50882; YTH; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Phosphoprotein; Reference proteome; RNA-binding.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT CHAIN 2..585
FT /note="YTH domain-containing family protein 3"
FT /id="PRO_0000230993"
FT DOMAIN 416..550
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 304..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..26
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..333
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 422..424
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT BINDING 428
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT BINDING 438..439
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT BINDING 468
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT BINDING 492
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT BINDING 497
FT /ligand="RNA"
FT /ligand_id="ChEBI:CHEBI:33697"
FT /ligand_part="N(6)-methyladenosine 5'-phosphate residue"
FT /ligand_part_id="ChEBI:CHEBI:74449"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
SQ SEQUENCE 585 AA; 63861 MW; C7021FE48DEA441E CRC64;
MSATSVDQRP KGQGNKVSVQ NGSIHQKDAV NDDDFEPYLS SQTNQSNSYP PMSDPYMPSY
YAPSIGFPYS LGEAAWSTAG DQPMPYLTTY GQMSNGEHHY IPDGVFSQPG ALGNTPPFLG
QHGFNFFPGN ADFSTWGTSG SQGQSTQSSA YSSSYGYPPS SLGRAITDGQ AGFGNDTLSK
VPGISSIEQG MTGLKIGGDL TAAVTKTVGT ALSSSGMTSI ATNSVPPVSS AAPKPTSWAA
IARKPAKPQP KLKPKGNVGI GGSAVPPPPI KHNMNIGTWD EKGSVVKAPP TQPVLPPQTI
IQQPQPLIQP PPLVQSQLPQ QQPQPPQPQQ QQGPQPQAQP HQVQPQQQQL QNRWVAPRNR
GAGFNQNNGA GSENFGLGVV PVSASPSSVE VHPVLEKLKA INNYNPKDFD WNLKNGRVFI
IKSYSEDDIH RSIKYSIWCS TEHGNKRLDA AYRSLNGKGP LYLLFSVNGS GHFCGVAEMK
SVVDYNAYAG VWSQDKWKGK FEVKWIFVKD VPNNQLRHIR LENNDNKPVT NSRDTQEVPL
EKAKQVLKII ATFKHTTSIF DDFAHYEKRQ EEEEAMRRER NRNKQ
