YTHD2_BOVIN
ID YTHD2_BOVIN Reviewed; 580 AA.
AC Q0VCZ3;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=YTH domain-containing family protein 2 {ECO:0000305};
GN Name=YTHDF2 {ECO:0000250|UniProtKB:Q91YT7};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) 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 and ribonuclease P/MRP complexes,
CC depending on the context. The YTHDF paralogs (YTHDF1, YTHDF2 and
CC YTHDF3) share m6A-containing mRNAs targets and act redundantly to
CC mediate mRNA degradation and cellular differentiation. M6A-containing
CC mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are
CC preferentially degraded by endoribonucleolytic cleavage: cooperative
CC binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment
CC of the ribonuclease P/MRP complex. Other m6A-containing mRNAs undergo
CC deadenylation via direct interaction between YTHDF2 and CNOT1, leading
CC to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-
CC containing mRNAs (By similarity). Required maternally to regulate
CC oocyte maturation: probably acts by binding to m6A-containing mRNAs,
CC thereby regulating maternal transcript dosage during oocyte maturation,
CC which is essential for the competence of oocytes to sustain early
CC zygotic development. Also required during spermatogenesis: regulates
CC spermagonial adhesion by promoting degradation of m6A-containing
CC transcripts coding for matrix metallopeptidases (By similarity). Also
CC involved in hematopoietic stem cells specification by binding to m6A-
CC containing mRNAs, leading to promote their degradation (By similarity).
CC Also acts as a regulator of neural development by promoting m6A-
CC dependent degradation of neural development-related mRNA targets (By
CC similarity). Inhibits neural specification of induced pluripotent stem
CC cells by binding to methylated neural-specific mRNAs and promoting
CC their degradation, thereby restraining neural differentiation.
CC Regulates circadian regulation of hepatic lipid metabolism: acts by
CC promoting m6A-dependent degradation of PPARA transcripts. Regulates the
CC innate immune response to infection by inhibiting the type I interferon
CC response: acts by binding to m6A-containing IFNB transcripts and
CC promoting their degradation. May also act as a promoter of cap-
CC independent mRNA translation following heat shock stress: upon stress,
CC relocalizes to the nucleus and specifically binds mRNAs with some m6A
CC methylation mark at their 5'-UTR, protecting demethylation of mRNAs by
CC FTO, thereby promoting cap-independent mRNA translation. Regulates
CC mitotic entry by promoting the phase-specific m6A-dependent degradation
CC of WEE1 transcripts. Promotes formation of phase-separated membraneless
CC compartments, such as P-bodies or stress granules, by undergoing
CC liquid-liquid phase separation upon binding to mRNAs containing
CC multiple m6A-modified residues: polymethylated mRNAs act as a
CC multivalent scaffold for the binding of YTHDF proteins, juxtaposing
CC their disordered regions and thereby leading to phase separation. The
CC resulting mRNA-YTHDF complexes then partition into different endogenous
CC phase-separated membraneless compartments, such as P-bodies, stress
CC granules or neuronal RNA granules. May also recognize and bind RNAs
CC modified by C5-methylcytosine (m5C) and act as a regulator of rRNA
CC processing (By similarity). {ECO:0000250|UniProtKB:Q91YT7,
CC ECO:0000250|UniProtKB:Q9Y5A9}.
CC -!- SUBUNIT: Interacts with CNOT1; interaction is direct and promotes
CC recruitment of the CCR4-NOT complex. Interacts with YTHDF3. Interacts
CC with RIDA/HRSP12; interaction leads to recruitment of the ribonuclease
CC P/MRP complex. {ECO:0000250|UniProtKB:Q9Y5A9}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9Y5A9}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q9Y5A9}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q9Y5A9}. Nucleus {ECO:0000250|UniProtKB:Q9Y5A9}.
CC Note=Localizes to the cytosol and relocates to the nucleus following
CC heat shock stress. Can partition into different structures: into P-
CC bodies in unstressed cells, and into stress granules during stress.
CC {ECO:0000250|UniProtKB:Q9Y5A9}.
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:Q9Y5A9}.
CC -!- PTM: Ubiquitinated by the SCF(SKP2) complex, leading to its
CC degradation. {ECO:0000250|UniProtKB:Q9Y5A9}.
CC -!- SIMILARITY: Belongs to the YTHDF family. YTHDF2 subfamily.
CC {ECO:0000305}.
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DR EMBL; BC119920; AAI19921.1; -; mRNA.
DR RefSeq; NP_001069721.1; NM_001076253.1.
DR AlphaFoldDB; Q0VCZ3; -.
DR SMR; Q0VCZ3; -.
DR STRING; 9913.ENSBTAP00000020940; -.
DR PaxDb; Q0VCZ3; -.
DR PRIDE; Q0VCZ3; -.
DR Ensembl; ENSBTAT00000020940; ENSBTAP00000020940; ENSBTAG00000015771.
DR GeneID; 541050; -.
DR KEGG; bta:541050; -.
DR CTD; 51441; -.
DR VEuPathDB; HostDB:ENSBTAG00000015771; -.
DR VGNC; VGNC:37042; YTHDF2.
DR eggNOG; KOG1901; Eukaryota.
DR GeneTree; ENSGT00940000156761; -.
DR HOGENOM; CLU_022715_0_0_1; -.
DR InParanoid; Q0VCZ3; -.
DR OMA; RTNGFGD; -.
DR OrthoDB; 1523251at2759; -.
DR TreeFam; TF323736; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000015771; Expressed in spermatid and 104 other tissues.
DR GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0062153; F:C5-methylcytidine-containing RNA binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048598; P:embryonic morphogenesis; ISS:UniProtKB.
DR GO; GO:0098508; P:endothelial to hematopoietic transition; ISS:UniProtKB.
DR GO; GO:0007276; P:gamete generation; ISS:UniProtKB.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006402; P:mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; ISS:UniProtKB.
DR GO; GO:0070925; P:organelle assembly; ISS:UniProtKB.
DR GO; GO:1903679; P:positive regulation of cap-independent translational initiation; ISS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; ISS:UniProtKB.
DR GO; GO:1903538; P:regulation of meiotic cell cycle process involved in oocyte maturation; ISS:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:2000232; P:regulation of rRNA processing; ISS:UniProtKB.
DR GO; GO:0007284; P:spermatogonial cell division; 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; Cell cycle; Cell division; Cytoplasm; Differentiation;
KW Immunity; Innate immunity; Mitosis; Nucleus; Oogenesis; Phosphoprotein;
KW Reference proteome; RNA-binding; Spermatogenesis; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT CHAIN 2..580
FT /note="YTH domain-containing family protein 2"
FT /id="PRO_0000284978"
FT DOMAIN 411..545
FT /note="YTH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00225"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..385
FT /note="Localization to mRNA processing bodies (P-bodies)"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT REGION 247..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..580
FT /note="Interaction with m6A-containing mRNAs"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..326
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..383
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 417..419
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 423
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 433..434
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 463
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 487
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:Q9Y5A9"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 4
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z739"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5A9"
SQ SEQUENCE 580 AA; 62449 MW; AEF0F9550CFC512F CRC64;
MSASSLLEQR PKGQGNKVQN GSVHQKDGLN DDDFEPYLSP QARPNNAYTA MSDSYLPSYY
SPSIGFSYSL GEAAWSTGGD TAMPYLTSYG QLSNGEPHFL PDAMFGQPGA LGSTPFLGQH
GFNFFPSGID FSAWGNNSSQ GQSTQSSGYS SNYAYAPSSL GGAMIDGQSA FASETLNKAP
GMNTIDQGMA ALKLGSTEVA SNVPKVVGSA VGSGSITSNI VASNSLPPAT IAPPKPASWA
DIASKPAKQQ PKLKTKNGIA GSSLPPPPIK HNMDIGTWDN KGPVAKAPSQ ALVQNIGQQP
TQGSPQPVGQ QANNSPPVAQ ASVGQQTQPL PPPPPQPAQL SVQQQAAQPT RWVAPRNRGS
GFGHNGVDGN GVGQTQAGSG STPSEPHPVL EKLRSINNYN PKDFDWNLKH GRVFIIKSYS
EDDIHRSIKY NIWCSTEHGN KRLDAAYRSM NGKGPVYLLF SVNGSGHFCG VAEMKSAVDY
NTCAGVWSQD KWKGRFDVRW IFVKDVPNSQ LRHIRLENNE NKPVTNSRDT QEVPLEKAKQ
VLKIIASYKH TTSIFDDFSH YEKRQEEEES VKKERQGRGK
