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Protein

YTH domain-containing family protein 2

Gene

YTHDF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates mRNA stability (PubMed:24284625, PubMed:26046440, PubMed:26318451). 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:25412658, PubMed:25412661). Acts as a regulator of mRNA stability: binding to m6A-containing mRNAs results in the localization to mRNA decay sites, such as processing bodies (P-bodies), leading to mRNA degradation (PubMed:24284625, PubMed:26046440). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also involved in haematopoietic stem cells specification: acts by binding to m6A-containing mRNAs, leading to decrease Notch dignaling and promote endothelial to haematopoietic transition (By similarity). Also acts as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). May inhibit replication of kaposis sarcoma-associated herpesvirus (KSHV); its role is however unclear and additional evidences are needed to confirm such results (PubMed:29109479).By similarity8 Publications
(Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282).1 Publication
(Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627).1 Publication

Caution

Its role in kaposis sarcoma-associated herpesvirus (KSHV) expression and virion production is unclear. According to a report, acts as an antiviral protein by binding to N6-methyladenosine (m6A)-containing viral RNAs and inhibiting replication of KSHV (PubMed:29109479). According to a second report, either acts as an enhancer or inhibitor of KSHV gene expression and virion production, depending on the stage of the KSHV life cycle (PubMed:29659627). Additional experiments will be needed to clarify its role (PubMed:29659627).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei422N6-methyladenosineCombined sources1 Publication1
Binding sitei462N6-methyladenosineCombined sources1 Publication1
Binding sitei486N6-methyladenosineCombined sources1 Publication1
Binding sitei491N6-methyladenosineCombined sources1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processDifferentiation, Oogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
YTH domain-containing family protein 2Curated
Alternative name(s):
CLL-associated antigen KW-141 Publication
High-glucose-regulated protein 81 Publication
Renal carcinoma antigen NY-REN-21 Publication
Gene namesi
Name:YTHDF2Imported
Synonyms:HGRG81 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000198492.14
HGNCiHGNC:31675 YTHDF2
MIMi610640 gene
neXtProtiNX_Q9Y5A9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi411R → A: Slightly decreased binding to RNAs. 1 Publication1
Mutagenesisi416K → A: Decreased binding to RNAs. 1 Publication1
Mutagenesisi432W → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 2 Publications1
Mutagenesisi441R → A: Slightly decreased binding to RNAs. 1 Publication1
Mutagenesisi486W → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 2 Publications1
Mutagenesisi491W → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 1 Publication1
Mutagenesisi527R → A: Decreased binding to RNAs. 1 Publication1

Organism-specific databases

PharmGKBiPA134964518

Polymorphism and mutation databases

BioMutaiYTHDF2
DMDMi41019527

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00002230752 – 579YTH domain-containing family protein 2Add BLAST578

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei2PhosphoserineCombined sources1
Modified residuei4PhosphoserineCombined sources1
Modified residuei5PhosphoserineCombined sources1
Modified residuei22PhosphoserineBy similarity1
Modified residuei39PhosphoserineCombined sources1
Modified residuei196PhosphoserineCombined sources1
Modified residuei359PhosphoserineCombined sources1
Modified residuei394PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y5A9
PaxDbiQ9Y5A9
PeptideAtlasiQ9Y5A9
PRIDEiQ9Y5A9
ProteomicsDBi86326
86327 [Q9Y5A9-2]

PTM databases

iPTMnetiQ9Y5A9
PhosphoSitePlusiQ9Y5A9
SwissPalmiQ9Y5A9

Miscellaneous databases

PMAP-CutDBiQ9Y5A9

Expressioni

Inductioni

Following heat shock stress.1 Publication

Gene expression databases

BgeeiENSG00000198492 Expressed in 99 organ(s), highest expression level in leukocyte
CleanExiHS_YTHDF2
ExpressionAtlasiQ9Y5A9 baseline and differential
GenevisibleiQ9Y5A9 HS

Organism-specific databases

HPAiHPA030063
HPA054080
HPA059621

Interactioni

Subunit structurei

Interacts with YTHDF3 (PubMed:28106072).1 Publication

Protein-protein interaction databases

BioGridi119543, 45 interactors
IntActiQ9Y5A9, 19 interactors
MINTiQ9Y5A9
STRINGi9606.ENSP00000362918

Structurei

Secondary structure

1579
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y5A9
SMRiQ9Y5A9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini410 – 544YTHPROSITE-ProRule annotationAdd BLAST135

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 384Localization to mRNA processing bodies (P-bodies)1 PublicationAdd BLAST383
Regioni385 – 579Interaction with m6A-containing mRNAs1 PublicationAdd BLAST195
Regioni416 – 418N6-methyladenosine bindingCombined sources1 Publication3
Regioni432 – 433N6-methyladenosine bindingCombined sources1 Publication2

Sequence similaritiesi

Belongs to the YTHDF2 family.Curated

Phylogenomic databases

eggNOGiKOG1901 Eukaryota
ENOG410YABQ LUCA
GeneTreeiENSGT00390000017549
HOVERGENiHBG060315
InParanoidiQ9Y5A9
KOiK20102
OMAiKDFDWNP
OrthoDBiEOG091G0D17
PhylomeDBiQ9Y5A9
TreeFamiTF323736

Family and domain databases

InterProiView protein in InterPro
IPR007275 YTH_domain
PfamiView protein in Pfam
PF04146 YTH, 1 hit
PROSITEiView protein in PROSITE
PS50882 YTH, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y5A9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSASSLLEQR PKGQGNKVQN GSVHQKDGLN DDDFEPYLSP QARPNNAYTA
60 70 80 90 100
MSDSYLPSYY SPSIGFSYSL GEAAWSTGGD TAMPYLTSYG QLSNGEPHFL
110 120 130 140 150
PDAMFGQPGA LGSTPFLGQH GFNFFPSGID FSAWGNNSSQ GQSTQSSGYS
160 170 180 190 200
SNYAYAPSSL GGAMIDGQSA FANETLNKAP GMNTIDQGMA ALKLGSTEVA
210 220 230 240 250
SNVPKVVGSA VGSGSITSNI VASNSLPPAT IAPPKPASWA DIASKPAKQQ
260 270 280 290 300
PKLKTKNGIA GSSLPPPPIK HNMDIGTWDN KGPVAKAPSQ ALVQNIGQPT
310 320 330 340 350
QGSPQPVGQQ ANNSPPVAQA SVGQQTQPLP PPPPQPAQLS VQQQAAQPTR
360 370 380 390 400
WVAPRNRGSG FGHNGVDGNG VGQSQAGSGS TPSEPHPVLE KLRSINNYNP
410 420 430 440 450
KDFDWNLKHG RVFIIKSYSE DDIHRSIKYN IWCSTEHGNK RLDAAYRSMN
460 470 480 490 500
GKGPVYLLFS VNGSGHFCGV AEMKSAVDYN TCAGVWSQDK WKGRFDVRWI
510 520 530 540 550
FVKDVPNSQL RHIRLENNEN KPVTNSRDTQ EVPLEKAKQV LKIIASYKHT
560 570
TSIFDDFSHY EKRQEEEESV KKERQGRGK
Length:579
Mass (Da):62,334
Last modified:January 16, 2004 - v2
Checksum:iBF3959B5561A464E
GO
Isoform 2 (identifier: Q9Y5A9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Note: May be due to intron retention. No experimental confirmation available.
Show »
Length:529
Mass (Da):56,877
Checksum:i7BDF43E1C22B2C56
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
S4R3J8S4R3J8_HUMAN
YTH domain-containing family protei...
YTHDF2
200Annotation score:
S4R3V3S4R3V3_HUMAN
YTH domain-containing family protei...
YTHDF2
241Annotation score:

Sequence cautioni

The sequence AAD42861 differs from that shown. Reason: Frameshift at position 565.Curated
The sequence AAF08813 differs from that shown. Reason: Frameshift at position 565.Curated
The sequence AAL99921 differs from that shown.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053744217T → S. Corresponds to variant dbSNP:rs16838382Ensembl.1
Natural variantiVAR_053745454P → S. Corresponds to variant dbSNP:rs35288745Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0092971 – 50Missing in isoform 2. 2 PublicationsAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF155095 mRNA Translation: AAD42861.1 Frameshift.
AF192968 mRNA Translation: AAF08813.1 Frameshift.
AF432214 mRNA Translation: AAL99921.1 Sequence problems.
AK292581 mRNA Translation: BAF85270.1
AK303833 mRNA Translation: BAG64779.1
AL645729 Genomic DNA No translation available.
AL356786 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07673.1
CH471059 Genomic DNA Translation: EAX07675.1
CH471059 Genomic DNA Translation: EAX07674.1
BC002559 mRNA Translation: AAH02559.1
CCDSiCCDS41296.1 [Q9Y5A9-1]
CCDS53287.1 [Q9Y5A9-2]
RefSeqiNP_001166299.1, NM_001172828.1 [Q9Y5A9-2]
NP_001166599.1, NM_001173128.1 [Q9Y5A9-1]
NP_057342.2, NM_016258.2 [Q9Y5A9-1]
UniGeneiHs.532286

Genome annotation databases

EnsembliENST00000373812; ENSP00000362918; ENSG00000198492 [Q9Y5A9-1]
ENST00000541996; ENSP00000439394; ENSG00000198492 [Q9Y5A9-2]
ENST00000542507; ENSP00000444660; ENSG00000198492 [Q9Y5A9-1]
GeneIDi51441
KEGGihsa:51441
UCSCiuc001brc.4 human [Q9Y5A9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF155095 mRNA Translation: AAD42861.1 Frameshift.
AF192968 mRNA Translation: AAF08813.1 Frameshift.
AF432214 mRNA Translation: AAL99921.1 Sequence problems.
AK292581 mRNA Translation: BAF85270.1
AK303833 mRNA Translation: BAG64779.1
AL645729 Genomic DNA No translation available.
AL356786 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07673.1
CH471059 Genomic DNA Translation: EAX07675.1
CH471059 Genomic DNA Translation: EAX07674.1
BC002559 mRNA Translation: AAH02559.1
CCDSiCCDS41296.1 [Q9Y5A9-1]
CCDS53287.1 [Q9Y5A9-2]
RefSeqiNP_001166299.1, NM_001172828.1 [Q9Y5A9-2]
NP_001166599.1, NM_001173128.1 [Q9Y5A9-1]
NP_057342.2, NM_016258.2 [Q9Y5A9-1]
UniGeneiHs.532286

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4RDNX-ray2.10A/B408-552[»]
4RDOX-ray2.15A/B/C/D/E/F408-552[»]
4WQNX-ray2.12A/B383-553[»]
ProteinModelPortaliQ9Y5A9
SMRiQ9Y5A9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119543, 45 interactors
IntActiQ9Y5A9, 19 interactors
MINTiQ9Y5A9
STRINGi9606.ENSP00000362918

PTM databases

iPTMnetiQ9Y5A9
PhosphoSitePlusiQ9Y5A9
SwissPalmiQ9Y5A9

Polymorphism and mutation databases

BioMutaiYTHDF2
DMDMi41019527

Proteomic databases

EPDiQ9Y5A9
PaxDbiQ9Y5A9
PeptideAtlasiQ9Y5A9
PRIDEiQ9Y5A9
ProteomicsDBi86326
86327 [Q9Y5A9-2]

Protocols and materials databases

DNASUi51441
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373812; ENSP00000362918; ENSG00000198492 [Q9Y5A9-1]
ENST00000541996; ENSP00000439394; ENSG00000198492 [Q9Y5A9-2]
ENST00000542507; ENSP00000444660; ENSG00000198492 [Q9Y5A9-1]
GeneIDi51441
KEGGihsa:51441
UCSCiuc001brc.4 human [Q9Y5A9-1]

Organism-specific databases

CTDi51441
EuPathDBiHostDB:ENSG00000198492.14
GeneCardsiYTHDF2
HGNCiHGNC:31675 YTHDF2
HPAiHPA030063
HPA054080
HPA059621
MIMi610640 gene
neXtProtiNX_Q9Y5A9
PharmGKBiPA134964518
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1901 Eukaryota
ENOG410YABQ LUCA
GeneTreeiENSGT00390000017549
HOVERGENiHBG060315
InParanoidiQ9Y5A9
KOiK20102
OMAiKDFDWNP
OrthoDBiEOG091G0D17
PhylomeDBiQ9Y5A9
TreeFamiTF323736

Miscellaneous databases

ChiTaRSiYTHDF2 human
GenomeRNAii51441
PMAP-CutDBiQ9Y5A9
PROiPR:Q9Y5A9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198492 Expressed in 99 organ(s), highest expression level in leukocyte
CleanExiHS_YTHDF2
ExpressionAtlasiQ9Y5A9 baseline and differential
GenevisibleiQ9Y5A9 HS

Family and domain databases

InterProiView protein in InterPro
IPR007275 YTH_domain
PfamiView protein in Pfam
PF04146 YTH, 1 hit
PROSITEiView protein in PROSITE
PS50882 YTH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiYTHD2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5A9
Secondary accession number(s): A6NKG4
, A8K966, B4E1G7, D3DPM8, Q5VSZ9, Q8TDH0, Q9BUJ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 12, 2003
Last sequence update: January 16, 2004
Last modified: November 7, 2018
This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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