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Protein

YTH domain-containing family protein 2

Gene

YTHDF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 the efficiency of mRNA splicing, processing and stability (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). 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).7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei422 – 4221N6-methyladenosineCombined sources1 Publication
Binding sitei462 – 4621N6-methyladenosineCombined sources1 Publication
Binding sitei486 – 4861N6-methyladenosineCombined sources1 Publication
Binding sitei491 – 4911N6-methyladenosineCombined sources1 Publication

GO - Molecular functioni

  • N6-methyladenosine-containing RNA binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB

GO - Biological processi

  • humoral immune response Source: ProtInc
  • positive regulation of cap-independent translational initiation Source: UniProtKB
  • regulation of mRNA stability Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

RNA-binding

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

HGNCiHGNC:31675. YTHDF2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytoplasmic mRNA processing body Source: UniProtKB
  • cytosol Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi411 – 4111R → A: Slightly decreased binding to RNAs. 1 Publication
Mutagenesisi416 – 4161K → A: Decreased binding to RNAs. 1 Publication
Mutagenesisi432 – 4321W → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 2 Publications
Mutagenesisi441 – 4411R → A: Slightly decreased binding to RNAs. 1 Publication
Mutagenesisi486 – 4861W → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 2 Publications
Mutagenesisi491 – 4911W → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 1 Publication
Mutagenesisi527 – 5271R → A: Decreased binding to RNAs. 1 Publication

Organism-specific databases

PharmGKBiPA134964518.

Polymorphism and mutation databases

BioMutaiYTHDF2.
DMDMi41019527.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 579578YTH domain-containing family protein 2PRO_0000223075Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources1 Publication
Modified residuei2 – 21PhosphoserineCombined sources
Modified residuei4 – 41PhosphoserineCombined sources
Modified residuei5 – 51PhosphoserineCombined sources
Modified residuei22 – 221PhosphoserineBy similarity
Modified residuei39 – 391PhosphoserineCombined sources
Modified residuei196 – 1961PhosphoserineCombined sources
Modified residuei359 – 3591PhosphoserineCombined sources
Modified residuei394 – 3941PhosphoserineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y5A9.
MaxQBiQ9Y5A9.
PaxDbiQ9Y5A9.
PeptideAtlasiQ9Y5A9.
PRIDEiQ9Y5A9.

PTM databases

iPTMnetiQ9Y5A9.
PhosphoSiteiQ9Y5A9.
SwissPalmiQ9Y5A9.

Miscellaneous databases

PMAP-CutDBQ9Y5A9.

Expressioni

Inductioni

Following heat shock stress.1 Publication

Gene expression databases

BgeeiENSG00000198492.
CleanExiHS_YTHDF2.
ExpressionAtlasiQ9Y5A9. baseline and differential.
GenevisibleiQ9Y5A9. HS.

Organism-specific databases

HPAiHPA054080.
HPA059621.

Interactioni

Protein-protein interaction databases

BioGridi119543. 41 interactions.
IntActiQ9Y5A9. 16 interactions.
STRINGi9606.ENSP00000362918.

Structurei

Secondary structure

1
579
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi411 – 4188Combined sources
Helixi420 – 42910Combined sources
Beta strandi430 – 4323Combined sources
Helixi436 – 44914Combined sources
Beta strandi455 – 4617Combined sources
Beta strandi464 – 47310Combined sources
Beta strandi478 – 4814Combined sources
Beta strandi486 – 4883Combined sources
Beta strandi494 – 50613Combined sources
Helixi507 – 5093Combined sources
Turni510 – 5123Combined sources
Turni516 – 5205Combined sources
Helixi523 – 5253Combined sources
Helixi534 – 54613Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4RDNX-ray2.10A/B408-552[»]
4RDOX-ray2.15A/B/C/D/E/F408-552[»]
4WQNX-ray2.12A/B383-553[»]
ProteinModelPortaliQ9Y5A9.
SMRiQ9Y5A9. Positions 386-573.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini410 – 544135YTHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 384383Localization to mRNA processing bodies (P-bodies)1 PublicationAdd
BLAST
Regioni385 – 579195Interaction with m6A-containing mRNAs1 PublicationAdd
BLAST
Regioni416 – 4183N6-methyladenosine bindingCombined sources1 Publication
Regioni432 – 4332N6-methyladenosine bindingCombined sources1 Publication

Sequence similaritiesi

Contains 1 YTH domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR007275. YTH_domain.
[Graphical view]
PfamiPF04146. YTH. 1 hit.
[Graphical view]
PROSITEiPS50882. YTH. 1 hit.
[Graphical view]

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

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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti217 – 2171T → S.
Corresponds to variant rs16838382 [ dbSNP | Ensembl ].
VAR_053744
Natural varianti454 – 4541P → S.
Corresponds to variant rs35288745 [ dbSNP | Ensembl ].
VAR_053745

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5050Missing in isoform 2. 2 PublicationsVSP_009297Add
BLAST

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, AL356786 Genomic DNA. Translation: CAH72429.1.
AL356786, AL645729 Genomic DNA. Translation: CAI21658.1.
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

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, AL356786 Genomic DNA. Translation: CAH72429.1.
AL356786, AL645729 Genomic DNA. Translation: CAI21658.1.
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
EntryMethodResolution (Å)ChainPositionsPDBsum
4RDNX-ray2.10A/B408-552[»]
4RDOX-ray2.15A/B/C/D/E/F408-552[»]
4WQNX-ray2.12A/B383-553[»]
ProteinModelPortaliQ9Y5A9.
SMRiQ9Y5A9. Positions 386-573.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119543. 41 interactions.
IntActiQ9Y5A9. 16 interactions.
STRINGi9606.ENSP00000362918.

PTM databases

iPTMnetiQ9Y5A9.
PhosphoSiteiQ9Y5A9.
SwissPalmiQ9Y5A9.

Polymorphism and mutation databases

BioMutaiYTHDF2.
DMDMi41019527.

Proteomic databases

EPDiQ9Y5A9.
MaxQBiQ9Y5A9.
PaxDbiQ9Y5A9.
PeptideAtlasiQ9Y5A9.
PRIDEiQ9Y5A9.

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.
GeneCardsiYTHDF2.
HGNCiHGNC:31675. YTHDF2.
HPAiHPA054080.
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-CutDBQ9Y5A9.
PROiQ9Y5A9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198492.
CleanExiHS_YTHDF2.
ExpressionAtlasiQ9Y5A9. baseline and differential.
GenevisibleiQ9Y5A9. HS.

Family and domain databases

InterProiIPR007275. YTH_domain.
[Graphical view]
PfamiPF04146. YTH. 1 hit.
[Graphical view]
PROSITEiPS50882. YTH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiYTHD2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5A9
Secondary accession number(s): A6NKG4
, A8K966, B4E1G7, D3DPM8, Q5VSZ9, Q8TDH0, Q9BUJ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 12, 2003
Last sequence update: January 16, 2004
Last modified: September 7, 2016
This is version 141 of the entry and version 2 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.