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Protein

YTH domain-containing protein 1

Gene

YTHDC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:26318451, PubMed:26876937, PubMed:25242552). 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:26318451, PubMed:25242552). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei377N6-methyladenosine1 Publication1
Binding sitei428N6-methyladenosine1 Publication1

GO - Molecular functioni

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

GO - Biological processi

  • mRNA splice site selection Source: UniProtKB
  • regulation of mRNA splicing, via spliceosome Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

mRNA processing, mRNA splicing

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000083896-MONOMER.
SignaLinkiQ96MU7.
SIGNORiQ96MU7.

Names & Taxonomyi

Protein namesi
Recommended name:
YTH domain-containing protein 1Curated
Alternative name(s):
Splicing factor YT5211 Publication
Short name:
YT521-B1 Publication
Gene namesi
Name:YTHDC1Imported
Synonyms:KIAA19661 Publication, YT5211 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:30626. YTHDC1.

Subcellular locationi

GO - Cellular componenti

  • nuclear speck Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi361K → L: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi362S → A: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi367N → D: Abolished binding to N6-methyladenosine (m6A)-containing RNAs. 1 Publication1
Mutagenesisi377W → A: Abolishes binding to N6-methyladenosine (m6A)-containing RNAs. Abolishes binding to m6A-containing mRNAs; when associated with A-428. 2 Publications1
Mutagenesisi377W → D: Abolishes RNA-binding and ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi380L → T: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 1 Publication1
Mutagenesisi387L → E: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi399L → E: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi401F → D: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi402S → A: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi409F → D: Abolishes RNA-binding and ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi411G → I: Abolishes RNA-binding and ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi428W → A: Abolishes binding to N6-methyladenosine (m6A)-containing RNAs. Abolishes binding to m6A-containing mRNAs; when associated with A-377. 2 Publications1
Mutagenesisi428W → D: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi438M → A: Reduced binding to N6-methyladenosine (m6A)-containing RNAs. 1 Publication1
Mutagenesisi447W → D: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi466N → D: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi475R → A: Reduced binding affinity for N6-methyladenosine (m6A)-containing RNAs by 100-fold. 1 Publication1
Mutagenesisi475R → D: Does not affect ability to influence alternative splice site selection. 1 Publication1
Mutagenesisi475R → F: Reduced binding affinity for N6-methyladenosine (m6A)-containing RNAs by 9-fold. 1 Publication1
Mutagenesisi476D → K: Does not affect ability to influence alternative splice site selection. 1 Publication1

Organism-specific databases

DisGeNETi91746.
OpenTargetsiENSG00000083896.
ENSG00000275272.
PharmGKBiPA143485673.

Polymorphism and mutation databases

BioMutaiYTHDC1.
DMDMi47606762.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002230761 – 727YTH domain-containing protein 1Add BLAST727

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei35PhosphoserineBy similarity1
Cross-linki96Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei118PhosphoserineCombined sources1
Modified residuei120PhosphoserineCombined sources1
Modified residuei146PhosphoserineCombined sources1
Modified residuei148PhosphothreonineCombined sources1
Modified residuei308PhosphoserineCombined sources1
Modified residuei315PhosphoserineCombined sources1
Modified residuei317PhosphoserineCombined sources1
Modified residuei318PhosphoserineCombined sources1
Modified residuei320PhosphoserineCombined sources1
Modified residuei424PhosphoserineCombined sources1
Modified residuei435PhosphoserineCombined sources1
Modified residuei545PhosphoserineCombined sources1

Post-translational modificationi

Tyrosine phosphorylated.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ96MU7.
MaxQBiQ96MU7.
PaxDbiQ96MU7.
PeptideAtlasiQ96MU7.
PRIDEiQ96MU7.

PTM databases

iPTMnetiQ96MU7.
PhosphoSitePlusiQ96MU7.
SwissPalmiQ96MU7.

Expressioni

Gene expression databases

BgeeiENSG00000083896.
CleanExiHS_YTHDC1.
ExpressionAtlasiQ96MU7. baseline and differential.
GenevisibleiQ96MU7. HS.

Organism-specific databases

HPAiHPA036462.

Interactioni

Subunit structurei

Interacts with KHDRBS1/SAM68 (By similarity). Interacts with SRSF1 (By similarity). Interacts with SRSF2 (By similarity). Interacts with TRA2B (By similarity). Interacts with SRSF3 (PubMed:26876937). Interacts with SRSF10 (PubMed:26876937). Interacts with KHDRBS3 (By similarity). Interacts with EMD (PubMed:12755701). Interacts with RBMX (PubMed:19282290).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CLK2P497605EBI-2849854,EBI-750020
DVL3Q929975EBI-2849854,EBI-739789
HNRPKQ6IBN13EBI-2849854,EBI-3440248
KHDRBS2Q5VWX15EBI-2849854,EBI-742808
KHDRBS3O755255EBI-2849854,EBI-722504
RBMY1JQ154155EBI-2849854,EBI-8642021
SDCBP2Q9H1905EBI-2849854,EBI-742426
SRPK1Q96SB43EBI-2849854,EBI-539478
SRPK2P783623EBI-2849854,EBI-593303
TRA2BP629953EBI-2849854,EBI-725485

Protein-protein interaction databases

BioGridi124871. 62 interactors.
IntActiQ96MU7. 35 interactors.
MINTiMINT-266035.
STRINGi9606.ENSP00000339245.

Structurei

Secondary structure

1727
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi345 – 352Combined sources8
Beta strandi355 – 363Combined sources9
Helixi365 – 374Combined sources10
Beta strandi376 – 378Combined sources3
Helixi381 – 391Combined sources11
Beta strandi394 – 403Combined sources10
Beta strandi406 – 409Combined sources4
Beta strandi411 – 415Combined sources5
Beta strandi422 – 424Combined sources3
Helixi437 – 439Combined sources3
Beta strandi442 – 449Combined sources8
Helixi455 – 458Combined sources4
Helixi464 – 466Combined sources3
Beta strandi467 – 469Combined sources3
Beta strandi478 – 480Combined sources3
Helixi482 – 491Combined sources10
Beta strandi496 – 498Combined sources3
Helixi500 – 506Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YUDNMR-A337-509[»]
4R3HX-ray1.90A/B345-509[»]
4R3IX-ray1.80A345-509[»]
ProteinModelPortaliQ96MU7.
SMRiQ96MU7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96MU7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini355 – 492YTHPROSITE-ProRule annotationAdd BLAST138

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni361 – 363N6-methyladenosine bindingBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi172 – 260Glu-richAdd BLAST89
Compositional biasi508 – 581Arg-richAdd BLAST74
Compositional biasi601 – 643Pro-richAdd BLAST43
Compositional biasi647 – 727Arg-richAdd BLAST81

Domaini

The YTH domain mediates RNA-binding.1 Publication

Sequence similaritiesi

Contains 1 YTH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1902. Eukaryota.
ENOG4111F6P. LUCA.
GeneTreeiENSGT00390000017549.
HOGENOMiHOG000088650.
HOVERGENiHBG055528.
InParanoidiQ96MU7.
KOiK20100.
PhylomeDBiQ96MU7.
TreeFamiTF325590.

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.

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

Isoform 1 (identifier: Q96MU7-1) [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
MAADSREEKD GELNVLDDIL TEVPEQDDEL YNPESEQDKN EKKGSKRKSD
60 70 80 90 100
RMESTDTKRQ KPSVHSRQLV SKPLSSSVSN NKRIVSTKGK SATEYKNEEY
110 120 130 140 150
QRSERNKRLD ADRKIRLSSS ASREPYKNQP EKTCVRKRDP ERRAKSPTPD
160 170 180 190 200
GSERIGLEVD RRASRSSQSS KEEVNSEEYG SDHETGSSGS SDEQGNNTEN
210 220 230 240 250
EEEGVEEDVE EDEEVEEDAE EDEEVDEDGE EEEEEEEEEE EEEEEEEEEY
260 270 280 290 300
EQDERDQKEE GNDYDTRSEA SDSGSESVSF TDGSVRSGSG TDGSDEKKKE
310 320 330 340 350
RKRARGISPI VFDRSGSSAS ESYAGSEKKH EKLSSSVRAV RKDQTSKLKY
360 370 380 390 400
VLQDARFFLI KSNNHENVSL AKAKGVWSTL PVNEKKLNLA FRSARSVILI
410 420 430 440 450
FSVRESGKFQ GFARLSSESH HGGSPIHWVL PAGMSAKMLG GVFKIDWICR
460 470 480 490 500
RELPFTKSAH LTNPWNEHKP VKIGRDGQEI ELECGTQLCL LFPPDESIDL
510 520 530 540 550
YQVIHKMRHK RRMHSQPRSR GRPSRREPVR DVGRRRPEDY DIHNSRKKPR
560 570 580 590 600
IDYPPEFHQR PGYLKDPRYQ EVDRRFSGVR RDVFLNGSYN DYVREFHNMG
610 620 630 640 650
PPPPWQGMPP YPGMEQPPHH PYYQHHAPPP QAHPPYSGHH PVPHEARYRD
660 670 680 690 700
KRVHDYDMRV DDFLRRTQAV VSGRRSRPRE RDRERERDRP RDNRRDRERD
710 720
RGRDRERERE RLCDRDRDRG ERGRYRR
Length:727
Mass (Da):84,700
Last modified:May 24, 2004 - v3
Checksum:i536032FD44582EAF
GO
Isoform 2 (identifier: Q96MU7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     325-342: Missing.

Show »
Length:709
Mass (Da):82,692
Checksum:iC02121B27DDEFF0E
GO

Sequence cautioni

The sequence AAY41024 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAB71181 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti619H → Q in BAB71181 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053746183H → R.Corresponds to variant rs3813832dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006818325 – 342Missing in isoform 2. 2 PublicationsAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056430 mRNA. Translation: BAB71181.1. Different initiation.
AC074378 Genomic DNA. Translation: AAY41024.1. Sequence problems.
BC041119 mRNA. Translation: AAH41119.1.
BC053863 mRNA. Translation: AAH53863.1.
AB075846 mRNA. Translation: BAB85552.1.
CCDSiCCDS33992.1. [Q96MU7-1]
CCDS3522.2. [Q96MU7-2]
RefSeqiNP_001026902.1. NM_001031732.3. [Q96MU7-1]
NP_001317627.1. NM_001330698.1.
NP_588611.2. NM_133370.3. [Q96MU7-2]
UniGeneiHs.175955.

Genome annotation databases

EnsembliENST00000344157; ENSP00000339245; ENSG00000083896. [Q96MU7-1]
ENST00000355665; ENSP00000347888; ENSG00000083896. [Q96MU7-2]
ENST00000613637; ENSP00000484604; ENSG00000275272. [Q96MU7-2]
ENST00000615500; ENSP00000479213; ENSG00000275272. [Q96MU7-1]
GeneIDi91746.
KEGGihsa:91746.
UCSCiuc003hdx.4. human. [Q96MU7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK056430 mRNA. Translation: BAB71181.1. Different initiation.
AC074378 Genomic DNA. Translation: AAY41024.1. Sequence problems.
BC041119 mRNA. Translation: AAH41119.1.
BC053863 mRNA. Translation: AAH53863.1.
AB075846 mRNA. Translation: BAB85552.1.
CCDSiCCDS33992.1. [Q96MU7-1]
CCDS3522.2. [Q96MU7-2]
RefSeqiNP_001026902.1. NM_001031732.3. [Q96MU7-1]
NP_001317627.1. NM_001330698.1.
NP_588611.2. NM_133370.3. [Q96MU7-2]
UniGeneiHs.175955.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YUDNMR-A337-509[»]
4R3HX-ray1.90A/B345-509[»]
4R3IX-ray1.80A345-509[»]
ProteinModelPortaliQ96MU7.
SMRiQ96MU7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124871. 62 interactors.
IntActiQ96MU7. 35 interactors.
MINTiMINT-266035.
STRINGi9606.ENSP00000339245.

PTM databases

iPTMnetiQ96MU7.
PhosphoSitePlusiQ96MU7.
SwissPalmiQ96MU7.

Polymorphism and mutation databases

BioMutaiYTHDC1.
DMDMi47606762.

Proteomic databases

EPDiQ96MU7.
MaxQBiQ96MU7.
PaxDbiQ96MU7.
PeptideAtlasiQ96MU7.
PRIDEiQ96MU7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344157; ENSP00000339245; ENSG00000083896. [Q96MU7-1]
ENST00000355665; ENSP00000347888; ENSG00000083896. [Q96MU7-2]
ENST00000613637; ENSP00000484604; ENSG00000275272. [Q96MU7-2]
ENST00000615500; ENSP00000479213; ENSG00000275272. [Q96MU7-1]
GeneIDi91746.
KEGGihsa:91746.
UCSCiuc003hdx.4. human. [Q96MU7-1]

Organism-specific databases

CTDi91746.
DisGeNETi91746.
GeneCardsiYTHDC1.
HGNCiHGNC:30626. YTHDC1.
HPAiHPA036462.
neXtProtiNX_Q96MU7.
OpenTargetsiENSG00000083896.
ENSG00000275272.
PharmGKBiPA143485673.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1902. Eukaryota.
ENOG4111F6P. LUCA.
GeneTreeiENSGT00390000017549.
HOGENOMiHOG000088650.
HOVERGENiHBG055528.
InParanoidiQ96MU7.
KOiK20100.
PhylomeDBiQ96MU7.
TreeFamiTF325590.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000083896-MONOMER.
SignaLinkiQ96MU7.
SIGNORiQ96MU7.

Miscellaneous databases

ChiTaRSiYTHDC1. human.
EvolutionaryTraceiQ96MU7.
GeneWikiiYTHDC1.
GenomeRNAii91746.
PROiQ96MU7.

Gene expression databases

BgeeiENSG00000083896.
CleanExiHS_YTHDC1.
ExpressionAtlasiQ96MU7. baseline and differential.
GenevisibleiQ96MU7. 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 nameiYTDC1_HUMAN
AccessioniPrimary (citable) accession number: Q96MU7
Secondary accession number(s): Q4W5Q3, Q7Z622, Q8TF35
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 12, 2003
Last sequence update: May 24, 2004
Last modified: November 30, 2016
This is version 144 of the entry and version 3 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, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.