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Protein

YTH domain-containing protein 1

Gene

YTHDC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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, PubMed:28984244). 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). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity).By similarity6 Publications

Sites

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processmRNA processing, mRNA splicing

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000083896.12
HGNCiHGNC:30626 YTHDC1
neXtProtiNX_Q96MU7

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

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
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
ProteomicsDBi77413
77414 [Q96MU7-2]

PTM databases

iPTMnetiQ96MU7
PhosphoSitePlusiQ96MU7
SwissPalmiQ96MU7

Expressioni

Gene expression databases

BgeeiENSG00000083896 Expressed in 242 organ(s), highest expression level in female gonad
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, PubMed:28984244). Interacts with SRSF10 (PubMed:26876937). Interacts with KHDRBS3 (By similarity). Interacts with EMD (PubMed:12755701). Interacts with RBMX (PubMed:19282290). Interacts with ZCCHC8 (PubMed:28984244).By similarity4 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi124871, 94 interactors
IntActiQ96MU7, 38 interactors
MINTiQ96MU7
STRINGi9606.ENSP00000339245

Structurei

Secondary structure

1727
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiKOG1902 Eukaryota
ENOG4111F6P LUCA
GeneTreeiENSGT00390000017549
HOGENOMiHOG000088650
HOVERGENiHBG055528
InParanoidiQ96MU7
KOiK20100
PhylomeDBiQ96MU7
TreeFamiTF325590

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.

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

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QR07J3QR07_HUMAN
YTH domain-containing protein 1
YTHDC1
735Annotation score:
J3KRG5J3KRG5_HUMAN
YTH domain-containing protein 1
YTHDC1
93Annotation score:
J3KS01J3KS01_HUMAN
YTH domain-containing protein 1
YTHDC1
37Annotation score:
J3KRW0J3KRW0_HUMAN
YTH domain-containing protein 1
YTHDC1
12Annotation score:

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 dbSNP:rs3813832Ensembl.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

Similar proteinsi

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, 94 interactors
IntActiQ96MU7, 38 interactors
MINTiQ96MU7
STRINGi9606.ENSP00000339245

PTM databases

iPTMnetiQ96MU7
PhosphoSitePlusiQ96MU7
SwissPalmiQ96MU7

Polymorphism and mutation databases

BioMutaiYTHDC1
DMDMi47606762

Proteomic databases

EPDiQ96MU7
MaxQBiQ96MU7
PaxDbiQ96MU7
PeptideAtlasiQ96MU7
PRIDEiQ96MU7
ProteomicsDBi77413
77414 [Q96MU7-2]

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
EuPathDBiHostDB:ENSG00000083896.12
GeneCardsiYTHDC1
HGNCiHGNC:30626 YTHDC1
HPAiHPA036462
neXtProtiNX_Q96MU7
OpenTargetsiENSG00000083896
PharmGKBiPA143485673
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1902 Eukaryota
ENOG4111F6P LUCA
GeneTreeiENSGT00390000017549
HOGENOMiHOG000088650
HOVERGENiHBG055528
InParanoidiQ96MU7
KOiK20100
PhylomeDBiQ96MU7
TreeFamiTF325590

Enzyme and pathway databases

SignaLinkiQ96MU7
SIGNORiQ96MU7

Miscellaneous databases

ChiTaRSiYTHDC1 human
EvolutionaryTraceiQ96MU7
GeneWikiiYTHDC1
GenomeRNAii91746
PROiPR:Q96MU7

Gene expression databases

BgeeiENSG00000083896 Expressed in 242 organ(s), highest expression level in female gonad
CleanExiHS_YTHDC1
ExpressionAtlasiQ96MU7 baseline and differential
GenevisibleiQ96MU7 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 nameiYTDC1_HUMAN
AccessioniPrimary (citable) accession number: Q96MU7
Secondary accession number(s): Q4W5Q3, Q7Z622, Q8TF35
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 12, 2003
Last sequence update: May 24, 2004
Last modified: November 7, 2018
This is version 155 of the entry and version 3 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, 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
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Main funding by: National Institutes of Health

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