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Protein

3'-5' RNA helicase YTHDC2

Gene

Ythdc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

3'-5' RNA helicase that plays a key role in the male and female germline by promoting transition from mitotic to meiotic divisions in stem cells (PubMed:28380054, PubMed:28809393, PubMed:29087293, PubMed:29033321, PubMed:29360036). Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs that plays a role in the efficiency of RNA processing and stability (PubMed:29360036). Essential for ensuring a successful progression of the meiotic program in the germline by regulating the level of m6A-containing RNAs (PubMed:29033321). Acts by binding and promoting degradation of m6A-containing mRNAs: the 3'-5' RNA helicase activity is required for this process and RNA degradation may be mediated by XRN1 exoribonuclease (PubMed:29033321). Required for both spermatogenesis and oogenesis (PubMed:28809393, PubMed:29033321).5 Publications

Miscellaneous

'Ketu' is a harbinger of misfortune in Vedic mythology (PubMed:29360036).1 Publication

Catalytic activityi

ATP + H2O = ADP + phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1325N6-methyladenosineBy similarity1
Binding sitei1375N6-methyladenosineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi231 – 238ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHelicase, Hydrolase, RNA-binding
Biological processDifferentiation, Meiosis, Oogenesis, Spermatogenesis
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
3'-5' RNA helicase YTHDC2Curated (EC:3.6.4.131 Publication)
Alternative name(s):
Keen to exit meiosis leaving testes under-populated protein1 Publication
Short name:
Ketu1 Publication
YTH domain-containing protein C21 Publication
Short name:
mYTHDC21 Publication
Gene namesi
Name:Ythdc21 PublicationImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:2448561 Ythdc2

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

Pathology & Biotechi

Disruption phenotypei

Mice are viable and reach adulthood (PubMed:28809393, PubMed:29087293, PubMed:29033321). However, both male and female mice are infertile; male mice have smaller testes, and female mice have smaller ovaries and show progressive loss of germ cells (PubMed:28809393, PubMed:29087293, PubMed:29033321). Mutant germ cells enter meiosis but proceed prematurely to aberrant metaphase and apoptosis, and display defects in transitioning from spermatogonial to meiotic gene expression programs (PubMed:29087293, PubMed:29033321). Mutant testes reveal an up-regulation of N6-methyladenosine (m6A)-enriched transcripts (PubMed:29033321).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi327H → R in ketu; homozygotes mice are both male- and female-sterile. In the testis, mutant germ cells carry out an abortive attempt at meiosis: They express hallmark meiotic proteins and initiate recombination, but fail to fully extinguish the spermatogonial mitotic division program, proceed prematurely to an aberrant metaphase-like state, and undergo apoptosis. The mutation probably causes misfolding or protein aggregation. Slightly reduced helicase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003782751 – 14453'-5' RNA helicase YTHDC2Add BLAST1445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1104PhosphoserineCombined sources1
Modified residuei1105PhosphoserineCombined sources1
Modified residuei1107PhosphoserineCombined sources1
Modified residuei1278PhosphoserineCombined sources1
Modified residuei1282PhosphoserineCombined sources1
Modified residuei1296PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiB2RR83
MaxQBiB2RR83
PaxDbiB2RR83
PeptideAtlasiB2RR83
PRIDEiB2RR83

PTM databases

iPTMnetiB2RR83
PhosphoSitePlusiB2RR83

Expressioni

Tissue specificityi

Highly expressed in testis (PubMed:28809393, PubMed:29087293, PubMed:29033321, PubMed:29360036). Present in germ cells (at protein level) (PubMed:29033321). Not detected in spermatogonia next to the tubule wall but is strongly expressed in spermatocytes, suggesting that it is up-regulated in germ cells upon entry into meiosis (at protein level) (PubMed:29087293).4 Publications

Developmental stagei

Expression rises between 7 and 12 d.p.p. and remains steady through adulthood.1 Publication

Gene expression databases

BgeeiENSMUSG00000034653 Expressed in 232 organ(s), highest expression level in cumulus cell
ExpressionAtlasiB2RR83 baseline and differential
GenevisibleiB2RR83 MM

Interactioni

Subunit structurei

Interacts with MEIOC; binds transcripts that regulate the mitotic cell cycle inhibiting progression into metaphase, thereby allowing meiotic prophase to proceed normally (PubMed:28380054, PubMed:29087293). Interacts (via ANK repeats) with XRN1 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MeiocA2AG064EBI-8572369,EBI-11664020

GO - Molecular functioni

Protein-protein interaction databases

IntActiB2RR83, 2 interactors
MINTiB2RR83
STRINGi10090.ENSMUSP00000048340

Structurei

3D structure databases

ProteinModelPortaliB2RR83
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 121R3HPROSITE-ProRule annotationAdd BLAST69
Domaini218 – 384Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST167
Repeati521 – 553ANK 1Add BLAST33
Repeati554 – 586ANK 2Add BLAST33
Domaini627 – 799Helicase C-terminalPROSITE-ProRule annotationAdd BLAST173
Domaini1303 – 1433YTHPROSITE-ProRule annotationAdd BLAST131

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1309 – 1311N6-methyladenosine bindingBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi331 – 334DEAH box4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi16 – 50Gly-richAdd BLAST35
Compositional biasi1263 – 1296Ser-richAdd BLAST34

Domaini

The YTH domain mediates RNA-binding. It recognizes and binds N6-methyladenosine (m6A)-containing RNAs.By similarity

Sequence similaritiesi

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0920 Eukaryota
KOG0922 Eukaryota
KOG1902 Eukaryota
COG1643 LUCA
GeneTreeiENSGT00760000119189
HOGENOMiHOG000155703
InParanoidiB2RR83
KOiK20099
OMAiDAMDTWE
OrthoDBiEOG091G0CXN
PhylomeDBiB2RR83
TreeFamiTF318311

Family and domain databases

CDDicd00204 ANK, 1 hit
cd00079 HELICc, 1 hit
cd06007 R3H_DEXH_helicase, 1 hit
Gene3Di1.25.40.20, 1 hit
3.30.1370.50, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011545 DEAD/DEAH_box_helicase_dom
IPR011709 DUF1605
IPR007502 Helicase-assoc_dom
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR034083 R3H_DEXH_helicase
IPR001374 R3H_dom
IPR036867 R3H_dom_sf
IPR007275 YTH_domain
IPR031083 YTHDC2-related
PANTHERiPTHR18934:SF125 PTHR18934:SF125, 1 hit
PfamiView protein in Pfam
PF00270 DEAD, 1 hit
PF04408 HA2, 1 hit
PF00271 Helicase_C, 1 hit
PF07717 OB_NTP_bind, 1 hit
PF01424 R3H, 1 hit
PF04146 YTH, 1 hit
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00847 HA2, 1 hit
SM00490 HELICc, 1 hit
SM00393 R3H, 1 hit
SUPFAMiSSF48403 SSF48403, 1 hit
SSF52540 SSF52540, 2 hits
SSF82708 SSF82708, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
PS51061 R3H, 1 hit
PS50882 YTH, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

B2RR83-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSRPSSVSPR PPAPSGGGTG GGGGGSGGGG GGGGGGPASC GPGGGGRAKG
60 70 80 90 100
LKDIRIDEEV KIAVNIALER FRYGDQREME FPSSLTSTER AFIHRLSQSL
110 120 130 140 150
GLVSKSKGKG ANRYLTVKKK DGSETAHAMM TCNLTHNTKH AVRSLIQRFP
160 170 180 190 200
VTNKERTELL PKTERGNVFA VEAENREMSK TSGRLNNGIP QVPVKRGESE
210 220 230 240 250
FDSFRQSLPV FEKQEEIVKI IKENKVVLIV GETGSGKTTQ IPQFLLDDCF
260 270 280 290 300
KNGIPCRIFC TQPRRLAAIA VAERVAAERR ERIGQTIGYQ IRLESRVSPK
310 320 330 340 350
TLLTFCTNGV LLRTLMAGDS TLSTVTHVIV DEVHERDRFS DFLLTKLRDL
360 370 380 390 400
LQKHPTLKLI LSSAALDVNL FIRYFGSCPV IYIQGRPFEV KEMFLEDILR
410 420 430 440 450
TTGYTNKEML KYKKEKQREE KQQTTLTEWY SAQENTFKPE SQRQRAVASV
460 470 480 490 500
SEEYDLLDDG GDAVFSQLTE KDVNCLEPWL IKEMDACLSD IWLHKDVDAF
510 520 530 540 550
AQVFHLILTE NVSVDYRHSE TSATALMVAA GRGFTSQVEQ LISMGANVHS
560 570 580 590 600
KASNGWMALD WAKHFGQTEI VDLLESYSAS LEFGNLDESS LVQTNGNDLS
610 620 630 640 650
AEDRELLKAY HHSFDDEKVD LDLIMHLLYN ICHSCDAGAI LIFLPGYDEI
660 670 680 690 700
VGLRDRILFD DKRFADNTHR YQVFMLHSNM QTSDQKKVLK NPPAGVRKII
710 720 730 740 750
LSTNIAETSI TVNDVVFVID SGKVKEKSFD ALNFVTMLKM VWISKASAIQ
760 770 780 790 800
RKGRAGRCRP GICFRLFSRL RFQNMLEFQT PELLRMPLQE LCLHTKLLAP
810 820 830 840 850
VNCTIADFLM KAPEPPPALI VRNAVQMLKT IDAMDAWEDL TELGYHLADL
860 870 880 890 900
PVEPHLGKMV LCAVVLKCLD PILTIACTLA YRDPFVLPTQ ASQKRAAMLC
910 920 930 940 950
RKRFTAGTFS DHMALLRAFQ AWQKARSDGW ERAFCEKNFL SQATMEIIIG
960 970 980 990 1000
MRTQLLGQLR ASGFVRARGG GDIRDVNTNS ENWAVVKAAL VAGMYPNLVH
1010 1020 1030 1040 1050
VDRENVILTG PKEKKVRFHP TSVLSQPQYK KIPPANGQAA AIQALPTDWL
1060 1070 1080 1090 1100
IYDEMTRAHR IANIRCCSAV TPVTVLVFCG PARLASNALQ EPSSFRADGI
1110 1120 1130 1140 1150
PNDSSDSEME DRTTANLAAL KLDEWLNFKL EPEAASLLLQ LRQKWHSLFL
1160 1170 1180 1190 1200
RRMRAPSKPW SQVDEATIRA IIAVLSTEEQ SAGLQQPSGI GQRPRPMSSE
1210 1220 1230 1240 1250
ELPLASSWRS NNSRKSTADT EFADGSTTGE RVLMKSPSPA LHPPQKYKDR
1260 1270 1280 1290 1300
GILHPKRSTD DRSDQSSVKS TDSSSYPSPC ASPSPPSSGK GSKSPSPRPN
1310 1320 1330 1340 1350
MPIRYFIMKS SNLRNLEISQ QKGIWSTTPS NERKLNRAFW ESSMVYLVFS
1360 1370 1380 1390 1400
VQGSGHFQGF SRMSSEIGRE KSQDWGSAGL GGVFKVEWIR KESLPFQFAH
1410 1420 1430 1440
HLLNPWNDNK KVQISRDGQE LEPQVGEQLL QLWERLPLGE KTTSD
Length:1,445
Mass (Da):161,092
Last modified:July 1, 2008 - v1
Checksum:iA693BF57FEAF7511
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YV44A0A0J9YV44_MOUSE
3'-5' RNA helicase YTHDC2
Ythdc2
585Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC138263 mRNA Translation: AAI38264.1
BC171951 mRNA Translation: AAI71951.1
CCDSiCCDS50278.1
RefSeqiNP_001156485.1, NM_001163013.1
UniGeneiMm.244482

Genome annotation databases

EnsembliENSMUST00000037763; ENSMUSP00000048340; ENSMUSG00000034653
GeneIDi240255
KEGGimmu:240255
UCSCiuc008evb.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC138263 mRNA Translation: AAI38264.1
BC171951 mRNA Translation: AAI71951.1
CCDSiCCDS50278.1
RefSeqiNP_001156485.1, NM_001163013.1
UniGeneiMm.244482

3D structure databases

ProteinModelPortaliB2RR83
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiB2RR83, 2 interactors
MINTiB2RR83
STRINGi10090.ENSMUSP00000048340

PTM databases

iPTMnetiB2RR83
PhosphoSitePlusiB2RR83

Proteomic databases

EPDiB2RR83
MaxQBiB2RR83
PaxDbiB2RR83
PeptideAtlasiB2RR83
PRIDEiB2RR83

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037763; ENSMUSP00000048340; ENSMUSG00000034653
GeneIDi240255
KEGGimmu:240255
UCSCiuc008evb.2 mouse

Organism-specific databases

CTDi64848
MGIiMGI:2448561 Ythdc2

Phylogenomic databases

eggNOGiKOG0920 Eukaryota
KOG0922 Eukaryota
KOG1902 Eukaryota
COG1643 LUCA
GeneTreeiENSGT00760000119189
HOGENOMiHOG000155703
InParanoidiB2RR83
KOiK20099
OMAiDAMDTWE
OrthoDBiEOG091G0CXN
PhylomeDBiB2RR83
TreeFamiTF318311

Miscellaneous databases

ChiTaRSiYthdc2 mouse
PROiPR:B2RR83
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034653 Expressed in 232 organ(s), highest expression level in cumulus cell
ExpressionAtlasiB2RR83 baseline and differential
GenevisibleiB2RR83 MM

Family and domain databases

CDDicd00204 ANK, 1 hit
cd00079 HELICc, 1 hit
cd06007 R3H_DEXH_helicase, 1 hit
Gene3Di1.25.40.20, 1 hit
3.30.1370.50, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011545 DEAD/DEAH_box_helicase_dom
IPR011709 DUF1605
IPR007502 Helicase-assoc_dom
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR034083 R3H_DEXH_helicase
IPR001374 R3H_dom
IPR036867 R3H_dom_sf
IPR007275 YTH_domain
IPR031083 YTHDC2-related
PANTHERiPTHR18934:SF125 PTHR18934:SF125, 1 hit
PfamiView protein in Pfam
PF00270 DEAD, 1 hit
PF04408 HA2, 1 hit
PF00271 Helicase_C, 1 hit
PF07717 OB_NTP_bind, 1 hit
PF01424 R3H, 1 hit
PF04146 YTH, 1 hit
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00847 HA2, 1 hit
SM00490 HELICc, 1 hit
SM00393 R3H, 1 hit
SUPFAMiSSF48403 SSF48403, 1 hit
SSF52540 SSF52540, 2 hits
SSF82708 SSF82708, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit
PS51061 R3H, 1 hit
PS50882 YTH, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiYTDC2_MOUSE
AccessioniPrimary (citable) accession number: B2RR83
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2009
Last sequence update: July 1, 2008
Last modified: November 7, 2018
This is version 92 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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