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Protein

N6-adenosine-methyltransferase subunit METTL14

Gene

Mettl14

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues of some mRNAs and regulates the circadian clock and differentiation of embryonic stem cells (PubMed:24394384). In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core (By similarity). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in the efficiency of mRNA splicing, processing and mRNA stability (By similarity). M6A regulates the length of the circadian clock: acts as a early pace-setter in the circadian loop. M6A also acts as a regulator of mRNA stability: in embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (PubMed:24394384).By similarity1 Publication

Catalytic activityi

S-adenosyl-L-methionine + m7G(5')pppAm = S-adenosyl-L-homocysteine + m7G(5')pppm6Am.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei146Interaction with METTL3By similarity1
Binding sitei242Interaction with METTL3By similarity1
Binding sitei245Interaction with METTL3By similarity1
Binding sitei298Interaction with METTL3By similarity1
Binding sitei399Interaction with METTL3By similarity1

GO - Molecular functioni

  • mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity Source: UniProtKB
  • mRNA binding Source: UniProtKB

GO - Biological processi

  • mRNA destabilization Source: UniProtKB
  • mRNA methylation Source: UniProtKB
  • mRNA splicing, via spliceosome Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

RNA-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-MMU-72203. Processing of Capped Intron-Containing Pre-mRNA.

Names & Taxonomyi

Protein namesi
Recommended name:
N6-adenosine-methyltransferase subunit METTL14 (EC:2.1.1.621 Publication)
Alternative name(s):
Methyltransferase-like protein 14
Gene namesi
Name:Mettl14
Synonyms:Kiaa1627
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2442926. Mettl14.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003257911 – 456N6-adenosine-methyltransferase subunit METTL14Add BLAST456

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei399PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-399 is important for interaction with METTL3: phosphorylated Ser-399 forms a salt bridge with 'Arg-471' of METTL3.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ3UIK4.
PaxDbiQ3UIK4.
PRIDEiQ3UIK4.

PTM databases

iPTMnetiQ3UIK4.
PhosphoSitePlusiQ3UIK4.

Expressioni

Gene expression databases

BgeeiENSMUSG00000028114.
CleanExiMM_G430022H21RIK.
ExpressionAtlasiQ3UIK4. baseline and differential.
GenevisibleiQ3UIK4. MM.

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with METTL3 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6-methyltransferase complex composed of WTAP, METTL3 and METTL14.By similarity

Protein-protein interaction databases

DIPiDIP-60725N.
STRINGi10090.ENSMUSP00000029759.

Structurei

3D structure databases

ProteinModelPortaliQ3UIK4.
SMRiQ3UIK4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 136Interaction with METTL3By similarity2
Regioni237 – 238Interaction with METTL3By similarity2
Regioni245 – 254Positively charged region required for RNA-bindingBy similarity10
Regioni255 – 258Interaction with METTL3By similarity4
Regioni278 – 287Interaction with METTL3By similarity10
Regioni297 – 298Positively charged region required for RNA-bindingBy similarity2
Regioni308 – 312Interaction with METTL3By similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi409 – 452Gly-richAdd BLAST44

Sequence similaritiesi

Belongs to the MT-A70-like family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2097. Eukaryota.
ENOG410XQ0H. LUCA.
GeneTreeiENSGT00550000075003.
HOGENOMiHOG000047862.
InParanoidiQ3UIK4.
KOiK05925.
OMAiFWNWDDI.
OrthoDBiEOG091G0BBQ.
PhylomeDBiQ3UIK4.
TreeFamiTF323641.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR007757. MT-A70-like.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PfamiPF05063. MT-A70. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51143. MT_A70. 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: Q3UIK4-1) [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
MDSRLQEIRE RQKLRRQLLA QQLGAESADS IGAVLNSKDE QREIAETRET
60 70 80 90 100
CRASYDTSAP NSKRKCLDEG ETDEDKVEEY KDELEMQQEE ENLPYEEEIY
110 120 130 140 150
KDSSTFLKGT QSLNPHNDYC QHFVDTGHRP QNFIRDVGLA DRFEEYPKLR
160 170 180 190 200
ELIRLKDELI AKSNTPPMYL QADIEAFDIR ELTPKFDVIL LEPPLEEYYR
210 220 230 240 250
ETGITANEKC WTWDDIMKLE IDEIAAPRSF IFLWCGSGEG LDLGRVCLRK
260 270 280 290 300
WGYRRCEDIC WIKTNKNNPG KTKTLDPKAV FQRTKEHCLM GIKGTVKRST
310 320 330 340 350
DGDFIHANVD IDLIITEEPE IGNIEKPVEI FHIIEHFCLG RRRLHLFGRD
360 370 380 390 400
STIRPGWLTV GPTLTNSNYN AETYASYFSA PNSYLTGCTE EIERLRPKSP
410 420 430 440 450
PPKSKSDRGG GAPRGGGRGG TSAGRGRERN RSNFRGERGG FRGGRGGTHR

GGFTPR
Length:456
Mass (Da):52,122
Last modified:October 11, 2005 - v1
Checksum:iC9CB9440B203957F
GO
Isoform 2 (identifier: Q3UIK4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     286-456: EHCLMGIKGT...GTHRGGFTPR → YPHISTGLPP...EGEPRAQLSS

Note: No experimental confirmation available.
Show »
Length:350
Mass (Da):40,721
Checksum:i49D51AD5037F2955
GO

Sequence cautioni

The sequence BAC98219 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti348G → E in AAH52204 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_032406286 – 456EHCLM…GFTPR → YPHISTGLPPEHSELKVCVL SRQAVLKVIKKLKLAYYHQK IRHQVGDCLLRNVTSEGEPR AQLSS in isoform 2. 1 PublicationAdd BLAST171

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129409 mRNA. Translation: BAC98219.1. Different initiation.
AK146881 mRNA. Translation: BAE27502.1.
BC052204 mRNA. Translation: AAH52204.1.
CCDSiCCDS38622.1. [Q3UIK4-1]
RefSeqiNP_964000.2. NM_201638.2. [Q3UIK4-1]
UniGeneiMm.260039.

Genome annotation databases

EnsembliENSMUST00000029759; ENSMUSP00000029759; ENSMUSG00000028114. [Q3UIK4-1]
GeneIDi210529.
KEGGimmu:210529.
UCSCiuc008rfi.2. mouse. [Q3UIK4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK129409 mRNA. Translation: BAC98219.1. Different initiation.
AK146881 mRNA. Translation: BAE27502.1.
BC052204 mRNA. Translation: AAH52204.1.
CCDSiCCDS38622.1. [Q3UIK4-1]
RefSeqiNP_964000.2. NM_201638.2. [Q3UIK4-1]
UniGeneiMm.260039.

3D structure databases

ProteinModelPortaliQ3UIK4.
SMRiQ3UIK4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60725N.
STRINGi10090.ENSMUSP00000029759.

PTM databases

iPTMnetiQ3UIK4.
PhosphoSitePlusiQ3UIK4.

Proteomic databases

MaxQBiQ3UIK4.
PaxDbiQ3UIK4.
PRIDEiQ3UIK4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029759; ENSMUSP00000029759; ENSMUSG00000028114. [Q3UIK4-1]
GeneIDi210529.
KEGGimmu:210529.
UCSCiuc008rfi.2. mouse. [Q3UIK4-1]

Organism-specific databases

CTDi57721.
MGIiMGI:2442926. Mettl14.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG2097. Eukaryota.
ENOG410XQ0H. LUCA.
GeneTreeiENSGT00550000075003.
HOGENOMiHOG000047862.
InParanoidiQ3UIK4.
KOiK05925.
OMAiFWNWDDI.
OrthoDBiEOG091G0BBQ.
PhylomeDBiQ3UIK4.
TreeFamiTF323641.

Enzyme and pathway databases

ReactomeiR-MMU-72203. Processing of Capped Intron-Containing Pre-mRNA.

Miscellaneous databases

PROiQ3UIK4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028114.
CleanExiMM_G430022H21RIK.
ExpressionAtlasiQ3UIK4. baseline and differential.
GenevisibleiQ3UIK4. MM.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR007757. MT-A70-like.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PfamiPF05063. MT-A70. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51143. MT_A70. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMET14_MOUSE
AccessioniPrimary (citable) accession number: Q3UIK4
Secondary accession number(s): Q6ZPL2, Q80UR9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: October 11, 2005
Last modified: November 30, 2016
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.