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Protein

N6-adenosine-methyltransferase subunit METTL14

Gene

METTL14

Organism
Homo sapiens (Human)
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:24316715, PubMed:24407421, PubMed:25719671, PubMed:27281194). In the heterodimer formed with METTL3, METTL14 probably constitutes the RNA-binding scaffold rather than the catalytic core (PubMed:27281194). 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 (PubMed:24316715, PubMed:24407421, PubMed:25719671). 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 (By similarity).By similarity4 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei146 – 1461Interaction with METTL3Combined sources1 Publication
Binding sitei242 – 2421Interaction with METTL3Combined sources1 Publication
Binding sitei245 – 2451Interaction with METTL3Combined sources1 Publication
Binding sitei298 – 2981Interaction with METTL3Combined sources1 Publication
Binding sitei399 – 3991Interaction with METTL3Combined sources1 Publication

GO - Molecular functioni

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

GO - Biological processi

  • gene expression Source: Reactome
  • 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-HSA-72203. Processing of Capped Intron-Containing Pre-mRNA.

Names & Taxonomyi

Protein namesi
Recommended name:
N6-adenosine-methyltransferase subunit METTL14Curated (EC:2.1.1.621 Publication)
Alternative name(s):
Methyltransferase-like protein 14Imported
Gene namesi
Name:METTL14Imported
Synonyms:KIAA16271 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:29330. METTL14.

Subcellular locationi

GO - Cellular componenti

  • MIS complex Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi173 – 1731D → A: Little or no effect on S-adenosyl-L-methionine-binding or methyltransferase activity; when associated with A-192. 1 Publication
Mutagenesisi192 – 1921E → A: Little or no effect on S-adenosyl-L-methionine-binding or methyltransferase activity; when associated with A-173. 1 Publication
Mutagenesisi245 – 2451R → E: Reduced RNA-binding. Reduced RNA-binding; when associated with E-255. 1 Publication
Mutagenesisi255 – 2551R → E: Reduced RNA-binding; when associated with E-245. 1 Publication
Mutagenesisi297 – 2982KR → EE: Reduced RNA-binding. 1 Publication

Organism-specific databases

PharmGKBiPA164722277.

Polymorphism and mutation databases

BioMutaiMETTL14.
DMDMi172045930.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 456456N6-adenosine-methyltransferase subunit METTL14PRO_0000325790Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei399 – 3991PhosphoserineCombined sources1 Publication

Post-translational modificationi

Phosphorylation at Ser-399 is important for interaction with METTL3: phosphorylated Ser-399 forms a salt bridge with 'Arg-471' of METTL3.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9HCE5.
MaxQBiQ9HCE5.
PaxDbiQ9HCE5.
PeptideAtlasiQ9HCE5.
PRIDEiQ9HCE5.

PTM databases

iPTMnetiQ9HCE5.
PhosphoSiteiQ9HCE5.

Miscellaneous databases

PMAP-CutDBQ9HCE5.

Expressioni

Gene expression databases

BgeeiENSG00000145388.
ExpressionAtlasiQ9HCE5. baseline and differential.
GenevisibleiQ9HCE5. HS.

Organism-specific databases

HPAiHPA038002.

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with METTL3 to form an antiparallel heterodimer that constitutes an active methyltransferase (PubMed:27281194). Component of the WMM complex, a N6-methyltransferase complex composed of WTAP, METTL3 and METTL14.4 Publications

Protein-protein interaction databases

BioGridi121744. 6 interactions.
DIPiDIP-60726N.
IntActiQ9HCE5. 4 interactions.
STRINGi9606.ENSP00000373474.

Structurei

Secondary structure

1
456
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi119 – 1268Combined sources
Helixi130 – 1334Combined sources
Turni140 – 1456Combined sources
Helixi147 – 16317Combined sources
Beta strandi168 – 1714Combined sources
Turni174 – 1763Combined sources
Helixi179 – 1813Combined sources
Beta strandi186 – 1916Combined sources
Helixi196 – 2005Combined sources
Helixi213 – 2175Combined sources
Helixi221 – 2233Combined sources
Beta strandi225 – 23410Combined sources
Helixi240 – 25112Combined sources
Beta strandi254 – 26411Combined sources
Beta strandi266 – 2683Combined sources
Beta strandi280 – 2823Combined sources
Beta strandi285 – 29410Combined sources
Turni298 – 3003Combined sources
Turni302 – 3043Combined sources
Beta strandi309 – 3179Combined sources
Helixi329 – 3379Combined sources
Beta strandi343 – 3464Combined sources
Helixi350 – 3523Combined sources
Beta strandi358 – 3614Combined sources
Helixi371 – 3766Combined sources
Helixi390 – 3956Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5IL0X-ray1.88B109-408[»]
5IL1X-ray1.71B109-408[»]
5IL2X-ray1.61B109-408[»]
ProteinModelPortaliQ9HCE5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni135 – 1362Interaction with METTL3Combined sources1 Publication
Regioni237 – 2382Interaction with METTL3Combined sources1 Publication
Regioni245 – 25410Positively charged region required for RNA-binding1 Publication
Regioni255 – 2584Interaction with METTL3Combined sources1 Publication
Regioni278 – 28710Interaction with METTL3Combined sources1 Publication
Regioni297 – 2982Positively charged region required for RNA-binding1 Publication
Regioni308 – 3125Interaction with METTL3Combined sources1 Publication

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi409 – 45244Gly-richAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2097. Eukaryota.
ENOG410XQ0H. LUCA.
GeneTreeiENSGT00550000075003.
HOGENOMiHOG000047862.
InParanoidiQ9HCE5.
KOiK05925.
OMAiFWNWDDI.
OrthoDBiEOG091G0BBQ.
PhylomeDBiQ9HCE5.
TreeFamiTF323641.

Family and domain databases

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]

Sequencei

Sequence statusi: Complete.

Q9HCE5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDSRLQEIRE RQKLRRQLLA QQLGAESADS IGAVLNSKDE QREIAETRET
60 70 80 90 100
CRASYDTSAP NAKRKYLDEG ETDEDKMEEY KDELEMQQDE 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 FRGGRGGAHR

GGFPPR
Length:456
Mass (Da):52,150
Last modified:March 18, 2008 - v2
Checksum:i73A45B66BB76E241
GO

Sequence cautioni

The sequence BAB13453 differs from that shown. Reason: Erroneous initiation. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046847 mRNA. Translation: BAB13453.1. Different initiation.
AK055555 mRNA. Translation: BAB70954.1.
AC110079 Genomic DNA. No translation available.
CH471229 Genomic DNA. Translation: EAW73651.1.
BC006565 mRNA. Translation: AAH06565.1.
BC007449 mRNA. Translation: AAH07449.1.
CCDSiCCDS34053.1.
RefSeqiNP_066012.1. NM_020961.3.
UniGeneiHs.596872.
Hs.657806.

Genome annotation databases

EnsembliENST00000388822; ENSP00000373474; ENSG00000145388.
GeneIDi57721.
KEGGihsa:57721.
UCSCiuc003icf.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB046847 mRNA. Translation: BAB13453.1. Different initiation.
AK055555 mRNA. Translation: BAB70954.1.
AC110079 Genomic DNA. No translation available.
CH471229 Genomic DNA. Translation: EAW73651.1.
BC006565 mRNA. Translation: AAH06565.1.
BC007449 mRNA. Translation: AAH07449.1.
CCDSiCCDS34053.1.
RefSeqiNP_066012.1. NM_020961.3.
UniGeneiHs.596872.
Hs.657806.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5IL0X-ray1.88B109-408[»]
5IL1X-ray1.71B109-408[»]
5IL2X-ray1.61B109-408[»]
ProteinModelPortaliQ9HCE5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121744. 6 interactions.
DIPiDIP-60726N.
IntActiQ9HCE5. 4 interactions.
STRINGi9606.ENSP00000373474.

PTM databases

iPTMnetiQ9HCE5.
PhosphoSiteiQ9HCE5.

Polymorphism and mutation databases

BioMutaiMETTL14.
DMDMi172045930.

Proteomic databases

EPDiQ9HCE5.
MaxQBiQ9HCE5.
PaxDbiQ9HCE5.
PeptideAtlasiQ9HCE5.
PRIDEiQ9HCE5.

Protocols and materials databases

DNASUi57721.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000388822; ENSP00000373474; ENSG00000145388.
GeneIDi57721.
KEGGihsa:57721.
UCSCiuc003icf.4. human.

Organism-specific databases

CTDi57721.
GeneCardsiMETTL14.
HGNCiHGNC:29330. METTL14.
HPAiHPA038002.
MIMi616504. gene.
neXtProtiNX_Q9HCE5.
PharmGKBiPA164722277.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2097. Eukaryota.
ENOG410XQ0H. LUCA.
GeneTreeiENSGT00550000075003.
HOGENOMiHOG000047862.
InParanoidiQ9HCE5.
KOiK05925.
OMAiFWNWDDI.
OrthoDBiEOG091G0BBQ.
PhylomeDBiQ9HCE5.
TreeFamiTF323641.

Enzyme and pathway databases

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

Miscellaneous databases

GenomeRNAii57721.
PMAP-CutDBQ9HCE5.
PROiQ9HCE5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145388.
ExpressionAtlasiQ9HCE5. baseline and differential.
GenevisibleiQ9HCE5. HS.

Family and domain databases

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_HUMAN
AccessioniPrimary (citable) accession number: Q9HCE5
Secondary accession number(s): A6NIG1, Q969V2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: September 7, 2016
This is version 97 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, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.