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Protein

N6-adenosine-methyltransferase non-catalytic subunit

Gene

METTL14

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

Functioni

The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N6 position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis (PubMed:24316715, PubMed:24407421, PubMed:25719671, PubMed:27373337, PubMed:27281194). In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing (PubMed:24316715, PubMed:24407421, PubMed:25719671). M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (By similarity). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity).By similarity6 Publications

Caution

The ability of METTL14 to have catalytic activity is unclear and a number of experimental evidences suggest that has no methyltransferase activity by itself (PubMed:27627798, PubMed:27281194, PubMed:27373337). According to some reports, has some methyltransferase activity in vitro (PubMed:24316715). However, other studies showed that METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core (PubMed:27627798, PubMed:27281194, PubMed:27373337). 3D-structure studies showed that METTL14 contains a degenerate active site that is unable to accommodate donor and acceptor substrates (PubMed:27627798).4 Publications
A disulfide bond between Cys-338 and Cys-388 is observed in a structure (PubMed:27627798). Its existence is however unsure in vivo.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei146Interaction with METTL3Combined sources1 Publication1
Binding sitei242Interaction with METTL3Combined sources1 Publication1
Binding sitei245Interaction with METTL3Combined sources1 Publication1
Binding sitei298Interaction with METTL3Combined sources1 Publication1
Binding sitei399Interaction with METTL3Combined sources1 Publication1

GO - Molecular functioni

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

GO - Biological processi

  • forebrain radial glial cell differentiation Source: UniProtKB
  • gliogenesis Source: UniProtKB
  • mRNA catabolic process Source: Ensembl
  • mRNA destabilization Source: UniProtKB
  • mRNA methylation Source: UniProtKB
  • mRNA splicing, via spliceosome Source: UniProtKB
  • spermatogenesis Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB

Keywordsi

Molecular functionRNA-binding
Biological processDifferentiation, Spermatogenesis

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
N6-adenosine-methyltransferase non-catalytic subunitCurated
Alternative name(s):
Methyltransferase-like protein 14Imported
Short name:
hMETTL141 Publication
Gene namesi
Name:METTL14Imported
Synonyms:KIAA16271 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000145388.14
HGNCiHGNC:29330 METTL14
MIMi616504 gene
neXtProtiNX_Q9HCE5

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
Mutagenesisi173D → A: Little or no effect on S-adenosyl-L-methionine-binding or methyltransferase activity; when associated with A-192. 1 Publication1
Mutagenesisi192E → A: Little or no effect on methyltransferase activity. Little or no effect on S-adenosyl-L-methionine-binding or methyltransferase activity; when associated with A-173. 3 Publications1
Mutagenesisi198Y → A: Does not affect methyltransferase activity of the heterodimer complex formed with METTL3. 1 Publication1
Mutagenesisi245R → E: Reduced RNA-binding. Reduced RNA-binding; when associated with E-255. 1 Publication1
Mutagenesisi254 – 255RR → AA: Strongly reduced methyltransferase activity of the heterodimer complex formed with METTL3. 1 Publication2
Mutagenesisi255R → E: Reduced RNA-binding; when associated with E-245. 1 Publication1
Mutagenesisi297 – 298KR → EE: Reduced RNA-binding. 1 Publication2
Mutagenesisi298R → P: Strongly decreased methyltransferase activity of the heterodimer complex formed with METTL3, probably due to reduced RNA-binding. 1 Publication1
Mutagenesisi312D → A: Decreased methyltransferase activity of the heterodimer complex formed with METTL3. 1 Publication1
Mutagenesisi338C → A: Does not affect methyltransferase activity of the heterodimer complex formed with METTL3. 1 Publication1
Mutagenesisi362 – 363PT → AA: Little or no effect on methyltransferase activity of the heterodimer complex formed with METTL3. 1 Publication2

Organism-specific databases

DisGeNETi57721
OpenTargetsiENSG00000145388
PharmGKBiPA164722277

Polymorphism and mutation databases

BioMutaiMETTL14
DMDMi172045930

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003257901 – 456N6-adenosine-methyltransferase non-catalytic subunitAdd BLAST456

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei399PhosphoserineCombined sources1 Publication1

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
PhosphoSitePlusiQ9HCE5

Miscellaneous databases

PMAP-CutDBiQ9HCE5

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:27627798, PubMed:27373337, PubMed:27281194). Component of the WMM complex, a N6-methyltransferase complex composed of WTAP, METTL3 and METTL14.6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi121744, 6 interactors
DIPiDIP-60726N
IntActiQ9HCE5, 5 interactors
STRINGi9606.ENSP00000373474

Structurei

Secondary structure

1456
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi119 – 126Combined sources8
Helixi130 – 133Combined sources4
Turni140 – 145Combined sources6
Helixi147 – 163Combined sources17
Beta strandi168 – 171Combined sources4
Turni174 – 176Combined sources3
Helixi179 – 181Combined sources3
Beta strandi186 – 191Combined sources6
Helixi196 – 200Combined sources5
Helixi213 – 217Combined sources5
Helixi221 – 223Combined sources3
Beta strandi225 – 234Combined sources10
Helixi240 – 251Combined sources12
Beta strandi254 – 264Combined sources11
Beta strandi266 – 268Combined sources3
Beta strandi280 – 282Combined sources3
Beta strandi285 – 294Combined sources10
Turni298 – 300Combined sources3
Turni302 – 304Combined sources3
Beta strandi309 – 317Combined sources9
Helixi329 – 337Combined sources9
Beta strandi343 – 346Combined sources4
Helixi350 – 352Combined sources3
Beta strandi358 – 361Combined sources4
Helixi371 – 376Combined sources6
Beta strandi387 – 389Combined sources3
Helixi390 – 395Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IL0X-ray1.88B109-408[»]
5IL1X-ray1.71B109-408[»]
5IL2X-ray1.61B109-408[»]
5K7MX-ray1.65B111-456[»]
5K7UX-ray1.70B111-456[»]
5K7WX-ray1.65B111-456[»]
5L6DX-ray1.85B107-395[»]
5L6EX-ray1.90B107-395[»]
5TEYX-ray1.80B1-399[»]
ProteinModelPortaliQ9HCE5
SMRiQ9HCE5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 136Interaction with METTL3Combined sources1 Publication2
Regioni237 – 238Interaction with METTL3Combined sources1 Publication2
Regioni245 – 254Positively charged region required for RNA-binding1 Publication10
Regioni255 – 258Interaction with METTL3Combined sources1 Publication4
Regioni278 – 287Interaction with METTL3Combined sources1 Publication10
Regioni297 – 298Positively charged region required for RNA-binding1 Publication2
Regioni308 – 312Interaction with METTL3Combined sources1 Publication5

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
InParanoidiQ9HCE5
KOiK05925
OMAiRTNINKP
OrthoDBiEOG091G0BBQ
PhylomeDBiQ9HCE5
TreeFamiTF323641

Family and domain databases

InterProiView protein in InterPro
IPR007757 MT-A70-like
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF05063 MT-A70, 1 hit
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51143 MT_A70, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiMET14_HUMAN
AccessioniPrimary (citable) accession number: Q9HCE5
Secondary accession number(s): A6NIG1, Q969V2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: May 23, 2018
This is version 113 of the entry and version 2 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. 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

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