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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:29348140, 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, PubMed:29348140). 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 similarity7 Publications

Caution

The effect of phosphorylation at Ser-399 is unclear. According to a report, phosphorylation at Ser-399 is important for interaction with METTL3: phosphorylated Ser-399 forms a salt bridge with 'Arg-471' of METTL3 (PubMed:27281194). According to another report, phosphorylation at Ser-399 does not affect interaction with METTL3 (PubMed:29348140).2 Publications
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

GO - Biological processi

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
Mutagenesisi63 – 65KRK → GGG: Does not affect nuclear localization. 1 Publication3
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
Mutagenesisi399S → A or E: Does not affect interaction with METTL3. 1 Publication1

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 sources2 Publications1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9HCE5
MaxQBiQ9HCE5
PaxDbiQ9HCE5
PeptideAtlasiQ9HCE5
PRIDEiQ9HCE5
ProteomicsDBi81687

PTM databases

iPTMnetiQ9HCE5
PhosphoSitePlusiQ9HCE5

Miscellaneous databases

PMAP-CutDBiQ9HCE5

Expressioni

Gene expression databases

BgeeiENSG00000145388 Expressed in 202 organ(s), highest expression level in testis
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 a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:24407421, PubMed:24981863, PubMed:24316715, PubMed:29507755, PubMed:29348140). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:24407421, PubMed:24981863, PubMed:24316715, PubMed:29507755). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29507755).8 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi121744, 6 interactors
ComplexPortaliCPX-1605 WMM N6-adenosine-methyltransferase complex
DIPiDIP-60726N
IntActiQ9HCE5, 5 interactors
STRINGi9606.ENSP00000373474

Structurei

Secondary structure

1456
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RBL4D6RBL4_HUMAN
N6-adenosine-methyltransferase non-...
METTL14
137Annotation score:
D6RD73D6RD73_HUMAN
N6-adenosine-methyltransferase non-...
METTL14
121Annotation score:
A0A0D9SF88A0A0D9SF88_HUMAN
N6-adenosine-methyltransferase non-...
METTL14
64Annotation score:
A0A0D9SFW0A0A0D9SFW0_HUMAN
N6-adenosine-methyltransferase non-...
METTL14
89Annotation score:

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

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
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...

Protein-protein interaction databases

BioGridi121744, 6 interactors
ComplexPortaliCPX-1605 WMM N6-adenosine-methyltransferase complex
DIPiDIP-60726N
IntActiQ9HCE5, 5 interactors
STRINGi9606.ENSP00000373474

PTM databases

iPTMnetiQ9HCE5
PhosphoSitePlusiQ9HCE5

Polymorphism and mutation databases

BioMutaiMETTL14
DMDMi172045930

Proteomic databases

EPDiQ9HCE5
MaxQBiQ9HCE5
PaxDbiQ9HCE5
PeptideAtlasiQ9HCE5
PRIDEiQ9HCE5
ProteomicsDBi81687

Protocols and materials databases

DNASUi57721
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57721
DisGeNETi57721
EuPathDBiHostDB:ENSG00000145388.14
GeneCardsiMETTL14
HGNCiHGNC:29330 METTL14
HPAiHPA038002
MIMi616504 gene
neXtProtiNX_Q9HCE5
OpenTargetsiENSG00000145388
PharmGKBiPA164722277
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2097 Eukaryota
ENOG410XQ0H LUCA
GeneTreeiENSGT00550000075003
HOGENOMiHOG000047862
InParanoidiQ9HCE5
KOiK05925
OMAiRTNINKP
OrthoDBiEOG091G0BBQ
PhylomeDBiQ9HCE5
TreeFamiTF323641

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiMETTL14 human
GenomeRNAii57721
PMAP-CutDBiQ9HCE5
PROiPR:Q9HCE5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145388 Expressed in 202 organ(s), highest expression level in testis
ExpressionAtlasiQ9HCE5 baseline and differential
GenevisibleiQ9HCE5 HS

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
ProtoNetiSearch...

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: October 10, 2018
This is version 116 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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