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Protein

N6-adenosine-methyltransferase non-catalytic subunit

Gene

Mettl14

Organism
Mus musculus (Mouse)
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:24394384, PubMed:28965759). 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 mRNA stability and processing (By similarity). M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (PubMed:24394384). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (PubMed:24394384). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (PubMed:28914256). 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 (PubMed:28965759).By similarity3 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. According to some reports, has some methyltransferase activity in vitro (PubMed:24394384). However, other studies showed that METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. 3D-structure studies showed that METTL14 contains a degenerate active site that is unable to accommodate donor and acceptor substrates.By similarity1 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

Keywordsi

Molecular functionRNA-binding
Biological processDifferentiation, Spermatogenesis

Enzyme and pathway databases

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

Names & Taxonomyi

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

Organism-specific databases

MGIiMGI:2442926 Mettl14

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

Disruption phenotypei

Conditional knockout mice lacking Mettl3 and Mettl14 in germ cells show impaired spermatogenesis, leading to male infertility (PubMed:28914256). Conditional knockout mice lacking Mettl14 in the developing nervous system die by postnatal day 25 due to protracted cell-cycle progression of cortical neural progenitor cells and reduced differentiation of radial glial cells during embryonic cortical neurogenesis (PubMed:28965759).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003257911 – 456N6-adenosine-methyltransferase non-catalytic subunitAdd BLAST456

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei399PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ3UIK4
PaxDbiQ3UIK4
PRIDEiQ3UIK4

PTM databases

iPTMnetiQ3UIK4
PhosphoSitePlusiQ3UIK4

Expressioni

Tissue specificityi

Expressed in testis (PubMed:28914256). Highly expressed in radial glial cells during embryonic cortical neurogenesis (PubMed:28965759).2 Publications

Gene expression databases

BgeeiENSMUSG00000028114 Expressed in 235 organ(s), highest expression level in metanephros
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 (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Mettl3Q8C3P72EBI-16089028,EBI-8311763

Protein-protein interaction databases

ComplexPortaliCPX-1609 WMM N6-adenosine-methyltransferase complex
DIPiDIP-60725N
IntActiQ3UIK4, 2 interactors
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
OMAiRTNINKP
OrthoDBiEOG091G0BBQ
PhylomeDBiQ3UIK4
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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3UYS3G3UYS3_MOUSE
N6-adenosine-methyltransferase non-...
Mettl14
377Annotation score:
E9QPC5E9QPC5_MOUSE
N6-adenosine-methyltransferase non-...
Mettl14
217Annotation score:
G3UXL6G3UXL6_MOUSE
N6-adenosine-methyltransferase non-...
Mettl14
211Annotation score:

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

Similar proteinsi

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

ComplexPortaliCPX-1609 WMM N6-adenosine-methyltransferase complex
DIPiDIP-60725N
IntActiQ3UIK4, 2 interactors
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
OMAiRTNINKP
OrthoDBiEOG091G0BBQ
PhylomeDBiQ3UIK4
TreeFamiTF323641

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q3UIK4
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028114 Expressed in 235 organ(s), highest expression level in metanephros
CleanExiMM_G430022H21RIK
ExpressionAtlasiQ3UIK4 baseline and differential
GenevisibleiQ3UIK4 MM

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_MOUSE
AccessioniPrimary (citable) accession number: Q3UIK4
Secondary accession number(s): Q6ZPL2, Q80UR9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: October 11, 2005
Last modified: September 12, 2018
This is version 93 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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