Q9NRN9 · METL5_HUMAN
- ProteinrRNA N6-adenosine-methyltransferase METTL5
- GeneMETTL5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids209 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (PubMed:31328227, PubMed:32217665, PubMed:33357433, PubMed:33428944, PubMed:35033535).
N6-methylation of adenine1832 in 18S rRNA resides in the decoding center of 18S rRNA and is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation (PubMed:33357433).
N6-methylation of adenine1832 in 18S rRNA resides in the decoding center of 18S rRNA and is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation (PubMed:33357433).
Catalytic activity
- adenosine1832 in 18S rRNA + S-adenosyl-L-methionine = H+ + N6-methyladenosine1832 in 18S rRNA + S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
Activity regulation
rRNA N6-adenosine-methyltransferase activity is inhibited by zinc.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
1.1 μM | 18S rRNA | |||||
1 μM | S-adenosyl-L-methionine |
kcat is 13.1 h-1 for 18S rRNA (PubMed:33428944).
kcat is 17.6 h-1 for S-adenosyl-L-methionine (PubMed:33428944).
kcat is 17.6 h-1 for S-adenosyl-L-methionine (PubMed:33428944).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 28 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 31 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 59 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 62 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 64 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 81 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 108-109 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: DV |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell projection | |
Cellular Component | cytosol | |
Cellular Component | fibrillar center | |
Cellular Component | nucleolus | |
Cellular Component | nucleus | |
Cellular Component | postsynapse | |
Cellular Component | presynapse | |
Molecular Function | nucleic acid binding | |
Molecular Function | rRNA (adenine-N6-)-methyltransferase activity | |
Molecular Function | S-adenosyl-L-methionine binding | |
Biological Process | positive regulation of translation | |
Biological Process | rRNA methylation | |
Biological Process | rRNA processing | |
Biological Process | stem cell differentiation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namerRNA N6-adenosine-methyltransferase METTL5
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NRN9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Intellectual developmental disorder, autosomal recessive 72 (MRT72)
- Note
- DescriptionA form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT72 patients manifest moderate to severe intellectual disability, microcephaly, and dysmorphic facial features.
- See alsoMIM:618665
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_086154 | 61 | found in patients with intellectual disability and microcephaly; uncertain significance; impaired interaction with TRMT112 | |||
Sequence: G → D | ||||||
Mutagenesis | 126-128 | In METTL5-3A; abolished methyltransferase activity. | ||||
Sequence: NPP → AAA | ||||||
Natural variant | VAR_051507 | 202 | in dbSNP:rs1051387 | |||
Sequence: V → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 246 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000251919 | 1-209 | rRNA N6-adenosine-methyltransferase METTL5 | |||
Sequence: MKKVRLKELESRLQQVDGFEKPKLLLEQYPTRPHIAACMLYTIHNTYDDIENKVVADLGCGCGVLSIGTAMLGAGLCVGFDIDEDALEIFNRNAEEFELTNIDMVQCDVCLLSNRMSKSFDTVIMNPPFGTKNNKGTDMAFLKTALEMARTAVYSLHKSSTREHVQKKAAEWKIKIDIIAELRYDLPASYKFHKKKSVDIEVDLIRFSF |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed from very early development (8 post-conceptual weeks) and expression persists through adulthood in multiple substructures of the brain, including the cerebellar cortex, hippocampus, and striatum.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heterodimer; heterodimerizes with TRMT112.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NRN9 | TRMT112 Q9UI30 | 8 | EBI-12360031, EBI-373326 | |
BINARY | Q9NRN9 | ZBTB5 O15062 | 3 | EBI-12360031, EBI-722671 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length209
- Mass (Da)23,719
- Last updated2000-10-01 v1
- Checksum060B1C2C0D2BA169
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 27 | in Ref. 2; BAA91622 | ||||
Sequence: E → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF201938 EMBL· GenBank· DDBJ | AAF86874.1 EMBL· GenBank· DDBJ | mRNA | ||
AK001321 EMBL· GenBank· DDBJ | BAA91622.1 EMBL· GenBank· DDBJ | mRNA | ||
AC009967 EMBL· GenBank· DDBJ | AAY14869.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471058 EMBL· GenBank· DDBJ | EAX11254.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471058 EMBL· GenBank· DDBJ | EAX11255.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC093014 EMBL· GenBank· DDBJ | AAH93014.1 EMBL· GenBank· DDBJ | mRNA | ||
BC000921 EMBL· GenBank· DDBJ | AAH00921.1 EMBL· GenBank· DDBJ | mRNA |