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Protein

tRNA (cytosine(34)-C(5))-methyltransferase

Gene

NSUN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

RNA methyltransferase that methylates tRNAs, and possibly RNA polymerase III transcripts. Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors. May act downstream of Myc to regulate epidermal cell growth and proliferation. Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity.3 Publications

Catalytic activityi

S-adenosyl-L-methionine + cytosine(34) in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine(34) in tRNA precursor.1 Publication

Enzyme regulationi

Inhibited by magnesium ions.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei215S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei242S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei268S-adenosyl-L-methioninePROSITE-ProRule annotation1
Active sitei321NucleophilePROSITE-ProRule annotation1

GO - Molecular functioni

  • poly(A) RNA binding Source: UniProtKB
  • tRNA (cytosine-5-)-methyltransferase activity Source: UniProtKB
  • tRNA binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis, tRNA processing

Keywords - Ligandi

RNA-binding, S-adenosyl-L-methionine, tRNA-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS12087-MONOMER.
ZFISH:HS12087-MONOMER.
BRENDAi2.1.1.203. 2681.
ReactomeiR-HSA-6782315. tRNA modification in the nucleus and cytosol.
SIGNORiQ08J23.

Names & Taxonomyi

Protein namesi
Recommended name:
tRNA (cytosine(34)-C(5))-methyltransferase (EC:2.1.1.203)
Alternative name(s):
Myc-induced SUN domain-containing protein
Short name:
Misu
NOL1/NOP2/Sun domain family member 2
Substrate of AIM1/Aurora kinase B
tRNA (cytosine-5-)-methyltransferase
tRNA methyltransferase 4 homolog
Short name:
hTrm4
Gene namesi
Name:NSUN2
Synonyms:SAKI, TRM4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:25994. NSUN2.

Subcellular locationi

GO - Cellular componenti

  • chromatoid body Source: Ensembl
  • cytoplasm Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: HPA
  • spindle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal recessive 5 (MRT5)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
See also OMIM:611091
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068530679G → R in MRT5; impairs proper intracellular localization. 1 PublicationCorresponds to variant rs587776908dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi139S → A: Induces a constitutive association with NPM1. 1 Publication1
Mutagenesisi139S → E: Mimicks constitutive phosphorylation and abolishes methyltransferase activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi54888.
MalaCardsiNSUN2.
MIMi611091. phenotype.
OpenTargetsiENSG00000037474.
Orphaneti88616. Autosomal recessive non-syndromic intellectual disability.
235. Dubowitz syndrome.
PharmGKBiPA134953940.

Polymorphism and mutation databases

BioMutaiNSUN2.
DMDMi148887180.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002892231 – 767tRNA (cytosine(34)-C(5))-methyltransferaseAdd BLAST767

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei139Phosphoserine; by AURKB1 Publication1
Modified residuei456PhosphoserineCombined sources1
Modified residuei473PhosphoserineCombined sources1
Modified residuei586N6-acetyllysine; alternateBy similarity1
Modified residuei586N6-malonyllysine; alternate1 Publication1
Modified residuei593PhosphoserineCombined sources1
Cross-linki640Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei718PhosphothreonineBy similarity1
Modified residuei724PhosphoserineBy similarity1
Modified residuei743PhosphoserineCombined sources1
Modified residuei751PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-139 by AURKB during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ08J23.
MaxQBiQ08J23.
PaxDbiQ08J23.
PeptideAtlasiQ08J23.
PRIDEiQ08J23.

PTM databases

iPTMnetiQ08J23.
PhosphoSitePlusiQ08J23.
SwissPalmiQ08J23.

Expressioni

Tissue specificityi

Expressed in adult and fetal brain and in lymphoblastoid cells.1 Publication

Gene expression databases

BgeeiENSG00000037474.
CleanExiHS_NSUN2.
ExpressionAtlasiQ08J23. baseline and differential.
GenevisibleiQ08J23. HS.

Organism-specific databases

HPAiHPA037896.

Interactioni

Subunit structurei

Interacts with NPM1 and NCL during interphase; interaction is disrupted following phosphorylation at Ser-139.1 Publication

Protein-protein interaction databases

BioGridi120236. 82 interactors.
DIPiDIP-52456N.
IntActiQ08J23. 22 interactors.
MINTiMINT-4851220.
STRINGi9606.ENSP00000264670.

Structurei

3D structure databases

ProteinModelPortaliQ08J23.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni184 – 190S-adenosyl-L-methionine bindingPROSITE-ProRule annotation7

Sequence similaritiesi

Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2198. Eukaryota.
COG0144. LUCA.
GeneTreeiENSGT00660000095589.
HOGENOMiHOG000205147.
HOVERGENiHBG106711.
InParanoidiQ08J23.
KOiK15335.
OMAiTEVSDEH.
OrthoDBiEOG091G04FO.
PhylomeDBiQ08J23.
TreeFamiTF300702.

Family and domain databases

Gene3Di3.40.50.150. 2 hits.
InterProiIPR001678. MeTrfase_RsmB/NOP2.
IPR023267. RCMT.
IPR023270. RCMT_NCL1.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PfamiPF01189. Methyltr_RsmB-F. 1 hit.
[Graphical view]
PRINTSiPR02008. RCMTFAMILY.
PR02011. RCMTNCL1.
SUPFAMiSSF53335. SSF53335. 2 hits.
PROSITEiPS51686. SAM_MT_RSMB_NOP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q08J23-1) [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
MGRRSRGRRL QQQQRPEDAE DGAEGGGKRG EAGWEGGYPE IVKENKLFEH
60 70 80 90 100
YYQELKIVPE GEWGQFMDAL REPLPATLRI TGYKSHAKEI LHCLKNKYFK
110 120 130 140 150
ELEDLEVDGQ KVEVPQPLSW YPEELAWHTN LSRKILRKSP HLEKFHQFLV
160 170 180 190 200
SETESGNISR QEAVSMIPPL LLNVRPHHKI LDMCAAPGSK TTQLIEMLHA
210 220 230 240 250
DMNVPFPEGF VIANDVDNKR CYLLVHQAKR LSSPCIMVVN HDASSIPRLQ
260 270 280 290 300
IDVDGRKEIL FYDRILCDVP CSGDGTMRKN IDVWKKWTTL NSLQLHGLQL
310 320 330 340 350
RIATRGAEQL AEGGRMVYST CSLNPIEDEA VIASLLEKSE GALELADVSN
360 370 380 390 400
ELPGLKWMPG ITQWKVMTKD GQWFTDWDAV PHSRHTQIRP TMFPPKDPEK
410 420 430 440 450
LQAMHLERCL RILPHHQNTG GFFVAVLVKK SSMPWNKRQP KLQGKSAETR
460 470 480 490 500
ESTQLSPADL TEGKPTDPSK LESPSFTGTG DTEIAHATED LENNGSKKDG
510 520 530 540 550
VCGPPPSKKM KLFGFKEDPF VFIPEDDPLF PPIEKFYALD PSFPRMNLLT
560 570 580 590 600
RTTEGKKRQL YMVSKELRNV LLNNSEKMKV INTGIKVWCR NNSGEEFDCA
610 620 630 640 650
FRLAQEGIYT LYPFINSRII TVSMEDVKIL LTQENPFFRK LSSETYSQAK
660 670 680 690 700
DLAKGSIVLK YEPDSANPDA LQCPIVLCGW RGKASIRTFV PKNERLHYLR
710 720 730 740 750
MMGLEVLGEK KKEGVILTNE SAASTGQPDN DVTEGQRAGE PNSPDAEEAN
760
SPDVTAGCDP AGVHPPR
Length:767
Mass (Da):86,471
Last modified:May 29, 2007 - v2
Checksum:iFE4B34309978A8D2
GO
Isoform 2 (identifier: Q08J23-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-120: SHAKEILHCLKNKYFKELEDLEVDGQKVEVPQPLSW → R

Note: No experimental confirmation available.
Show »
Length:732
Mass (Da):82,393
Checksum:i3C092217D0A3A22B
GO
Isoform 3 (identifier: Q08J23-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-236: Missing.

Note: No experimental confirmation available.
Show »
Length:531
Mass (Da):59,384
Checksum:i69211E04631124B4
GO

Sequence cautioni

The sequence BAA91075 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB14762 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti316M → V in BAA91075 (PubMed:14702039).Curated1
Sequence conflicti327E → G in BAF83833 (PubMed:14702039).Curated1
Sequence conflicti484I → V in BAG51521 (PubMed:14702039).Curated1
Sequence conflicti594G → D in BAB14762 (PubMed:14702039).Curated1
Sequence conflicti605Q → R in BAF34150 (PubMed:17215513).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032604627V → I.Corresponds to variant rs2303708dbSNPEnsembl.1
Natural variantiVAR_068530679G → R in MRT5; impairs proper intracellular localization. 1 PublicationCorresponds to variant rs587776908dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0535981 – 236Missing in isoform 3. 1 PublicationAdd BLAST236
Alternative sequenceiVSP_04262185 – 120SHAKE…QPLSW → R in isoform 2. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB255451 mRNA. Translation: BAF34150.1.
AK000310 mRNA. Translation: BAA91075.1. Different initiation.
AK023994 mRNA. Translation: BAB14762.1. Different initiation.
AK055456 mRNA. Translation: BAG51521.1.
AK291144 mRNA. Translation: BAF83833.1.
AK298980 mRNA. Translation: BAG61074.1.
AC010366 Genomic DNA. No translation available.
AC027334 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08105.1.
CH471102 Genomic DNA. Translation: EAX08106.1.
BC001041 mRNA. Translation: AAH01041.3.
BC137083 mRNA. Translation: AAI37084.1.
CCDSiCCDS3869.1. [Q08J23-1]
CCDS54832.1. [Q08J23-2]
RefSeqiNP_001180384.1. NM_001193455.1. [Q08J23-2]
NP_060225.4. NM_017755.5. [Q08J23-1]
UniGeneiHs.481526.

Genome annotation databases

EnsembliENST00000264670; ENSP00000264670; ENSG00000037474. [Q08J23-1]
ENST00000506139; ENSP00000420957; ENSG00000037474. [Q08J23-2]
GeneIDi54888.
KEGGihsa:54888.
UCSCiuc003jdu.4. human. [Q08J23-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB255451 mRNA. Translation: BAF34150.1.
AK000310 mRNA. Translation: BAA91075.1. Different initiation.
AK023994 mRNA. Translation: BAB14762.1. Different initiation.
AK055456 mRNA. Translation: BAG51521.1.
AK291144 mRNA. Translation: BAF83833.1.
AK298980 mRNA. Translation: BAG61074.1.
AC010366 Genomic DNA. No translation available.
AC027334 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08105.1.
CH471102 Genomic DNA. Translation: EAX08106.1.
BC001041 mRNA. Translation: AAH01041.3.
BC137083 mRNA. Translation: AAI37084.1.
CCDSiCCDS3869.1. [Q08J23-1]
CCDS54832.1. [Q08J23-2]
RefSeqiNP_001180384.1. NM_001193455.1. [Q08J23-2]
NP_060225.4. NM_017755.5. [Q08J23-1]
UniGeneiHs.481526.

3D structure databases

ProteinModelPortaliQ08J23.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120236. 82 interactors.
DIPiDIP-52456N.
IntActiQ08J23. 22 interactors.
MINTiMINT-4851220.
STRINGi9606.ENSP00000264670.

PTM databases

iPTMnetiQ08J23.
PhosphoSitePlusiQ08J23.
SwissPalmiQ08J23.

Polymorphism and mutation databases

BioMutaiNSUN2.
DMDMi148887180.

Proteomic databases

EPDiQ08J23.
MaxQBiQ08J23.
PaxDbiQ08J23.
PeptideAtlasiQ08J23.
PRIDEiQ08J23.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264670; ENSP00000264670; ENSG00000037474. [Q08J23-1]
ENST00000506139; ENSP00000420957; ENSG00000037474. [Q08J23-2]
GeneIDi54888.
KEGGihsa:54888.
UCSCiuc003jdu.4. human. [Q08J23-1]

Organism-specific databases

CTDi54888.
DisGeNETi54888.
GeneCardsiNSUN2.
H-InvDBHIX0004733.
HGNCiHGNC:25994. NSUN2.
HPAiHPA037896.
MalaCardsiNSUN2.
MIMi610916. gene.
611091. phenotype.
neXtProtiNX_Q08J23.
OpenTargetsiENSG00000037474.
Orphaneti88616. Autosomal recessive non-syndromic intellectual disability.
235. Dubowitz syndrome.
PharmGKBiPA134953940.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2198. Eukaryota.
COG0144. LUCA.
GeneTreeiENSGT00660000095589.
HOGENOMiHOG000205147.
HOVERGENiHBG106711.
InParanoidiQ08J23.
KOiK15335.
OMAiTEVSDEH.
OrthoDBiEOG091G04FO.
PhylomeDBiQ08J23.
TreeFamiTF300702.

Enzyme and pathway databases

BioCyciMetaCyc:HS12087-MONOMER.
ZFISH:HS12087-MONOMER.
BRENDAi2.1.1.203. 2681.
ReactomeiR-HSA-6782315. tRNA modification in the nucleus and cytosol.
SIGNORiQ08J23.

Miscellaneous databases

ChiTaRSiNSUN2. human.
GeneWikiiNSUN2.
GenomeRNAii54888.
PROiQ08J23.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000037474.
CleanExiHS_NSUN2.
ExpressionAtlasiQ08J23. baseline and differential.
GenevisibleiQ08J23. HS.

Family and domain databases

Gene3Di3.40.50.150. 2 hits.
InterProiIPR001678. MeTrfase_RsmB/NOP2.
IPR023267. RCMT.
IPR023270. RCMT_NCL1.
IPR029063. SAM-dependent_MTases.
[Graphical view]
PfamiPF01189. Methyltr_RsmB-F. 1 hit.
[Graphical view]
PRINTSiPR02008. RCMTFAMILY.
PR02011. RCMTNCL1.
SUPFAMiSSF53335. SSF53335. 2 hits.
PROSITEiPS51686. SAM_MT_RSMB_NOP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNSUN2_HUMAN
AccessioniPrimary (citable) accession number: Q08J23
Secondary accession number(s): A8K529
, B2RNR4, B3KP09, B4DQW2, G3V1R4, Q9BVN4, Q9H858, Q9NXD9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: November 30, 2016
This is version 110 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.