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Protein

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

Gene

NSUN2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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

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

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, RNA-binding, Transferase, tRNA-binding
Biological processCell cycle, Cell division, Mitosis, tRNA processing
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciMetaCyc: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

EuPathDBiHostDB:ENSG00000037474.14
HGNCiHGNC:25994 NSUN2
MIMi610916 gene
neXtProtiNX_Q08J23

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

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 dbSNP:rs587776908EnsemblClinVar.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
Cross-linki46Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei139Phosphoserine; by AURKB1 Publication1
Modified residuei456PhosphoserineCombined sources1
Cross-linki464Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki470Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei473PhosphoserineCombined sources1
Cross-linki511Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki516Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei586N6-acetyllysine; alternateBy similarity1
Modified residuei586N6-malonyllysine; alternate1 Publication1
Cross-linki586Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei593PhosphoserineCombined sources1
Cross-linki640Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki654Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki660Glycyl 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
ProteomicsDBi58697
58698 [Q08J23-2]

PTM databases

GlyConnecti1859
iPTMnetiQ08J23
PhosphoSitePlusiQ08J23
SwissPalmiQ08J23

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000037474 Expressed in 201 organ(s), highest expression level in left lobe of thyroid gland
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, 89 interactors
DIPiDIP-52456N
IntActiQ08J23, 33 interactors
MINTiQ08J23
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
OMAiTFVRCEN
OrthoDBiEOG091G04FO
PhylomeDBiQ08J23
TreeFamiTF300702

Family and domain databases

InterProiView protein in InterPro
IPR001678 MeTrfase_RsmB/NOP2
IPR023267 RCMT
IPR023270 RCMT_NCL1
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF01189 Methyltr_RsmB-F, 1 hit
PRINTSiPR02008 RCMTFAMILY
PR02011 RCMTNCL1
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51686 SAM_MT_RSMB_NOP, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

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

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140T9Y7A0A140T9Y7_HUMAN
tRNA (cytosine(34)-C(5))-methyltran...
NSUN2
202Annotation score:
A0A140T9Z1A0A140T9Z1_HUMAN
tRNA (cytosine(34)-C(5))-methyltran...
NSUN2
102Annotation score:

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 dbSNP:rs2303708EnsemblClinVar.1
Natural variantiVAR_068530679G → R in MRT5; impairs proper intracellular localization. 1 PublicationCorresponds to variant dbSNP:rs587776908EnsemblClinVar.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

Similar proteinsi

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, 89 interactors
DIPiDIP-52456N
IntActiQ08J23, 33 interactors
MINTiQ08J23
STRINGi9606.ENSP00000264670

PTM databases

GlyConnecti1859
iPTMnetiQ08J23
PhosphoSitePlusiQ08J23
SwissPalmiQ08J23

Polymorphism and mutation databases

BioMutaiNSUN2
DMDMi148887180

Proteomic databases

EPDiQ08J23
MaxQBiQ08J23
PaxDbiQ08J23
PeptideAtlasiQ08J23
PRIDEiQ08J23
ProteomicsDBi58697
58698 [Q08J23-2]

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
EuPathDBiHostDB:ENSG00000037474.14
GeneCardsiNSUN2
H-InvDBiHIX0004733
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
OMAiTFVRCEN
OrthoDBiEOG091G04FO
PhylomeDBiQ08J23
TreeFamiTF300702

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiNSUN2 human
GeneWikiiNSUN2
GenomeRNAii54888
PROiPR:Q08J23
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000037474 Expressed in 201 organ(s), highest expression level in left lobe of thyroid gland
CleanExiHS_NSUN2
ExpressionAtlasiQ08J23 baseline and differential
GenevisibleiQ08J23 HS

Family and domain databases

InterProiView protein in InterPro
IPR001678 MeTrfase_RsmB/NOP2
IPR023267 RCMT
IPR023270 RCMT_NCL1
IPR029063 SAM-dependent_MTases
PfamiView protein in Pfam
PF01189 Methyltr_RsmB-F, 1 hit
PRINTSiPR02008 RCMTFAMILY
PR02011 RCMTNCL1
SUPFAMiSSF53335 SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51686 SAM_MT_RSMB_NOP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNSUN2_HUMAN
AccessioniPrimary (citable) accession number: Q08J23
Secondary accession number(s): A8K529
, B2RNR4, B3KP09, B4DQW2, G3V1R4, Q9BVN4, Q9H858, Q9NXD9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: November 7, 2018
This is version 126 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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