tRNA (cytosine-5-)-methyltransferase NSUN2

Names and origin

Protein names

Recommended name:
    tRNA (cytosine-5-)-methyltransferase NSUN2
    EC=2.1.1.29
Alternative name(s):
    NOL1/NOP2/Sun domain family member 2
    tRNA (cytosine-5-)-methyltransferase
    tRNA methyltransferase 4 homolog
      Short name=hTrm4
    Substrate of AIM1/Aurora kinase B

Gene names

Name:	NSUN2
Synonyms:	SAKI, TRM4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	767 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	RNA methyltransferase that methylates tRNAs, and possibly RNA polymerase III transcripts. Methylates cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. Not able to modify tRNAs at positions 48 or 49. May act downstream of Myc to regulate epidermal cell growth and proliferation.
Catalytic activity	S-adenosyl-L-methionine + tRNA = S-adenosyl-L-homocysteine + tRNA containing 5-methylcytosine.
Subunit structure	Interacts with NPM1 and NCL during interphase; interaction is disrupted following phosphorylation at Ser-139.
Subcellular location	Nucleus › nucleolus. Cytoplasm. Note= Concentrated in the nucleolus during interphase and distributed in the perichromosome and cytoplasm during mitosis.
Post-translational modification	Phosphorylated at Ser-139 by Aurora-B/STK12 during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1.
Sequence similarities	Belongs to the methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.

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Ontologies

Keywords
Biological process	tRNA processing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	RNA-binding S-adenosyl-L-methionine tRNA-binding
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	tRNA methylation Ref.6 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Ref.6 Inferred from direct assay. Source: UniProtKB nucleolus Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	tRNA (cytosine-5-)-methyltransferase activity Ref.6 Inferred from direct assay. Source: UniProtKB tRNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 767

767

tRNA (cytosine-5-)-methyltransferase NSUN2

PRO_0000289223

Regions

Region

184 – 190

7

S-adenosyl-L-methionine binding By similarity

Sites

Active site

321

1

Nucleophile Potential

Binding site

215

1

S-adenosyl-L-methionine By similarity

Binding site

242

1

S-adenosyl-L-methionine By similarity

Binding site

268

1

S-adenosyl-L-methionine By similarity

Amino acid modifications

Modified residue

139

1

Phosphoserine; by STK12

Modified residue

456

1

Phosphoserine

Modified residue

461

1

Phosphothreonine

Modified residue

473

1

Phosphoserine

Modified residue

593

1

Phosphoserine

Modified residue

724

1

Phosphoserine By similarity

Modified residue

743

1

Phosphoserine

Modified residue

751

1

Phosphoserine

Natural variations

Natural variant

627

1

V → I: dbSNP rs2303708.

VAR_032604

Experimental info

Mutagenesis

139

1

S → A: Induces a constitutive association with NPM1

Mutagenesis

139

1

S → E: Mimicks constitutive phosphorylation and abolishes methyltransferase activity

Sequence conflict

316

1

M → V in BAA91075. Ref.3

Sequence conflict

594

1

G → D in BAB14762. Ref.3

Sequence conflict

605

1

Q → R in BAF34150. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

Q08J23-1 [UniParc].

Last modified May 29, 2007. Version 2.
Checksum: FE4B34309978A8D2
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FASTA

767

86,471

        10         20         30         40         50         60 
MGRRSRGRRL QQQQRPEDAE DGAEGGGKRG EAGWEGGYPE IVKENKLFEH YYQELKIVPE 

        70         80         90        100        110        120 
GEWGQFMDAL REPLPATLRI TGYKSHAKEI LHCLKNKYFK ELEDLEVDGQ KVEVPQPLSW 

       130        140        150        160        170        180 
YPEELAWHTN LSRKILRKSP HLEKFHQFLV SETESGNISR QEAVSMIPPL LLNVRPHHKI 

       190        200        210        220        230        240 
LDMCAAPGSK TTQLIEMLHA DMNVPFPEGF VIANDVDNKR CYLLVHQAKR LSSPCIMVVN 

       250        260        270        280        290        300 
HDASSIPRLQ IDVDGRKEIL FYDRILCDVP CSGDGTMRKN IDVWKKWTTL NSLQLHGLQL 

       310        320        330        340        350        360 
RIATRGAEQL AEGGRMVYST CSLNPIEDEA VIASLLEKSE GALELADVSN ELPGLKWMPG 

       370        380        390        400        410        420 
ITQWKVMTKD GQWFTDWDAV PHSRHTQIRP TMFPPKDPEK LQAMHLERCL RILPHHQNTG 

       430        440        450        460        470        480 
GFFVAVLVKK SSMPWNKRQP KLQGKSAETR ESTQLSPADL TEGKPTDPSK LESPSFTGTG 

       490        500        510        520        530        540 
DTEIAHATED LENNGSKKDG VCGPPPSKKM KLFGFKEDPF VFIPEDDPLF PPIEKFYALD 

       550        560        570        580        590        600 
PSFPRMNLLT RTTEGKKRQL YMVSKELRNV LLNNSEKMKV INTGIKVWCR NNSGEEFDCA 

       610        620        630        640        650        660 
FRLAQEGIYT LYPFINSRII TVSMEDVKIL LTQENPFFRK LSSETYSQAK DLAKGSIVLK 

       670        680        690        700        710        720 
YEPDSANPDA LQCPIVLCGW RGKASIRTFV PKNERLHYLR MMGLEVLGEK KKEGVILTNE 

       730        740        750        760 
SAASTGQPDN DVTEGQRAGE PNSPDAEEAN SPDVTAGCDP AGVHPPR

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Aurora-B regulates RNA methyltransferase NSUN2." Sakita-Suto S., Kanda A., Suzuki F., Sato S., Takata T., Tatsuka M. Mol. Biol. Cell 18:1107-1117(2007) [PubMed: 17215513] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-139, INTERACTION WITH NPM1 AND NCL, MUTAGENESIS OF SER-139.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 89-767. Tissue: Placenta.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 209-767.
[4]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-743 AND SER-751, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743 AND SER-751, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA)." Brzezicha B., Schmidt M., Makalowska I., Jarmolowski A., Pienkowska J., Szweykowska-Kulinska Z. Nucleic Acids Res. 34:6034-6043(2006) [PubMed: 17071714] [Abstract] Cited for: FUNCTION.
[7]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-461, MASS SPECTROMETRY.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743 AND SER-751, MASS SPECTROMETRY.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-473; SER-593; SER-743 AND SER-751, MASS SPECTROMETRY.

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Cross-references

Sequence databases
	AB255451 mRNA. Translation: BAF34150.1. BC001041 mRNA. Translation: AAH01041.3. AK000310 mRNA. Translation: BAA91075.1. Different initiation. AK023994 mRNA. Translation: BAB14762.1. Different initiation.
RefSeq	NP_060225.4.
UniGene	Hs.481526
3D structure databases
ModBase	Search...
Proteomic databases
PeptideAtlas	Q08J23.
Genome annotation databases
Ensembl	ENSG00000037474. Homo sapiens. [Contig view]
GeneID	54888.
KEGG	hsa:54888.
NMPDR	fig\|9606.3.peg.25032.
Organism-specific databases
HGNC	HGNC:25994. NSUN2.
MIM	610916. gene.
PharmGKB	PA134953940.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q08J23.
Gene expression databases
ArrayExpress	Q08J23.
CleanEx	HS_NSUN2.
Family and domain databases
InterPro	IPR001678. Fmu_NOL1/Nop2p. [Graphical view]
Pfam	PF01189. Nol1_Nop2_Fmu. 2 hits. [Graphical view]
PROSITE	PS01153. NOL1_NOP2_SUN. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	57879.
SOURCE	Search...

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Entry information

Entry name

NSUN2_HUMAN

Accession

Primary (citable) accession number: Q08J23
Secondary accession number(s): Q9BVN4, Q9H858, Q9NXD9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 29, 2007
Last sequence update:	May 29, 2007
Last modified:	November 25, 2008
This is version 23 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents