Reviewed, UniProtKB/Swiss-Prot O14717 (TRDMT_HUMAN)

Names and origin

Protein names

Recommended name:
    tRNA (cytosine-5-)-methyltransferase
    EC=2.1.1.29
Alternative name(s):
    DNA (cytosine-5)-methyltransferase-like protein 2
      Short name=Dnmt2
    DNA methyltransferase homolog HsaIIP
      Short name=DNA MTase homolog HsaIIP
      Short name=M.HsaIIP
    PuMet

Gene names

Name:	TRDMT1
Synonyms:	DNMT2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	391 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp). Ref.7
Catalytic activity	S-adenosyl-L-methionine + tRNA = S-adenosyl-L-homocysteine + tRNA containing 5-methylcytosine.
Subcellular location	Nucleus Probable.
Tissue specificity	Ubiquitous. Higher expression in testis, ovary and thymus and at much lower levels in spleen, prostate, colon, small intestine, and peripheral blood leukocytes.
Sequence similarities	Belongs to the C5-methyltransferase family.

Ontologies

Keywords
Biological process	tRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	RNA-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA methylation Inferred from electronic annotation. Source: InterPro tRNA processing Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA (cytosine-5-)-methyltransferase activity Ref.1 Traceable author statement. Source: ProtInc DNA binding Inferred from electronic annotation. Source: InterPro RNA binding Inferred from electronic annotation. Source: UniProtKB-KW tRNA (cytosine-5-)-methyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform A (identifier: O14717-1)

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.

Isoform B (identifier: O14717-2)

The sequence of this isoform differs from the canonical sequence as follows:
     84-107: Missing.

Isoform C (identifier: O14717-3)

The sequence of this isoform differs from the canonical sequence as follows:
     84-129: Missing.

Isoform D (identifier: O14717-4)

The sequence of this isoform differs from the canonical sequence as follows:
     59-63: GITLE → DWPAG
     64-391: Missing.

Isoform E (identifier: O14717-5)

The sequence of this isoform differs from the canonical sequence as follows:
     59-71: GITLEEFDRLSFD → ITKITKVYSFGKC
     72-391: Missing.

Isoform F (identifier: O14717-6)

The sequence of this isoform differs from the canonical sequence as follows:
     59-107: GITLEEFDRL...SFLHILDILP → RPLDTNNRKL...SVRAITLSSP
     108-391: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 391

391

tRNA (cytosine-5-)-methyltransferase

PRO_0000088040

Sites

Active site

79

1

By similarity

Natural variations

Alternative sequence

59 – 107

49

GITLE…LDILP → RPLDTNNRKLWLSVPRVYII SNLSWHSKFKATIFSYCKAS VRAITLSSP in isoform F.

VSP_005634

Alternative sequence

59 – 71

13

GITLE…RLSFD → ITKITKVYSFGKC in isoform E.

VSP_005632

Alternative sequence

59 – 63

5

GITLE → DWPAG in isoform D.

VSP_005630

Alternative sequence

64 – 391

328

Missing in isoform D.

VSP_005631

Alternative sequence

72 – 391

320

Missing in isoform E.

VSP_005633

Alternative sequence

84 – 129

46

Missing in isoform C.

VSP_005629

Alternative sequence

84 – 107

24

Missing in isoform B.

VSP_005628

Alternative sequence

108 – 391

284

Missing in isoform F.

VSP_005635

Natural variant

101

1

H → Y: dbSNP rs11254413. Ref.5

VAR_051961

Experimental info

Sequence conflict

148

1

L → I in AAC39764. Ref.3

Secondary structure

1

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391

Helix Strand Turn

Details...

Beta strand

4 – 9

6

Helix

15 – 23

9

Beta strand

26 – 33

8

Helix

37 – 46

10

Helix

57 – 59

3

Helix

62 – 68

7

Beta strand

71 – 75

5

Helix

98 – 105

8

Helix

106 – 108

3

Beta strand

114 – 121

8

Helix

124 – 126

3

Helix

128 – 139

12

Beta strand

142 – 149

8

Helix

151 – 154

4

Beta strand

162 – 172

11

Beta strand

182 – 185

4

Helix

253 – 256

4

Helix

263 – 266

4

Helix

270 – 276

7

Helix

277 – 279

3

Turn

295 – 299

5

Beta strand

307 – 309

3

Helix

316 – 321

6

Turn

322 – 325

4

Helix

328 – 336

9

Helix

345 – 351

7

Helix

366 – 375

10

Helix

379 – 390

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified January 1, 1998. Version 1. Checksum: BCA549E4EB2E6950	FASTA	391	44,597
	10 20 30 40 50 60 MEPLRVLELY SGVGGMHHAL RESCIPAQVV AAIDVNTVAN EVYKYNFPHT QLLAKTIEGI 70 80 90 100 110 120 TLEEFDRLSF DMILMSPPCQ PFTRIGRQGD MTDSRTNSFL HILDILPRLQ KLPKYILLEN 130 140 150 160 170 180 VKGFEVSSTR DLLIQTIENC GFQYQEFLLS PTSLGIPNSR LRYFLIAKLQ SEPLPFQAPG 190 200 210 220 230 240 QVLMEFPKIE SVHPQKYAMD VENKIQEKNV EPNISFDGSI QCSGKDAILF KLETAEEIHR 250 260 270 280 290 300 KNQQDSDLSV KMLKDFLEDD TDVNQYLLPP KSLLRYALLL DIVQPTCRRS VCFTKGYGSY 310 320 330 340 350 360 IEGTGSVLQT AEDVQVENIY KSLTNLSQEE QITKLLILKL RYFTPKEIAN LLGFPPEFGF 370 380 390 PEKITVKQRY RLLGNSLNVH VVAKLIKILY E
	Isoform B. Checksum: 3801D5651DBC2614	FASTA	367	41,858
	10 20 30 40 50 60 MEPLRVLELY SGVGGMHHAL RESCIPAQVV AAIDVNTVAN EVYKYNFPHT QLLAKTIEGI 70 80 90 100 110 120 TLEEFDRLSF DMILMSPPCQ PFTRLQKLPK YILLENVKGF EVSSTRDLLI QTIENCGFQY 130 140 150 160 170 180 QEFLLSPTSL GIPNSRLRYF LIAKLQSEPL PFQAPGQVLM EFPKIESVHP QKYAMDVENK 190 200 210 220 230 240 IQEKNVEPNI SFDGSIQCSG KDAILFKLET AEEIHRKNQQ DSDLSVKMLK DFLEDDTDVN 250 260 270 280 290 300 QYLLPPKSLL RYALLLDIVQ PTCRRSVCFT KGYGSYIEGT GSVLQTAEDV QVENIYKSLT 310 320 330 340 350 360 NLSQEEQITK LLILKLRYFT PKEIANLLGF PPEFGFPEKI TVKQRYRLLG NSLNVHVVAK LIKILYE
	Isoform C. Checksum: 65939D1BE01D958B	FASTA	345	39,313
	10 20 30 40 50 60 MEPLRVLELY SGVGGMHHAL RESCIPAQVV AAIDVNTVAN EVYKYNFPHT QLLAKTIEGI 70 80 90 100 110 120 TLEEFDRLSF DMILMSPPCQ PFTRDLLIQT IENCGFQYQE FLLSPTSLGI PNSRLRYFLI 130 140 150 160 170 180 AKLQSEPLPF QAPGQVLMEF PKIESVHPQK YAMDVENKIQ EKNVEPNISF DGSIQCSGKD 190 200 210 220 230 240 AILFKLETAE EIHRKNQQDS DLSVKMLKDF LEDDTDVNQY LLPPKSLLRY ALLLDIVQPT 250 260 270 280 290 300 CRRSVCFTKG YGSYIEGTGS VLQTAEDVQV ENIYKSLTNL SQEEQITKLL ILKLRYFTPK 310 320 330 340 EIANLLGFPP EFGFPEKITV KQRYRLLGNS LNVHVVAKLI KILYE
	Isoform D. Checksum: 3DBEA06674461233	FASTA	63	6,965
	10 20 30 40 50 60 MEPLRVLELY SGVGGMHHAL RESCIPAQVV AAIDVNTVAN EVYKYNFPHT QLLAKTIEDW PAG
	Isoform E. Checksum: 862BC392F37BFA8C	FASTA	71	7,908
	10 20 30 40 50 60 MEPLRVLELY SGVGGMHHAL RESCIPAQVV AAIDVNTVAN EVYKYNFPHT QLLAKTIEIT 70 KITKVYSFGK C
	Isoform F. Checksum: BDD5DD4DC6D6BD3E	FASTA	107	12,087
	10 20 30 40 50 60 MEPLRVLELY SGVGGMHHAL RESCIPAQVV AAIDVNTVAN EVYKYNFPHT QLLAKTIERP 70 80 90 100 LDTNNRKLWL SVPRVYIISN LSWHSKFKAT IFSYCKASVR AITLSSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast." Yoder J.A., Bestor T.H. Hum. Mol. Genet. 7:279-284(1998) [PubMed: 9425235] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[2]	"Cloning and analysis of a novel human putative DNA methyltransferase." Van den Wyngaert I., Sprengel J., Kass S.U., Luyten W.H.M.L. FEBS Lett. 426:283-289(1998) [PubMed: 9599025] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[3]	"Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells." Okano M., Xie S., Li E. Nucleic Acids Res. 26:2536-2540(1998) [PubMed: 9592134] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Tissue: Heart.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM A), VARIANT TYR-101. Tissue: Uterus.
[6]	"Five novel alternatively spliced transcripts of DNA (cytosine-5) methyltransferase 2 in human peripheral blood leukocytes." Franchina M., Hooper J., Kay P.H. Int. J. Biochem. Cell Biol. 33:1104-1115(2001) [PubMed: 11551826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-179 (ISOFORMS A; B; C; D; E AND F). Tissue: Peripheral blood leukocyte.
[7]	"Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2." Goll M.G., Kirpekar F., Maggert K.A., Yoder J.A., Hsieh C.L., Zhang X., Golic K.G., Jacobsen S.E., Bestor T.H. Science 311:395-398(2006) [PubMed: 16424344] [Abstract] Cited for: FUNCTION.
[8]	"Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA." Dong A., Yoder J.A., Zhang X., Zhou L., Bestor T.H., Cheng X. Nucleic Acids Res. 29:439-448(2001) [PubMed: 11139614] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF012128 mRNA. Translation: AAC51939.1.
AJ223333 mRNA. Translation: CAA11272.1.
AF045888 mRNA. Translation: AAC39764.1.
AL133415, AC067747 Genomic DNA. Translation: CAB87964.1.
BC047733 mRNA. Translation: AAH47733.1.
AF329940 mRNA. Translation: AAK68034.1.
AF329941 mRNA. Translation: AAK68035.1.
AF329942 mRNA. Translation: AAK68036.1.
AF329943 mRNA. Translation: AAK68037.1.
AF329944 mRNA. Translation: AAK68033.1.

IPI

IPI00034003.
IPI00219905.
IPI00219906.
IPI00219907.
IPI00219908.
IPI00221269.

RefSeq

NP_004403.1.
NP_788270.1.
NP_788271.1.

UniGene

Hs.351665

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G55	X-ray	1.80	A	2-391	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O14717. 15 interactions.

Proteomic databases

PRIDE

O14717.

Genome annotation databases

Ensembl

ENSG00000107614. Homo sapiens. [Contig view]

GeneID

1787.

KEGG

hsa:1787.

Organism-specific databases

GeneCards

GC10M017225.

H-InvDB

HIX0021612.

HGNC

HGNC:2977. TRDMT1.

HPA

CAB009468.

MIM

602478. gene.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O14717.

OMA

O14717. EIANLHG.

Enzyme and pathway databases

BRENDA

2.1.1.29. 247.

Gene expression databases

ArrayExpress

O14717.

Bgee

O14717.

CleanEx

HS_TRDMT1.

GermOnline

ENSG00000107614. Homo sapiens.

Family and domain databases

InterPro

IPR001525. C5_DNA_meth.
IPR018117. C5_DNA_meth_AS.
[Graphical view]

PANTHER

PTHR10629. C5_DNA_meth. 1 hit.

Pfam

PF00145. DNA_methylase. 2 hits.
[Graphical view]

PRINTS

PR00105. C5METTRFRASE.

TIGRFAMs

TIGR00675. dcm. 1 hit.

PROSITE

PS00094. C5_MTASE_1. False negative.
PS00095. C5_MTASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

7271.

SOURCE

Search...

Entry information

Entry name

TRDMT_HUMAN

Accession

Primary (citable) accession number: O14717
Secondary accession number(s): O43669, Q86WW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	January 1, 1998
Last modified:	June 16, 2009
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)