Q9UBP6 (TRMB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
tRNA (guanine-N(7)-)-methyltransferase
EC=2.1.1.33

Alternative name(s):
Methyltransferase-like protein 1
tRNA (guanine(46)-N(7))-methyltransferase
tRNA(m7G46)-methyltransferase

Gene names

Name:	METTL1
Synonyms:	C12orf1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	276 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. Ref.6
Catalytic activity	S-adenosyl-L-methionine + guanine46 in tRNA = S-adenosyl-L-homocysteine + N(7)-methylguanine46 in tRNA.
Pathway	tRNA modification; N(7)-methylguanine-tRNA biosynthesis.
Subunit structure	Forms a complex with WDR4.
Subcellular location	Nucleus Ref.7.
Tissue specificity	Ubiquitous. Ref.1
Post-translational modification	Phosphorylation at Ser-27 inactivates its catalytic activity but does not affect the interaction with WDR4.
Sequence similarities	Belongs to the methyltransferase superfamily. TrmB family.
Sequence caution	The sequence CAA65470.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	tRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding S-adenosyl-L-methionine tRNA-binding
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	tRNA (guanine-N7-)-methyltransferase activity Inferred from direct assay Ref.7. Source: UniProtKB tRNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UBP6-1)

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 2 (identifier: Q9UBP6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     92-155: VELSPLFPDT...PNFFYKGQLT → ADKDVLPLPR...VHSFRRAPTV
     156-276: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 276

276

tRNA (guanine-N(7)-)-methyltransferase

PRO_0000171431

Regions

Region

107 – 108

2

S-adenosyl-L-methionine binding

Region

140 – 141

2

S-adenosyl-L-methionine binding

Region

238 – 240

3

S-adenosyl-L-methionine binding

Sites

Active site

163

1

By similarity

Binding site

84

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

160

1

S-adenosyl-L-methionine; via carbonyl oxygen

Amino acid modifications

Modified residue

27

1

Phosphoserine; by PKB and RPS6KA3 Ref.7

Natural variations

Alternative sequence

92 – 155

64

VELSP…KGQLT → ADKDVLPLPRPTFQADKAQV ANHQSHPASRICLRAKSWGA GVYHNRCAGATRLDVHSFRR APTV in isoform 2.

VSP_044671

Alternative sequence

156 – 276

121

Missing in isoform 2.

VSP_044672

Experimental info

Mutagenesis

27

1

S → A: Able to complement a trm8-delta mutant yeast. Ref.7

Mutagenesis

27

1

S → D or E: Abolishes ability to complement a trm8-delta mutant yeast. Ref.7

Sequence conflict

18

1

K → R in BAD96922. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

276

Helix Strand Turn

Details...

Helix

41 – 43

3

Turn

47 – 49

3

Beta strand

78 – 83

6

Helix

89 – 94

6

Helix

95 – 97

3

Beta strand

101 – 108

8

Helix

110 – 125

16

Beta strand

134 – 138

5

Turn

141 – 143

3

Helix

145 – 148

4

Beta strand

154 – 161

8

Helix

178 – 187

10

Beta strand

188 – 199

12

Helix

201 – 212

12

Beta strand

217 – 220

4

Helix

222 – 225

4

Helix

231 – 233

3

Turn

234 – 236

3

Helix

239 – 246

8

Beta strand

252 – 258

7

Turn

262 – 264

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 715AE85A18632892	FASTA	276	31,471
	10 20 30 40 50 60 MAAETRNVAG AEAPPPQKRY YRQRAHSNPM ADHTLRYPVK PEEMDWSELY PEFFAPLTQN 70 80 90 100 110 120 QSHDDPKDKK EKRAQAQVEF ADIGCGYGGL LVELSPLFPD TLILGLEIRV KVSDYVQDRI 130 140 150 160 170 180 RALRAAPAGG FQNIACLRSN AMKHLPNFFY KGQLTKMFFL FPDPHFKRTK HKWRIISPTL 190 200 210 220 230 240 LAEYAYVLRV GGLVYTITDV LELHDWMCTH FEEHPLFERV PLEDLSEDPV VGHLGTSTEE 250 260 270 GKKVLRNGGK NFPAIFRRIQ DPVLQAVTSQ TSLPGH
	Isoform 2 [UniParc]. Checksum: CFC2A730BA85E8D4	FASTA	155	17,423
	10 20 30 40 50 60 MAAETRNVAG AEAPPPQKRY YRQRAHSNPM ADHTLRYPVK PEEMDWSELY PEFFAPLTQN 70 80 90 100 110 120 QSHDDPKDKK EKRAQAQVEF ADIGCGYGGL LADKDVLPLP RPTFQADKAQ VANHQSHPAS 130 140 150 RICLRAKSWG AGVYHNRCAG ATRLDVHSFR RAPTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular analysis of METTL1, a novel human methyltransferase-like gene with a high degree of phylogenetic conservation." Bahr A., Hankeln T., Fiedler T., Hegemann J., Schmidt E.R. Genomics 57:424-428(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[2]	"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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Kidney proximal tubule.
[4]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA." Alexandrov A., Martzen M.R., Phizicky E.M. RNA 8:1253-1266(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH WDR4.
[7]	"The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells." Cartlidge R.A., Knebel A., Peggie M., Alexandrov A., Phizicky E.M., Cohen P. EMBO J. 24:1696-1705(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH WDR4, PHOSPHORYLATION AT SER-27, MUTAGENESIS OF SER-27.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Crystal structure of human methyltransferase-like protein 1." Structural genomics consortium (SGC) Submitted (APR-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 32-265 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y18643 mRNA. Translation: CAA77239.1.
Y18642 Genomic DNA. Translation: CAA77238.1.
X96698 mRNA. Translation: CAA65470.1. Different initiation.
AK314851 mRNA. Translation: BAG37368.1.
AK223202 mRNA. Translation: BAD96922.1.
AC025165 Genomic DNA. No translation available.
BC000550 mRNA. Translation: AAH00550.1.

IPI

IPI00290184.
IPI00853470.

RefSeq

NP_005362.3. NM_005371.5.
NP_075422.3. NM_023033.3.

UniGene

Hs.42957.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3CKK	X-ray	1.55	A	32-265	[»]

ProteinModelPortal

Q9UBP6.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UBP6. 1 interaction.

STRING

9606.ENSP00000314441.

PTM databases

PhosphoSite

Q9UBP6.

Polymorphism databases

DMDM

32171926.

Proteomic databases

PaxDb

Q9UBP6.

PRIDE

Q9UBP6.

Protocols and materials databases

DNASU

4234.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000257848; ENSP00000257848; ENSG00000037897.
ENST00000324871; ENSP00000314441; ENSG00000037897.

GeneID

4234.

KEGG

hsa:4234.

UCSC

uc010ssd.2. human.

Organism-specific databases

CTD

4234.

GeneCards

GC12M058163.

HGNC

HGNC:7030. METTL1.

HPA

HPA020914.

MIM

604466. gene.

neXtProt

NX_Q9UBP6.

PharmGKB

PA30766.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0220.

HOGENOM

HOG000260965.

HOVERGEN

HBG044569.

InParanoid

Q9UBP6.

KO

K03439.

OMA

RAHSNPI.

OrthoDB

EOG4FJ89F.

PhylomeDB

Q9UBP6.

Enzyme and pathway databases

UniPathway

UPA00989.

Gene expression databases

ArrayExpress

Q9UBP6.

Bgee

Q9UBP6.

CleanEx

HS_METTL1.

Genevestigator

Q9UBP6.

GermOnline

ENSG00000037897. Homo sapiens.

Family and domain databases

InterPro

IPR003358. tRNA_(Gua-N-7)_MeTrfase.
IPR025763. tRNA_(Gua-N-7)_MeTrfase_euk.
[Graphical view]

Pfam

PF02390. Methyltransf_4. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00091. TIGR00091. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UBP6.

GenomeRNAi

4234.

NextBio

16693.

SOURCE

Search...

Entry information

Entry name

TRMB_HUMAN

Accession

Primary (citable) accession number: Q9UBP6
Secondary accession number(s): B2RBX1 , H7BXF2, Q14105, Q53FS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2003
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.