O43148 (MCES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
mRNA cap guanine-N7 methyltransferase
EC=2.1.1.56

Alternative name(s):
RG7MT1
mRNA (guanine-N(7)-)-methyltransferase
mRNA cap methyltransferase
Short name=hCMT1
Short name=hMet
Short name=hcm1p

Gene names

Name:	RNMT
Synonyms:	KIAA0398

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	476 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	mRNA-capping methyltransferase that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Binds RNA containing 5'-terminal GpppC. Ref.1 Ref.2 Ref.8 Ref.12
Catalytic activity	S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA.
Subunit structure	Interacts with importin alpha, leading to stimulate both RNA-binding and methyltransferase activity. Interaction with importin alpha and beta is required for its nuclear localization, importin beta dissociating in response to RanGTP, allowing RNMT-importin alpha to bind RNA substrates. Interacts with elongating form of polymerase II and RNGTT. Interacts with RAM/FAM103A1, the interaction significantly enhances RNA-binding and cap methyltransferase activity. Ref.2 Ref.9 Ref.12
Subcellular location	Nucleus Ref.9 Ref.10.
Tissue specificity	Widely expressed. Ref.1 Ref.2
Sequence similarities	Belongs to the methyltransferase superfamily. mRNA cap methyltransferase family.

Ontologies

Keywords
Biological process	mRNA capping mRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mRNA capping Inferred from mutant phenotype Ref.1. Source: UniProtKB transcription from RNA polymerase II promoter Traceable author statement. Source: Reactome viral reproduction Traceable author statement. Source: Reactome
Cellular component	nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Molecular function	RNA binding Inferred from mutant phenotype Ref.1. Source: UniProtKB mRNA (guanine-N7-)-methyltransferase activity Inferred from mutant phenotype Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O43148-1)

Also known as: hCMT1a;

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: O43148-2)

Also known as: hCMT1b;

The sequence of this isoform differs from the canonical sequence as follows:
     465-476: SIYLVFAFEKQQ → RLTVTIMREAWLSTVGPGRAPVAASSVKWGTPRPAMQFIL

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 476

476

mRNA cap guanine-N7 methyltransferase

PRO_0000248321

Regions

Region

176 – 177

2

mRNA cap binding By similarity

Motif

126 – 128

3

Nuclear localization signal

Sites

Binding site

180

1

S-adenosyl-L-methionine By similarity

Binding site

205

1

S-adenosyl-L-methionine; via carbonyl oxygen By similarity

Binding site

208

1

mRNA cap By similarity

Binding site

214

1

mRNA cap By similarity

Binding site

227

1

S-adenosyl-L-methionine By similarity

Binding site

239

1

mRNA cap Probable

Binding site

261

1

S-adenosyl-L-methionine By similarity

Binding site

284

1

S-adenosyl-L-methionine; via carbonyl oxygen By similarity

Binding site

288

1

mRNA cap By similarity

Binding site

370

1

mRNA cap By similarity

Binding site

467

1

mRNA cap By similarity

Amino acid modifications

Modified residue

24

1

Phosphoserine By similarity

Modified residue

28

1

Phosphoserine By similarity

Natural variations

Alternative sequence

465 – 476

12

SIYLV…FEKQQ → RLTVTIMREAWLSTVGPGRA PVAASSVKWGTPRPAMQFIL in isoform 2.

VSP_020241

Experimental info

Mutagenesis

80 – 83

4

KKRK → AAAA: Does not abolish nuclear localization. Abolishes nuclear localization; when associated with 103-AAAAA-107 and I-127. Ref.10

Mutagenesis

103 – 107

5

KKRKR → AAAAA: Does not abolish nuclear localization. Abolishes nuclear localization; when associated with 80-AAAA-83 and I-127. Ref.10

Mutagenesis

127

1

R → I: Does not abolish nuclear localization. Abolishes nuclear localization; when associated with 80-AAAA-83 and 103-AAAAA-107. Ref.10

Mutagenesis

203

1

D → A: Loss of activity. Ref.8

Mutagenesis

239

1

R → A: Loss of activity. Ref.8

Mutagenesis

289

1

Y → A: Loss of activity. Ref.8

Mutagenesis

291

1

F → A: Strongly impairs enzyme activity. Ref.8

Mutagenesis

354

1

F → A: Loss of activity. Ref.8

Sequence conflict

179

1

M → I in BAA82447. Ref.3

Secondary structure

1

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476

Helix Strand Turn

Details...

Helix

170 – 193

24

Beta strand

200 – 204

5

Turn

207 – 211

5

Helix

212 – 217

6

Beta strand

221 – 228

8

Helix

230 – 244

15

Beta strand

245 – 247

3

Beta strand

254 – 259

6

Turn

262 – 264

3

Turn

268 – 270

3

Beta strand

278 – 285

8

Helix

287 – 292

6

Helix

294 – 305

12

Beta strand

308 – 319

12

Helix

321 – 328

8

Beta strand

331 – 337

7

Beta strand

339 – 346

8

Beta strand

357 – 362

6

Beta strand

369 – 371

3

Helix

375 – 381

7

Helix

382 – 385

4

Beta strand

387 – 394

8

Helix

395 – 402

8

Helix

406 – 415

10

Beta strand

453 – 456

4

Helix

458 – 464

7

Beta strand

467 – 474

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (hCMT1a) [UniParc]. Last modified June 1, 1998. Version 1. Checksum: EC919BC41BD5E2B3	FASTA	476	54,844
	10 20 30 40 50 60 MANSAKAEEY EKMSLEQAKA SVNSETESSF NINENTTASG TGLSEKTSVC RQVDIARKRK 70 80 90 100 110 120 EFEDDLVKES SSCGKDTPSK KRKLDPEIVP EEKDCGDAEG NSKKRKRETE DVPKDKSSTG 130 140 150 160 170 180 DGTQNKRKIA LEDVPEKQKN LEEGHSSTVA AHYNELQEVG LEKRSQSRIF YLRNFNNWMK 190 200 210 220 230 240 SVLIGEFLEK VRQKKKRDIT VLDLGCGKGG DLLKWKKGRI NKLVCTDIAD VSVKQCQQRY 250 260 270 280 290 300 EDMKNRRDSE YIFSAEFITA DSSKELLIDK FRDPQMCFDI CSCQFVCHYS FESYEQADMM 310 320 330 340 350 360 LRNACERLSP GGYFIGTTPN SFELIRRLEA SETESFGNEI YTVKFQKKGD YPLFGCKYDF 370 380 390 400 410 420 NLEGVVDVPE FLVYFPLLNE MAKKYNMKLV YKKTFLEFYE EKIKNNENKM LLKRMQALEP 430 440 450 460 470 YPANESSKLV SEKVDDYEHA AKYMKNSQVR LPLGTLSKSE WEATSIYLVF AFEKQQ
	Isoform 2 (hCMT1b) [UniParc]. Checksum: 00F822E6867D6D6A	FASTA	504	57,725
	10 20 30 40 50 60 MANSAKAEEY EKMSLEQAKA SVNSETESSF NINENTTASG TGLSEKTSVC RQVDIARKRK 70 80 90 100 110 120 EFEDDLVKES SSCGKDTPSK KRKLDPEIVP EEKDCGDAEG NSKKRKRETE DVPKDKSSTG 130 140 150 160 170 180 DGTQNKRKIA LEDVPEKQKN LEEGHSSTVA AHYNELQEVG LEKRSQSRIF YLRNFNNWMK 190 200 210 220 230 240 SVLIGEFLEK VRQKKKRDIT VLDLGCGKGG DLLKWKKGRI NKLVCTDIAD VSVKQCQQRY 250 260 270 280 290 300 EDMKNRRDSE YIFSAEFITA DSSKELLIDK FRDPQMCFDI CSCQFVCHYS FESYEQADMM 310 320 330 340 350 360 LRNACERLSP GGYFIGTTPN SFELIRRLEA SETESFGNEI YTVKFQKKGD YPLFGCKYDF 370 380 390 400 410 420 NLEGVVDVPE FLVYFPLLNE MAKKYNMKLV YKKTFLEFYE EKIKNNENKM LLKRMQALEP 430 440 450 460 470 480 YPANESSKLV SEKVDDYEHA AKYMKNSQVR LPLGTLSKSE WEATRLTVTI MREAWLSTVG 490 500 PGRAPVAASS VKWGTPRPAM QFIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of three human cDNAs encoding mRNA (guanine-7-)methyltransferase, an mRNA cap methylase." Tsukamoto T., Shibagaki Y., Niikura Y., Kiyohisa M. Biochem. Biophys. Res. Commun. 251:27-34(1998) [PubMed: 9790902] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY.
[2]	"Recombinant human mRNA cap methyltransferase binds capping enzyme/RNA polymerase IIo complexes." Pillutla R.C., Yue Z., Maldonado E., Shatkin A.J. J. Biol. Chem. 273:21443-21446(1998) [PubMed: 9705270] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH POLYMERASE II AND RNGTT.
[3]	"The Candida albicans gene for mRNA 5'-cap methyltransferase: identification of the additional residues essential for catalysis." Yamada-Okabe T., Mio T., Kashima Y., Matsui M., Arisawa M., Yamada-Okabe H. Microbiology 145:3023-3033(1999) [PubMed: 10589710] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed: 9455477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[5]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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 1). Tissue: Ovary.
[8]	"Characterization of human, Schizosaccharomyces pombe, and Candida albicans mRNA cap methyltransferases and complete replacement of the yeast capping apparatus by mammalian enzymes." Saha N., Schwer B., Shuman S. J. Biol. Chem. 274:16553-16562(1999) [PubMed: 10347220] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-203; ARG-239; TYR-289; PHE-291 AND PHE-354.
[9]	"Cap methyltransferase selective binding and methylation of GpppG-RNA are stimulated by importin-alpha." Wen Y., Shatkin A.J. Genes Dev. 14:2944-2949(2000) [PubMed: 11114884] [Abstract] Cited for: SUBCELLULAR LOCATION, RNA-BINDING, INTERACTION WITH IMPORTIN ALPHA.
[10]	"Human mRNA cap methyltransferase: alternative nuclear localization signal motifs ensure nuclear localization required for viability." Shafer B., Chu C., Shatkin A.J. Mol. Cell. Biol. 25:2644-2649(2005) [PubMed: 15767670] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 80-LYS--LYS-83; 103-LYS--ARG-107 AND ARG-127.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"RAM/Fam103a1 is required for mRNA cap methylation." Gonatopoulos-Pournatzis T., Dunn S., Bounds R., Cowling V.H. Mol. Cell 44:585-596(2011) [PubMed: 22099306] [Abstract] Cited for: FUNCTION, SUBUNIT, INTERACTION WITH RAM/FAM103A1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB022604 mRNA. Translation: BAA74464.1.
AB022605 mRNA. Translation: BAA74463.1.
AF067791 mRNA. Translation: AAC63269.1.
AB020966 mRNA. Translation: BAA82447.1.
AB007858 mRNA. Translation: BAA23694.1.
EF445026 Genomic DNA. Translation: ACA06068.1.
CH471113 Genomic DNA. Translation: EAX01505.1.
CH471113 Genomic DNA. Translation: EAX01506.1.
BC036798 mRNA. Translation: AAH36798.1.

IPI

IPI00410657.
IPI00747403.

RefSeq

NP_003790.1. NM_003799.1.

UniGene

Hs.592347.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BGV	X-ray	2.30	A/B/C/D	165-476	[»]
3EPP	X-ray	2.41	A/B	165-476	[»]

ProteinModelPortal

O43148.

SMR

O43148. Positions 169-476.

ModBase

Search...

Protein-protein interaction databases

IntAct

O43148. 1 interaction.

STRING

O43148.

PTM databases

PhosphoSite

O43148.

Proteomic databases

PRIDE

O43148.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000262173; ENSP00000262173; ENSG00000101654.
ENST00000383314; ENSP00000372804; ENSG00000101654.

GeneID

8731.

KEGG

hsa:8731.

UCSC

uc002ksk.1. human.
uc010dlk.1. human.

Organism-specific databases

CTD

8731.

GeneCards

GC18P013716.

H-InvDB

HIX0023009.

HGNC

HGNC:10075. RNMT.

HPA

HPA039409.

MIM

603514. gene.

neXtProt

NX_O43148.

PharmGKB

PA34448.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17386.

HOVERGEN

HBG081963.

InParanoid

O43148.

OMA

FMRNFNN.

OrthoDB

EOG4FXR80.

PhylomeDB

O43148.

Enzyme and pathway databases

Reactome

REACT_1675. mRNA Processing.
REACT_1788. Transcription.
REACT_6185. HIV Infection.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

O43148.

Bgee

O43148.

CleanEx

HS_RNMT.

Genevestigator

O43148.

GermOnline

ENSG00000101654. Homo sapiens.

Family and domain databases

InterPro

IPR016899. mRNA_G-N7_MeTrfase.
IPR004971. Pox_MCEL.
[Graphical view]

KO

K00565.

Pfam

PF03291. Pox_MCEL. 1 hit.
[Graphical view]

PIRSF

PIRSF028762. ABD1. 1 hit.

ProtoNet

Search...

Other

NextBio

32753.

SOURCE

Search...

Entry information

Entry name

MCES_HUMAN

Accession

Primary (citable) accession number: O43148
Secondary accession number(s): B0YJ90 , D3DUJ5, O94996, Q9UIJ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	June 1, 1998
Last modified:	January 25, 2012
This is version 83 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.