Reviewed, UniProtKB/Swiss-Prot O55236 (MCE1_MOUSE)

Names and origin

Protein names

Recommended name:
    mRNA-capping enzyme
Alternative name(s):
    HCE
    MCE1
Including the following 2 domains:
    1- Recommended name:
            Polynucleotide 5'-triphosphatase
                Short name=mRNA 5'-triphosphatase
                Short name=TPase
              EC=3.1.3.33
    2- Recommended name:
            mRNA guanylyltransferase
              EC=2.7.7.50
        Alternative name(s):
            GTP--RNA guanylyltransferase
              Short name=GTase

Gene names

Name:	Rngtt
Synonyms:	Cap1a

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	597 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Bifunctional mRNA-capping enzyme exhibiting RNA 5'-triphosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part. Catalyzes the first two steps of cap formation: by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and by transferring the gmp moiety of GTP to the 5'-diphosphate terminus.
Catalytic activity	A 5'-phosphopolynucleotide + H2O = a polynucleotide + phosphate. GTP + (5')pp-Pur-mRNA = diphosphate + G(5')ppp-Pur-mRNA.
Enzyme regulation	RNA triphosphatase activity is inhibited by vanadate, iodoacetate and magnesium.
Subunit structure	Interacts with SUPT5H and RNMT By similarity.
Subcellular location	Nucleus.
Miscellaneous	Binds to the elongating phosphorylated form of RNA polymerase II. Can interact indirectly by binding to pol II C-terminal domain and directly by RNA binding. The GTase domain, rather than the TPase domain mediates these interactions.
Sequence similarities	In the N-terminal section; belongs to the non-receptor class of the protein-tyrosine phosphatase family. In the C-terminal section; belongs to the eukaryotic GTase family.

Ontologies

Keywords
Biological process	mRNA capping mRNA processing
Cellular component	Nucleus
Ligand	GTP-binding Nucleotide-binding
Molecular function	Hydrolase Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	mRNA capping Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid dephosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW mRNA guanylyltransferase activity Inferred from electronic annotation. Source: EC polynucleotide 5'-phosphatase activity Inferred from electronic annotation. Source: EC protein tyrosine phosphatase activity Inferred from electronic annotation. Source: InterPro protein tyrosine/serine/threonine phosphatase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 597

597

mRNA-capping enzyme

PRO_0000210109

Regions

Region

1 – 212

212

TPase

Region

229 – 597

369

GTase

Compositional bias

195 – 205

11

Asp/Glu-rich

Sites

Active site

126

1

For RNA 5'-triphosphatase activity By similarity

Active site

294

1

N6-GMP-lysine intermediate

Amino acid modifications

Modified residue

210

1

Phosphoserine By similarity

Experimental info

Mutagenesis

36

1

D → A: No effect.

Mutagenesis

66

1

D → A: Decrease of >90% of TPase activity.

Mutagenesis

110

1

C → S: No effect.

Mutagenesis

125

1

H → A: Decrease of 55-60% of TPase activity.

Mutagenesis

126

1

C → S: Loss of TPase activity.

Mutagenesis

132

1

R → A: Loss of TPase activity.

Mutagenesis

133

1

T → A: Decrease of 55-60% of TPase activity.

Mutagenesis

138

1

C → S: No effect.

Mutagenesis

168

1

D → A: No effect.

Mutagenesis

290

1

K → A: No effect.

Mutagenesis

294

1

K → A: Loss of GTase activity. Ref.1

Mutagenesis

315

1

R → A: Almost complete loss of RNA-binding and loss of GTase activity.

Mutagenesis

315

1

R → K: At least 60% of RNA-binding activity and loss of GTase activity.

Mutagenesis

530

1

R → A: Almost complete loss of RNA-binding and loss of GTase activity.

Mutagenesis

530

1

R → K: Loss of GTase activity.

Mutagenesis

533

1

K → A: Almost complete loss of RNA-binding and loss of GTase activity.

Mutagenesis

533

1

K → R: At least 60% of RNA-binding activity and loss of GTase activity.

Mutagenesis

537

1

N → A: Almost complete loss of RNA-binding and loss of GTase activity.

Mutagenesis

537

1

N → Q: At least 60% of RNA binding activity and loss of GTase activity.

Secondary structure

1

.

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597

Helix Strand Turn

Details...

Turn

21 – 23

3

Beta strand

24 – 27

4

Helix

33 – 35

3

Turn

36 – 38

3

Helix

41 – 43

3

Helix

47 – 56

10

Beta strand

61 – 66

6

Beta strand

71 – 74

4

Helix

77 – 80

4

Turn

81 – 83

3

Beta strand

85 – 88

4

Helix

100 – 110

11

Beta strand

121 – 125

5

Beta strand

127 – 130

4

Helix

131 – 145

15

Helix

149 – 159

11

Helix

167 – 177

11

Helix

180 – 182

3

Helix

191 – 194

4

Sequences

	Sequence		Length	Mass (Da)
	O55236-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: B2A9E711889D8EA7	FASTA	597	68,684
	10 20 30 40 50 60 MAYNKIPPRW LNCPRRGQPV AGRFLPLKTM LGPRYDSQVA EENRFHPSML SNYLKSLKVK 70 80 90 100 110 120 MSLLVDLTNT SRFYDRNDIE KEGIKYIKLQ CKGHGECPTT ENTETFIRLC ERFNERSPPE 130 140 150 160 170 180 LIGVHCTHGF NRTGFLICAF LVEKMDWSIE AAVATFAQAR PPGIYKGDYL KELFRRYGDI 190 200 210 220 230 240 EEAPPPPVLP DWCFEDEDEE DEDEDGKKDS EPGSSASFSK RRKERLKLGA IFLEGITVKG 250 260 270 280 290 300 VTQVTTQPKL GEVQQKCHQF CGWEGSGFPG AQPVSMDKQN IRLLEQKPYK VSWKADGTRY 310 320 330 340 350 360 MMLIDGTNEV FMIDRDNSVF HVSNLEFPFR KDLRMHLSNT LLDGEMIIDK VNGQAVPRYL 370 380 390 400 410 420 IYDIIKFNAQ PVGDCDFNIR LQCIEREIIS PRHEKMKTGL IDKTQEPFSV RPKQFFDINI 430 440 450 460 470 480 SRKLLEGNFA KEVSHEMDGL IFQPIGKYKP GRCDDILKWK PPSLNSVDFR LKITRMGGEG 490 500 510 520 530 540 LLPQNVGLLY VGGYERPFAQ IKVTKELKQY DNKIIECKFE NNSWVFMRQR IDKSFPNAYN 550 560 570 580 590 TAMAVCNSIS NPVTKEMLFE FIDRCAAAAQ GQKRKYPLDP DTELMPPPPP KRLHRPT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian capping enzyme complements mutant Saccharomyces cerevisiae lacking mRNA guanylyltransferase and selectively binds the elongating form of RNA polymerase II." Yue Z., Maldonado E., Pillutla R., Cho H., Reinberg D., Shatkin A.J. Proc. Natl. Acad. Sci. U.S.A. 94:12898-12903(1997) [PubMed: 9371772] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-294.
[2]	"5'-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II." McCracken S., Fong N., Rosonina E., Yankulov K., Brothers G., Siderovski D., Hessel A., Foster S., Shuman S., Bentley D.L. Genes Dev. 11:3306-3318(1997) [PubMed: 9407024] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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]. Strain: FVB/N. Tissue: Mammary gland.
[4]	"Mammalian capping enzyme binds RNA and uses protein tyrosine phosphatase mechanism." Wen Y., Yue Z., Shatkin A.J. Proc. Natl. Acad. Sci. U.S.A. 95:12226-12231(1998) [PubMed: 9770468] [Abstract] Cited for: CHARACTERIZATION, MUTAGENESIS.
[5]	"Structure and mechanism of the RNA triphosphatase component of mammalian mRNA capping enzyme." Changela A., Ho C.K., Martins A., Shuman S., Mondragon A. EMBO J. 20:2575-2586(2001) [PubMed: 11350947] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF025653 mRNA. Translation: AAB91558.1.
AF034568 mRNA. Translation: AAB88903.1.
BC043657 mRNA. Translation: AAH43657.1.

IPI

IPI00116711.

RefSeq

NP_036014.1.

UniGene

Mm.240024
Mm.464346

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I9S	X-ray	1.65	A	1-210	[»]
1I9T	X-ray	1.70	A	1-210	[»]

ModBase

Search...

PTM databases

PhosphoSite

O55236.

Proteomic databases

PRIDE

O55236.

Genome annotation databases

Ensembl

ENSMUSG00000028274. Mus musculus. [Contig view]

GeneID

24018.

KEGG

mmu:24018.

Organism-specific databases

MGI

MGI:1329041. Rngtt.

Phylogenomic databases

HOGENOM

O55236.

HOVERGEN

O55236.

OMA

O55236. FFDIHAS.

Enzyme and pathway databases

BRENDA

2.7.7.50. 244.
3.1.3.33. 244.

Gene expression databases

ArrayExpress

O55236.

Bgee

O55236.

CleanEx

MM_RNGTT.

GermOnline

ENSMUSG00000028274. Mus musculus.

Family and domain databases

InterPro

IPR017074. mRNA_cap_enz_bifunc.
IPR001339. mRNA_cap_enzyme.
IPR013846. mRNA_cap_enzyme_C.
IPR000387. Tyr_Pase.
IPR016130. Tyr_Pase_AS.
IPR000340. Tyr_Pase_dual_specific.
[Graphical view]

Pfam

PF00782. DSPc. 1 hit.
PF03919. mRNA_cap_C. 1 hit.
PF01331. mRNA_cap_enzyme. 1 hit.
[Graphical view]

PIRSF

PIRSF036958. mRNA_capping_HCE. 1 hit.

PROSITE

PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

303959.

SOURCE

Search...

Entry information

Entry name

MCE1_MOUSE

Accession

Primary (citable) accession number: O55236

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	June 16, 2009
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)