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O60942 (MCE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
mRNA-capping enzyme
Alternative name(s):
HCAP1
HCE

Including the following 2 domains:

  1. Polynucleotide 5'-triphosphatase
    EC=3.1.3.33
    Alternative name(s):
    mRNA 5'-triphosphatase
    Short name=TPase
  2. mRNA guanylyltransferase
    EC=2.7.7.50
    Alternative name(s):
    GTP--RNA guanylyltransferase
    Short name=GTase
Gene names
Name:RNGTT
Synonyms:CAP1A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length597 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.2 Ref.3 Ref.11

Catalytic activity

A 5'-phosphopolynucleotide + H2O = a polynucleotide + phosphate. Ref.3 Ref.11

GTP + (5')pp-Pur-mRNA = diphosphate + G(5')ppp-Pur-mRNA. Ref.3 Ref.11

Subunit structure

Interacts with POLR2A (via C-terminus); this enhances guanylyltransferase activity. Binds (via GTase domain) to the elongating phosphorylated form of RNA polymerase II; can form direct interactions with the phosphorylated POLR2A C-terminal domain and indirect interactions via bound RNA By similarity. Interacts with SUPT5H and RNMT. Interacts with HIV-1 Tat. Ref.7 Ref.8 Ref.9

Subcellular location

Nucleus By similarity.

Tissue specificity

Isoform 1 and isoform 4 (at a lesser extent) are expressed in cerebrum, cerebellum, thyroid, lung, heart, liver, kidney, spleen, large intestine, testis, skin and muscle.

Miscellaneous

Isoform 2 to isoform 4 lack mRNA 5'-guanylyltransferase activity due to disruptions of the GTase domain.

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 processHost-virus interaction
mRNA capping
mRNA processing
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandGTP-binding
Nucleotide-binding
   Molecular functionHydrolase
Nucleotidyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_process7-methylguanosine mRNA capping

Inferred from direct assay Ref.3. Source: UniProtKB

RNA processing

Inferred from direct assay Ref.11. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement Ref.3. Source: ProtInc

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA guanylyltransferase activity

Inferred from direct assay Ref.11. Source: UniProtKB

mRNA guanylyltransferase activity

Inferred from direct assay Ref.3. Source: UniProtKB

polynucleotide 5'-phosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein tyrosine phosphatase activity

Inferred from electronic annotation. Source: InterPro

protein tyrosine/serine/threonine phosphatase activity

Inferred from electronic annotation. Source: InterPro

triphosphatase activity

Inferred from direct assay Ref.3. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60942-1)

Also known as: HCE1; HCAP1A;

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: O60942-2)

Also known as: HCE1A;

The sequence of this isoform differs from the canonical sequence as follows:
     424-446: Missing.
Isoform 3 (identifier: O60942-3)

Also known as: HCE1B;

The sequence of this isoform differs from the canonical sequence as follows:
     424-446: Missing.
     481-597: Missing.
Isoform 4 (identifier: O60942-4)

Also known as: HCAP1B;

The sequence of this isoform differs from the canonical sequence as follows:
     504-597: TKELKQYDNK...PPPKRPRPLT → CLFIFSVLFL...KISCSSTLGG

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 597597mRNA-capping enzyme
PRO_0000210108

Regions

Nucleotide binding343 – 3453GTP Potential
Nucleotide binding458 – 4603GTP Potential
Nucleotide binding528 – 5336GTP Potential
Region1 – 212212TPase
Region229 – 597369GTase
Region330 – 38657Interaction with POLR2A By similarity
Compositional bias195 – 20511Asp/Glu-rich

Sites

Active site1261For RNA 5'-triphosphatase activity By similarity
Active site2941N6-GMP-lysine intermediate Ref.11
Binding site2991GTP By similarity
Binding site3151GTP Potential

Natural variations

Alternative sequence424 – 44623Missing in isoform 2 and isoform 3.
VSP_003202
Alternative sequence481 – 597117Missing in isoform 3.
VSP_003203
Alternative sequence504 – 59794TKELK…PRPLT → CLFIFSVLFLDVLLSGIHQN LANNNQHIKISCSSTLGG in isoform 4.
VSP_003204
Natural variant5941R → H. Ref.6
Corresponds to variant rs17856595 [ dbSNP | Ensembl ].
VAR_046481

Experimental info

Mutagenesis2341E → A: No effect on GTase activity. Ref.11
Mutagenesis2941K → A: Loss of GTase activity. Ref.2
Mutagenesis2991R → A: Loss of GTase activity. Ref.2
Mutagenesis3451E → A: Loss of GTase activity. Ref.2
Mutagenesis4581K → A: Loss of GTase activity. Ref.2 Ref.11
Mutagenesis4601K → A: Loss of GTase activity. Ref.2 Ref.11
Mutagenesis5281R → A: Strongly reduced GTase activity. Ref.11
Mutagenesis5301R → A: Loss of GTase activity. Ref.11
Mutagenesis5321D → A: Loss of GTase activity. Ref.11
Mutagenesis5331K → A: Loss of GTase activity. Ref.11
Sequence conflict301M → I in AAB91559. Ref.1
Sequence conflict2121P → T in AAH19954. Ref.6
Sequence conflict4841Q → P in AAB91559. Ref.1

Secondary structure

............................................................................................ 597
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (HCE1) (HCAP1A) [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 51CEEC1B190603DE

FASTA59768,557
        10         20         30         40         50         60 
MAHNKIPPRW LNCPRRGQPV AGRFLPLKTM LGPRYDSQVA EENRFHPSML SNYLKSLKVK 

        70         80         90        100        110        120 
MGLLVDLTNT SRFYDRNDIE KEGIKYIKLQ CKGHGECPTT ENTETFIRLC ERFNERNPPE 

       130        140        150        160        170        180 
LIGVHCTHGF NRTGFLICAF LVEKMDWSIE AAVATFAQAR PPGIYKGDYL KELFRRYGDI 

       190        200        210        220        230        240 
EEAPPPPLLP DWCFEDDEDE DEDEDGKKES EPGSSASFGK RRKERLKLGA IFLEGVTVKG 

       250        260        270        280        290        300 
VTQVTTQPKL GEVQQKCHQF CGWEGSGFPG AQPVSMDKQN IKLLDLKPYK VSWKADGTRY 

       310        320        330        340        350        360 
MMLIDGTNEV FMIDRDNSVF HVSNLEFPFR KDLRMHLSNT LLDGEMIIDR VNGQAVPRYL 

       370        380        390        400        410        420 
IYDIIKFNSQ PVGDCDFNVR LQCIEREIIS PRHEKMKTGL IDKTQEPFSV RNKPFFDICT 

       430        440        450        460        470        480 
SRKLLEGNFA KEVSHEMDGL IFQPTGKYKP GRCDDILKWK PPSLNSVDFR LKITRMGGEG 

       490        500        510        520        530        540 
LLPQNVGLLY VGGYERPFAQ IKVTKELKQY DNKIIECKFE NNSWVFMRQR TDKSFPNAYN 

       550        560        570        580        590 
TAMAVCNSIS NPVTKEMLFE FIDRCTAASQ GQKRKHHLDP DTELMPPPPP KRPRPLT 

« Hide

Isoform 2 (HCE1A) [UniParc].

Checksum: CFE64E51F6F88232
Show »

FASTA57466,042
Isoform 3 (HCE1B) [UniParc].

Checksum: 4F3B52CA4F6CC56B
Show »

FASTA45752,533
Isoform 4 (HCAP1B) [UniParc].

Checksum: DF795898785EC2D4
Show »

FASTA54161,705

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Isolation and characterization of a human cDNA for mRNA 5'-capping enzyme."
Yamada-Okabe T., Doi R., Shimmi O., Arisawa M., Yamada-Okabe H.
Nucleic Acids Res. 26:1700-1706(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), MUTAGENESIS OF LYS-294; ARG-299; GLU-345; LYS-458 AND LYS-460, FUNCTION.
[3]"Cloning and characterization of two human cDNAs encoding the mRNA capping enzyme."
Tsukamoto T., Shibagaki Y., Murakoshi T., Suzuki M., Nakamura A., Gotoh H., Mizumoto K.
Biochem. Biophys. Res. Commun. 243:101-108(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), FUNCTION, CATALYTIC ACTIVITY.
Tissue: Colon adenocarcinoma.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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].
[6]"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], VARIANT HIS-594.
Tissue: Skin.
[7]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RNMT.
[8]"Transcription elongation factor hSPT5 stimulates mRNA capping."
Wen Y., Shatkin A.J.
Genes Dev. 13:1774-1779(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SUPT5H.
[9]"HIV-1 Tat protein interacts with mammalian capping enzyme and stimulates capping of TAR RNA."
Chiu Y.-L., Coronel E., Ho C.K., Shuman S., Rana T.M.
J. Biol. Chem. 276:12959-12966(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 TAT.
[10]"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].
[11]"Structure of the guanylyltransferase domain of human mRNA capping enzyme."
Chu C., Das K., Tyminski J.R., Bauman J.D., Guan R., Qiu W., Montelione G.T., Arnold E., Shatkin A.J.
Proc. Natl. Acad. Sci. U.S.A. 108:10104-10108(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 229-567, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLU-234; LYS-458; LYS-460; ARG-528; ARG-530; ASP-532 AND LYS-533, ACTIVE SITE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF025654 mRNA. Translation: AAB91559.1.
AB009022 mRNA. Translation: BAA25894.1.
AB009023 mRNA. Translation: BAA25895.1.
AB009024 mRNA. Translation: BAA25896.1.
AB012142 mRNA. Translation: BAA25198.1.
AB012143 mRNA. Translation: BAA25199.1.
AL079342 expand/collapse EMBL AC list , AL096868, AL133408, AL445530 Genomic DNA. Translation: CAI22537.1.
AL096868 expand/collapse EMBL AC list , AL079342, AL133408, AL445530 Genomic DNA. Translation: CAI21547.1.
AL133408 expand/collapse EMBL AC list , AL079342, AL096868, AL445530 Genomic DNA. Translation: CAI21542.1.
AL445530 expand/collapse EMBL AC list , AL079342, AL096868, AL133408 Genomic DNA. Translation: CAI22048.1.
CH471051 Genomic DNA. Translation: EAW48566.1.
CH471051 Genomic DNA. Translation: EAW48567.1.
CH471051 Genomic DNA. Translation: EAW48569.1.
CH471051 Genomic DNA. Translation: EAW48570.1.
BC019954 mRNA. Translation: AAH19954.1.
CCDSCCDS5017.1. [O60942-1]
CCDS69153.1. [O60942-2]
PIRJC5936.
JC5937.
RefSeqNP_001273355.1. NM_001286426.1. [O60942-2]
NP_001273357.1. NM_001286428.1.
NP_003791.3. NM_003800.4. [O60942-1]
UniGeneHs.567378.
Hs.627135.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2C46X-ray1.60A/B/C/D1-219[»]
3S24X-ray3.01A/B/C/D/E/F/G229-567[»]
ProteinModelPortalO60942.
SMRO60942. Positions 4-199, 229-565.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114270. 8 interactions.
IntActO60942. 1 interaction.
STRING9606.ENSP00000358497.

PTM databases

PhosphoSiteO60942.

Proteomic databases

MaxQBO60942.
PaxDbO60942.
PRIDEO60942.

Protocols and materials databases

DNASU8732.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265607; ENSP00000265607; ENSG00000111880. [O60942-2]
ENST00000369485; ENSP00000358497; ENSG00000111880. [O60942-1]
GeneID8732.
KEGGhsa:8732.
UCSCuc003pmr.2. human. [O60942-1]
uc003pms.2. human. [O60942-2]

Organism-specific databases

CTD8732.
GeneCardsGC06M089376.
HGNCHGNC:10073. RNGTT.
HPAHPA003750.
MIM603512. gene.
neXtProtNX_O60942.
PharmGKBPA34446.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5226.
HOVERGENHBG006332.
InParanoidO60942.
KOK13917.
OMARFNERSP.
OrthoDBEOG7HB592.
PhylomeDBO60942.
TreeFamTF314914.

Enzyme and pathway databases

BioCycMetaCyc:HS03479-MONOMER.
BRENDA2.7.7.50. 2681.
ReactomeREACT_116125. Disease.
REACT_1788. Transcription.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressO60942.
BgeeO60942.
CleanExHS_RNGTT.
GenevestigatorO60942.

Family and domain databases

Gene3D2.40.50.140. 1 hit.
3.90.190.10. 1 hit.
InterProIPR000340. Dual-sp_phosphatase_cat-dom.
IPR017074. mRNA_cap_enz_bifunc.
IPR001339. mRNA_cap_enzyme.
IPR013846. mRNA_cap_enzyme_C.
IPR012340. NA-bd_OB-fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR000387. Tyr/Dual-sp_Pase.
IPR016130. Tyr_Pase_AS.
[Graphical view]
PfamPF00782. DSPc. 1 hit.
PF03919. mRNA_cap_C. 1 hit.
PF01331. mRNA_cap_enzyme. 1 hit.
[Graphical view]
PIRSFPIRSF036958. mRNA_capping_HCE. 1 hit.
SUPFAMSSF50249. SSF50249. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEPS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRNGTT. human.
EvolutionaryTraceO60942.
GeneWikiRNGTT.
GenomeRNAi8732.
NextBio32757.
PROO60942.
SOURCESearch...

Entry information

Entry nameMCE1_HUMAN
AccessionPrimary (citable) accession number: O60942
Secondary accession number(s): E1P513 expand/collapse secondary AC list , E1P514, O43483, O60257, O60351, Q5TCW8, Q8WUM8
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM