Reviewed, UniProtKB/Swiss-Prot O60942 (MCE1_HUMAN)

Names and origin

Protein names

Recommended name:
    mRNA-capping enzyme
Alternative name(s):
    HCE
    HCAP1
Including the following 2 domains:
    1- Recommended name:
            Polynucleotide 5'-triphosphatase
              EC=3.1.3.33
        Alternative name(s):
            mRNA 5'-triphosphatase
              Short name=TPase
    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

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	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 + H(2)O = a polynucleotide + phosphate. GTP + (5')pp-Pur-mRNA = diphosphate + G(5')ppp-Pur-mRNA.
Subunit structure	Interacts with SUPT5H and RNMT. Interacts with HIV-1 Tat.
Subcellular location	NucleusBy 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 process	Host-virus interaction mRNA capping mRNA processing
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW mRNA capping Ref.3 Traceable author statement. Source: ProtInc protein amino acid dephosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	nucleoplasm Ref.2 Inferred from Experiment. Source: Reactome
Molecular function	mRNA guanylyltransferase activity Ref.3 Traceable author statement. Source: ProtInc 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...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 597

597

mRNA-capping enzyme

PRO_0000210108

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

Natural variations

Alternative sequence

424 – 446

23

Missing in isoform 2 and isoform 3.

VSP_003202

Alternative sequence

481 – 597

117

Missing in isoform 3.

VSP_003203

Alternative sequence

504 – 597

94

TKELK…PRPLT → CLFIFSVLFLDVLLSGIHQN LANNNQHIKISCSSTLGG in isoform 4.

VSP_003204

Natural variant

594

1

R → H: dbSNP rs17856595.

VAR_046481

Experimental info

Mutagenesis

294

1

K → A: Loss of GTase activity

Mutagenesis

299

1

R → A: Loss of GTase activity

Mutagenesis

345

1

E → A: Loss of GTase activity

Mutagenesis

458

1

K → A: Loss of GTase activity

Mutagenesis

460

1

K → A: Loss of GTase activity

Sequence conflict

30

1

M → I in AAB91559. Ref.1

Sequence conflict

212

1

P → T in AAH19954. Ref.6

Sequence conflict

484

1

Q → P in AAB91559. Ref.1

Secondary structure

1

.

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597

Helix Strand Turn

Details...

Turn

21 – 23

3

Beta strand

24 – 27

4

Helix

33 – 38

6

Helix

41 – 43

3

Helix

47 – 57

11

Beta strand

60 – 66

7

Helix

77 – 80

4

Turn

81 – 83

3

Beta strand

85 – 88

4

Helix

100 – 110

11

Beta strand

120 – 125

6

Beta strand

127 – 130

4

Helix

131 – 143

13

Helix

149 – 159

11

Helix

167 – 177

11

Helix

180 – 182

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HCE1) (HCAP1A) [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 51CEEC1B190603DE	FASTA	597	68,557
	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
	Isoform 2 (HCE1A) [UniParc]. Checksum: CFE64E51F6F88232		574	66,042
	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 SRKKYKPGRC DDILKWKPPS LNSVDFRLKI TRMGGEGLLP QNVGLLYVGG YERPFAQIKV 490 500 510 520 530 540 TKELKQYDNK IIECKFENNS WVFMRQRTDK SFPNAYNTAM AVCNSISNPV TKEMLFEFID 550 560 570 RCTAASQGQK RKHHLDPDTE LMPPPPPKRP RPLT
	Isoform 3 (HCE1B) [UniParc]. Checksum: 4F3B52CA4F6CC56B		457	52,533
	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 SRKKYKPGRC DDILKWKPPS LNSVDFRLKI TRMGGEG
	Isoform 4 (HCAP1B) [UniParc]. Checksum: DF795898785EC2D4		541	61,705
	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 IKVCLFIFSV LFLDVLLSGI HQNLANNNQH IKISCSSTLG G

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] (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: 9512541] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), MUTAGENESIS.
[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: 9473487] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4). 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. , 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: 14574404] [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. , 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: 15489334] [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: 9705270] [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: 10421630] [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: 11278368] [Abstract] Cited for: INTERACTION WITH HIV-1 TAT.
[10]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-210, MASS SPECTROMETRY. Tissue: Epithelium.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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 , AL096868, AL133408, AL445530 Genomic DNA. Translation: CAI22537.1. AL096868 , AL079342, AL133408, AL445530 Genomic DNA. Translation: CAI21547.1. AL133408