Modomics - A Database of RNA Modifications

ID Card:

Full name: RNA cap gamma-methyltransferase
Synonym: 7SK snRNA methylphosphate capping enzyme (MePCE), Bicoid-interacting protein 3 homolog
GI: 74758999
Orf: BCDIN3
COG: COG2264
UniProt: Q7L2J0
Structures: | 5UNA | 6DCB | 6DCC |
Alpha Fold Predicted Structure: AF-Q7L2J0-F1
Enzyme type: methyltransferase
Position of modification - modification: n:0 - m7GpppN


PDB Structures:


5UNA

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Among RNA 5'-cap structures, γ-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second nonenzymatic role as a core component of the 7SK ribonuclear protein (RNP), an essential regulator of RNA transcription. We report 2.0- and 2.1-Å X-ray crystal structures of the human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5'-hairpin-single-stranded RNA region, thus explaining MePCE's specificity for 7SK and U6. The structures reveal SAH and product RNA in a near-transition-state geometry. Unexpectedly, binding experiments showed that MePCE has higher affinity for capped versus uncapped 7SK, and kinetic data support a model of slow product release. This work reveals the molecular mechanism of methyl transfer and 7SK retention by MePCE for subsequent assembly of 7SK RNP.

Download RCSB-PDB Structures:

Pdb Files   5UNA.pdb   6DCB.pdb   6DCC.pdb  
Pdbx/mmCIF Files   5UNA.cif   6DCB.cif   6DCC.cif  


Protein sequence:

MIEMAAEKEPFLVPAPPPPLKDESGGGGGPTVPPHQEAASGELRGGTERGPGRCAPSAGSPAAAVGRESPGAAATSSSGPQAQQHRGGGPQAQSHGEARLSDPPGRAAPPDVGEERRGGGGTELGPPAPPRPRNGYQPHRPPGGGGGKRRNSCNVGGGGGGFKHPAFKRRRRVNSDCDSVLPSNFLLGGNIFDPLNLNSLLDEEVSRTLNAETPKSSPLPAKGRDPVEILIPKDITDPLSLNTCTDEGHVVLASPLKTGRKRHRHRGQHHQQQQAAGGSESHPVPPTAPLTPLLHGEGASQQPRHRGQNRDAPQPYELNTAINCRDEVVSPLPSALQGPSGSLSAPPAASVISAPPSSSSRHRKRRRTSSKSEAGARGGGQGSKEKGRGSWGGRHHHHHPLPAAGFKKQQRKFQYGNYCKYYGYRNPSCEDGRLRVLKPEWFRGRDVLDLGCNVGHLTLSIACKWGPSRMVGLDIDSRLIHSARQNIRHYLSEELRLPPQTLEGDPGAEGEEGTTTVRKRSCFPASLTASRGPIAAPQVPLDGADTSVFPNNVVFVTGNYVLDRDDLVEAQTPEYDVVLCLSLTKWVHLNWGDEGLKRMFRRIYRHLRPGGILVLEPQPWSSYGKRKTLTETIYKNYYRIQLKPEQFSSYLTSPDVGFSSYELVATPHNTSKGFQRPVYLFHKARSPSH

Comments:

7SK snRNA methyl phosphate capping enzyme belongs to the S-adenosyl-L-methionine-dependent methyltransferase enzyme family (SMA). Specifically, BCDIN3 ads a methyl phosphate at the 5'-end of the 7SK snRNA (7SKRNA), stabilizing it (Xue et al. 2010 ; Jeronimo et al. 2007 ).

Noteworthy, it also has a non-enzymatic function as part of the 7SK RNP complex, sequestering the positive transcription elongation factor b(P-TEFb) in large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation nd subsequent transcriptional elongation (Xue et al. 2010 ; Jeronimo et al. 2007 ).




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
pppN:mpppN snRNA 7SK 0 Nucleus 19906723   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M I E M A A E K E P F L V P A P P P P L K D E S G G G G G P T V P P H Q E A A S G E L R G G T E R G P G R C A P S A G S P A A A V G R E S P G A A A T S S S G P Q A Q Q H R G G G P Q A Q S H G E A R L S D P P G R A A P P D V G E E R R G G G G T E L G P P A P P R P R N G Y Q P H R P P G G G G G K R R N S C N V G G G G G G F K H P A F K R R R R V N S D C D S V L P S N F L L G G N I F D P L N L N S L L D E E V S R T L N A E T P K S S P L P A K G R D P V E I L I P K D I T D P L S L N T C T D E G H V V L A S P L K T G R K R H R H R G Q H H Q Q Q Q A A G G S E S H P V P P T A P L T P L L H G E G A S Q Q P R H R G Q N R D A P Q P Y E L N T A I N C R D E V V S P L P S A L Q G P S G S L S A P P A A S V I S A P P S S S S R H R K R R R T S S K S E A G A R G G G Q G S K E K G R G S W G G R H H H H H P L P A A G F K K Q Q R K F Q Y G N Y C K Y Y G Y R N P S C E D G R L R V L K P E W F R G R D V L D L G C N V G H L T L S I A C K W G P S R M V G L D I D S R L I H S A R Q N I R H Y L S E E L R L P P Q T L E G D P G A E G E E G T T T V R K R S C F P A S L T A S R G P I A A P Q V P L D G A D T S V F P N N V V F V T G N Y V L D R D D L V E A Q T P E Y D V V L C L S L T K W V H L N W G D E G L K R M F R R I Y R H L R P G G I L V L E P Q P W S S Y G K R K T L T E T I Y K N Y Y R I Q L K P E Q F S S Y L T S P D V G F S S Y E L V A T P H N T S K G F Q R P V Y L F H K A R S P S H

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-Q7L2J0-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q7L2J0-F1.cif  
DSSP Secondary Structures   Q7L2J0.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Therien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B Mol Cell [details] 17643375 -
A capping-independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP. Xue Y, Yang Z, Chen R, Zhou Q Nucleic Acids Res [details] 19906723 -