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Protein

m7GpppX diphosphatase

Gene

DCPS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with very poor efficiency. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) to m7GMP (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCPS to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. Inhibits activation-induced cell death.10 Publications

Catalytic activityi

A 5'-(N7-methyl 5'-triphosphoguanosine)-[mRNA] + H2O = N7-methylguanosine 5'-phosphate + a 5'-diphospho-[mRNA].4 Publications

Enzyme regulationi

The hydrolytic product 7-methylguanosine diphosphate (m7GDP) efficiently inhibits the decapping scavenger activity and acts as a competitive inhibitor in vitro. Inhibited by 2,4-diaminoquinazoline.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei175Substrate2 Publications1
Binding sitei185Substrate2 Publications1
Binding sitei205Substrate2 Publications1
Binding sitei207Substrate2 Publications1
Active sitei277Nucleophile1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processmRNA processing, mRNA splicing

Enzyme and pathway databases

BRENDAi3.6.1.59 2681
ReactomeiR-HSA-429958 mRNA decay by 3' to 5' exoribonuclease

Names & Taxonomyi

Protein namesi
Recommended name:
m7GpppX diphosphatase (EC:3.6.1.59)
Alternative name(s):
DCS-1
Decapping scavenger enzyme
Hint-related 7meGMP-directed hydrolase
Histidine triad nucleotide-binding protein 5
Histidine triad protein member 5
Short name:
HINT-5
Scavenger mRNA-decapping enzyme DcpS
Gene namesi
Name:DCPS
Synonyms:DCS1, HINT5
ORF Names:HSPC015
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000110063.8
HGNCiHGNC:29812 DCPS
MIMi610534 gene
neXtProtiNX_Q96C86

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Al-Raqad syndrome (ARS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by delayed psychomotor development, moderate to severe intellectual disability, poor or absent speech, microcephaly, congenital hypotonia, and severe growth delay.
See also OMIM:616459
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073956316T → M in ARS; results in a severe decrease of decapase activity. 1 PublicationCorresponds to variant dbSNP:rs137941190EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10 – 13Missing : Increases cytoplasmic localization. 1 Publication4
Mutagenesisi58R → A: Increases decapping activity to 125% of wild-type. 1 Publication1
Mutagenesisi61I → A: No effect. 1 Publication1
Mutagenesisi63F → A: No effect. 1 Publication1
Mutagenesisi83I → A: Strongly reduces decapping activity. 1 Publication1
Mutagenesisi85E → A: Reduces decapping activity. 1 Publication1
Mutagenesisi108F → A: Reduces decapping activity. 1 Publication1
Mutagenesisi110N → A: Loss of decapping activity. 1 Publication1
Mutagenesisi113Y → A: Loss of decapping activity. 1 Publication1
Mutagenesisi128K → A: No effect. 1 Publication1
Mutagenesisi138K → D: Increases decapping activity to 250% of wild-type. 1 Publication1
Mutagenesisi145R → A: Increases decapping activity to 180% of wild-type. 1 Publication1
Mutagenesisi146Q → P: Increases decapping activity to 140% of wild-type. 1 Publication1
Mutagenesisi148L → A: Inhibits nuclear export to the cytoplasm. 1 Publication1
Mutagenesisi150L → A: Inhibits nuclear export to the cytoplasm. 1 Publication1
Mutagenesisi175W → A: Loss of decapping activity. 1 Publication1
Mutagenesisi185E → A: Loss of decapping activity. 1 Publication1
Mutagenesisi204P → A: Reduces decapping activity. 1 Publication1
Mutagenesisi205D → A: Reduces decapping activity. 1 Publication1
Mutagenesisi206L → A: No effect. 1 Publication1
Mutagenesisi207K → A: Reduces decapping activity. 1 Publication1
Mutagenesisi207K → R: No effect. 1 Publication1
Mutagenesisi217Y → A: No effect. 1 Publication1
Mutagenesisi217Y → F: Reduces decapping activity. 1 Publication1
Mutagenesisi268H → N: Loss of decapping activity. 1 Publication1
Mutagenesisi272S → A: No effect. 1 Publication1
Mutagenesisi273Y → A: Reduces decapping activity. 1 Publication1
Mutagenesisi273Y → F: Activates decapping activity to 120% of wild-type. 1 Publication1
Mutagenesisi277H → N: Loss of decapping activity. Does not inhibit cap structure and capped RNA binding. Preferentially hydrolyzes cap structure (m7GpppG) at least 2500-fold more efficiently than capped RNA (m7Gppp-RNA). 3 Publications1
Mutagenesisi279H → N: Loss of decapping activity. 1 Publication1
Mutagenesisi294R → A or K: No effect. 1 Publication1
Mutagenesisi322R → A: No effect. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi28960
MalaCardsiDCPS
MIMi616459 phenotype
OpenTargetsiENSG00000110063
PharmGKBiPA134863866

Chemistry databases

ChEMBLiCHEMBL1949488
DrugBankiDB01649 7-Methyl-Gpppa
DB03958 7-methyl-guanosine-5'-triphosphate-5'-guanosine
DB01960 7n-Methyl-8-Hydroguanosine-5'-Diphosphate
DB03593 N7-Methyl-Guanosine-5'-Monophosphate

Polymorphism and mutation databases

BioMutaiDCPS
DMDMi116241325

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001097942 – 337m7GpppX diphosphataseAdd BLAST336

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei24PhosphoserineCombined sources1
Modified residuei101PhosphoserineBy similarity1
Modified residuei138N6-acetyllysineCombined sources1
Modified residuei142N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96C86
MaxQBiQ96C86
PaxDbiQ96C86
PeptideAtlasiQ96C86
PRIDEiQ96C86

2D gel databases

REPRODUCTION-2DPAGEiIPI00335385

PTM databases

iPTMnetiQ96C86
PhosphoSitePlusiQ96C86

Expressioni

Tissue specificityi

Detected in liver, brain, kidney, testis and prostate.1 Publication

Inductioni

Up-regulated by menadione. Up-regulated by the transcription factor LTF isoform delta-lactoferrin (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000110063
CleanExiHS_DCPS
GenevisibleiQ96C86 HS

Organism-specific databases

HPAiHPA039632
HPA058597

Interactioni

Subunit structurei

Homodimer. Associates with components of the exosome multienzyme ribonuclease complex, such as EXOSC3 and EXOSC4. Interacts with NDOR1.6 Publications

Protein-protein interaction databases

BioGridi118787, 38 interactors
IntActiQ96C86, 6 interactors
STRINGi9606.ENSP00000263579

Chemistry databases

BindingDBiQ96C86

Structurei

Secondary structure

1337
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi43 – 45Combined sources3
Beta strandi48 – 56Combined sources9
Turni57 – 60Combined sources4
Beta strandi61 – 67Combined sources7
Beta strandi79 – 86Combined sources8
Helixi91 – 98Combined sources8
Beta strandi103 – 110Combined sources8
Beta strandi113 – 119Combined sources7
Helixi122 – 124Combined sources3
Beta strandi127 – 132Combined sources6
Helixi137 – 143Combined sources7
Beta strandi148 – 153Combined sources6
Helixi155 – 160Combined sources6
Helixi162 – 167Combined sources6
Helixi174 – 180Combined sources7
Beta strandi183 – 185Combined sources3
Helixi186 – 188Combined sources3
Beta strandi191 – 193Combined sources3
Turni196 – 198Combined sources3
Beta strandi200 – 204Combined sources5
Helixi213 – 215Combined sources3
Beta strandi217 – 225Combined sources9
Helixi230 – 232Combined sources3
Helixi235 – 237Combined sources3
Helixi238 – 256Combined sources19
Helixi260 – 262Combined sources3
Beta strandi263 – 270Combined sources8
Beta strandi272 – 275Combined sources4
Beta strandi277 – 282Combined sources6
Turni292 – 294Combined sources3
Beta strandi295 – 297Combined sources3
Helixi298 – 307Combined sources10
Helixi311 – 314Combined sources4
Beta strandi317 – 322Combined sources6
Helixi326 – 333Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ST0X-ray1.90A/B1-337[»]
1ST4X-ray2.02A/B1-337[»]
1XMLX-ray2.00A/B1-337[»]
1XMMX-ray2.50A/B/C/D1-337[»]
3BL7X-ray2.31A/B38-337[»]
3BL9X-ray1.80A/B38-337[»]
3BLAX-ray2.60A/B38-337[»]
4QDEX-ray2.90A/B/C/D2-337[»]
4QDVX-ray2.80A/B/C/D2-337[»]
4QEBX-ray3.21A/B/C/D2-337[»]
ProteinModelPortaliQ96C86
SMRiQ96C86
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96C86

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni268 – 279Substrate bindingAdd BLAST12

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi10 – 13nuclear localization signal (NLS)4
Motifi142 – 154nuclear export sequence (NES)Add BLAST13
Motifi275 – 279Histidine triad motif5

Domaini

The C-terminal histidine triad (HIT) motif and the N-terminal domain are required for the decapping activity. The N-terminus is necessary but not sufficient for binding cap structures.1 Publication

Sequence similaritiesi

Belongs to the HIT family.Curated

Phylogenomic databases

eggNOGiKOG3969 Eukaryota
COG5075 LUCA
GeneTreeiENSGT00390000003924
HOGENOMiHOG000182411
HOVERGENiHBG051322
InParanoidiQ96C86
KOiK12584
OMAiIWCEKSH
OrthoDBiEOG091G0DTP
PhylomeDBiQ96C86
TreeFamiTF105622

Family and domain databases

Gene3Di3.30.200.40, 1 hit
3.30.428.10, 1 hit
InterProiView protein in InterPro
IPR008594 DcpS/DCS2
IPR019808 Histidine_triad_CS
IPR036265 HIT-like_sf
IPR011145 Scavenger_mRNA_decap_enz_N
PANTHERiPTHR12978 PTHR12978, 1 hit
PfamiView protein in Pfam
PF05652 DcpS, 1 hit
PIRSFiPIRSF028973 Scavenger_mRNA_decap_enz, 1 hit
SUPFAMiSSF102860 SSF102860, 1 hit
SSF54197 SSF54197, 1 hit
PROSITEiView protein in PROSITE
PS00892 HIT_1, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q96C86-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADAAPQLGK RKRELDVEEA HAASTEEKEA GVGNGTCAPV RLPFSGFRLQ
60 70 80 90 100
KVLRESARDK IIFLHGKVNE ASGDGDGEDA VVILEKTPFQ VEQVAQLLTG
110 120 130 140 150
SPELQLQFSN DIYSTYHLFP PRQLNDVKTT VVYPATEKHL QKYLRQDLRL
160 170 180 190 200
IRETGDDYRN ITLPHLESQS LSIQWVYNIL DKKAEADRIV FENPDPSDGF
210 220 230 240 250
VLIPDLKWNQ QQLDDLYLIA ICHRRGIRSL RDLTPEHLPL LRNILHQGQE
260 270 280 290 300
AILQRYRMKG DHLRVYLHYL PSYYHLHVHF TALGFEAPGS GVERAHLLAE
310 320 330
VIENLECDPR HYQQRTLTFA LRADDPLLKL LQEAQQS
Length:337
Mass (Da):38,609
Last modified:October 17, 2006 - v2
Checksum:iC9C5A33C212D7A52
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti69N → K in AAK91763 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02795873G → E1 PublicationCorresponds to variant dbSNP:rs11557735Ensembl.1
Natural variantiVAR_073956316T → M in ARS; results in a severe decrease of decapase activity. 1 PublicationCorresponds to variant dbSNP:rs137941190EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AH010984 Genomic DNA Translation: AAK91763.1
AY040771 mRNA Translation: AAK91765.1
AF532613 mRNA Translation: AAM90310.1
AY077684 mRNA Translation: AAL77216.1
AF077201 mRNA Translation: AAD26996.1
BC014532 mRNA Translation: AAH14532.1
CCDSiCCDS8473.1
RefSeqiNP_054745.1, NM_014026.4
UniGeneiHs.504249
Hs.651497

Genome annotation databases

EnsembliENST00000263579; ENSP00000263579; ENSG00000110063
GeneIDi28960
KEGGihsa:28960
UCSCiuc001qdp.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDCPS_HUMAN
AccessioniPrimary (citable) accession number: Q96C86
Secondary accession number(s): Q8NHL8, Q9Y2S5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: October 17, 2006
Last modified: March 28, 2018
This is version 151 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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