UniProtKB - Q96DE0 (NUD16_HUMAN)
Protein
U8 snoRNA-decapping enzyme
Gene
NUDT16
Organism
Homo sapiens (Human)
Status
Functioni
RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Part of the U8 snoRNP complex that is required for the accumulation of mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does not hydrolyze cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs but with less efficiencies. Has broad substrate specificity with manganese or cobalt as cofactor and can act on various RNA species. Binds to the U8 snoRNA; metal is not required for RNA-binding. May play a role in the regulation of snoRNAs and mRNAs degradation. Acts also as a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP), xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine triphosphate (ITP) to their respective monophosphate derivatives and does not distinguish between the deoxy- and ribose forms (PubMed:20385596, PubMed:26121039). The order of activity with different substrates is IDP > dIDP >> GDP = dGDP > XDP = ITP = dITP (PubMed:20385596). Binds strongly to GTP, ITP and XTP. Participates in the hydrolysis of dIDP/IDP and probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions (PubMed:20385596).7 Publications
Catalytic activityi
- a 5'-end (N7-methyl 5'-triphosphoguanosine)-adenosine in mRNA + H2O = a 5'-end phospho-adenosine in mRNA + 2 H+ + N7-methyl-GDP5 PublicationsEC:3.6.1.625 PublicationsThis reaction proceeds in the forward5 Publications direction.
- a 5'-end (N7-methyl 5'-triphosphoguanosine)-guanosine in mRNA + H2O = a 5'-end phospho-guanosine in mRNA + 2 H+ + N7-methyl-GDP5 PublicationsEC:3.6.1.625 PublicationsThis reaction proceeds in the forward5 Publications direction.
- EC:3.6.1.642 Publications
- EC:3.6.1.642 Publications
Cofactori
Mg2+3 Publications, Mn2+2 Publications, Co2+2 PublicationsNote: Binds 3 or 4 divalent metal cations. Acts specifically on U8 snoRNA with magnesium as cofactor. Has broad substrate specificity with bound manganese or cobalt (in vitro).2 Publications
Activity regulationi
The phosphatase activity is inhibited by the product IMP.1 Publication
Kineticsi
kcat is 0.931 sec(-1) with IDP. kcat is 0.966 sec(-1) with dIDP. kcat is 0.518 sec(-1) with GDP. kcat is 0.492 sec(-1) with dGDP. kcat is 2.6 sec(-1) with XDP. kcat is 3.06 sec(-1) with ITP. kcat is 3.2 sec(-1) with dITP. The catalytic efficiency for IDP is at least 1.3-fold higher than for dIDP, 9.6-fold higher than for GDP and dGDP, 100-fold higher than for XDP, ITP and dITP.1 Publication
- KM=0.062 µM for IDP (at 37 degrees Celsius)1 Publication
- KM=0.088 µM for dIDP (at 37 degrees Celsius)1 Publication
- KM=0.330 µM for GDP (at 37 degrees Celsius)1 Publication
- KM=0.319 mM for dGDP (at 37 degrees Celsius)1 Publication
- KM=15.7 mM for XDP (at 37 degrees Celsius)1 Publication
- KM=22.1 mM for ITP (at 37 degrees Celsius)1 Publication
- KM=24.1 mM for dITP (at 37 degrees Celsius)1 Publication
pH dependencei
Gradually increased from pH 6.5 to 8.5 in its IDP hydrolyzing activity.1 Publication
Temperature dependencei
Exhibited a temperature-dependent increase in its IDP hydrolyzing activity up to 60 degrees Celsius.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 24 | Substrate1 Publication | 1 | |
Binding sitei | 50 | Substrate1 Publication | 1 | |
Binding sitei | 57 | Substrate; via amide nitrogen1 Publication | 1 | |
Metal bindingi | 59 | Magnesium or manganese 1; via carbonyl oxygen1 Publication | 1 | |
Metal bindingi | 76 | Magnesium or manganese 21 Publication | 1 | |
Metal bindingi | 76 | Magnesium or manganese 3By similarity | 1 | |
Metal bindingi | 80 | Magnesium or manganese 11 Publication | 1 | |
Metal bindingi | 80 | Magnesium or manganese 3By similarity | 1 | |
Metal bindingi | 136 | Magnesium or manganese 3By similarity | 1 | |
Metal bindingi | 136 | Magnesium or manganese 4By similarity | 1 | |
Binding sitei | 170 | Substrate1 Publication | 1 |
GO - Molecular functioni
- chloride ion binding Source: UniProtKB
- cobalt ion binding Source: UniProtKB
- dITP diphosphatase activity Source: UniProtKB
- GTP binding Source: UniProtKB
- identical protein binding Source: IntAct
- inosine-diphosphatase activity Source: UniProtKB-EC
- ITP binding Source: UniProtKB
- m7G(5')pppN diphosphatase activity Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- manganese ion binding Source: UniProtKB
- metalloexopeptidase activity Source: UniProtKB
- mRNA binding Source: UniProtKB
- nucleotide phosphatase activity, acting on free nucleotides Source: UniProtKB
- phosphodiesterase decapping endonuclease activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- snoRNA binding Source: UniProtKB
- XTP binding Source: UniProtKB
GO - Biological processi
- adenosine to inosine editing Source: UniProtKB
- dITP catabolic process Source: UniProtKB
- IDP catabolic process Source: UniProtKB
- mRNA catabolic process Source: UniProtKB
- negative regulation of rRNA processing Source: UniProtKB
- nucleobase-containing small molecule catabolic process Source: Reactome
- positive regulation of cell cycle process Source: UniProtKB
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of double-strand break repair Source: UniProtKB
- RNA phosphodiester bond hydrolysis, endonucleolytic Source: UniProtKB
- snoRNA catabolic process Source: UniProtKB
- XDP catabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, RNA-binding |
Biological process | Nucleotide metabolism |
Ligand | Magnesium, Manganese, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:MONOMER-17869 |
BRENDAi | 3.6.1.62, 2681 3.6.1.64, 2681 |
PathwayCommonsi | Q96DE0 |
Reactomei | R-HSA-2393930, Phosphate bond hydrolysis by NUDT proteins |
Names & Taxonomyi
Protein namesi | Recommended name: U8 snoRNA-decapping enzyme (EC:3.6.1.625 Publications)Alternative name(s): Inosine diphosphate phosphatase Nucleoside diphosphate-linked moiety X motif 16 Short name: Nudix motif 16 Nudix hydrolase 16 U8 snoRNA-binding protein H29K1 Publication m7GpppN-mRNA hydrolase |
Gene namesi | Name:NUDT16 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000198585.11 |
HGNCi | HGNC:26442, NUDT16 |
MIMi | 617381, gene |
neXtProti | NX_Q96DE0 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
- nucleoplasm By similarity
- nucleolus By similarity
Other locations
- Cytoplasm 2 Publications
Note: Localized predominantly in the cytoplasm (PubMed:21070968). Localized in nucleolus, and in a minor proportion in distinct foci in the nucleoplasm (By similarity).By similarity1 Publication
Nucleus
- nucleolus Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 131870 |
OpenTargetsi | ENSG00000198585 |
PharmGKBi | PA134955224 |
Miscellaneous databases
Pharosi | Q96DE0, Tbio |
Polymorphism and mutation databases
BioMutai | NUDT16 |
DMDMi | 68565926 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000057117 | 1 – 195 | U8 snoRNA-decapping enzymeAdd BLAST | 195 |
Proteomic databases
EPDi | Q96DE0 |
jPOSTi | Q96DE0 |
MassIVEi | Q96DE0 |
MaxQBi | Q96DE0 |
PaxDbi | Q96DE0 |
PeptideAtlasi | Q96DE0 |
PRIDEi | Q96DE0 |
ProteomicsDBi | 19864 24755 76283 [Q96DE0-1] |
TopDownProteomicsi | Q96DE0-1 [Q96DE0-1] |
PTM databases
iPTMneti | Q96DE0 |
PhosphoSitePlusi | Q96DE0 |
Expressioni
Tissue specificityi
Expressed strongly in lung, kidney, adrenal gland, testis, heart and brain.1 Publication
Gene expression databases
Bgeei | ENSG00000198585, Expressed in amniotic fluid and 211 other tissues |
Genevisiblei | Q96DE0, HS |
Organism-specific databases
HPAi | ENSG00000198585, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer.
3 PublicationsBinary interactionsi
Q96DE0
With | #Exp. | IntAct |
---|---|---|
itself | 2 | EBI-5464685,EBI-5464685 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 126295, 13 interactors |
IntActi | Q96DE0, 3 interactors |
MINTi | Q96DE0 |
STRINGi | 9606.ENSP00000422375 |
Miscellaneous databases
RNActi | Q96DE0, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96DE0 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96DE0 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 18 – 173 | Nudix hydrolasePROSITE-ProRule annotationAdd BLAST | 156 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 61 – 82 | Nudix boxAdd BLAST | 22 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502S20E, Eukaryota |
GeneTreei | ENSGT00390000016224 |
HOGENOMi | CLU_110418_1_0_1 |
InParanoidi | Q96DE0 |
OMAi | VDSCYAP |
OrthoDBi | 1385294at2759 |
PhylomeDBi | Q96DE0 |
Family and domain databases
InterProi | View protein in InterPro IPR015797, NUDIX_hydrolase-like_dom_sf IPR000086, NUDIX_hydrolase_dom |
Pfami | View protein in Pfam PF00293, NUDIX, 1 hit |
SUPFAMi | SSF55811, SSF55811, 1 hit |
PROSITEi | View protein in PROSITE PS51462, NUDIX, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q96DE0-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGARRLELG EALALGSGWR HACHALLYAP DPGMLFGRIP LRYAILMQMR
60 70 80 90 100
FDGRLGFPGG FVDTQDRSLE DGLNRELREE LGEAAAAFRV ERTDYRSSHV
110 120 130 140 150
GSGPRVVAHF YAKRLTLEEL LAVEAGATRA KDHGLEVLGL VRVPLYTLRD
160 170 180 190
GVGGLPTFLE NSFIGSAREQ LLEALQDLGL LQSGSISGLK IPAHH
Sequence cautioni
The sequence BAB71024 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 22 | A → V in AAH31215 (PubMed:15489334).Curated | 1 | ||
Isoform 3 (identifier: Q96DE0-3) | |||||
Sequence conflicti | 128 | Missing in BP199028 (PubMed:16344560).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045449 | 1 – 46 | Missing in isoform 3. 1 PublicationAdd BLAST | 46 | |
Alternative sequenceiVSP_045450 | 1 – 33 | Missing in isoform 2. 1 PublicationAdd BLAST | 33 | |
Alternative sequenceiVSP_045451 | 138 – 195 | LGLVR…IPAHH → GPAWDSVPFPISSSPKAFSP PRKHPWRKVFAPLTLPSPQL SWWSWDRDHLYSELVLPTWA FCKGLSHPLPGEILSRTHSS MSLCCSLLTV in isoform 2 and isoform 4. 1 PublicationAdd BLAST | 58 | |
Alternative sequenceiVSP_045452 | 174 – 195 | ALQDL…IPAHH → AALHGPMKTEMRTLVLGREG RTWECFLIGSER in isoform 3. 1 PublicationAdd BLAST | 22 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK055827 mRNA Translation: BAB71024.1 Different initiation. AK304650 mRNA Translation: BAG65426.1 BP199028 mRNA No translation available. AC010210 Genomic DNA No translation available. BC009546 mRNA Translation: AAH09546.1 BC031215 mRNA Translation: AAH31215.2 |
CCDSi | CCDS3070.2 [Q96DE0-1] CCDS54640.1 [Q96DE0-4] CCDS54641.1 [Q96DE0-3] |
RefSeqi | NP_001165376.1, NM_001171905.1 [Q96DE0-3] NP_001165377.1, NM_001171906.1 [Q96DE0-4] NP_689608.2, NM_152395.2 [Q96DE0-1] |
Genome annotation databases
Ensembli | ENST00000502852; ENSP00000422375; ENSG00000198585 [Q96DE0-4] ENST00000521288; ENSP00000429274; ENSG00000198585 [Q96DE0-1] ENST00000537561; ENSP00000440230; ENSG00000198585 [Q96DE0-3] |
GeneIDi | 131870 |
KEGGi | hsa:131870 |
UCSCi | uc003eog.3, human [Q96DE0-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK055827 mRNA Translation: BAB71024.1 Different initiation. AK304650 mRNA Translation: BAG65426.1 BP199028 mRNA No translation available. AC010210 Genomic DNA No translation available. BC009546 mRNA Translation: AAH09546.1 BC031215 mRNA Translation: AAH31215.2 |
CCDSi | CCDS3070.2 [Q96DE0-1] CCDS54640.1 [Q96DE0-4] CCDS54641.1 [Q96DE0-3] |
RefSeqi | NP_001165376.1, NM_001171905.1 [Q96DE0-3] NP_001165377.1, NM_001171906.1 [Q96DE0-4] NP_689608.2, NM_152395.2 [Q96DE0-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2XSQ | X-ray | 1.72 | A | 1-195 | [»] | |
3COU | X-ray | 1.80 | A | 1-195 | [»] | |
3MGM | X-ray | 1.80 | A/B | 1-195 | [»] | |
5VY2 | X-ray | 2.30 | A/B | 1-195 | [»] | |
5W6X | X-ray | 2.10 | A/B | 1-195 | [»] | |
5W6Z | X-ray | 2.61 | A/B/D/E | 1-195 | [»] | |
5WJI | X-ray | 2.30 | A/B | 1-195 | [»] | |
6B09 | X-ray | 3.20 | A/B | 1-195 | [»] | |
6CO2 | X-ray | 2.49 | A/B | 1-195 | [»] | |
6X7U | X-ray | 2.70 | A/C | 1-184 | [»] | |
6X7V | X-ray | 2.30 | A/B/C/D | 1-195 | [»] | |
SMRi | Q96DE0 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 126295, 13 interactors |
IntActi | Q96DE0, 3 interactors |
MINTi | Q96DE0 |
STRINGi | 9606.ENSP00000422375 |
PTM databases
iPTMneti | Q96DE0 |
PhosphoSitePlusi | Q96DE0 |
Polymorphism and mutation databases
BioMutai | NUDT16 |
DMDMi | 68565926 |
Proteomic databases
EPDi | Q96DE0 |
jPOSTi | Q96DE0 |
MassIVEi | Q96DE0 |
MaxQBi | Q96DE0 |
PaxDbi | Q96DE0 |
PeptideAtlasi | Q96DE0 |
PRIDEi | Q96DE0 |
ProteomicsDBi | 19864 24755 76283 [Q96DE0-1] |
TopDownProteomicsi | Q96DE0-1 [Q96DE0-1] |
Protocols and materials databases
Antibodypediai | 46680, 43 antibodies |
Genome annotation databases
Ensembli | ENST00000502852; ENSP00000422375; ENSG00000198585 [Q96DE0-4] ENST00000521288; ENSP00000429274; ENSG00000198585 [Q96DE0-1] ENST00000537561; ENSP00000440230; ENSG00000198585 [Q96DE0-3] |
GeneIDi | 131870 |
KEGGi | hsa:131870 |
UCSCi | uc003eog.3, human [Q96DE0-1] |
Organism-specific databases
CTDi | 131870 |
DisGeNETi | 131870 |
EuPathDBi | HostDB:ENSG00000198585.11 |
GeneCardsi | NUDT16 |
HGNCi | HGNC:26442, NUDT16 |
HPAi | ENSG00000198585, Low tissue specificity |
MIMi | 617381, gene |
neXtProti | NX_Q96DE0 |
OpenTargetsi | ENSG00000198585 |
PharmGKBi | PA134955224 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S20E, Eukaryota |
GeneTreei | ENSGT00390000016224 |
HOGENOMi | CLU_110418_1_0_1 |
InParanoidi | Q96DE0 |
OMAi | VDSCYAP |
OrthoDBi | 1385294at2759 |
PhylomeDBi | Q96DE0 |
Enzyme and pathway databases
BioCyci | MetaCyc:MONOMER-17869 |
BRENDAi | 3.6.1.62, 2681 3.6.1.64, 2681 |
PathwayCommonsi | Q96DE0 |
Reactomei | R-HSA-2393930, Phosphate bond hydrolysis by NUDT proteins |
Miscellaneous databases
BioGRID-ORCSi | 131870, 4 hits in 847 CRISPR screens |
ChiTaRSi | NUDT16, human |
EvolutionaryTracei | Q96DE0 |
GenomeRNAii | 131870 |
Pharosi | Q96DE0, Tbio |
PROi | PR:Q96DE0 |
RNActi | Q96DE0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000198585, Expressed in amniotic fluid and 211 other tissues |
Genevisiblei | Q96DE0, HS |
Family and domain databases
InterProi | View protein in InterPro IPR015797, NUDIX_hydrolase-like_dom_sf IPR000086, NUDIX_hydrolase_dom |
Pfami | View protein in Pfam PF00293, NUDIX, 1 hit |
SUPFAMi | SSF55811, SSF55811, 1 hit |
PROSITEi | View protein in PROSITE PS51462, NUDIX, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NUD16_HUMAN | |
Accessioni | Q96DE0Primary (citable) accession number: Q96DE0 Secondary accession number(s): B4E3B4 Q96N82 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 5, 2005 |
Last sequence update: | July 5, 2005 | |
Last modified: | December 2, 2020 | |
This is version 156 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families