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Protein

Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1

Gene

HDDC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

ppGpp hydrolyzing enzyme involved in starvation response.1 Publication

Catalytic activityi

Guanosine 3',5'-bis(diphosphate) + H2O = guanosine 5'-diphosphate + diphosphate.1 Publication

Cofactori

Mn2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi35Manganese1
Metal bindingi61Manganese1
Metal bindingi62Manganese1
Active sitei65Nucleophile1 Publication1
Active sitei66Nucleophile1 Publication1
Metal bindingi122Manganese1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:G66-32897-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1 (EC:3.1.7.2)
Alternative name(s):
HD domain-containing protein 3
Metazoan SpoT homolog 1
Short name:
MESH1
Penta-phosphate guanosine-3'-pyrophosphohydrolase
Short name:
(ppGpp)ase
Gene namesi
Name:HDDC3
Synonyms:MESH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:30522. HDDC3.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24R → A: Abrogates ppGpp hydrolase activity. 1 Publication1
Mutagenesisi65E → A: Abrogates ppGpp hydrolase activity. 1 Publication1
Mutagenesisi66D → A: Reduces ppGpp hydrolase activity. 1 Publication1

Organism-specific databases

DisGeNETi374659.
OpenTargetsiENSG00000184508.
PharmGKBiPA142671696.

Polymorphism and mutation databases

DMDMi122065202.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002631102 – 179Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1Add BLAST178

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylglycineCombined sources1
Modified residuei25N6-acetyllysineCombined sources1
Modified residuei97N6-acetyllysineCombined sources1
Modified residuei123N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ8N4P3.
MaxQBiQ8N4P3.
PaxDbiQ8N4P3.
PeptideAtlasiQ8N4P3.
PRIDEiQ8N4P3.

PTM databases

iPTMnetiQ8N4P3.
PhosphoSitePlusiQ8N4P3.

Expressioni

Gene expression databases

BgeeiENSG00000184508.
CleanExiHS_HDDC3.
ExpressionAtlasiQ8N4P3. baseline and differential.
GenevisibleiQ8N4P3. HS.

Organism-specific databases

HPAiHPA040895.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC172P0C7W63EBI-750003,EBI-2548868
CEP57L1Q8IYX8-23EBI-750003,EBI-10181988
EXOC5Q8IW243EBI-750003,EBI-10171392
GKAP1Q5VSY03EBI-750003,EBI-743722
GOLGA8DPQ0D2H93EBI-750003,EBI-10181276
GOLGA8GQ08AF83EBI-750003,EBI-10181260
NMIQ132874EBI-750003,EBI-372942
NMIQ8WTW23EBI-750003,EBI-10174268
TNIP1Q150253EBI-750003,EBI-357849
TPM3Q5VU623EBI-750003,EBI-10184033

Protein-protein interaction databases

BioGridi131914. 13 interactors.
IntActiQ8N4P3. 13 interactors.
MINTiMINT-1475376.
STRINGi9606.ENSP00000330721.

Structurei

Secondary structure

1179
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 18Combined sources15
Turni19 – 21Combined sources3
Helixi34 – 45Combined sources12
Helixi52 – 60Combined sources9
Helixi63 – 66Combined sources4
Helixi71 – 88Combined sources18
Helixi97 – 107Combined sources11
Helixi108 – 110Combined sources3
Helixi113 – 132Combined sources20
Helixi140 – 157Combined sources18
Helixi162 – 173Combined sources12
Turni174 – 176Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NR1X-ray1.90A/B2-179[»]
ProteinModelPortaliQ8N4P3.
SMRiQ8N4P3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N4P3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 127HDAdd BLAST96

Sequence similaritiesi

Belongs to the MESH1 family.Curated
Contains 1 HD domain.Curated

Phylogenomic databases

eggNOGiKOG1157. Eukaryota.
COG0317. LUCA.
GeneTreeiENSGT00390000011608.
HOVERGENiHBG081594.
KOiK01139.
OMAiRCTPEGW.
OrthoDBiEOG091G0L17.
PhylomeDBiQ8N4P3.
TreeFamiTF313524.

Family and domain databases

Gene3Di1.10.3210.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
[Graphical view]
PfamiPF13328. HD_4. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N4P3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGSEAAQLLE AADFAARKHR QQRRKDPEGT PYINHPIGVA RILTHEAGIT
60 70 80 90 100
DIVVLQAALL HDTVEDTDTT LDEVELHFGA QVRRLVEEVT DDKTLPKLER
110 120 130 140 150
KRLQVEQAPH SSPGAKLVKL ADKLYNLRDL NRCTPEGWSE HRVQEYFEWA
160 170
AQVVKGLQGT NRQLEEALKH LFKQRGLTI
Length:179
Mass (Da):20,329
Last modified:January 9, 2007 - v3
Checksum:iE0946B0FA7BD8109
GO
Isoform 2 (identifier: Q8N4P3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-140: GWSE → VKIQ
     141-179: Missing.

Note: No experimental confirmation available.
Show »
Length:140
Mass (Da):15,733
Checksum:iF3E269D4D804DEEE
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_021866137 – 140GWSE → VKIQ in isoform 2. 1 Publication4
Alternative sequenceiVSP_021867141 – 179Missing in isoform 2. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC068831 Genomic DNA. No translation available.
BC033794 mRNA. Translation: AAH33794.1.
CCDSiCCDS10366.1. [Q8N4P3-2]
CCDS66866.1. [Q8N4P3-1]
RefSeqiNP_001273380.1. NM_001286451.1. [Q8N4P3-1]
NP_940929.1. NM_198527.3. [Q8N4P3-2]
UniGeneiHs.349979.

Genome annotation databases

EnsembliENST00000330334; ENSP00000330721; ENSG00000184508. [Q8N4P3-2]
ENST00000394272; ENSP00000377814; ENSG00000184508. [Q8N4P3-1]
GeneIDi374659.
KEGGihsa:374659.
UCSCiuc002bqe.6. human. [Q8N4P3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC068831 Genomic DNA. No translation available.
BC033794 mRNA. Translation: AAH33794.1.
CCDSiCCDS10366.1. [Q8N4P3-2]
CCDS66866.1. [Q8N4P3-1]
RefSeqiNP_001273380.1. NM_001286451.1. [Q8N4P3-1]
NP_940929.1. NM_198527.3. [Q8N4P3-2]
UniGeneiHs.349979.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NR1X-ray1.90A/B2-179[»]
ProteinModelPortaliQ8N4P3.
SMRiQ8N4P3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi131914. 13 interactors.
IntActiQ8N4P3. 13 interactors.
MINTiMINT-1475376.
STRINGi9606.ENSP00000330721.

PTM databases

iPTMnetiQ8N4P3.
PhosphoSitePlusiQ8N4P3.

Polymorphism and mutation databases

DMDMi122065202.

Proteomic databases

EPDiQ8N4P3.
MaxQBiQ8N4P3.
PaxDbiQ8N4P3.
PeptideAtlasiQ8N4P3.
PRIDEiQ8N4P3.

Protocols and materials databases

DNASUi374659.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330334; ENSP00000330721; ENSG00000184508. [Q8N4P3-2]
ENST00000394272; ENSP00000377814; ENSG00000184508. [Q8N4P3-1]
GeneIDi374659.
KEGGihsa:374659.
UCSCiuc002bqe.6. human. [Q8N4P3-1]

Organism-specific databases

CTDi374659.
DisGeNETi374659.
GeneCardsiHDDC3.
H-InvDBHIX0012581.
HGNCiHGNC:30522. HDDC3.
HPAiHPA040895.
neXtProtiNX_Q8N4P3.
OpenTargetsiENSG00000184508.
PharmGKBiPA142671696.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1157. Eukaryota.
COG0317. LUCA.
GeneTreeiENSGT00390000011608.
HOVERGENiHBG081594.
KOiK01139.
OMAiRCTPEGW.
OrthoDBiEOG091G0L17.
PhylomeDBiQ8N4P3.
TreeFamiTF313524.

Enzyme and pathway databases

BioCyciZFISH:G66-32897-MONOMER.

Miscellaneous databases

EvolutionaryTraceiQ8N4P3.
GenomeRNAii374659.
PROiQ8N4P3.

Gene expression databases

BgeeiENSG00000184508.
CleanExiHS_HDDC3.
ExpressionAtlasiQ8N4P3. baseline and differential.
GenevisibleiQ8N4P3. HS.

Family and domain databases

Gene3Di1.10.3210.10. 2 hits.
InterProiIPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
[Graphical view]
PfamiPF13328. HD_4. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMESH1_HUMAN
AccessioniPrimary (citable) accession number: Q8N4P3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: January 9, 2007
Last modified: November 30, 2016
This is version 114 of the entry and version 3 of the sequence. [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, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.