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Q8N4P3 (MESH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HDDC3
Synonyms:MESH1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length179 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

ppGpp hydrolyzing enzyme involved in starvation response. Ref.6

Catalytic activity

Guanosine 3',5'-bis(diphosphate) + H2O = guanosine 5'-diphosphate + diphosphate. Ref.6

Cofactor

Manganese. Ref.6

Sequence similarities

Belongs to the MESH1 family.

Contains 1 HD domain.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   LigandManganese
Metal-binding
   Molecular functionHydrolase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Molecular_functionguanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N4P3-1)

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: Q8N4P3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     137-140: GWSE → VKIQ
     141-179: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 179178Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1
PRO_0000263110

Regions

Domain32 – 12796HD

Sites

Active site651Nucleophile Probable
Active site661Nucleophile Probable
Metal binding351Manganese
Metal binding611Manganese
Metal binding621Manganese
Metal binding1221Manganese

Amino acid modifications

Modified residue21N-acetylglycine Ref.3
Modified residue251N6-acetyllysine Ref.4
Modified residue971N6-acetyllysine Ref.4
Modified residue1231N6-acetyllysine Ref.4

Natural variations

Alternative sequence137 – 1404GWSE → VKIQ in isoform 2.
VSP_021866
Alternative sequence141 – 17939Missing in isoform 2.
VSP_021867

Experimental info

Mutagenesis241R → A: Abrogates ppGpp hydrolase activity. Ref.6
Mutagenesis651E → A: Abrogates ppGpp hydrolase activity. Ref.6
Mutagenesis661D → A: Reduces ppGpp hydrolase activity. Ref.6

Secondary structure

...................... 179
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 9, 2007. Version 3.
Checksum: E0946B0FA7BD8109

FASTA17920,329
        10         20         30         40         50         60 
MGSEAAQLLE AADFAARKHR QQRRKDPEGT PYINHPIGVA RILTHEAGIT DIVVLQAALL 

        70         80         90        100        110        120 
HDTVEDTDTT LDEVELHFGA QVRRLVEEVT DDKTLPKLER KRLQVEQAPH SSPGAKLVKL 

       130        140        150        160        170 
ADKLYNLRDL NRCTPEGWSE HRVQEYFEWA AQVVKGLQGT NRQLEEALKH LFKQRGLTI 

« Hide

Isoform 2 [UniParc].

Checksum: F3E269D4D804DEEE
Show »

FASTA14015,733

References

« Hide 'large scale' references
[1]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Cervix.
[3]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[4]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-25; LYS-97 AND LYS-123, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses."
Sun D., Lee G., Lee J.H., Kim H.-Y., Rhee H.W., Park S.-Y., Kim K.J., Kim Y., Kim B.Y., Hong J.-I., Park C., Choy H.E., Kim J.H., Jeon Y.H., Chung J.
Nat. Struct. Mol. Biol. 17:1188-1194(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 2-179, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, COFACTOR, MUTAGENESIS OF ARG-24; GLU-65 AND ASP-66, MANGANESE-BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC068831 Genomic DNA. No translation available.
BC033794 mRNA. Translation: AAH33794.1.
CCDSCCDS10366.1. [Q8N4P3-2]
CCDS66866.1. [Q8N4P3-1]
RefSeqNP_001273380.1. NM_001286451.1. [Q8N4P3-1]
NP_940929.1. NM_198527.3. [Q8N4P3-2]
UniGeneHs.349979.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3NR1X-ray1.90A/B2-179[»]
ProteinModelPortalQ8N4P3.
SMRQ8N4P3. Positions 2-179.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid131914. 3 interactions.
IntActQ8N4P3. 1 interaction.
MINTMINT-1475376.
STRING9606.ENSP00000330721.

PTM databases

PhosphoSiteQ8N4P3.

Polymorphism databases

DMDM122065202.

Proteomic databases

MaxQBQ8N4P3.
PaxDbQ8N4P3.
PRIDEQ8N4P3.

Protocols and materials databases

DNASU374659.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330334; ENSP00000330721; ENSG00000184508. [Q8N4P3-2]
ENST00000394272; ENSP00000377814; ENSG00000184508. [Q8N4P3-1]
GeneID374659.
KEGGhsa:374659.
UCSCuc002bqe.4. human. [Q8N4P3-2]

Organism-specific databases

CTD374659.
GeneCardsGC15M091474.
H-InvDBHIX0012581.
HGNCHGNC:30522. HDDC3.
HPAHPA040895.
neXtProtNX_Q8N4P3.
PharmGKBPA142671696.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG113345.
HOVERGENHBG081594.
InParanoidQ8N4P3.
KOK01139.
OMANRCTPEG.
OrthoDBEOG7X3QTC.
PhylomeDBQ8N4P3.
TreeFamTF313524.

Gene expression databases

ArrayExpressQ8N4P3.
BgeeQ8N4P3.
CleanExHS_HDDC3.
GenevestigatorQ8N4P3.

Family and domain databases

InterProIPR003607. HD/PDEase_dom.
[Graphical view]
SMARTSM00471. HDc. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8N4P3.
GenomeRNAi374659.
NextBio100241.
PROQ8N4P3.

Entry information

Entry nameMESH1_HUMAN
AccessionPrimary (citable) accession number: Q8N4P3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: January 9, 2007
Last modified: July 9, 2014
This is version 92 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM