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Q8N4P3

- MESH1_HUMAN

UniProt

Q8N4P3 - MESH1_HUMAN

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Protein

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

Gene

HDDC3

Organism
Homo sapiens (Human)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi35 – 351Manganese
Metal bindingi61 – 611Manganese
Metal bindingi62 – 621Manganese
Active sitei65 – 651Nucleophile1 Publication
Active sitei66 – 661Nucleophile1 Publication
Metal bindingi122 – 1221Manganese

GO - Molecular functioni

  1. guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity Source: UniProtKB-EC
  2. metal ion binding Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Manganese, Metal-binding

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
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:30522. HDDC3.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 241R → A: Abrogates ppGpp hydrolase activity. 1 Publication
Mutagenesisi65 – 651E → A: Abrogates ppGpp hydrolase activity. 1 Publication
Mutagenesisi66 – 661D → A: Reduces ppGpp hydrolase activity. 1 Publication

Organism-specific databases

PharmGKBiPA142671696.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 179178Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1PRO_0000263110Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylglycine1 Publication
Modified residuei25 – 251N6-acetyllysine1 Publication
Modified residuei97 – 971N6-acetyllysine1 Publication
Modified residuei123 – 1231N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ8N4P3.
PaxDbiQ8N4P3.
PRIDEiQ8N4P3.

PTM databases

PhosphoSiteiQ8N4P3.

Expressioni

Gene expression databases

BgeeiQ8N4P3.
CleanExiHS_HDDC3.
ExpressionAtlasiQ8N4P3. baseline and differential.
GenevestigatoriQ8N4P3.

Organism-specific databases

HPAiHPA040895.

Interactioni

Protein-protein interaction databases

BioGridi131914. 4 interactions.
IntActiQ8N4P3. 1 interaction.
MINTiMINT-1475376.
STRINGi9606.ENSP00000330721.

Structurei

Secondary structure

1
179
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1815Combined sources
Turni19 – 213Combined sources
Helixi34 – 4512Combined sources
Helixi52 – 609Combined sources
Helixi63 – 664Combined sources
Helixi71 – 8818Combined sources
Helixi97 – 10711Combined sources
Helixi108 – 1103Combined sources
Helixi113 – 13220Combined sources
Helixi140 – 15718Combined sources
Helixi162 – 17312Combined sources
Turni174 – 1763Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3NR1X-ray1.90A/B2-179[»]
ProteinModelPortaliQ8N4P3.
SMRiQ8N4P3. Positions 2-179.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N4P3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 12796HDAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG113345.
GeneTreeiENSGT00390000011608.
HOVERGENiHBG081594.
KOiK01139.
OMAiNRCTPEG.
OrthoDBiEOG7X3QTC.
PhylomeDBiQ8N4P3.
TreeFamiTF313524.

Family and domain databases

InterProiIPR003607. HD/PDEase_dom.
[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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei137 – 1404GWSE → VKIQ in isoform 2. 1 PublicationVSP_021866
Alternative sequencei141 – 17939Missing in isoform 2. 1 PublicationVSP_021867Add
BLAST

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.4. human. [Q8N4P3-2]

Polymorphism databases

DMDMi122065202.

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 .
CCDSi CCDS10366.1. [Q8N4P3-2 ]
CCDS66866.1. [Q8N4P3-1 ]
RefSeqi NP_001273380.1. NM_001286451.1. [Q8N4P3-1 ]
NP_940929.1. NM_198527.3. [Q8N4P3-2 ]
UniGenei Hs.349979.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3NR1 X-ray 1.90 A/B 2-179 [» ]
ProteinModelPortali Q8N4P3.
SMRi Q8N4P3. Positions 2-179.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 131914. 4 interactions.
IntActi Q8N4P3. 1 interaction.
MINTi MINT-1475376.
STRINGi 9606.ENSP00000330721.

PTM databases

PhosphoSitei Q8N4P3.

Polymorphism databases

DMDMi 122065202.

Proteomic databases

MaxQBi Q8N4P3.
PaxDbi Q8N4P3.
PRIDEi Q8N4P3.

Protocols and materials databases

DNASUi 374659.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000330334 ; ENSP00000330721 ; ENSG00000184508 . [Q8N4P3-2 ]
ENST00000394272 ; ENSP00000377814 ; ENSG00000184508 . [Q8N4P3-1 ]
GeneIDi 374659.
KEGGi hsa:374659.
UCSCi uc002bqe.4. human. [Q8N4P3-2 ]

Organism-specific databases

CTDi 374659.
GeneCardsi GC15M091474.
H-InvDB HIX0012581.
HGNCi HGNC:30522. HDDC3.
HPAi HPA040895.
neXtProti NX_Q8N4P3.
PharmGKBi PA142671696.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG113345.
GeneTreei ENSGT00390000011608.
HOVERGENi HBG081594.
KOi K01139.
OMAi NRCTPEG.
OrthoDBi EOG7X3QTC.
PhylomeDBi Q8N4P3.
TreeFami TF313524.

Miscellaneous databases

EvolutionaryTracei Q8N4P3.
GenomeRNAii 374659.
NextBioi 100241.
PROi Q8N4P3.

Gene expression databases

Bgeei Q8N4P3.
CleanExi HS_HDDC3.
ExpressionAtlasi Q8N4P3. baseline and differential.
Genevestigatori Q8N4P3.

Family and domain databases

InterProi IPR003607. HD/PDEase_dom.
[Graphical view ]
SMARTi SM00471. HDc. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. 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.

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 26, 2014
This is version 95 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

External Data

Dasty 3