Q8N4P3 (MESH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	HDDC3
Synonyms:	MESH1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	179 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	ppGpp hydrolyzing enzyme involved in starvation response. Ref.5
Catalytic activity	Guanosine 3',5'-bis(diphosphate) + H2O = guanosine 5'-diphosphate + diphosphate. Ref.5
Cofactor	Manganese. Ref.5
Sequence similarities	Belongs to the MESH1 family. Contains 1 HD domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	Manganese Metal-binding
Molecular function	Hydrolase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	metabolic process Inferred from electronic annotation. Source: GOC
Molecular_function	guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity Inferred from electronic annotation. Source: 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 179

179

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

PRO_0000263110

Regions

Domain

32 – 127

96

HD

Sites

Active site

65

1

Nucleophile Probable

Active site

66

1

Nucleophile Probable

Metal binding

35

1

Manganese

Metal binding

61

1

Manganese

Metal binding

62

1

Manganese

Metal binding

122

1

Manganese

Amino acid modifications

Modified residue

25

1

N6-acetyllysine Ref.3

Modified residue

97

1

N6-acetyllysine Ref.3

Modified residue

123

1

N6-acetyllysine Ref.3

Natural variations

Alternative sequence

137 – 140

4

GWSE → VKIQ in isoform 2.

VSP_021866

Alternative sequence

141 – 179

39

Missing in isoform 2.

VSP_021867

Experimental info

Mutagenesis

24

1

R → A: Abrogates ppGpp hydrolase activity. Ref.5

Mutagenesis

65

1

E → A: Abrogates ppGpp hydrolase activity. Ref.5

Mutagenesis

66

1

D → A: Reduces ppGpp hydrolase activity. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

179

Helix Strand Turn

Details...

Helix

4 – 18

15

Turn

19 – 21

3

Helix

34 – 45

12

Helix

52 – 60

9

Helix

63 – 66

4

Helix

71 – 88

18

Helix

97 – 107

11

Helix

108 – 110

3

Helix

113 – 132

20

Helix

140 – 157

18

Helix

162 – 173

12

Turn

174 – 176

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 9, 2007. Version 3. Checksum: E0946B0FA7BD8109	FASTA	179	20,329
	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
	Isoform 2 [UniParc]. Checksum: F3E269D4D804DEEE	FASTA	140	15,733
	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 ADKLYNLRDL NRCTPEVKIQ

References

	« Hide 'large scale' referencesShow '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. , 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]	"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, MASS SPECTROMETRY.
[4]	"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].
[5]	"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.

IPI

IPI00394782.
IPI00789618.

RefSeq

NP_940929.1. NM_198527.2.

UniGene

Hs.349979.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3NR1	X-ray	1.90	A/B	2-179	[»]

ProteinModelPortal

Q8N4P3.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8N4P3. 1 interaction.

MINT

MINT-1475376.

STRING

9606.ENSP00000330721.

PTM databases

PhosphoSite

Q8N4P3.

Polymorphism databases

DMDM

122065202.

Proteomic databases

PaxDb

Q8N4P3.

PRIDE

Q8N4P3.

Protocols and materials databases

DNASU

374659.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000330334; ENSP00000330721; ENSG00000184508.
ENST00000394272; ENSP00000377814; ENSG00000184508.

GeneID

374659.

KEGG

hsa:374659.

UCSC

uc002bqe.4. human.

Organism-specific databases

CTD

374659.

GeneCards

GC15M091474.

H-InvDB

HIX0012581.

HGNC

HGNC:30522. HDDC3.

HPA

HPA040895.

neXtProt

NX_Q8N4P3.

PharmGKB

PA142671696.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG113345.

HOVERGEN

HBG081594.

InParanoid

Q8N4P3.

KO

K01139.

OMA

PEGWSEH.

OrthoDB

EOG49PB0R.

Gene expression databases

ArrayExpress

Q8N4P3.

Bgee

Q8N4P3.

CleanEx

HS_HDDC3.

Genevestigator

Q8N4P3.

GermOnline

ENSG00000184508. Homo sapiens.

Family and domain databases

InterPro

IPR026020. (p)ppGpp_Synthase.
IPR003607. HD/PDEase_dom.
[Graphical view]

PANTHER

PTHR21262. PTHR21262. 1 hit.

SMART

SM00471. HDc. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8N4P3.

GenomeRNAi

374659.

NextBio

100241.

Entry information

Entry name

MESH1_HUMAN

Accession

Primary (citable) accession number: Q8N4P3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	January 9, 2007
Last modified:	May 1, 2013
This is version 81 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.