MESH1_HUMAN
ID MESH1_HUMAN Reviewed; 179 AA.
AC Q8N4P3;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1;
DE EC=3.1.7.2;
DE AltName: Full=HD domain-containing protein 3;
DE AltName: Full=Metazoan SpoT homolog 1;
DE Short=MESH1;
DE AltName: Full=Penta-phosphate guanosine-3'-pyrophosphohydrolase;
DE Short=(ppGpp)ase;
GN Name=HDDC3; Synonyms=MESH1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-25; LYS-97 AND LYS-123, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 2-179, FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVE SITE, COFACTOR, MUTAGENESIS OF ARG-24; GLU-65 AND ASP-66,
RP AND MANGANESE-BINDING SITES.
RX PubMed=20818390; DOI=10.1038/nsmb.1906;
RA Sun D., Lee G., Lee J.H., Kim H.-Y., Rhee H.W., Park S.-Y., Kim K.J.,
RA Kim Y., Kim B.Y., Hong J.-I., Park C., Choy H.E., Kim J.H., Jeon Y.H.,
RA Chung J.;
RT "A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation
RT responses.";
RL Nat. Struct. Mol. Biol. 17:1188-1194(2010).
CC -!- FUNCTION: ppGpp hydrolyzing enzyme involved in starvation response.
CC {ECO:0000269|PubMed:20818390}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine 3',5'-bis(diphosphate) + H2O = diphosphate + GDP +
CC H(+); Xref=Rhea:RHEA:14253, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58189, ChEBI:CHEBI:77828; EC=3.1.7.2;
CC Evidence={ECO:0000269|PubMed:20818390};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:20818390};
CC -!- INTERACTION:
CC Q8N4P3; P0C7W6: CCDC172; NbExp=4; IntAct=EBI-750003, EBI-2548868;
CC Q8N4P3; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-750003, EBI-10181988;
CC Q8N4P3; O00471: EXOC5; NbExp=3; IntAct=EBI-750003, EBI-949824;
CC Q8N4P3; Q5VSY0: GKAP1; NbExp=3; IntAct=EBI-750003, EBI-743722;
CC Q8N4P3; Q0D2H9: GOLGA8DP; NbExp=3; IntAct=EBI-750003, EBI-10181276;
CC Q8N4P3; Q08AF8: GOLGA8G; NbExp=3; IntAct=EBI-750003, EBI-10181260;
CC Q8N4P3; Q13287: NMI; NbExp=7; IntAct=EBI-750003, EBI-372942;
CC Q8N4P3; Q15025: TNIP1; NbExp=3; IntAct=EBI-750003, EBI-357849;
CC Q8N4P3; Q5VU62: TPM3; NbExp=3; IntAct=EBI-750003, EBI-10184033;
CC Q8N4P3-2; Q6PJH3: AKAP9; NbExp=3; IntAct=EBI-12037393, EBI-11745576;
CC Q8N4P3-2; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-12037393, EBI-10175300;
CC Q8N4P3-2; P43358: MAGEA4; NbExp=3; IntAct=EBI-12037393, EBI-743122;
CC Q8N4P3-2; Q9BUK6: MSTO1; NbExp=3; IntAct=EBI-12037393, EBI-2340176;
CC Q8N4P3-2; Q13287: NMI; NbExp=6; IntAct=EBI-12037393, EBI-372942;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N4P3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N4P3-2; Sequence=VSP_021866, VSP_021867;
CC -!- SIMILARITY: Belongs to the MESH1 family. {ECO:0000305}.
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DR EMBL; AC068831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033794; AAH33794.1; -; mRNA.
DR CCDS; CCDS10366.1; -. [Q8N4P3-2]
DR CCDS; CCDS66866.1; -. [Q8N4P3-1]
DR RefSeq; NP_001273380.1; NM_001286451.1. [Q8N4P3-1]
DR RefSeq; NP_940929.1; NM_198527.3. [Q8N4P3-2]
DR PDB; 3NR1; X-ray; 1.90 A; A/B=2-179.
DR PDB; 5VXA; X-ray; 2.10 A; A/B=1-179.
DR PDBsum; 3NR1; -.
DR PDBsum; 5VXA; -.
DR AlphaFoldDB; Q8N4P3; -.
DR SMR; Q8N4P3; -.
DR BioGRID; 131914; 67.
DR IntAct; Q8N4P3; 15.
DR STRING; 9606.ENSP00000377814; -.
DR iPTMnet; Q8N4P3; -.
DR PhosphoSitePlus; Q8N4P3; -.
DR BioMuta; HDDC3; -.
DR DMDM; 122065202; -.
DR EPD; Q8N4P3; -.
DR jPOST; Q8N4P3; -.
DR MassIVE; Q8N4P3; -.
DR MaxQB; Q8N4P3; -.
DR PaxDb; Q8N4P3; -.
DR PeptideAtlas; Q8N4P3; -.
DR PRIDE; Q8N4P3; -.
DR ProteomicsDB; 71953; -. [Q8N4P3-1]
DR ProteomicsDB; 71954; -. [Q8N4P3-2]
DR Antibodypedia; 43848; 122 antibodies from 21 providers.
DR DNASU; 374659; -.
DR Ensembl; ENST00000330334.7; ENSP00000330721.3; ENSG00000184508.12. [Q8N4P3-2]
DR Ensembl; ENST00000394272.8; ENSP00000377814.4; ENSG00000184508.12. [Q8N4P3-1]
DR Ensembl; ENST00000646620.1; ENSP00000493549.1; ENSG00000184508.12. [Q8N4P3-1]
DR GeneID; 374659; -.
DR KEGG; hsa:374659; -.
DR MANE-Select; ENST00000394272.8; ENSP00000377814.4; NM_001286451.2; NP_001273380.1.
DR UCSC; uc002bqe.6; human. [Q8N4P3-1]
DR CTD; 374659; -.
DR DisGeNET; 374659; -.
DR GeneCards; HDDC3; -.
DR HGNC; HGNC:30522; HDDC3.
DR HPA; ENSG00000184508; Low tissue specificity.
DR neXtProt; NX_Q8N4P3; -.
DR OpenTargets; ENSG00000184508; -.
DR PharmGKB; PA142671696; -.
DR VEuPathDB; HostDB:ENSG00000184508; -.
DR eggNOG; KOG1157; Eukaryota.
DR GeneTree; ENSGT00390000011608; -.
DR HOGENOM; CLU_084517_1_0_1; -.
DR OMA; FVWASEV; -.
DR PhylomeDB; Q8N4P3; -.
DR TreeFam; TF313524; -.
DR PathwayCommons; Q8N4P3; -.
DR SignaLink; Q8N4P3; -.
DR BioGRID-ORCS; 374659; 13 hits in 1075 CRISPR screens.
DR EvolutionaryTrace; Q8N4P3; -.
DR GenomeRNAi; 374659; -.
DR Pharos; Q8N4P3; Tbio.
DR PRO; PR:Q8N4P3; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8N4P3; protein.
DR Bgee; ENSG00000184508; Expressed in parotid gland and 154 other tissues.
DR ExpressionAtlas; Q8N4P3; baseline and differential.
DR Genevisible; Q8N4P3; HS.
DR GO; GO:0008893; F:guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR CDD; cd00077; HDc; 1.
DR InterPro; IPR003607; HD/PDEase_dom.
DR InterPro; IPR006674; HD_domain.
DR SMART; SM00471; HDc; 1.
DR PROSITE; PS51831; HD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Hydrolase; Manganese;
KW Metal-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..179
FT /note="Guanosine-3',5'-bis(diphosphate) 3'-
FT pyrophosphohydrolase MESH1"
FT /id="PRO_0000263110"
FT DOMAIN 32..127
FT /note="HD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT ACT_SITE 65
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:20818390"
FT ACT_SITE 66
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:20818390"
FT BINDING 35
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 61
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 62
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 122
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 25
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 97
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 123
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 137..140
FT /note="GWSE -> VKIQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021866"
FT VAR_SEQ 141..179
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021867"
FT MUTAGEN 24
FT /note="R->A: Abrogates ppGpp hydrolase activity."
FT /evidence="ECO:0000269|PubMed:20818390"
FT MUTAGEN 65
FT /note="E->A: Abrogates ppGpp hydrolase activity."
FT /evidence="ECO:0000269|PubMed:20818390"
FT MUTAGEN 66
FT /note="D->A: Reduces ppGpp hydrolase activity."
FT /evidence="ECO:0000269|PubMed:20818390"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:3NR1"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 34..45
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 71..88
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 97..107
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 113..132
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 140..157
FT /evidence="ECO:0007829|PDB:3NR1"
FT HELIX 162..173
FT /evidence="ECO:0007829|PDB:3NR1"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:3NR1"
SQ SEQUENCE 179 AA; 20329 MW; E0946B0FA7BD8109 CRC64;
MGSEAAQLLE AADFAARKHR QQRRKDPEGT PYINHPIGVA RILTHEAGIT DIVVLQAALL
HDTVEDTDTT LDEVELHFGA QVRRLVEEVT DDKTLPKLER KRLQVEQAPH SSPGAKLVKL
ADKLYNLRDL NRCTPEGWSE HRVQEYFEWA AQVVKGLQGT NRQLEEALKH LFKQRGLTI
