AP4A_CAEEL
ID AP4A_CAEEL Reviewed; 138 AA.
AC Q9U2M7;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical];
DE EC=3.6.1.-;
DE AltName: Full=Diadenosine 5',5'''-P1,P4-tetraphosphate asymmetrical hydrolase;
DE Short=Ap4A hydrolase;
DE Short=Ap4Aase;
DE Short=Diadenosine tetraphosphatase;
DE AltName: Full=Nudix hydrolase 4;
GN Name=ndx-4; ORFNames=Y37H9A.6;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS),
RP FUNCTION, AND COFACTOR.
RC STRAIN=Bristol N2;
RX PubMed=11738085; DOI=10.1016/s0167-4838(01)00263-1;
RA Abdelghany H.M., Gasmi L., Cartwright J.L., Bailey S., Rafferty J.B.,
RA McLennan A.G.;
RT "Cloning, characterisation and crystallisation of a diadenosine 5',5''-
RT P(1),P(4)-tetraphosphate pyrophosphohydrolase from Caenorhabditis
RT elegans.";
RL Biochim. Biophys. Acta 1550:27-36(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP MUTAGENESIS.
RC STRAIN=Bristol N2;
RX PubMed=12475970; DOI=10.1074/jbc.m211983200;
RA Abdelghany H.M., Bailey S., Blackburn G.M., Rafferty J.B., McLennan A.G.;
RT "Analysis of the catalytic and binding residues of the diadenosine
RT tetraphosphate pyrophosphohydrolase from Caenorhabditis elegans by site-
RT directed mutagenesis.";
RL J. Biol. Chem. 278:4435-4439(2003).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND SUBUNIT.
RX PubMed=11937063; DOI=10.1016/s0969-2126(02)00746-3;
RA Bailey S., Sedelnikova S.E., Blackburn G.M., Abdelghany H.M., Baker P.J.,
RA McLennan A.G., Rafferty J.B.;
RT "The crystal structure of diadenosine tetraphosphate hydrolase from
RT Caenorhabditis elegans in free and binary complex forms.";
RL Structure 10:589-600(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=11856844; DOI=10.1107/s0907444902000768;
RA Bailey S., Sedelnikova S.E., Blackburn G.M., Abdelghany H.M.,
RA McLennan A.G., Rafferty J.B.;
RT "Crystallization of a complex of Caenorhabditis elegans diadenosine
RT tetraphosphate hydrolase and a non-hydrolysable substrate analogue,
RT AppCH2ppA.";
RL Acta Crystallogr. D 58:526-528(2002).
CC -!- FUNCTION: Asymmetrically hydrolyzes Ap4A to yield AMP and ATP.
CC {ECO:0000269|PubMed:11738085}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + P(1),P(4)-bis(5'-adenosyl) tetraphosphate = AMP + ATP +
CC 2 H(+); Xref=Rhea:RHEA:32039, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58141, ChEBI:CHEBI:456215;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11738085};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:11738085};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11738085};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11738085};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:11738085};
CC Note=Divalent metal ions. Mg(2+), Co(2+), Mn(2+), Zn(2+) or Ca(2+).
CC {ECO:0000269|PubMed:11738085};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11937063}.
CC -!- DOMAIN: Mutagenesis suggests that interactions with P1- and P4-
CC phosphate are minimum indicating the enzyme may have a wide substrate
CC range.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AL032625; CAB63351.1; -; Genomic_DNA.
DR RefSeq; NP_493413.1; NM_061012.4.
DR PDB; 1KT9; X-ray; 1.98 A; A=1-138.
DR PDB; 1KTG; X-ray; 1.80 A; A/B=1-138.
DR PDBsum; 1KT9; -.
DR PDBsum; 1KTG; -.
DR AlphaFoldDB; Q9U2M7; -.
DR SMR; Q9U2M7; -.
DR BioGRID; 54272; 3.
DR DIP; DIP-24985N; -.
DR STRING; 6239.Y37H9A.6; -.
DR EPD; Q9U2M7; -.
DR PaxDb; Q9U2M7; -.
DR PeptideAtlas; Q9U2M7; -.
DR EnsemblMetazoa; Y37H9A.6.1; Y37H9A.6.1; WBGene00003581.
DR EnsemblMetazoa; Y37H9A.6.2; Y37H9A.6.2; WBGene00003581.
DR GeneID; 189639; -.
DR KEGG; cel:CELE_Y37H9A.6; -.
DR UCSC; Y37H9A.6.2; c. elegans.
DR CTD; 189639; -.
DR WormBase; Y37H9A.6; CE20230; WBGene00003581; ndx-4.
DR eggNOG; KOG2839; Eukaryota.
DR GeneTree; ENSGT00390000002416; -.
DR HOGENOM; CLU_037162_14_5_1; -.
DR InParanoid; Q9U2M7; -.
DR OMA; WRDYEQA; -.
DR OrthoDB; 1107148at2759; -.
DR PhylomeDB; Q9U2M7; -.
DR BRENDA; 3.6.1.17; 1045.
DR Reactome; R-CEL-3299685; Detoxification of Reactive Oxygen Species.
DR SABIO-RK; Q9U2M7; -.
DR EvolutionaryTrace; Q9U2M7; -.
DR PRO; PR:Q9U2M7; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003581; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0043135; F:5-phosphoribosyl 1-pyrophosphate pyrophosphatase activity; IDA:WormBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004081; F:bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity; IDA:UniProtKB.
DR GO; GO:0006172; P:ADP biosynthetic process; IDA:WormBase.
DR GO; GO:0006167; P:AMP biosynthetic process; IDA:WormBase.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; IDA:WormBase.
DR GO; GO:0015967; P:diadenosine tetraphosphate catabolic process; IDA:WormBase.
DR GO; GO:0019693; P:ribose phosphate metabolic process; IDA:WormBase.
DR CDD; cd03428; Ap4A_hydrolase_human_like; 1.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR003565; Tetra_PHTase.
DR Pfam; PF00293; NUDIX; 1.
DR PRINTS; PR01405; TETRPHPHTASE.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Calcium; Cobalt; Hydrolase; Magnesium;
KW Manganese; Nucleotide-binding; Reference proteome; Zinc.
FT CHAIN 1..138
FT /note="Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical]"
FT /id="PRO_0000057106"
FT DOMAIN 1..132
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 37..58
FT /note="Nudix box"
FT MUTAGEN 27
FT /note="Y->A: No Effect on substrate binding or catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 27
FT /note="Y->D: Slight increase in substrate binding and no
FT effect on catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 31
FT /note="H->A: Increases substrate binding and reduces
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 31
FT /note="H->V: Increases substrate binding and reduces
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 36
FT /note="K->M: No effect on substrate binding and reduces
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 38
FT /note="H->G: Slight decrease in substrate binding and
FT slight increase in catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 38
FT /note="H->K: Slight decrease in substrate binding and
FT slight increase in catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 52
FT /note="E->Q: No effect on substrate binding and strongly
FT reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 56
FT /note="E->Q: No effect on substrate binding and strongly
FT reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 76
FT /note="Y->A: Increases substrate binding and slightly
FT reduces catalytic activity. Reduces catalytic activity;
FT when associated with A-121."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 79
FT /note="K->M: Slight increase in substrate binding and
FT reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 81
FT /note="K->M: Slight increase in substrate binding and
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 83
FT /note="K->M: Increases substrate binding and reduces
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 103
FT /note="E->Q: No effect on substrate binding and reduces
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12475970"
FT MUTAGEN 121
FT /note="Y->A: Increases substrate binding and slightly
FT reduces catalytic activity. Reduces catalytic activity;
FT when associated with A-76."
FT /evidence="ECO:0000269|PubMed:12475970"
FT STRAND 3..14
FT /evidence="ECO:0007829|PDB:1KTG"
FT STRAND 17..27
FT /evidence="ECO:0007829|PDB:1KTG"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:1KTG"
FT HELIX 45..57
FT /evidence="ECO:0007829|PDB:1KTG"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:1KTG"
FT STRAND 64..78
FT /evidence="ECO:0007829|PDB:1KTG"
FT STRAND 81..92
FT /evidence="ECO:0007829|PDB:1KTG"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:1KTG"
FT HELIX 112..119
FT /evidence="ECO:0007829|PDB:1KTG"
FT HELIX 122..137
FT /evidence="ECO:0007829|PDB:1KTG"
SQ SEQUENCE 138 AA; 15889 MW; 5C123085602CE5E5 CRC64;
MVVKAAGLVI YRKLAGKIEF LLLQASYPPH HWTPPKGHVD PGEDEWQAAI RETKEEANIT
KEQLTIHEDC HETLFYEAKG KPKSVKYWLA KLNNPDDVQL SHEHQNWKWC ELEDAIKIAD
YAEMGSLLRK FSAFLAGF
