DXO1_KLULA
ID DXO1_KLULA Reviewed; 403 AA.
AC Q6CPU0;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Decapping and exoribonuclease protein 1 {ECO:0000303|PubMed:28283058};
DE Short=KlDxo1 {ECO:0000303|PubMed:28283058};
DE EC=3.6.1.- {ECO:0000269|PubMed:22961381};
DE AltName: Full=5'-3' exoribonuclease Dxo1 {ECO:0000305};
DE EC=3.1.13.- {ECO:0000269|PubMed:22961381};
DE AltName: Full=NAD-capped RNA hydrolase Dxo1 {ECO:0000305};
DE Short=DeNADding enzyme Dxo1 {ECO:0000305};
DE EC=3.6.1.- {ECO:0000269|PubMed:28283058};
GN Name=DXO1 {ECO:0000303|PubMed:28283058}; OrderedLocusNames=KLLA0E02245g;
OS Kluyveromyces lactis (strain ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 /
OS NRRL Y-1140 / WM37) (Yeast) (Candida sphaerica).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX NCBI_TaxID=284590;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 8585 / CBS 2359 / DSM 70799 / NBRC 1267 / NRRL Y-1140 / WM37;
RX PubMed=15229592; DOI=10.1038/nature02579;
RA Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA Weissenbach J., Wincker P., Souciet J.-L.;
RT "Genome evolution in yeasts.";
RL Nature 430:35-44(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH MANGANESE, FUNCTION,
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF LEU-161; HIS-163 AND ASP-167.
RX PubMed=22961381; DOI=10.1038/nsmb.2381;
RA Chang J.H., Jiao X., Chiba K., Oh C., Martin C.E., Kiledjian M., Tong L.;
RT "Dxo1 is a new type of eukaryotic enzyme with both decapping and 5'-3'
RT exoribonuclease activity.";
RL Nat. Struct. Mol. Biol. 19:1011-1017(2012).
RN [3]
RP FUNCTION.
RX PubMed=28283058; DOI=10.1016/j.cell.2017.02.019;
RA Jiao X., Doamekpor S.K., Bird J.G., Nickels B.E., Tong L., Hart R.P.,
RA Kiledjian M.;
RT "5' end nicotinamide adenine dinucleotide cap in human cells promotes RNA
RT decay through DXO-mediated deNADding.";
RL Cell 168:1015-1027(2017).
CC -!- FUNCTION: Decapping enzyme for NAD-capped RNAs: specifically hydrolyzes
CC the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs
CC by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA
CC (PubMed:28283058). The NAD-cap is present at the 5'-end of some RNAs
CC and snoRNAs (By similarity). In contrast to the canonical 5'-end N7
CC methylguanosine (m7G) cap, the NAD cap promotes mRNA decay (By
CC similarity). Also acts as a non-canonical decapping enzyme that removes
CC the entire cap structure of m7G capped or incompletely capped RNAs and
CC mediates their subsequent degradation (PubMed:22961381). Has decapping
CC and 5'-3' exonuclease activities (PubMed:22961381). Has decapping
CC activity toward incomplete 5'-end cap mRNAs such as unmethylated 5'-
CC end-capped RNA to release GpppN and 5'-end monophosphate RNA
CC (PubMed:22961381). The 5'-end monophosphate RNA is then degraded by the
CC 5'-3' exoribonuclease activity, enabling this enzyme to decap and
CC degrade incompletely capped mRNAs (PubMed:22961381).
CC {ECO:0000250|UniProtKB:O70348, ECO:0000269|PubMed:22961381,
CC ECO:0000269|PubMed:28283058}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end NAD(+)-phospho-ribonucleoside in mRNA + H2O = a 5'-
CC end phospho-ribonucleoside in mRNA + H(+) + NAD(+);
CC Xref=Rhea:RHEA:60880, Rhea:RHEA-COMP:15692, Rhea:RHEA-COMP:15698,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:138282, ChEBI:CHEBI:144029;
CC Evidence={ECO:0000250|UniProtKB:O13836};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60881;
CC Evidence={ECO:0000250|UniProtKB:O13836};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside-
CC ribonucleotide in mRNA + H2O = a (N(7)-methyl 5'-triphospho-
CC guanosine)-nucleoside + a 5'-end phospho-ribonucleoside in mRNA +
CC H(+); Xref=Rhea:RHEA:66928, Rhea:RHEA-COMP:15692, Rhea:RHEA-
CC COMP:17313, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:138282,
CC ChEBI:CHEBI:172876, ChEBI:CHEBI:172877;
CC Evidence={ECO:0000269|PubMed:22961381};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66929;
CC Evidence={ECO:0000269|PubMed:22961381};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:22961381};
CC Note=Divalent metal cation. {ECO:0000269|PubMed:22961381};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q06349}.
CC -!- SIMILARITY: Belongs to the DXO/Dom3Z family. {ECO:0000305}.
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DR EMBL; CR382125; CAG99136.1; -; Genomic_DNA.
DR RefSeq; XP_454049.1; XM_454049.1.
DR PDB; 4GPS; X-ray; 2.40 A; A=1-403.
DR PDB; 4GPU; X-ray; 2.80 A; A=1-403.
DR PDBsum; 4GPS; -.
DR PDBsum; 4GPU; -.
DR AlphaFoldDB; Q6CPU0; -.
DR SMR; Q6CPU0; -.
DR STRING; 28985.XP_454049.1; -.
DR EnsemblFungi; CAG99136; CAG99136; KLLA0_E02245g.
DR GeneID; 2894233; -.
DR KEGG; kla:KLLA0_E02245g; -.
DR eggNOG; ENOG502RWNP; Eukaryota.
DR HOGENOM; CLU_696510_0_0_1; -.
DR InParanoid; Q6CPU0; -.
DR OMA; CIRSICK; -.
DR Proteomes; UP000000598; Chromosome E.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:GOC.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0110152; F:RNA NAD-cap (NAD-forming) hydrolase activity; IEA:RHEA.
DR GO; GO:0110155; P:NAD-cap decapping; IDA:UniProtKB.
DR GO; GO:0071028; P:nuclear mRNA surveillance; IMP:UniProtKB.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:UniProtKB.
DR InterPro; IPR039039; RAI1-like_fam.
DR PANTHER; PTHR12395; PTHR12395; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Exonuclease; Hydrolase; Metal-binding; Nuclease;
KW Nucleotide-binding; Reference proteome; RNA-binding.
FT CHAIN 1..403
FT /note="Decapping and exoribonuclease protein 1"
FT /id="PRO_0000422597"
FT BINDING 223
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22961381"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O70348"
FT BINDING 262
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22961381"
FT BINDING 273
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22961381"
FT BINDING 274
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22961381"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O70348"
FT BINDING 297
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O70348"
FT MUTAGEN 161
FT /note="L->W: Reduced decapping activity without affecting
FT the exonuclease activity. Reduced decapping and exonuclease
FT activities; when associated with G-163."
FT /evidence="ECO:0000269|PubMed:22961381"
FT MUTAGEN 163
FT /note="H->G: Does not affect the exonuclease activity.
FT Reduced decapping and exonuclease activities; when
FT associated with W-161. Reduced decapping and exonuclease
FT activities; when associated with K-167."
FT /evidence="ECO:0000269|PubMed:22961381"
FT MUTAGEN 167
FT /note="D->K: Does not affect the decapping and exonuclease
FT activities. Reduced decapping and exonuclease activities;
FT when associated with G-163."
FT /evidence="ECO:0000269|PubMed:22961381"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 62..75
FT /evidence="ECO:0007829|PDB:4GPS"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 108..111
FT /evidence="ECO:0007829|PDB:4GPS"
FT TURN 112..116
FT /evidence="ECO:0007829|PDB:4GPS"
FT TURN 119..122
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 136..147
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 162..170
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 213..226
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 239..248
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 250..260
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:4GPS"
FT TURN 266..269
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 285..299
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 305..311
FT /evidence="ECO:0007829|PDB:4GPS"
FT TURN 313..315
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 317..324
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 326..333
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4GPS"
FT HELIX 350..373
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 378..384
FT /evidence="ECO:0007829|PDB:4GPS"
FT STRAND 389..394
FT /evidence="ECO:0007829|PDB:4GPS"
SQ SEQUENCE 403 AA; 46312 MW; D2E6DA0EE3FE4894 CRC64;
MTTVSCDKDE NKVDQLGESL SQLRISTRKN NKPSQKKGSL VLSCKKFPHV SVNYVVDKTP
KLLTDCKEVH NCSYIINDAT LLWNEASRKP RLRPEVCTYI KDSKWENKAV KDSFIGIDLT
KGYDDYVPLD RNVLNSLVIL KEAYQRYEKT LNPEKTTFVS LRHHIIDIIM CPFLDEPLSL
LMTVQPDKNI LISVDKSKDK PNGIHETRNS FNKKICYTGF ALEDLLIESP TEGHILEHEL
YYSIVHGSLN DEIDLLIQAE MDSINTLTDT YTEIKSSVHF KLGNTYHRRK LLRMWIQTNL
LPKSDLLIGF RNSYSNELEQ LKAYKIQDIY HKINNSSIVG KPGKFYKFNP NVANDWFQHI
FQVLKQNLLL LSQESTSTTF KVQIDTNLTL SISPASQFVT ALG
