XRN2_CAEEL
ID XRN2_CAEEL Reviewed; 975 AA.
AC Q9U299;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=5'-3' exoribonuclease 2 homolog;
DE EC=3.1.13.- {ECO:0000269|PubMed:19734881, ECO:0000269|PubMed:24462208, ECO:0000269|PubMed:26779609};
GN Name=xrn-2 {ECO:0000312|WormBase:Y48B6A.3};
GN ORFNames=Y48B6A.3 {ECO:0000312|WormBase:Y48B6A.3};
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 [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 [2]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16122351; DOI=10.1371/journal.pbio.0030312;
RA Frand A.R., Russel S., Ruvkun G.;
RT "Functional genomic analysis of C. elegans molting.";
RL PLoS Biol. 3:E312-E312(2005).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19734881; DOI=10.1038/nature08349;
RA Chatterjee S., Grosshans H.;
RT "Active turnover modulates mature microRNA activity in Caenorhabditis
RT elegans.";
RL Nature 461:546-549(2009).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21397849; DOI=10.1016/j.devcel.2011.02.008;
RA Chatterjee S., Fasler M., Bussing I., Grosshans H.;
RT "Target-mediated protection of endogenous microRNAs in C. elegans.";
RL Dev. Cell 20:388-396(2011).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=23541767; DOI=10.1016/j.molcel.2013.02.023;
RA Bosse G.D., Ruegger S., Ow M.C., Vasquez-Rifo A., Rondeau E.L.,
RA Ambros V.R., Grosshans H., Simard M.J.;
RT "The decapping scavenger enzyme DCS-1 controls microRNA levels in
RT Caenorhabditis elegans.";
RL Mol. Cell 50:281-287(2013).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PAXT-1, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 234-ASP--ASP-236.
RX PubMed=24462208; DOI=10.1016/j.molcel.2014.01.001;
RA Miki T.S., Richter H., Rueegger S., Grosshans H.;
RT "PAXT-1 promotes XRN2 activity by stabilizing it through a conserved
RT domain.";
RL Mol. Cell 53:351-360(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 1-787 IN COMPLEX WITH PAXT-1,
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26779609; DOI=10.1038/nsmb.3155;
RA Richter H., Katic I., Gut H., Grosshans H.;
RT "Structural basis and function of XRN2 binding by XTB domains.";
RL Nat. Struct. Mol. Biol. 23:164-171(2016).
CC -!- FUNCTION: Possesses 5'->3' exoribonuclease activity (PubMed:19734881,
CC PubMed:21397849). Plays a role in maintenance of steady-state
CC concentration and turnover of microRNAs (miRNA) by degradation of
CC mature miRNA (PubMed:19734881, PubMed:21397849, PubMed:26779609).
CC Degradation role is enhanced when in complex with paxt-1
CC (PubMed:24462208, PubMed:26779609). Partially redundant to xrn-1 in
CC miRNA guide strand degradation (PubMed:19734881, PubMed:21397849).
CC Implicated in differential regulation of mRNAs such as let-7 by
CC controlling the accumulation of mature miRNA (PubMed:19734881,
CC PubMed:21397849). Positively regulates molting of the pharyngeal
CC cuticle (PubMed:16122351, PubMed:19734881).
CC {ECO:0000269|PubMed:16122351, ECO:0000269|PubMed:19734881,
CC ECO:0000269|PubMed:21397849, ECO:0000269|PubMed:24462208,
CC ECO:0000269|PubMed:26779609}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3913 uM for FAM fluorophore-coupled RNA substrate and a
CC quencher-coupled DNA primer {ECO:0000269|PubMed:26779609};
CC Vmax=0.000197 umol/sec/ug enzyme {ECO:0000269|PubMed:26779609};
CC -!- SUBUNIT: Interacts with paxt-1 (via N-terminus); the interaction is
CC direct and results in stabilization of xrn-2 in the complex.
CC {ECO:0000269|PubMed:24462208, ECO:0000269|PubMed:26779609}.
CC -!- INTERACTION:
CC Q9U299; Q21738: paxt-1; NbExp=5; IntAct=EBI-320499, EBI-11705385;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23541767}.
CC -!- TISSUE SPECIFICITY: Expressed in the pharyngeal myoepithelium and
CC intestine. Also expressed in several anterior neurons including the
CC sensory neurons, as well as the interneuron PVT and the pharyngeal
CC motorneuron M5. {ECO:0000269|PubMed:16122351}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout all developmental stages.
CC Detected in the M5 pharyngeal neuron only in larvae. Also persistently
CC expressed in the intestine of adults past the molting stage.
CC {ECO:0000269|PubMed:16122351, ECO:0000269|PubMed:24462208}.
CC -!- INDUCTION: Up-regulated prior to molting.
CC {ECO:0000269|PubMed:16122351}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in impaired miRNA
CC degradation leading to accumulation of mature miRNA passenger (miR*)
CC strands (PubMed:19734881, PubMed:21397849). Defective molting owing to
CC failure to shed cuticle from the pharynx in the late L4-stage larvae
CC (PubMed:16122351). Suppresses the vulval bursting phenotype of let-7
CC mutant (PubMed:19734881). Reduced paxt-1 expression (PubMed:24462208).
CC {ECO:0000269|PubMed:16122351, ECO:0000269|PubMed:19734881,
CC ECO:0000269|PubMed:21397849, ECO:0000269|PubMed:24462208}.
CC -!- SIMILARITY: Belongs to the 5'-3' exonuclease family. XRN2/RAT1
CC subfamily. {ECO:0000305}.
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DR EMBL; AL110490; CAB54449.2; -; Genomic_DNA.
DR PIR; T27005; T27005.
DR RefSeq; NP_496958.2; NM_064557.5.
DR PDB; 5FIR; X-ray; 2.84 A; A/C/E/G/I/K=1-787.
DR PDBsum; 5FIR; -.
DR AlphaFoldDB; Q9U299; -.
DR SMR; Q9U299; -.
DR BioGRID; 40353; 11.
DR ComplexPortal; CPX-420; xtbd-paxt-1 complex.
DR DIP; DIP-24636N; -.
DR IntAct; Q9U299; 3.
DR STRING; 6239.Y48B6A.3; -.
DR EPD; Q9U299; -.
DR PaxDb; Q9U299; -.
DR PeptideAtlas; Q9U299; -.
DR PRIDE; Q9U299; -.
DR EnsemblMetazoa; Y48B6A.3.1; Y48B6A.3.1; WBGene00006964.
DR GeneID; 175071; -.
DR KEGG; cel:CELE_Y48B6A.3; -.
DR UCSC; Y48B6A.3; c. elegans.
DR CTD; 175071; -.
DR WormBase; Y48B6A.3; CE42702; WBGene00006964; xrn-2.
DR eggNOG; KOG2044; Eukaryota.
DR GeneTree; ENSGT00670000098098; -.
DR HOGENOM; CLU_006038_1_2_1; -.
DR InParanoid; Q9U299; -.
DR OMA; CLHYYVH; -.
DR OrthoDB; 685597at2759; -.
DR PhylomeDB; Q9U299; -.
DR Reactome; R-CEL-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR SABIO-RK; Q9U299; -.
DR PRO; PR:Q9U299; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00006964; Expressed in embryo and 4 other tissues.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0008409; F:5'-3' exonuclease activity; ISS:UniProtKB.
DR GO; GO:0004534; F:5'-3' exoribonuclease activity; IDA:WormBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0000738; P:DNA catabolic process, exonucleolytic; ISS:UniProtKB.
DR GO; GO:0006353; P:DNA-templated transcription, termination; IEA:UniProtKB-KW.
DR GO; GO:0010587; P:miRNA catabolic process; IDA:WormBase.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0060965; P:negative regulation of miRNA-mediated gene silencing; IMP:WormBase.
DR GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IBA:GO_Central.
DR GO; GO:0040034; P:regulation of development, heterochronic; IGI:WormBase.
DR GO; GO:0040028; P:regulation of vulval development; IGI:WormBase.
DR InterPro; IPR027073; 5_3_exoribonuclease.
DR InterPro; IPR004859; Put_53exo.
DR InterPro; IPR041412; Xrn1_helical.
DR InterPro; IPR017151; Xrn2/3/4.
DR PANTHER; PTHR12341; PTHR12341; 1.
DR Pfam; PF17846; XRN_M; 2.
DR Pfam; PF03159; XRN_N; 1.
DR PIRSF; PIRSF037239; Exonuclease_Xrn2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Exonuclease; Hydrolase; Metal-binding;
KW mRNA processing; Nuclease; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Transcription termination; Zinc; Zinc-finger.
FT CHAIN 1..975
FT /note="5'-3' exoribonuclease 2 homolog"
FT /id="PRO_0000249916"
FT ZN_FING 262..279
FT /note="CCHC-type"
FT REGION 424..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 505..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..787
FT /note="Interaction with paxt-1"
FT /evidence="ECO:0000269|PubMed:24462208,
FT ECO:0000269|PubMed:26779609"
FT REGION 804..975
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..526
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 804..820
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 234..236
FT /note="DAD->AAA: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:24462208"
FT HELIX 5..13
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 48..54
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 56..63
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 74..92
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 108..142
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 166..185
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 187..191
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 205..217
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 227..231
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 236..243
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 305..315
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 327..341
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 358..373
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 385..397
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 399..407
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 542..551
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 558..581
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 598..601
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 604..606
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 620..627
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 630..635
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 638..645
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 669..671
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 672..674
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 681..688
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 689..694
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 697..702
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 708..713
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 719..728
FT /evidence="ECO:0007829|PDB:5FIR"
FT HELIX 738..741
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 747..749
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 773..775
FT /evidence="ECO:0007829|PDB:5FIR"
FT STRAND 778..784
FT /evidence="ECO:0007829|PDB:5FIR"
SQ SEQUENCE 975 AA; 110128 MW; 219234BA731ABCF6 CRC64;
MGVPAFFRWL TKKYPATVVN ANEDRQRDQD GNRVPVDCTQ PNPNFQEFDN LYLDMNGIIH
PCTHPEDRPA PKNEDEMFAL IFEYIDRIYS IVRPRRLLYM AIDGVAPRAK MNQQRSRRFR
ASKEMAEKEA SIEEQRNRLM AEGIAVPPKK KEEAHFDSNC ITPGTPFMAR LADALRYYIH
DRVTNDASWA NIEIILSDAN VPGEGEHKIM DYVRKQRGNP AHDPNTVHCL CGADADLIML
GIATHEANFN IIREEFVPNQ PRACDLCGQY GHELKECRGA ENETDLGDDY CKPEQREKNF
IFLRIPVLRE YLEKELSMPN LPFKFDVERA LDDWVFLCFF VGNDFLPHLP SLEIREGAID
RLIKLYKEMV YQMKGYLTKD GIPELDRVEM IMKGLGRVED EIFKRRQQDE ERFQENQRNK
KARMQMYGGG GRGGRGRGRG RGQQPAFVPT HGILAPMAAP MHHSGESTRQ MASEARQTAM
KFTNDANETA AANLKALLNV KGEESPADIA SRKRKAEQPL IKPEEEEDEG PKDDIRLYES
GWKDRYYRAK FDVGSDDIEF RHRVAWAYVE GLCWVLRYYY QGCASWDWYF PYHYAPFASD
FETVGEFQPD FTRPTKPFNP LEQLMSVFPA ASKQHLPVEW QKLMIQDDSP IIDLYPADFR
IDLNGKKYAW QGVALLPFVD ETRLLATLQS VYPTLTAEEK QRNTRGPNRI FIGRNHKSFE
FFQQVAESKS DDLVPLDPTL LNGVSGKIAY DSTATAPGLP FVSPVNHDEC QDLPTNCGIC
VLYEDPEYPQ DYIFPALRLD GAKEPEKTLK PDDWNDRRDG RYQPQVGFNR NAPRGSLDQS
GHRQVHHYVR GGGGGGGGYR GNSYDDRRGG GGGGGGYNDR QDFGRNYGGR DGGGPQRYHD
QQQQRQGGYQ GGGYGGGYGG GGGGGGGGGG GSYHQPYNQD QRRGGRGGGG GPPGYQRPPY
RGGGGGGYHG NSSWR
