PAN2_DROME
ID PAN2_DROME Reviewed; 1241 AA.
AC A1Z7K9;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=PAN2-PAN3 deadenylation complex catalytic subunit PAN2 {ECO:0000255|HAMAP-Rule:MF_03182};
DE EC=3.1.13.4 {ECO:0000255|HAMAP-Rule:MF_03182};
DE AltName: Full=PAB1P-dependent poly(A)-specific ribonuclease {ECO:0000255|HAMAP-Rule:MF_03182};
DE AltName: Full=Poly(A)-nuclease deadenylation complex subunit 2 {ECO:0000255|HAMAP-Rule:MF_03182};
DE Short=PAN deadenylation complex subunit 2 {ECO:0000255|HAMAP-Rule:MF_03182};
GN Name=PAN2 {ECO:0000255|HAMAP-Rule:MF_03182}; ORFNames=CG8232;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J., Frise E., Kapadia B., Park S., Wan K., Yu C.,
RA Celniker S.;
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH PAN3, AND SUBUNIT.
RC TISSUE=Larva, and Pupae;
RX PubMed=23932717; DOI=10.1016/j.molcel.2013.07.011;
RA Christie M., Boland A., Huntzinger E., Weichenrieder O., Izaurralde E.;
RT "Structure of the PAN3 pseudokinase reveals the basis for interactions with
RT the PAN2 deadenylase and the GW182 proteins.";
RL Mol. Cell 51:360-373(2013).
RN [5]
RP CATALYTIC ACTIVITY.
RX PubMed=24880343; DOI=10.1038/nsmb.2837;
RA Jonas S., Christie M., Peter D., Bhandari D., Loh B., Huntzinger E.,
RA Weichenrieder O., Izaurralde E.;
RT "An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate
RT mRNA deadenylation and decay.";
RL Nat. Struct. Mol. Biol. 21:599-608(2014).
RN [6]
RP INTERACTION WITH GYF.
RX PubMed=31114929; DOI=10.1093/nar/gkz429;
RA Ruscica V., Bawankar P., Peter D., Helms S., Igreja C., Izaurralde E.;
RT "Direct role for the Drosophila GIGYF protein in 4EHP-mediated mRNA
RT repression.";
RL Nucleic Acids Res. 47:7035-7048(2019).
CC -!- FUNCTION: Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation
CC complex, one of two cytoplasmic mRNA deadenylases involved in general
CC and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A)
CC tails of RNA and the activity is stimulated by poly(A)-binding protein
CC (PABP). PAN deadenylation is followed by rapid degradation of the
CC shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are
CC then degraded by two alternative mechanisms, namely exosome-mediated
CC 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA
CC decaping and subsequent 5'-3' exonucleolytic degradation by XRN1.
CC {ECO:0000255|HAMAP-Rule:MF_03182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03182,
CC ECO:0000269|PubMed:24880343};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03182};
CC Note=Binds 2 metal cations per subunit in the catalytic exonuclease
CC domain. {ECO:0000255|HAMAP-Rule:MF_03182};
CC -!- ACTIVITY REGULATION: Positively regulated by the regulatory subunit
CC PAN3. {ECO:0000255|HAMAP-Rule:MF_03182}.
CC -!- SUBUNIT: Forms a heterotrimer with an asymmetric homodimer of the
CC regulatory subunit PAN3 to form the poly(A)-nuclease (PAN)
CC deadenylation complex (By similarity) (PubMed:23932717). Interacts with
CC Gyf (PubMed:31114929). {ECO:0000255|HAMAP-Rule:MF_03182,
CC ECO:0000269|PubMed:23932717, ECO:0000269|PubMed:31114929}.
CC -!- INTERACTION:
CC A1Z7K9; Q8SY33: gw; NbExp=2; IntAct=EBI-193297, EBI-160693;
CC A1Z7K9; Q95RR8: PAN3; NbExp=3; IntAct=EBI-193297, EBI-119468;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP-
CC Rule:MF_03182}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03182}.
CC Note=Shuttles between nucleus and cytoplasm. {ECO:0000255|HAMAP-
CC Rule:MF_03182}.
CC -!- DOMAIN: Contains a pseudo-UCH domain. This ubiquitin C-terminal
CC hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain
CC is predicted to be catalytically inactive because it lacks the active
CC site catalytic triad characteristic of thiol proteases, with residues
CC at the equivalent structural positions that are incompatible with
CC catalysis, and it cannot bind ubiquitin. It functions as a structural
CC scaffold for intra- and intermolecular interactions in the complex.
CC {ECO:0000255|HAMAP-Rule:MF_03182}.
CC -!- DOMAIN: The linker, or PAN3 interaction domain (PID), between the WD40
CC repeats and the pseudo-UCH domain mediates interaction with PAN3.
CC {ECO:0000255|HAMAP-Rule:MF_03182}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. PAN2 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03182}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE013599; AAF59018.2; -; Genomic_DNA.
DR EMBL; BT031142; ABX00764.1; -; mRNA.
DR RefSeq; NP_610427.2; NM_136583.4.
DR AlphaFoldDB; A1Z7K9; -.
DR SMR; A1Z7K9; -.
DR IntAct; A1Z7K9; 3.
DR STRING; 7227.FBpp0087735; -.
DR PaxDb; A1Z7K9; -.
DR PRIDE; A1Z7K9; -.
DR DNASU; 35893; -.
DR EnsemblMetazoa; FBtr0088654; FBpp0087735; FBgn0033352.
DR GeneID; 35893; -.
DR KEGG; dme:Dmel_CG8232; -.
DR UCSC; CG8232-RA; d. melanogaster.
DR CTD; 9924; -.
DR FlyBase; FBgn0033352; PAN2.
DR VEuPathDB; VectorBase:FBgn0033352; -.
DR eggNOG; KOG1275; Eukaryota.
DR HOGENOM; CLU_002369_0_0_1; -.
DR InParanoid; A1Z7K9; -.
DR OMA; TQELLWT; -.
DR OrthoDB; 128953at2759; -.
DR PhylomeDB; A1Z7K9; -.
DR Reactome; R-DME-429947; Deadenylation of mRNA.
DR BioGRID-ORCS; 35893; 0 hits in 1 CRISPR screen.
DR ChiTaRS; PAN2; fly.
DR GenomeRNAi; 35893; -.
DR PRO; PR:A1Z7K9; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033352; Expressed in eye disc (Drosophila) and 22 other tissues.
DR ExpressionAtlas; A1Z7K9; baseline and differential.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0031251; C:PAN complex; ISS:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000900; F:mRNA regulatory element binding translation repressor activity; IMP:UniProtKB.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; ISS:FlyBase.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IGI:FlyBase.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IEA:UniProtKB-UniRule.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR HAMAP; MF_03182; PAN2; 1.
DR InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
DR InterPro; IPR030843; PAN2.
DR InterPro; IPR028881; PAN2_UCH_dom.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00929; RNase_T; 1.
DR Pfam; PF13423; UCH_1; 1.
DR SMART; SM00479; EXOIII; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Exonuclease; Hydrolase; Metal-binding; mRNA processing;
KW Nuclease; Nucleus; Reference proteome.
FT CHAIN 1..1241
FT /note="PAN2-PAN3 deadenylation complex catalytic subunit
FT PAN2"
FT /id="PRO_0000441673"
FT DOMAIN 474..966
FT /note="USP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT DOMAIN 1036..1208
FT /note="Exonuclease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REGION 359..473
FT /note="Linker"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REGION 626..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 817..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 857..884
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 971..1000
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 626..651
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 652..666
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 820..838
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 867..881
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 972..1000
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1039
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT BINDING 1041
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT BINDING 1148
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT BINDING 1200
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
SQ SEQUENCE 1241 AA; 138968 MW; BFFE4AB585B1FB5D CRC64;
MDYVYCGTDP IGASEDILSV YDAGSAPGNG HFSPSFNGFN IGTTDPEYVE LVPVLADGGE
HFGVSSVAFD DYEELLWMGN QGGHVTSYYT NSMQKYTSFQ VHATDIVRDI STLDSGVLAL
TQTSLRHQIR RGLPKFTFKS NNMKEMVSML QLSPHRLVMA GLQDELIDFD LRTLKETRIE
HVGAGGCTVL RKNSRYLFAG DQLGTVTLRD LNSLSVQHTI KTHTNILSDF SVQGNLLISC
GYSGRQNNLA IDRFLMVYDL RMLRLIAPIQ VMIDPQMLKF LPSLTSQLAV VSSYGQVQLV
DTVELSEPRV SMYQINTNGS QCLSFDISSS SQAMAFGDQS GHINMIAAVQ TPQPQFNLYS
RSTEFADVVP QLPMVSITDT NFPLSSVMLP HLTTGTQWFS DWPEELLRYR YHRPKTIDPE
VLSNMKMQGP IGYSPNPRTA RRNQIPYVIE QGGVCSPNGN GTAAATKAEN GVKIIPRRYR
KVELKYTKLG TQDFDFDQHN QTCFAGLEAT LPNSYCNAML QILYFTDALR VKLLEHSCIK
EFCLSCELGF LFNMLDKSTA SSPCQASNFL RSFRTVPEAS ALGLILTDRS SNVNLISLIQ
NWNRFILHQM HYEIFDSSKN ASTYSGSVQT STNAENAGSS ETSGSSDLYD SISDENSKED
DRERSKINAE TDISKIFGTK QICINRCIKC QEEKIKESIL LACNLSYPNH IKDSDQYFNF
GTILKRSLSS EKSIQAFCER CKKFSPTNQS VKVTSLPQIL SINCGLNNEK DITFLKRQLN
RCSEKTTVDA AASLSTSKPC RYGANCSRSD CHFMHPDRKS PSHTSQPNAV NNSPNGRQKS
WFPLTFTMGI NDQGEVQVQT QSDASSGKSE QEEETEKPPT KGLDNNRMYA LHAVVCQVDD
GTQKNLVSLI NVQRPYHTMK LAESADDPQS QWYIFNDFSI SPVSPQESVW FTLDWKVPCI
LFYRHVEDDS ESASTTSSTV TESEETIPSE SSSGSPTNLS NPFLEEIVSP MLGNLSADAT
LQPLQSDEMP QSGDLVAMDA EFVTLNPEEN EIRPDGKTAT IKPCHMSVAR ISCIRGQGPA
EGVPFMDDYI STQEKVVDYL TQFSGIKPGD LDANFSKKRL TALKYSYQKL KYLVDVGVIF
VGHGLKNDFR VINIYVPSEQ IIDTVHLFHM PHHRMVSLRF LAWHFLGTKI QSETHDSIED
ARTTLQLYKH YLKLQEEKKF ANALKNLYER GKQLQWKVPE D
