PAN3_DROME
ID PAN3_DROME Reviewed; 790 AA.
AC Q95RR8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=PAN2-PAN3 deadenylation complex subunit PAN3 {ECO:0000255|HAMAP-Rule:MF_03181};
DE AltName: Full=PAB1P-dependent poly(A)-specific ribonuclease {ECO:0000255|HAMAP-Rule:MF_03181};
DE AltName: Full=Poly(A)-nuclease deadenylation complex subunit 3 {ECO:0000255|HAMAP-Rule:MF_03181};
DE Short=PAN deadenylation complex subunit 3 {ECO:0000255|HAMAP-Rule:MF_03181};
GN Name=PAN3 {ECO:0000255|HAMAP-Rule:MF_03181}; ORFNames=CG11486;
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; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP INTERACTION WITH GW.
RX PubMed=21981923; DOI=10.1016/j.molcel.2011.09.007;
RA Braun J.E., Huntzinger E., Fauser M., Izaurralde E.;
RT "GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA
RT targets.";
RL Mol. Cell 44:120-133(2011).
RN [5]
RP FUNCTION, AND INTERACTION WITH GW.
RX PubMed=23172285; DOI=10.1093/nar/gks1078;
RA Huntzinger E., Kuzuoglu-Ozturk D., Braun J.E., Eulalio A., Wohlbold L.,
RA Izaurralde E.;
RT "The interactions of GW182 proteins with PABP and deadenylases are required
RT for both translational repression and degradation of miRNA targets.";
RL Nucleic Acids Res. 41:978-994(2013).
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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) OF 349-790 IN COMPLEX WITH AMP,
RP INTERACTION WITH PAN2, AND SUBUNIT.
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).
CC -!- FUNCTION: Regulatory subunit of the poly(A)-nuclease (PAN)
CC deadenylation complex, one of two cytoplasmic mRNA deadenylases
CC involved in general and miRNA-mediated mRNA turnover. PAN specifically
CC shortens poly(A) tails of RNA and the activity is stimulated by
CC poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid
CC degradation of the shortened mRNA tails by the CCR4-NOT complex.
CC Deadenylated mRNAs are then degraded by two alternative mechanisms,
CC namely exosome-mediated 3'-5' exonucleolytic degradation, or
CC deadenlyation-dependent mRNA decaping and subsequent 5'-3'
CC exonucleolytic degradation by XRN1. PAN3 acts as a positive regulator
CC for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its
CC interaction with RNA and PABP, and to miRNA targets via its interaction
CC with GW182 family proteins. {ECO:0000255|HAMAP-Rule:MF_03181,
CC ECO:0000269|PubMed:23172285}.
CC -!- SUBUNIT: Homodimer. Forms a heterotrimer with a catalytic subunit PAN2
CC to form the poly(A)-nuclease (PAN) deadenylation complex. Interacts
CC (via PAM-2 motif) with poly(A)-binding protein (via PABC domain),
CC conferring substrate specificity of the enzyme complex
CC (PubMed:23932717). Interacts with the GW182 family protein gw
CC (PubMed:21981923, PubMed:23172285). Interacts with Gyf
CC (PubMed:31114929). {ECO:0000255|HAMAP-Rule:MF_03181,
CC ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:23172285,
CC ECO:0000269|PubMed:23932717, ECO:0000269|PubMed:31114929}.
CC -!- INTERACTION:
CC Q95RR8; A1Z7K9: PAN2; NbExp=3; IntAct=EBI-119468, EBI-193297;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP-
CC Rule:MF_03181}.
CC -!- DOMAIN: The N-terminal zinc finger binds to poly(A) RNA.
CC {ECO:0000255|HAMAP-Rule:MF_03181}.
CC -!- DOMAIN: Contains a pseudokinase domain. The protein kinase domain is
CC predicted to be catalytically inactive because some of the residues
CC important for catalytic activity are substituted and it lacks the
CC equivalent of the binding site for a peptide substrate. However, it has
CC retained an ATP-binding site and ATP-binding is required for mRNA
CC degradation, stimulating the activity of the PAN2 nuclease in vitro
CC (PubMed:23932717). The nucleotide-binding site is juxtaposed to the
CC RNase active site of PAN2 in the complex and may actually bind
CC nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail
CC to the active site of the deadenylase and thus increasing the
CC efficiency with which this distributive enzyme degrades oligo(A) RNAs
CC (By similarity). {ECO:0000255|HAMAP-Rule:MF_03181,
CC ECO:0000269|PubMed:23932717}.
CC -!- DOMAIN: The pseudokinase domain, the coiled-coil (CC), and C-terminal
CC knob domain (CK) form a structural unit (PKC) that forms an extensive
CC high-affinity interaction surface for PAN2. {ECO:0000255|HAMAP-
CC Rule:MF_03181}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. PAN3 family.
CC {ECO:0000255|HAMAP-Rule:MF_03181}.
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DR EMBL; AE014296; AAN11527.1; -; Genomic_DNA.
DR EMBL; AY061183; AAL28731.1; -; mRNA.
DR RefSeq; NP_647767.1; NM_139510.4.
DR PDB; 4BWP; X-ray; 3.60 A; A/B=349-790.
DR PDBsum; 4BWP; -.
DR AlphaFoldDB; Q95RR8; -.
DR SMR; Q95RR8; -.
DR BioGRID; 63867; 65.
DR DIP; DIP-17364N; -.
DR IntAct; Q95RR8; 20.
DR STRING; 7227.FBpp0072861; -.
DR PaxDb; Q95RR8; -.
DR DNASU; 38369; -.
DR EnsemblMetazoa; FBtr0072991; FBpp0072861; FBgn0035397.
DR GeneID; 38369; -.
DR KEGG; dme:Dmel_CG11486; -.
DR UCSC; CG11486-RG; d. melanogaster.
DR CTD; 255967; -.
DR FlyBase; FBgn0035397; PAN3.
DR VEuPathDB; VectorBase:FBgn0035397; -.
DR eggNOG; KOG3741; Eukaryota.
DR GeneTree; ENSGT00390000001504; -.
DR InParanoid; Q95RR8; -.
DR PhylomeDB; Q95RR8; -.
DR Reactome; R-DME-429947; Deadenylation of mRNA.
DR SignaLink; Q95RR8; -.
DR BioGRID-ORCS; 38369; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38369; -.
DR PRO; PR:Q95RR8; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035397; Expressed in eye disc (Drosophila) and 26 other tissues.
DR ExpressionAtlas; Q95RR8; baseline and differential.
DR Genevisible; Q95RR8; DM.
DR GO; GO:0005737; C:cytoplasm; HDA:FlyBase.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0031251; C:PAN complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008143; F:poly(A) binding; IBA:GO_Central.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IBA:GO_Central.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; IEA:UniProtKB-UniRule.
DR HAMAP; MF_03181; PAN3; 1.
DR InterPro; IPR032050; DUF4797.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR030844; PAN3.
DR InterPro; IPR041332; Pan3_PK.
DR PANTHER; PTHR12272; PTHR12272; 1.
DR Pfam; PF16051; DUF4797; 1.
DR Pfam; PF18101; Pan3_PK; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Coiled coil; Cytoplasm; mRNA processing;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..790
FT /note="PAN2-PAN3 deadenylation complex subunit PAN3"
FT /id="PRO_0000426721"
FT REGION 166..191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..655
FT /note="Pseudokinase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT REGION 695..790
FT /note="Knob domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT COILED 656..694
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT COMPBIAS 166..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 423
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181,
FT ECO:0000269|PubMed:23932717"
FT BINDING 472..479
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181,
FT ECO:0000269|PubMed:23932717"
FT BINDING 552..553
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
SQ SEQUENCE 790 AA; 85391 MW; 19555B56DAA43E21 CRC64;
MCSTYGLLSF EFSDTAAMDP IFFSPTNGIP SESKLATYMN RQNVATPSGY GLNNGFSLLN
LDSPLNKKSQ VTPQSPEFIP TRLGSTPNFY APYHNAPMQL SNGLNGVNGL TAAAAAAAAA
AAAAAAAVPS STSSASSASV TISKTANGGA SMLALQKTAS IASVTIAQQQ PQHPQKQQQH
PPSVGGGAVS AASAPIAISG APPNPAAAPF VSSMSAQTPL KGRGAMMRQE SPTAAMISGA
GPGEKSPPHG MTPHGASPIP SALPTSVHQE NVGGTIYFYP TANAQNSQPV VNSMVVDGTH
PALHGVSAVA PMSAGVPAAM MYTGHVYPGP SSNVVTMQPK TLLESAFFMP DEMRAEVLAR
NEISNLIMDA AEAAQHALPL EVENYHALYP LEPPAQPLHA KLTFPATTYR ATHNTTGYKY
CLRRIHGFRL QSTKCMTLVE MWKKLQHTNV VQLREVFTTK AFGDNSLVLV YDYHPGSQTL
LAKYFTPAPE TNGYTDPFQG EARPFSHKSN MQRTSNGPLL PEATIWSIIM QLTAGLKAIH
HAGLACKVLD PTKIIVTGKR VRFSSCCISD ITQFDPNASN PLALVNMHQQ DDLTALGRLV
LALACRCLQS VQRDNVQSSI DMVTRNYSTD LRNFIVYLFT TNNRRSVTDL MPMIGARFYT
QLDALQSKID MQEDELAKEM ENGRLYRILV KLNSINERPD FNLDCTWSET GDRYMLKLFR
DYLFHSVTED GRPWLDHAHI VQCLNKLDAG SIERVQLMSR DEQSVLIVSY AELKNCLENA
FSELMSSAAN
