PAN3_YEAST
ID PAN3_YEAST Reviewed; 679 AA.
AC P36102; D6VXQ9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=PAN2-PAN3 deadenylation complex subunit PAN3 {ECO:0000255|HAMAP-Rule:MF_03181, ECO:0000305};
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}; Synonyms=ECM35;
GN OrderedLocusNames=YKL025C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 443-453 AND 517-524,
RP FUNCTION, AND INTERACTION WITH PAN2.
RX PubMed=8816488; DOI=10.1128/mcb.16.10.5744;
RA Brown C.E., Tarun S.Z. Jr., Boeck R., Sachs A.B.;
RT "PAN3 encodes a subunit of the Pab1p-dependent poly(A) nuclease in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 16:5744-5753(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=1358757; DOI=10.1101/gad.6.11.2088;
RA Lowell J.E., Rudner D.Z., Sachs A.B.;
RT "3'-UTR-dependent deadenylation by the yeast poly(A) nuclease.";
RL Genes Dev. 6:2088-2099(1992).
RN [5]
RP FUNCTION.
RX PubMed=9774670; DOI=10.1128/mcb.18.11.6548;
RA Brown C.E., Sachs A.B.;
RT "Poly(A) tail length control in Saccharomyces cerevisiae occurs by message-
RT specific deadenylation.";
RL Mol. Cell. Biol. 18:6548-6559(1998).
RN [6]
RP FUNCTION, AND INTERACTION WITH DUN1.
RX PubMed=11953437; DOI=10.1074/jbc.m202473200;
RA Hammet A., Pike B.L., Heierhorst J.;
RT "Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1
RT kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival
RT of replication blocks.";
RL J. Biol. Chem. 277:22469-22474(2002).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP INTERACTION WITH PAN2 AND PAB1.
RX PubMed=15169912; DOI=10.1128/mcb.24.12.5521-5533.2004;
RA Mangus D.A., Evans M.C., Agrin N.S., Smith M.M., Gongidi P., Jacobson A.;
RT "Positive and negative regulation of poly(A) nuclease.";
RL Mol. Cell. Biol. 24:5521-5533(2004).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15894541; DOI=10.1074/jbc.m504720200;
RA Dheur S., Nykamp K.R., Viphakone N., Swanson M.S., Minvielle-Sebastia L.;
RT "Yeast mRNA poly(A) tail length control can be reconstituted in vitro in
RT the absence of Pab1p-dependent poly(A) nuclease activity.";
RL J. Biol. Chem. 280:24532-24538(2005).
RN [11]
RP PHOSPHORYLATION BY PCL1-PHO85.
RX PubMed=16330754; DOI=10.1073/pnas.0509080102;
RA Dephoure N., Howson R.W., Blethrow J.D., Shokat K.M., O'Shea E.K.;
RT "Combining chemical genetics and proteomics to identify protein kinase
RT substrates.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17940-17945(2005).
RN [12]
RP INTERACTION WITH PAB1, AND MUTAGENESIS OF PHE-156.
RX PubMed=17595167; DOI=10.1074/jbc.m701256200;
RA Siddiqui N., Mangus D.A., Chang T.C., Palermino J.M., Shyu A.B.,
RA Gehring K.;
RT "Poly(A) nuclease interacts with the C-terminal domain of polyadenylate-
RT binding protein domain from poly(A)-binding protein.";
RL J. Biol. Chem. 282:25067-25075(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57 AND SER-252, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [15]
RP STRUCTURE BY NMR OF 1-41, FUNCTION, AND RNA-BINDING.
RX PubMed=24872509; DOI=10.15252/embj.201488373;
RA Wolf J., Valkov E., Allen M.D., Meineke B., Gordiyenko Y., McLaughlin S.H.,
RA Olsen T.M., Robinson C.V., Bycroft M., Stewart M., Passmore L.A.;
RT "Structural basis for Pan3 binding to Pan2 and its function in mRNA
RT recruitment and deadenylation.";
RL EMBO J. 33:1514-1526(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (3.80 ANGSTROMS) OF 226-679.
RX PubMed=24880344; DOI=10.1038/nsmb.2834;
RA Schaefer I.B., Rode M., Bonneau F., Schuessler S., Conti E.;
RT "The structure of the Pan2-Pan3 core complex reveals cross-talk between
RT deadenylase and pseudokinase.";
RL Nat. Struct. Mol. Biol. 21:591-598(2014).
CC -!- FUNCTION: Regulatory subunit of the poly(A)-nuclease (PAN)
CC deadenylation complex, one of two cytoplasmic mRNA deadenylases
CC involved in mRNA turnover. PAN specifically shortens poly(A) tails of
CC RNA and the activity is stimulated by poly(A)-binding protein PAB1. PAN
CC deadenylation is followed by rapid degradation of the shortened mRNA
CC tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by
CC two alternative mechanisms, namely exosome-mediated 3'-5'
CC exonucleolytic degradation, or deadenlyation-dependent mRNA decaping by
CC DCP1-DCP2 and subsequent 5'-3' exonucleolytic degradation by XRN1. May
CC also be involved in post-transcriptional maturation of mRNA poly(A)
CC tails, trimming the tails from their synthesized length to the slightly
CC shorter, apparently messenger-specific length found on newly exported
CC mRNAs. PAN3 acts as a positive regulator for PAN activity, recruiting
CC the catalytic subunit PAN2 to mRNA via its interaction with RNA and
CC with PAB1. PAN cooperates with protein kinase DUN1 in the regulation of
CC RAD5 mRNA levels and cell survival in response to replicational stress.
CC {ECO:0000255|HAMAP-Rule:MF_03181, ECO:0000269|PubMed:11953437,
CC ECO:0000269|PubMed:1358757, ECO:0000269|PubMed:15894541,
CC ECO:0000269|PubMed:24880344, ECO:0000269|PubMed:8816488,
CC ECO:0000269|PubMed:9774670}.
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 PAB1 (via PABC domain),
CC conferring substrate specificity of the enzyme complex.
CC {ECO:0000255|HAMAP-Rule:MF_03181, ECO:0000269|PubMed:11953437,
CC ECO:0000269|PubMed:15169912, ECO:0000269|PubMed:17595167,
CC ECO:0000269|PubMed:8816488}.
CC -!- INTERACTION:
CC P36102; P04147: PAB1; NbExp=5; IntAct=EBI-12895, EBI-12823;
CC P36102; P53010: PAN2; NbExp=9; IntAct=EBI-12895, EBI-12887;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03181,
CC ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:15894541}.
CC -!- DOMAIN: The N-terminal zinc finger binds to poly(A) RNA.
CC {ECO:0000255|HAMAP-Rule:MF_03181, ECO:0000269|PubMed:24872509}.
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
CC (PubMed:24880344). However, it has retained an ATP-binding site and
CC ATP-binding is required for mRNA degradation, stimulating the activity
CC of the PAN2 nuclease in vitro. The nucleotide-binding site is
CC juxtaposed to the RNase active site of PAN2 in the complex and may
CC actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the
CC poly(A)-tail to the active site of the deadenylase and thus increasing
CC the efficiency with which this distributive enzyme degrades oligo(A)
CC RNAs (By similarity). {ECO:0000250|UniProtKB:Q7SDP4, ECO:0000255|HAMAP-
CC Rule:MF_03181, ECO:0000269|PubMed:24880344}.
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 -!- PTM: Phosphorylated by the cyclin-CDK complex PCL1-PHO85.
CC {ECO:0000269|PubMed:16330754}.
CC -!- MISCELLANEOUS: Present with 1600 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. PAN3 family.
CC {ECO:0000255|HAMAP-Rule:MF_03181}.
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DR EMBL; Z28025; CAA81860.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA09129.1; -; Genomic_DNA.
DR PIR; S37842; S37842.
DR RefSeq; NP_012900.1; NM_001179591.1.
DR PDB; 4CYK; NMR; -; A=1-41.
DR PDB; 4XR7; X-ray; 3.80 A; B/C/E/F/H/I/K/L=226-679.
DR PDBsum; 4CYK; -.
DR PDBsum; 4XR7; -.
DR AlphaFoldDB; P36102; -.
DR BMRB; P36102; -.
DR SMR; P36102; -.
DR BioGRID; 34106; 151.
DR ComplexPortal; CPX-3294; PAN deadenylation complex.
DR DIP; DIP-3987N; -.
DR IntAct; P36102; 8.
DR MINT; P36102; -.
DR STRING; 4932.YKL025C; -.
DR iPTMnet; P36102; -.
DR MaxQB; P36102; -.
DR PaxDb; P36102; -.
DR PRIDE; P36102; -.
DR EnsemblFungi; YKL025C_mRNA; YKL025C; YKL025C.
DR GeneID; 853843; -.
DR KEGG; sce:YKL025C; -.
DR SGD; S000001508; PAN3.
DR VEuPathDB; FungiDB:YKL025C; -.
DR eggNOG; KOG3741; Eukaryota.
DR GeneTree; ENSGT00390000001504; -.
DR HOGENOM; CLU_016423_2_1_1; -.
DR InParanoid; P36102; -.
DR OMA; IGPHSQN; -.
DR BioCyc; YEAST:G3O-31832-MON; -.
DR PRO; PR:P36102; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P36102; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0000932; C:P-body; IBA:GO_Central.
DR GO; GO:0031251; C:PAN complex; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008143; F:poly(A) binding; IDA:SGD.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IDA:SGD.
DR GO; GO:0006281; P:DNA repair; IDA:SGD.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IDA:SGD.
DR GO; GO:0006301; P:postreplication repair; IGI:SGD.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR HAMAP; MF_03181; PAN3; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR030844; PAN3.
DR InterPro; IPR041332; Pan3_PK.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR000571; Znf_CCCH.
DR PANTHER; PTHR12272; PTHR12272; 1.
DR Pfam; PF18101; Pan3_PK; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS50103; ZF_C3H1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Coiled coil; Cytoplasm;
KW Direct protein sequencing; Metal-binding; mRNA processing;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..679
FT /note="PAN2-PAN3 deadenylation complex subunit PAN3"
FT /id="PRO_0000058223"
FT ZN_FING 8..37
FT /note="C3H1-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT REGION 275..548
FT /note="Pseudokinase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181,
FT ECO:0000305|PubMed:24880344"
FT REGION 588..679
FT /note="Knob domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181,
FT ECO:0000305|PubMed:24880344"
FT COILED 549..587
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181,
FT ECO:0000305|PubMed:24880344"
FT MOTIF 143..163
FT /note="PABPC-interacting motif-2 (PAM-2)"
FT /evidence="ECO:0000269|PubMed:17595167"
FT BINDING 325
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT BINDING 376..383
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT BINDING 430..431
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT MOD_RES 57
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 156
FT /note="F->A: Significantly decreases interaction with
FT PAN1."
FT /evidence="ECO:0000269|PubMed:17595167"
FT HELIX 6..9
FT /evidence="ECO:0007829|PDB:4CYK"
FT HELIX 15..19
FT /evidence="ECO:0007829|PDB:4CYK"
FT HELIX 24..27
FT /evidence="ECO:0007829|PDB:4CYK"
SQ SEQUENCE 679 AA; 76455 MW; DE03E15BF4A5DA7C CRC64;
MDKINPDWAK DIPCRNITIY GYCKKEKEGC PFKHSDNTTA TTINDVPPPI DVGEATTPTM
TSVPKFNAKV SASFTPMTVG SDSLTTVTNT TSAATNATGN IAMAATSATA STVNPMINPI
VNSSLVNNNN NNSNISISIP TTASSSNYDP FNAPIFTPSS TSSIHTNANA HSFPFPSIAN
SGGININATD DNSNNMSMAN NVPPPMQPPP IESSNLKYPR IYPPPHSLLQ YHLYAPEQPS
SLKSLLKPNE RSADQLFIPN NIREDLTKKN LSILQVFPSS GKVIPSIVQD YFNLVPLNFN
NNDFLNKTTL FKVFSNYDGK AYVLKRLPNI DKSMNPNKIS KIYQIWSKIN CTNLIKFRDI
FQTTKFGDLS ICLVFDYYPN SLSLYDYHFV NFPKFPITNN YLWIYLVQLT NVINSIHSQN
LSIGNTLNWR KVLITGDPGR IKLSHCNFMD LLFNDDTDTV VSSGGSTIEG QQQLDYKYLG
ELLFNLSINI ENSNNNTAPK EYRLEEITPQ SIDDMRQIDD KFKDVLKYLI SDNGDSKKSI
HDLTSHFYDK MFMVLESSQT YTEYMESVLS RELENGRLFR LVNKLNCIFG RIESRIDINW
SESGTKFPII LFYDYVFHQV DSNGKPIMDL THVLRCLNKL DAGIQEKLML VTPDELNCII
ISYKELKDLI ESTFRSITQ
