PAN2_CHATD
ID PAN2_CHATD Reviewed; 1170 AA.
AC G0SAK8;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 64.
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=CTHT_0042640;
OS Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=759272;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 1495 / CBS 144.50 / IMI 039719;
RX PubMed=21784248; DOI=10.1016/j.cell.2011.06.039;
RA Amlacher S., Sarges P., Flemming D., van Noort V., Kunze R., Devos D.P.,
RA Arumugam M., Bork P., Hurt E.;
RT "Insight into structure and assembly of the nuclear pore complex by
RT utilizing the genome of a eukaryotic thermophile.";
RL Cell 146:277-289(2011).
RN [2] {ECO:0007744|PDB:4CYJ}
RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 343-458, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, AND MUTAGENESIS OF GLU-899.
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 [3] {ECO:0007744|PDB:4D0K}
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 1-457.
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).
CC -!- FUNCTION: Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation
CC complex, one of two cytoplasmic mRNA deadenylases involved in mRNA
CC turnover. PAN specifically shortens poly(A) tails of RNA and the
CC 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
CC and subsequent 5'-3' exonucleolytic degradation by XRN1. May also be
CC involved in post-transcriptional maturation of mRNA poly(A) tails.
CC {ECO:0000255|HAMAP-Rule:MF_03182, ECO:0000269|PubMed:24872509}.
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:24872509};
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. {ECO:0000255|HAMAP-Rule:MF_03182,
CC ECO:0000269|PubMed:24872509}.
CC -!- INTERACTION:
CC G0SAK8; G0S0Y3: PAN3; NbExp=9; IntAct=EBI-9836534, EBI-9836608;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03182}.
CC -!- DOMAIN: The linker, or PAN3 interaction domain (PID), between the WD40
CC repeats and the USP domain mediates interaction with PAN3.
CC {ECO:0000269|PubMed:24872509}.
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; GL988043; EGS19780.1; -; Genomic_DNA.
DR RefSeq; XP_006694665.1; XM_006694602.1.
DR PDB; 4CYJ; X-ray; 2.59 A; E/F=343-458.
DR PDB; 4D0K; X-ray; 1.89 A; A=1-457.
DR PDBsum; 4CYJ; -.
DR PDBsum; 4D0K; -.
DR AlphaFoldDB; G0SAK8; -.
DR SMR; G0SAK8; -.
DR DIP; DIP-61541N; -.
DR IntAct; G0SAK8; 1.
DR MINT; G0SAK8; -.
DR STRING; 759272.G0SAK8; -.
DR PRIDE; G0SAK8; -.
DR EnsemblFungi; EGS19780; EGS19780; CTHT_0042640.
DR GeneID; 18258302; -.
DR KEGG; cthr:CTHT_0042640; -.
DR eggNOG; KOG1275; Eukaryota.
DR HOGENOM; CLU_002369_1_0_1; -.
DR OrthoDB; 128953at2759; -.
DR Proteomes; UP000008066; Unassembled WGS sequence.
DR GO; GO:0031251; C:PAN complex; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; 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 3D-structure; Cytoplasm; Exonuclease; Hydrolase; Metal-binding;
KW mRNA processing; Nuclease; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..1170
FT /note="PAN2-PAN3 deadenylation complex catalytic subunit
FT PAN2"
FT /id="PRO_0000441674"
FT REPEAT 104..144
FT /note="WD 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REPEAT 280..319
FT /note="WD 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT DOMAIN 459..846
FT /note="USP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182,
FT ECO:0000305|PubMed:24872509"
FT DOMAIN 894..1067
FT /note="Exonuclease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REGION 319..458
FT /note="Linker"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182,
FT ECO:0000305|PubMed:24872509"
FT REGION 399..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1094..1170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1094..1109
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 897
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT Rule:MF_03182"
FT BINDING 899
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT Rule:MF_03182"
FT BINDING 1006
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT Rule:MF_03182"
FT BINDING 1059
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:O95453, ECO:0000255|HAMAP-
FT Rule:MF_03182"
FT MUTAGEN 899
FT /note="E->A: Abolishes nuclease activity."
FT /evidence="ECO:0000269|PubMed:24872509"
FT STRAND 6..14
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:4D0K"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:4D0K"
FT TURN 51..54
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:4D0K"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 97..102
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 107..114
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 120..135
FT /evidence="ECO:0007829|PDB:4D0K"
FT TURN 136..139
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 151..164
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 167..172
FT /evidence="ECO:0007829|PDB:4D0K"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 186..196
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:4D0K"
FT TURN 226..229
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 261..267
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 270..278
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 285..290
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 297..301
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 304..310
FT /evidence="ECO:0007829|PDB:4D0K"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:4D0K"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:4CYJ"
FT HELIX 377..382
FT /evidence="ECO:0007829|PDB:4CYJ"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:4CYJ"
FT STRAND 389..393
FT /evidence="ECO:0007829|PDB:4CYJ"
SQ SEQUENCE 1170 AA; 130569 MW; 15A0AC212FBA37F8 CRC64;
MDADWDEVTR IAYPAPGTND FPRPATAVAF DPIAELLWAG FDRGRVCSFY GRDLTRYTAF
KIQPASEGPV RQFLFHDKGV IVLGTRSVHM AMRRGPALWN IRHENMKDLR CMSFTSKGTQ
EIIVAGWQDT MLVIDVLKGD IIKQIPAQHH YSIMKKSRYI CAATKTGSVD LIDPLSFKIV
RSWQAHASYI NDMDAQNDFI VTCGGSLKQQ AAQTYMLDPY VNVFDLKNMA SMKPMPFPPL
AAHVRLHPRM LTTAIVTSQH GQMHVVDIMN PNSSTVRYAN ISSYVKLFEI APSGEALVIG
DADCNIHLWG SPTKIHFTDM AIPIELPEPE EPAPVLDWSI ETPLSSIGLP YYREPLFSAW
PADIISDVGA PPLQLEPSFV ATLKQAEWGL YGKNTRNVRR NQVEDTRNTN KQSNALQAPK
FLSERARESA LSSGGDSSSD PQVDQEPEDP NEIESLKPEA PPLYRNLEIK YSKFGVDDFD
FGYYNKTRYA GLENHIPNSY ANSLLQLMHY TPLLRNMALQ HAATACVSDL CLLCELGFVF
DMLQKAEGAT CQATNMFKAL SGTPQAAPLG LLEEETHVPS LATMAQNLSR FLLEKIHNEY
RTIPPISTAL EQSLFNFPHP PTPDELVAKV LATSAVATIK CMNCRSETTR PGTTHVIDLL
YPPPKTAGRG GRASKVTFSQ VLKMGVERET TSKGWCSRCQ RYQNLQMRKT IHSVPAVLVV
NAGVSNQEHR KLWSTPGWLP EEIGIIVDQG QFFCFEGEDL KLHLQRGIHN ITVYSLIGMV
INIESHSPQK SHLVGIINVA HAEATPPGEN KWHLFNDFSV RPVSAAEALT FNAAWKMPAV
LLFQIKSANN KSNLDWKTNL DTSILYKDTN PNTEKKTYRT LDQERERPGP DTIVALDTEF
VSLKQPEIQM NSDGERETIR PMSHALARVS VVRGQGENEG SAFIDDYIAI REPVVDYLTL
YSGITASDLD PRTSKHNLVS LKTAYKKLWV LLNLGCKFLG HGLKQDFRVI NIQVPRAQVI
DTIEVFYLKS RLRKLSLAFL AWYLLKEDIQ LETHDSIEDA RTALKLYRKY LEFDDAGILE
AMLEDIYKAG RATNFKPPRR EDREKELQRQ STPPNSTAPN DCGAKPDGNG NENGGEPATP
ARKTGGITAP TFGAVNVFGT PSKASSPLPK
