PAN2_RAT
ID PAN2_RAT Reviewed; 1205 AA.
AC Q6IE70;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
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=Inactive ubiquitin carboxyl-terminal hydrolase 52 {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}; Synonyms=Usp52;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP IDENTIFICATION.
RX PubMed=15060002; DOI=10.1101/gr.1946304;
RA Puente X.S., Lopez-Otin C.;
RT "A genomic analysis of rat proteases and protease inhibitors.";
RL Genome Res. 14:609-622(2004).
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. Also
CC acts as an important regulator of the HIF1A-mediated hypoxic response.
CC Required for HIF1A mRNA stability independent of poly(A) tail length
CC regulation. {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 -!- 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. Interacts with ZFP36. {ECO:0000255|HAMAP-
CC Rule:MF_03182}.
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}.
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DR EMBL; AABR03055877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BN000323; CAE48378.1; -; mRNA.
DR RefSeq; NP_001008862.1; NM_001008862.1.
DR AlphaFoldDB; Q6IE70; -.
DR SMR; Q6IE70; -.
DR STRING; 10116.ENSRNOP00000039314; -.
DR iPTMnet; Q6IE70; -.
DR PhosphoSitePlus; Q6IE70; -.
DR PaxDb; Q6IE70; -.
DR GeneID; 408200; -.
DR KEGG; rno:408200; -.
DR UCSC; RGD:1303301; rat.
DR CTD; 9924; -.
DR RGD; 1303301; Pan2.
DR eggNOG; KOG1275; Eukaryota.
DR InParanoid; Q6IE70; -.
DR OrthoDB; 128953at2759; -.
DR PhylomeDB; Q6IE70; -.
DR TreeFam; TF105657; -.
DR Reactome; R-RNO-429947; Deadenylation of mRNA.
DR PRO; PR:Q6IE70; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; ISO:RGD.
DR GO; GO:0031251; C:PAN complex; ISS:UniProtKB.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; ISS:UniProtKB.
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; ISS:UniProtKB.
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 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 2: Evidence at transcript level;
KW Cytoplasm; Exonuclease; Hydrolase; Metal-binding; mRNA processing;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..1205
FT /note="PAN2-PAN3 deadenylation complex catalytic subunit
FT Pan2"
FT /id="PRO_0000280523"
FT REPEAT 153..193
FT /note="WD 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REPEAT 195..231
FT /note="WD 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REPEAT 244..280
FT /note="WD 3"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REPEAT 328..367
FT /note="WD 4"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT DOMAIN 485..924
FT /note="USP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT DOMAIN 975..1147
FT /note="Exonuclease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REGION 368..484
FT /note="Linker"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03182"
FT REGION 1179..1205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 978
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 980
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 1087
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 1139
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 MOD_RES 784
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q504Q3"
FT MOD_RES 1189
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q504Q3"
SQ SEQUENCE 1205 AA; 135627 MW; 525532F675D88D08 CRC64;
MNFEGLDPGL AEFSPAMHST LDPVLDAHLN PSLLQNVELD PEGVALEALP VQESVHIMEG
VYSELHSVVA EVGVPVSVSH FDLQEEMLWV GSHGGHATSF FGPALERYSS FQVNGSDDIR
QIQSLENGIL FLTKNNLKYM ARGGLIIFDY LLDESEDMHS LLLADNNTLL VGGLQNHVLE
IDLNTVQETQ KYAVETPGVT IMRQTNRFFF CGHTSGKVSL RDLRSFKVEH EFDAFSGSLS
DFDVHGNLLA ACGFSSRLTG LACDRFLKVY DLRMMRAITP LQVHVDPAFL RFIPTYTSRL
AIISQSGQCQ FCEPTGLANP ADIFHVNPVG PLLMTFDVSA SKQALAFGDS EGCVHLWTDS
PEPSFNPYSR ETEFALPCLV DSLPALDWSQ DLLPLSLIPV PLTTDALLSD WPAANSAPAP
RRAPPVDAEI LRTMKKVGFI GYAPNPRTRL RNQIPYRLKE SDHEFDNFSQ VTESPTGREE
EPLHTVSKKY RKVTIKYSKL GLEDFDFKHY NKTLFAGLEP HIPNAYCNCM IQVLYFLEPV
RCLIQNHLCQ KEFCLACELG FLFHMLDLSR GDPCQGSNFL RAFRTIPEAS ALGLILADSD
EASGKGSLAR LIQRWNRFIL TQLHQDMQEL EVPQAYRGAG GSFCSSGDSI IGQLFSCEME
NCSLCRCGSE TVRASSTLLF TLSYPEDKTG KNYDFAQVLK RSICLEQNTQ AWCDSCEKYQ
PTIQTRNIRH LPDILVINCE VNSSKEADFW RLQAEVAFKI AVKKFGGEVK SKEFALADRK
ELRSPEGFLC CSSMEELKNV WLPFSIRMKM TKNKGLDVCN WADEHELSSL GTPSQWGPAR
AEEEHGVYVY DLMATVVHIL DSRTGGSLVA HIKVGETYHQ RKEGVTHQQW YLFNDFLIEP
IDKYEAVQFD MNWKVPAILY YVKRNLNSRY NLNSKNPIEA SVLLAEASLA RKQRKTHTTF
IPLMLNEMPQ VGDLVGLDAE FVTLNEEEAE LRSDGTKSTI KPSQMSVARI TCVRGQGPNE
GIPFIDDYIS TQEQVVDYLT QYSGIKPGDL DAKISSKHLT TLKSTYLKLR FLIDIGVKFV
GHGLQKDFRV INLMVPKDQV LDTVYLFHMP RKRMISLRFL AWYFLDLKIQ GETHDSIEDA
RTALQLYRKY LELSKNGAEP ESFHKVLKGL YEKGRKMDWK VPEPESQSSP KSKAGLRPGA
LGWVG
