PAN3_MOUSE
ID PAN3_MOUSE Reviewed; 837 AA.
AC Q640Q5; Q3U5F2; Q8CE75; Q9CZM6;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 143.
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};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-293 (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 731-837 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo, Skin, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=18625844; DOI=10.1083/jcb.200801196;
RA Zheng D., Ezzeddine N., Chen C.Y., Zhu W., He X., Shyu A.B.;
RT "Deadenylation is prerequisite for P-body formation and mRNA decay in
RT mammalian cells.";
RL J. Cell Biol. 182:89-101(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH YTHDF3.
RX PubMed=32905781; DOI=10.1016/j.celrep.2020.108120;
RA Liu J., Gao M., Xu S., Chen Y., Wu K., Liu H., Wang J., Yang X., Wang J.,
RA Liu W., Bao X., Chen J.;
RT "YTHDF2/3 are required for somatic reprogramming through different RNA
RT deadenylation pathways.";
RL Cell Rep. 32:108120-108120(2020).
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 -!- 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 PABPC1 (via PABC
CC domain), conferring substrate specificity of the enzyme complex.
CC Interacts with the GW182 family proteins TNRC6A, TNRC6B and TNRC6C (By
CC similarity). Interacts with YTHDF3 (PubMed:32905781).
CC {ECO:0000255|HAMAP-Rule:MF_03181, ECO:0000269|PubMed:32905781}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000255|HAMAP-
CC Rule:MF_03181, ECO:0000269|PubMed:18625844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q640Q5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q640Q5-2; Sequence=VSP_041650, VSP_041651;
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 The nucleotide-binding site is juxtaposed to the RNase active site of
CC PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA
CC rather than ATP, feeding the poly(A)-tail to the active site of the
CC deadenylase and thus increasing the efficiency with which this
CC distributive enzyme degrades oligo(A) RNAs. {ECO:0000255|HAMAP-
CC Rule:MF_03181}.
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 -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. PAN3 family.
CC {ECO:0000255|HAMAP-Rule:MF_03181}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH82547.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=BAB28221.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=BAE32127.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305};
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DR EMBL; AK012409; BAB28221.1; ALT_SEQ; mRNA.
DR EMBL; AK028869; BAC26161.1; -; mRNA.
DR EMBL; AK153632; BAE32127.1; ALT_SEQ; mRNA.
DR EMBL; AC131730; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC134441; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC082547; AAH82547.1; ALT_SEQ; mRNA.
DR CCDS; CCDS39401.2; -. [Q640Q5-1]
DR RefSeq; NP_082567.3; NM_028291.4. [Q640Q5-1]
DR AlphaFoldDB; Q640Q5; -.
DR SMR; Q640Q5; -.
DR BioGRID; 215454; 1.
DR STRING; 10090.ENSMUSP00000031651; -.
DR iPTMnet; Q640Q5; -.
DR PhosphoSitePlus; Q640Q5; -.
DR EPD; Q640Q5; -.
DR MaxQB; Q640Q5; -.
DR PaxDb; Q640Q5; -.
DR PeptideAtlas; Q640Q5; -.
DR PRIDE; Q640Q5; -.
DR ProteomicsDB; 295458; -. [Q640Q5-1]
DR ProteomicsDB; 295459; -. [Q640Q5-2]
DR Antibodypedia; 22704; 145 antibodies from 21 providers.
DR DNASU; 72587; -.
DR Ensembl; ENSMUST00000031651; ENSMUSP00000031651; ENSMUSG00000029647. [Q640Q5-1]
DR GeneID; 72587; -.
DR KEGG; mmu:72587; -.
DR UCSC; uc009aod.2; mouse. [Q640Q5-1]
DR CTD; 255967; -.
DR MGI; MGI:1919837; Pan3.
DR VEuPathDB; HostDB:ENSMUSG00000029647; -.
DR eggNOG; KOG3741; Eukaryota.
DR GeneTree; ENSGT00390000001504; -.
DR InParanoid; Q640Q5; -.
DR OMA; AETMYSR; -.
DR OrthoDB; 1515085at2759; -.
DR TreeFam; TF105865; -.
DR Reactome; R-MMU-429947; Deadenylation of mRNA.
DR BioGRID-ORCS; 72587; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Pan3; mouse.
DR PRO; PR:Q640Q5; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q640Q5; protein.
DR Bgee; ENSMUSG00000029647; Expressed in animal zygote and 224 other tissues.
DR ExpressionAtlas; Q640Q5; baseline and differential.
DR Genevisible; Q640Q5; MM.
DR GO; GO:0000932; C:P-body; IDA:MGI.
DR GO; GO:0031251; C:PAN complex; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0000290; P:deadenylation-dependent decapping of nuclear-transcribed mRNA; IMP:MGI.
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; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0006605; P:protein targeting; IDA:MGI.
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 InterPro; IPR036855; Znf_CCCH_sf.
DR PANTHER; PTHR12272; PTHR12272; 1.
DR Pfam; PF18101; Pan3_PK; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00356; ZnF_C3H1; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF90229; SSF90229; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS50103; ZF_C3H1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Coiled coil; Cytoplasm; Metal-binding;
KW mRNA processing; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Zinc; Zinc-finger.
FT CHAIN 1..837
FT /note="PAN2-PAN3 deadenylation complex subunit Pan3"
FT /id="PRO_0000280526"
FT ZN_FING 49..77
FT /note="C3H1-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT REGION 111..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..696
FT /note="Pseudokinase domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT REGION 736..837
FT /note="Knob domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT COILED 230..245
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT MOTIF 74..94
FT /note="PABPC-interacting motif-2 (PAM-2)"
FT /evidence="ECO:0000305"
FT COMPBIAS 302..322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 467
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT BINDING 516..523
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT BINDING 590..591
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03181"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q58A45"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 281..301
FT /note="MSLSAGSSPLHSPKITPHTSP -> NKLPSESALDLKINPTVHETD (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041650"
FT VAR_SEQ 302..837
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041651"
SQ SEQUENCE 837 AA; 89745 MW; 323CACB0F32E745A CRC64;
MNSGGGGGLP PPSAAASPSS SSLAAAVAVA VAASSGVGGV PGGPAAAAGV KLKYCRYYAK
DKTCFYGEEC QFLHEDPAAG AAPGLGLHSN SVPLALAAAA GAAFPPGALP GGGAGPPAGP
KKPELGVPGA ATAGGGLDGP RVAIPGMDGG ALTDASLTES YFSTSFIGVN GFGSPVETKY
PLMQRMTSSS SSPSLLNDSA KPYTGHDLLT SSASSLFNDF GALNISQRRK TPNPTASEFI
PKGGSTSRLS NVSQSNMSAF SQVFSHPSMG SPATAGLAPG MSLSAGSSPL HSPKITPHTS
PAPRRRSHTP NPASFMVPPS ASTPANNPAP QPPSSGQVIQ KETVGGTTYF YTDTTPAPLT
GMVFPNYHIY PPTAPHVAYM QPKANAPSFF MADELRQELI NRHLITMAQI DQADMPAVPT
EVDSYHSLFP LEPLPPPNRI QKSSNFGYIT SCYKAVNSKD DLPYCLRRIH GFRLVNTKCM
VLVDMWKKIQ HSNIVTLREV FTTKAFAEPS LVFAYDFHAG GETMMSRHFN DPNSDAYFTK
RKWGQHDGPL PRQHAGLLPE SLIWAYIVQL SSALRTIHTA GLACRVMDPT KILITSKTRL
RVNCVGVFDV LTFDNSQNNN PLALMAQYQQ ADLISLGKVV LALACNSLAG IQRENLQKAM
ELVTINYSSD LKNLILYLLT DQNRMRSVND IMPMIGARFY TQLDAAQMRN DVIEEDLAKE
VQNGRLFRLL AKLGTINERP EFQKDPTWSE TGDRYLLKLF RDHLFHQVTE AGAPWIDLSH
IISCLNKLDA GVPEKISLIS RDEKSVLVVT YSDLKRCFEN TFQELIAAAN GNDRNSN
