ID   RPAP2_MOUSE             Reviewed;         614 AA.
AC   Q8VC34; Q3TLC8; Q3TSP8; Q3UKX0; Q8C7M5; Q8CBW8;
DT   03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 2.
DT   27-MAR-2024, entry version 140.
DE   RecName: Full=Putative RNA polymerase II subunit B1 CTD phosphatase Rpap2;
DE            EC=3.1.3.16 {ECO:0000305|PubMed:35975910};
DE   AltName: Full=RNA polymerase II-associated protein 2;
GN   Name=Rpap2;
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 MRNA] (ISOFORMS 1; 2; 3; 4 AND 5).
RC   STRAIN=C57BL/6J;
RC   TISSUE=Diencephalon, Hippocampus, Medulla oblongata, and Placenta;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J, and FVB/N; TISSUE=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   [3]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=35975910; DOI=10.1002/mc.23453;
RA   Mogre S., Blazanin N., Walsh H., Ibinson J., Minnich C., Andrew Hu C.C.,
RA   Glick A.B.;
RT   "TGFbeta1 regulates HRas-mediated activation of IRE1alpha through the PERK-
RT   RPAP2 axis in keratinocytes.";
RL   Mol. Carcinog. 61:958-971(2022).
CC   -!- FUNCTION: Protein phosphatase that displays CTD phosphatase activity
CC       and regulates transcription of snRNA genes. Recognizes and binds
CC       phosphorylated 'Ser-7' of the C-terminal heptapeptide repeat domain
CC       (CTD) of the largest RNA polymerase II subunit POLR2A, and mediates
CC       dephosphorylation of 'Ser-5' of the CTD, thereby promoting
CC       transcription of snRNA genes (By similarity). Downstream of
CC       EIF2AK3/PERK, dephosphorylates ERN1, a sensor for the endoplasmic
CC       reticulum unfolded protein response (UPR), to abort failed ER-stress
CC       adaptation and trigger apoptosis (PubMed:35975910).
CC       {ECO:0000250|UniProtKB:Q8IXW5, ECO:0000269|PubMed:35975910}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:20629, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15377, ChEBI:CHEBI:29999, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:83421; EC=3.1.3.16;
CC         Evidence={ECO:0000305|PubMed:35975910};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] +
CC         phosphate; Xref=Rhea:RHEA:47004, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15377, ChEBI:CHEBI:30013, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:61977; EC=3.1.3.16;
CC   -!- SUBUNIT: Associates with the RNA polymerase II complex. Interacts with
CC       transcribing RNA polymerase II phosphorylated on 'Ser-7' on CTD (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC       Note=Shuttles between the cytoplasm and the nucleus in a CRM1-dependent
CC       manner. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=1;
CC         IsoId=Q8VC34-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8VC34-2; Sequence=VSP_020686, VSP_020687;
CC       Name=3;
CC         IsoId=Q8VC34-3; Sequence=VSP_020685;
CC       Name=4;
CC         IsoId=Q8VC34-4; Sequence=VSP_020682, VSP_020685;
CC       Name=5;
CC         IsoId=Q8VC34-5; Sequence=VSP_020683, VSP_020684;
CC   -!- SIMILARITY: Belongs to the RPAP2 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00812, ECO:0000305}.
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DR   EMBL; AK034418; BAC28703.1; -; mRNA.
DR   EMBL; AK049889; BAC33973.1; -; mRNA.
DR   EMBL; AK145830; BAE26681.1; -; mRNA.
DR   EMBL; AK161901; BAE36627.1; -; mRNA.
DR   EMBL; AK166574; BAE38864.1; -; mRNA.
DR   EMBL; BC021895; AAH21895.1; -; mRNA.
DR   CCDS; CCDS19506.1; -. [Q8VC34-1]
DR   CCDS; CCDS51588.1; -. [Q8VC34-3]
DR   CCDS; CCDS51589.1; -. [Q8VC34-4]
DR   CCDS; CCDS71630.1; -. [Q8VC34-2]
DR   CCDS; CCDS71631.1; -. [Q8VC34-5]
DR   RefSeq; NP_001156933.1; NM_001163461.2. [Q8VC34-3]
DR   RefSeq; NP_001156934.1; NM_001163462.2. [Q8VC34-4]
DR   RefSeq; NP_001276498.1; NM_001289569.1. [Q8VC34-5]
DR   RefSeq; NP_001276499.1; NM_001289570.1. [Q8VC34-2]
DR   RefSeq; NP_659160.2; NM_144911.3. [Q8VC34-1]
DR   RefSeq; XP_006534963.1; XM_006534900.3. [Q8VC34-5]
DR   AlphaFoldDB; Q8VC34; -.
DR   SMR; Q8VC34; -.
DR   IntAct; Q8VC34; 1.
DR   MINT; Q8VC34; -.
DR   STRING; 10090.ENSMUSP00000070209; -.
DR   iPTMnet; Q8VC34; -.
DR   PhosphoSitePlus; Q8VC34; -.
DR   EPD; Q8VC34; -.
DR   MaxQB; Q8VC34; -.
DR   PaxDb; 10090-ENSMUSP00000070209; -.
DR   PeptideAtlas; Q8VC34; -.
DR   ProteomicsDB; 300470; -. [Q8VC34-1]
DR   ProteomicsDB; 300471; -. [Q8VC34-2]
DR   ProteomicsDB; 300472; -. [Q8VC34-3]
DR   ProteomicsDB; 300473; -. [Q8VC34-4]
DR   ProteomicsDB; 300474; -. [Q8VC34-5]
DR   Pumba; Q8VC34; -.
DR   Antibodypedia; 46923; 77 antibodies from 20 providers.
DR   DNASU; 231571; -.
DR   Ensembl; ENSMUST00000065422.12; ENSMUSP00000070209.6; ENSMUSG00000033773.15. [Q8VC34-1]
DR   Ensembl; ENSMUST00000112650.8; ENSMUSP00000108269.2; ENSMUSG00000033773.15. [Q8VC34-4]
DR   Ensembl; ENSMUST00000112651.8; ENSMUSP00000108270.2; ENSMUSG00000033773.15. [Q8VC34-5]
DR   Ensembl; ENSMUST00000112654.8; ENSMUSP00000108273.2; ENSMUSG00000033773.15. [Q8VC34-3]
DR   Ensembl; ENSMUST00000112655.8; ENSMUSP00000108274.2; ENSMUSG00000033773.15. [Q8VC34-2]
DR   GeneID; 231571; -.
DR   KEGG; mmu:231571; -.
DR   UCSC; uc008ymn.3; mouse. [Q8VC34-1]
DR   UCSC; uc008ymq.3; mouse. [Q8VC34-5]
DR   UCSC; uc033iky.1; mouse. [Q8VC34-2]
DR   AGR; MGI:2141142; -.
DR   CTD; 79871; -.
DR   MGI; MGI:2141142; Rpap2.
DR   VEuPathDB; HostDB:ENSMUSG00000033773; -.
DR   eggNOG; KOG4780; Eukaryota.
DR   GeneTree; ENSGT00390000017965; -.
DR   HOGENOM; CLU_019258_1_0_1; -.
DR   InParanoid; Q8VC34; -.
DR   OMA; ICQNKLE; -.
DR   OrthoDB; 1410801at2759; -.
DR   PhylomeDB; Q8VC34; -.
DR   TreeFam; TF331431; -.
DR   Reactome; R-MMU-6807505; RNA polymerase II transcribes snRNA genes.
DR   BioGRID-ORCS; 231571; 22 hits in 82 CRISPR screens.
DR   ChiTaRS; Rpap2; mouse.
DR   PRO; PR:Q8VC34; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q8VC34; Protein.
DR   Bgee; ENSMUSG00000033773; Expressed in animal zygote and 251 other cell types or tissues.
DR   ExpressionAtlas; Q8VC34; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005730; C:nucleolus; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0097550; C:transcription preinitiation complex; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0017018; F:myosin phosphatase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004722; F:protein serine/threonine phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0043175; F:RNA polymerase core enzyme binding; IEA:InterPro.
DR   GO; GO:0008420; F:RNA polymerase II CTD heptapeptide repeat phosphatase activity; ISS:UniProtKB.
DR   GO; GO:0036499; P:PERK-mediated unfolded protein response; ISS:UniProtKB.
DR   GO; GO:0009301; P:snRNA transcription; ISS:UniProtKB.
DR   Gene3D; 1.25.40.820; -; 1.
DR   InterPro; IPR039693; Rtr1/RPAP2.
DR   InterPro; IPR007308; Rtr1/RPAP2_dom.
DR   InterPro; IPR038534; Rtr1/RPAP2_sf.
DR   PANTHER; PTHR14732:SF0; RNA POLYMERASE II SUBUNIT B1 CTD PHOSPHATASE RPAP2-RELATED; 1.
DR   PANTHER; PTHR14732; UNCHARACTERIZED; 1.
DR   Pfam; PF04181; RPAP2_Rtr1; 1.
DR   PROSITE; PS51479; ZF_RTR1; 1.
DR   Genevisible; Q8VC34; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Coiled coil; Cytoplasm; Hydrolase;
KW   Metal-binding; Nucleus; Phosphoprotein; Protein phosphatase;
KW   Reference proteome; Transcription; Transcription regulation; Zinc;
KW   Zinc-finger.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IXW5"
FT   CHAIN           2..614
FT                   /note="Putative RNA polymerase II subunit B1 CTD
FT                   phosphatase Rpap2"
FT                   /id="PRO_0000250649"
FT   ZN_FING         77..160
FT                   /note="RTR1-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00812"
FT   REGION          1..38
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          200..266
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          41..68
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        10..25
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        241..266
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         100
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00812"
FT   BINDING         105
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00812"
FT   BINDING         136
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00812"
FT   BINDING         140
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00812"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IXW5"
FT   MOD_RES         9
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IXW5"
FT   MOD_RES         217
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5I0E6"
FT   MOD_RES         481
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IXW5"
FT   VAR_SEQ         1..79
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_020682"
FT   VAR_SEQ         1..77
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_020683"
FT   VAR_SEQ         78
FT                   /note="C -> M (in isoform 5)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_020684"
FT   VAR_SEQ         569..614
FT                   /note="Missing (in isoform 3 and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_020685"
FT   VAR_SEQ         569..570
FT                   /note="LT -> IL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_020686"
FT   VAR_SEQ         571..614
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_020687"
FT   CONFLICT        201
FT                   /note="E -> D (in Ref. 2; AAH21895)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        318
FT                   /note="K -> T (in Ref. 2; AAH21895)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        444
FT                   /note="I -> V (in Ref. 1; BAE26681)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        524
FT                   /note="G -> V (in Ref. 1; BAE38864)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   614 AA;  68530 MW;  3029373A246478D7 CRC64;
     MADSAVPCSL GPSTRASSTH RDATGTKQTR ALKRGDASKR QAELEAAIQR KVEFERKAVR
     IVEQLLEENI TEEFLKECGM FITPAHYSDV VDERSIIKLC GYPLCQKKLG VIPKQKYRIS
     TKTNKVYDIT ERKSFCSNFC YRASKFFETQ IPKTPVWVRE EERPPDFQLL KKGQSGSSGE
     VVQFFRDAVT AADVDGSGAL EAQCDPASSS SWSERASDEE EQGFVSSLLP GNRPKAVDTR
     PQPHTKSSIM RKKAAQNVDS KEGEQTVSEV TEQLDNCRLD SQEKVATCKR PLKKESTQIS
     SPGPLCDRFN TSAISEHKHG VSQVTLVGIS KKSAEHFRSK FAKSNPGSGS ASGLVHVRPE
     VAKANLLRVL SDTLTEWKTE ETLKFLYGQN HDSVCLKPSS ASEPDEELDE DDISCDPGSC
     GPALSQAQNT LDATLPFRGS DTAIKPLPSY ESLKKETEML NLRVREFYRG RCVLNEDTTK
     SQDSKESVLQ RDPSFPLIDS SSQNQIRRRI VLEKLSKVLP GLLGPLQITM GDIYTELKNL
     IQTFRLSNRN IIHKPVEWTL IAVVLLLLLT PILGIQKHSP KNVVFTQFIA TLLTELHLKF
     EDLEKLTMIF RTSC
//