ID   RPAP2_RAT               Reviewed;         609 AA.
AC   Q5I0E6; D4A5J9; D4A672;
DT   03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2005, sequence version 1.
DT   24-JAN-2024, entry version 107.
DE   RecName: Full=RNA polymerase II subunit B1 CTD phosphatase Rpap2;
DE            EC=3.1.3.16 {ECO:0000250|UniProtKB:Q8IXW5};
DE   AltName: Full=Putative RNA polymerase II-associated protein 2;
GN   Name=Rpap2;
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-222, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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 (By similarity).
CC       {ECO:0000250|UniProtKB:Q8IXW5}.
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:0000250|UniProtKB:Q8IXW5};
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=2;
CC       Name=1;
CC         IsoId=Q5I0E6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q5I0E6-2; Sequence=VSP_042584;
CC   -!- SIMILARITY: Belongs to the RPAP2 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00812, ECO:0000305}.
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DR   EMBL; BC088426; AAH88426.1; -; mRNA.
DR   RefSeq; NP_001014009.1; NM_001013987.1. [Q5I0E6-1]
DR   AlphaFoldDB; Q5I0E6; -.
DR   SMR; Q5I0E6; -.
DR   STRING; 10116.ENSRNOP00000002815; -.
DR   iPTMnet; Q5I0E6; -.
DR   PhosphoSitePlus; Q5I0E6; -.
DR   PaxDb; 10116-ENSRNOP00000002815; -.
DR   GeneID; 305120; -.
DR   KEGG; rno:305120; -.
DR   UCSC; RGD:1309034; rat. [Q5I0E6-1]
DR   AGR; RGD:1309034; -.
DR   CTD; 79871; -.
DR   RGD; 1309034; Rpap2.
DR   VEuPathDB; HostDB:ENSRNOG00000023484; -.
DR   eggNOG; KOG4780; Eukaryota.
DR   HOGENOM; CLU_019258_1_0_1; -.
DR   InParanoid; Q5I0E6; -.
DR   OrthoDB; 1410801at2759; -.
DR   PhylomeDB; Q5I0E6; -.
DR   TreeFam; TF331431; -.
DR   Reactome; R-RNO-6807505; RNA polymerase II transcribes snRNA genes.
DR   PRO; PR:Q5I0E6; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000023484; Expressed in thymus and 20 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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; Q5I0E6; RN.
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..609
FT                   /note="RNA polymerase II subunit B1 CTD phosphatase Rpap2"
FT                   /id="PRO_0000250651"
FT   ZN_FING         77..160
FT                   /note="RTR1-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00812"
FT   REGION          1..37
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          208..272
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          33..69
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        11..31
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        257..272
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         222
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         476
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8IXW5"
FT   VAR_SEQ         214..218
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_042584"
SQ   SEQUENCE   609 AA;  67892 MW;  AB4E505B6037636D CRC64;
     MADSAVPYSL GPSARASSTH RVATGTKQTS ALKRRDASKR QAELEAALQR KVESERRAVR
     LVEQLLEENI TEEFLKECGM FITPAHYSDV VDERAIIKLC GYPLCQKKLG VIPKQKYRIS
     TKTNKVYDIT ERKSFCSNFC YKASKFFEAQ IPKTPVWVRE EERPPEFQLL KKGQSGCSGE
     VVQFFRDAVT AADVDAYGAF DAQCEPASSS TWSERASDER ASDEEGPGFV SSLLPGNRPK
     AVGTKPQPHR QSSTVKKKAA QKMTSKHGEQ TVSEVTEQLS NCRLDSQEKV ATCKLPAKKE
     NTQISSPGPL CDRLNTSTVS ENKHSVSQVT LVGISKKSAE HFRSKFAKSN PGSGSASGLV
     QVRPEVAKAN LLRVLKDTLT EWKTDETLKF LYGQDHGSVC LQPSAASGPD EELDEDDISC
     QAQNTLDETL PFRGSDTAIK PLPSYESLKK ETEMLNLRVR EFYRGRCVLN EDSTKSQDSK
     ENELQRDPSF PLIDSSSQNQ IRRRIVLEKL SKVLPGLLGP LQITMGDIYT ELKNLVQTFR
     LSNRNIIHKP VEWTLIAVVL LSLLTPILGI QKHSPKNVVF TQFIATLLTE LHLKCEDLEN
     LAMIFRTSC
//