ID CTDS2_HUMAN Reviewed; 271 AA. AC O14595; A8K5H4; Q53ZR2; Q6NZY3; Q9UEX1; DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 09-NOV-2004, sequence version 2. DT 24-JAN-2024, entry version 182. DE RecName: Full=Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2; DE EC=3.1.3.16; DE AltName: Full=Nuclear LIM interactor-interacting factor 2; DE Short=NLI-interacting factor 2; DE AltName: Full=Protein OS-4; DE AltName: Full=Small C-terminal domain phosphatase 2; DE AltName: Full=Small CTD phosphatase 2; DE Short=SCP2; GN Name=CTDSP2; Synonyms=NIF2, OS4, SCP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9315096; DOI=10.1038/sj.onc.1201294; RA Su Y.A., Lee M.M., Hutter C.M., Meltzer P.S.; RT "Characterization of a highly conserved gene (OS4) amplified with CDK4 in RT human sarcomas."; RL Oncogene 15:1289-1294(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=12721286; DOI=10.1074/jbc.m301791200; RA Yeo M., Lin P.S., Dahmus M.E., Gill G.N.; RT "A novel RNA polymerase II C-terminal domain phosphatase that RT preferentially dephosphorylates serine 5."; RL J. Biol. Chem. 278:26078-26085(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal pancreas; RA Morikane K., Hollingsworth M.A.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Leukocyte; 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 [7] RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH REST. RX PubMed=15681389; DOI=10.1126/science.1100801; RA Yeo M., Lee S.-K., Lee B., Ruiz E.C., Pfaff S.L., Gill G.N.; RT "Small CTD phosphatases function in silencing neuronal gene expression."; RL Science 307:596-600(2005). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 87-271 IN COMPLEX WITH MAGNESIUM. RX PubMed=18058037; DOI=10.1007/s10969-007-9036-1; RA Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P., RA Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S., RA Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y., RA Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R., Sali A., RA Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K.; RT "Structural genomics of protein phosphatases."; RL J. Struct. Funct. Genomics 8:121-140(2007). CC -!- FUNCTION: Preferentially catalyzes the dephosphorylation of 'Ser-5' CC within the tandem 7 residue repeats in the C-terminal domain (CTD) of CC the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA CC polymerase II transcription, possibly by controlling the transition CC from initiation/capping to processive transcript elongation. Recruited CC by REST to neuronal genes that contain RE-1 elements, leading to CC neuronal gene silencing in non-neuronal cells. May contribute to the CC development of sarcomas. {ECO:0000269|PubMed:12721286, CC ECO:0000269|PubMed:15681389}. 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 -!- 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 -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Binds 1 Mg(2+) ion per monomer.; CC -!- SUBUNIT: Monomer (By similarity). Interacts with REST. {ECO:0000250, CC ECO:0000269|PubMed:15681389, ECO:0000269|PubMed:18058037}. CC -!- INTERACTION: CC O14595; P10275: AR; NbExp=3; IntAct=EBI-2802973, EBI-608057; CC O14595; Q99618: CDCA3; NbExp=10; IntAct=EBI-2802973, EBI-739534; CC O14595; P80188: LCN2; NbExp=3; IntAct=EBI-2802973, EBI-11911016; CC O14595; O15049: N4BP3; NbExp=3; IntAct=EBI-2802973, EBI-2512055; CC O14595; Q15797: SMAD1; NbExp=2; IntAct=EBI-2802973, EBI-1567153; CC O14595; P14079: tax; Xeno; NbExp=3; IntAct=EBI-2802973, EBI-9675698; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expression is restricted to non-neuronal tissues. CC Highest expression in pancreas and lowest in liver. CC {ECO:0000269|PubMed:15681389}. CC -!- INDUCTION: In primary sarcomas. CC -!- SEQUENCE CAUTION: CC Sequence=AAB71816.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAP34399.1; Type=Frameshift; Evidence={ECO:0000305}; 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; AF000152; AAB71816.1; ALT_FRAME; mRNA. DR EMBL; AY279531; AAP34399.1; ALT_FRAME; mRNA. DR EMBL; AF022231; AAD09331.1; -; mRNA. DR EMBL; AK291289; BAF83978.1; -; mRNA. DR EMBL; CH471054; EAW97083.1; -; Genomic_DNA. DR EMBL; BC065920; AAH65920.1; -; mRNA. DR CCDS; CCDS41801.1; -. DR RefSeq; NP_005721.3; NM_005730.3. DR PDB; 2Q5E; X-ray; 2.51 A; A/B/C/D/E/F/G/H=87-271. DR PDBsum; 2Q5E; -. DR AlphaFoldDB; O14595; -. DR SMR; O14595; -. DR BioGRID; 115412; 67. DR DIP; DIP-61245N; -. DR IntAct; O14595; 43. DR MINT; O14595; -. DR STRING; 9606.ENSP00000381148; -. DR DEPOD; CTDSP2; -. DR iPTMnet; O14595; -. DR PhosphoSitePlus; O14595; -. DR SwissPalm; O14595; -. DR BioMuta; CTDSP2; -. DR jPOST; O14595; -. DR MassIVE; O14595; -. DR MaxQB; O14595; -. DR PaxDb; 9606-ENSP00000381148; -. DR PeptideAtlas; O14595; -. DR ProteomicsDB; 48104; -. DR Antibodypedia; 8503; 323 antibodies from 28 providers. DR DNASU; 10106; -. DR Ensembl; ENST00000398073.7; ENSP00000381148.2; ENSG00000175215.11. DR GeneID; 10106; -. DR KEGG; hsa:10106; -. DR MANE-Select; ENST00000398073.7; ENSP00000381148.2; NM_005730.4; NP_005721.3. DR UCSC; uc001sqm.4; human. DR AGR; HGNC:17077; -. DR CTD; 10106; -. DR DisGeNET; 10106; -. DR GeneCards; CTDSP2; -. DR HGNC; HGNC:17077; CTDSP2. DR HPA; ENSG00000175215; Low tissue specificity. DR MIM; 608711; gene. DR neXtProt; NX_O14595; -. DR OpenTargets; ENSG00000175215; -. DR PharmGKB; PA128394568; -. DR VEuPathDB; HostDB:ENSG00000175215; -. DR eggNOG; KOG1605; Eukaryota. DR GeneTree; ENSGT01040000240451; -. DR InParanoid; O14595; -. DR OMA; ANTIAKX; -. DR OrthoDB; 5473812at2759; -. DR PhylomeDB; O14595; -. DR TreeFam; TF313556; -. DR PathwayCommons; O14595; -. DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes. DR SignaLink; O14595; -. DR SIGNOR; O14595; -. DR BioGRID-ORCS; 10106; 48 hits in 1176 CRISPR screens. DR ChiTaRS; CTDSP2; human. DR EvolutionaryTrace; O14595; -. DR GeneWiki; CTDSP2; -. DR GenomeRNAi; 10106; -. DR Pharos; O14595; Tbio. DR PRO; PR:O14595; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; O14595; Protein. DR Bgee; ENSG00000175215; Expressed in mucosa of stomach and 211 other cell types or tissues. DR ExpressionAtlas; O14595; baseline and differential. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. 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:0008420; F:RNA polymerase II CTD heptapeptide repeat phosphatase activity; IDA:UniProtKB. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB. DR CDD; cd07521; HAD_FCP1-like; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 1. DR InterPro; IPR011948; Dullard_phosphatase. DR InterPro; IPR004274; FCP1_dom. DR InterPro; IPR036412; HAD-like_sf. DR InterPro; IPR023214; HAD_sf. DR InterPro; IPR040078; RNA_Pol_CTD_Phosphatase. DR NCBIfam; TIGR02251; HIF-SF_euk; 1. DR PANTHER; PTHR12210:SF187; CARBOXY-TERMINAL DOMAIN RNA POLYMERASE II POLYPEPTIDE A SMALL PHOSPHATASE 2; 1. DR PANTHER; PTHR12210; DULLARD PROTEIN PHOSPHATASE; 1. DR Pfam; PF03031; NIF; 1. DR SFLD; SFLDG01124; C0.1:_RNA_Pol_CTD_Phosphatase; 1. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SMART; SM00577; CPDc; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR PROSITE; PS50969; FCP1; 1. DR Genevisible; O14595; HS. PE 1: Evidence at protein level; KW 3D-structure; Hydrolase; Magnesium; Metal-binding; Nucleus; Phosphoprotein; KW Protein phosphatase; Reference proteome. FT CHAIN 1..271 FT /note="Carboxy-terminal domain RNA polymerase II FT polypeptide A small phosphatase 2" FT /id="PRO_0000212574" FT DOMAIN 97..255 FT /note="FCP1 homology" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00336" FT ACT_SITE 107 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250" FT ACT_SITE 109 FT /note="Proton donor" FT /evidence="ECO:0000250" FT BINDING 107 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:18058037" FT BINDING 109 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:18058037" FT BINDING 218 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:18058037" FT SITE 163 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250" FT SITE 201 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CONFLICT 9 FT /note="Q -> H (in Ref. 3; AAD09331)" FT /evidence="ECO:0000305" FT TURN 96..100 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 103..106 FT /evidence="ECO:0007829|PDB:2Q5E" FT TURN 110..112 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 113..118 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 124..131 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 134..142 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 146..156 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 157..162 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 167..177 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 183..187 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 192..195 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 198..200 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 210..212 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 213..218 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 220..223 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 227..229 FT /evidence="ECO:0007829|PDB:2Q5E" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 244..255 FT /evidence="ECO:0007829|PDB:2Q5E" FT HELIX 261..268 FT /evidence="ECO:0007829|PDB:2Q5E" SQ SEQUENCE 271 AA; 30664 MW; E4FA4A1657F2B03F CRC64; MEHGSIITQA RREDALVLTK QGLVSKSSPK KPRGRNIFKA LFCCFRAQHV GQSSSSTELA AYKEEANTIA KSDLLQCLQY QFYQIPGTCL LPEVTEEDQG RICVVIDLDE TLVHSSFKPI NNADFIVPIE IEGTTHQVYV LKRPYVDEFL RRMGELFECV LFTASLAKYA DPVTDLLDRC GVFRARLFRE SCVFHQGCYV KDLSRLGRDL RKTLILDNSP ASYIFHPENA VPVQSWFDDM ADTELLNLIP IFEELSGAED VYTSLGQLRA P //