CTDS2_HUMAN
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 03-AUG-2022, entry version 174.
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};
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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; 56.
DR DIP; DIP-61245N; -.
DR IntAct; O14595; 41.
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; O14595; -.
DR PeptideAtlas; O14595; -.
DR PRIDE; O14595; -.
DR ProteomicsDB; 48104; -.
DR Antibodypedia; 8503; 298 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 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 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; 32 hits in 1083 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 209 other tissues.
DR ExpressionAtlas; O14595; baseline and differential.
DR Genevisible; O14595; HS.
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:0004721; F:phosphoprotein phosphatase activity; IBA:GO_Central.
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 Gene3D; 3.40.50.1000; -; 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 Pfam; PF03031; NIF; 1.
DR SFLD; SFLDG01124; C0.1:_RNA_Pol_CTD_Phosphatase; 1.
DR SMART; SM00577; CPDc; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR TIGRFAMs; TIGR02251; HIF-SF_euk; 1.
DR PROSITE; PS50969; FCP1; 1.
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
