Full text data of CTDSP1
CTDSP1
(NIF3, NLIIF, SCP1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1; 3.1.3.16 (Nuclear LIM interactor-interacting factor 3; NLI-IF; NLI-interacting factor 3; Small C-terminal domain phosphatase 1; SCP1; Small CTD phosphatase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1; 3.1.3.16 (Nuclear LIM interactor-interacting factor 3; NLI-IF; NLI-interacting factor 3; Small C-terminal domain phosphatase 1; SCP1; Small CTD phosphatase 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9GZU7
ID CTDS1_HUMAN Reviewed; 261 AA.
AC Q9GZU7; C9IYG0; Q7Z5Q3; Q7Z5Q4;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1;
DE EC=3.1.3.16;
DE AltName: Full=Nuclear LIM interactor-interacting factor 3;
DE Short=NLI-IF;
DE Short=NLI-interacting factor 3;
DE AltName: Full=Small C-terminal domain phosphatase 1;
DE Short=SCP1;
DE Short=Small CTD phosphatase 1;
GN Name=CTDSP1; Synonyms=NIF3, NLIIF, SCP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=10967134; DOI=10.1007/s003350010151;
RA Marquet S., Lepage P., Hudson T.J., Musser J.M., Schurr E.;
RT "Complete nucleotide sequence and genomic structure of the human
RT NRAMP1 gene region on chromosome region 2q35.";
RL Mamm. Genome 11:755-762(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 50-260 (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH GTF2F1, AND
RP MUTAGENESIS OF ASP-96 AND ASP-98.
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
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
RT expression.";
RL Science 307:596-600(2005).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 77-261 IN COMPLEX WITH
RP MAGNESIUM AND INHIBITOR.
RX PubMed=15304220; DOI=10.1016/j.molcel.2004.06.035;
RA Kamenski T., Heilmeier S., Meinhart A., Cramer P.;
RT "Structure and mechanism of RNA polymerase II CTD phosphatases.";
RL Mol. Cell 15:399-407(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 77-256 OF MUTANT ASN-96 IN
RP COMPLEX WITH SUBSTRATE PEPTIDES, AND SUBSTRATE SPECIFICITY.
RX PubMed=17157258; DOI=10.1016/j.molcel.2006.10.027;
RA Zhang Y., Kim Y., Genoud N., Gao J., Kelly J.W., Pfaff S.L.,
RA Gill G.N., Dixon J.E., Noel J.P.;
RT "Determinants for dephosphorylation of the RNA polymerase II C-
RT terminal domain by Scp1.";
RL Mol. Cell 24:759-770(2006).
CC -!- FUNCTION: Preferentially catalyzes the dephosphorylation of 'Ser-
CC 5' within the tandem 7 residues repeats in the C-terminal domain
CC (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively
CC regulates RNA polymerase II transcription, possibly by controlling
CC the transition from initiation/capping to processive transcript
CC elongation. Recruited by REST to neuronal genes that contain RE-1
CC elements, leading to neuronal gene silencing in non-neuronal
CC cells.
CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- COFACTOR: Binds 1 magnesium ion per monomer.
CC -!- ENZYME REGULATION: Stimulated by GTF2F1. Inhibited by
CC beryllofluoride anions.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5;
CC -!- SUBUNIT: Monomer (By similarity). Interacts with GTF2F1. Interacts
CC with REST.
CC -!- INTERACTION:
CC P58466:Ctdsp1 (xeno); NbExp=2; IntAct=EBI-751587, EBI-7091612;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with RNA
CC polymerase II.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9GZU7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZU7-2; Sequence=VSP_045866;
CC Name=3;
CC IsoId=Q9GZU7-3; Sequence=VSP_045865, VSP_045866;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expression is restricted to non-neuronal
CC tissues. Highest expression in skeletal muscle, spleen, lung and
CC placenta.
CC -!- SIMILARITY: Contains 1 FCP1 homology domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP34398.1; Type=Frameshift; Positions=72;
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DR EMBL; AF229163; AAG15404.1; -; Genomic_DNA.
DR EMBL; AF229162; AAG15402.1; -; mRNA.
DR EMBL; AY279529; AAP34397.1; -; mRNA.
DR EMBL; AY279530; AAP34398.1; ALT_FRAME; mRNA.
DR EMBL; BX446444; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC021016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012977; AAH12977.1; -; mRNA.
DR RefSeq; NP_001193807.1; NM_001206878.1.
DR RefSeq; NP_067021.1; NM_021198.2.
DR RefSeq; NP_872580.1; NM_182642.2.
DR UniGene; Hs.444468; -.
DR PDB; 1T9Z; X-ray; 2.30 A; A=77-261.
DR PDB; 1TA0; X-ray; 2.10 A; A=77-261.
DR PDB; 2GHQ; X-ray; 2.05 A; A/B=77-256.
DR PDB; 2GHT; X-ray; 1.80 A; A/B=77-256.
DR PDB; 3L0B; X-ray; 2.35 A; A/B=77-256.
DR PDB; 3L0C; X-ray; 2.45 A; A/B=77-256.
DR PDB; 3L0Y; X-ray; 2.30 A; A/B=77-256.
DR PDB; 3PGL; X-ray; 2.35 A; A/B=77-256.
DR PDBsum; 1T9Z; -.
DR PDBsum; 1TA0; -.
DR PDBsum; 2GHQ; -.
DR PDBsum; 2GHT; -.
DR PDBsum; 3L0B; -.
DR PDBsum; 3L0C; -.
DR PDBsum; 3L0Y; -.
DR PDBsum; 3PGL; -.
DR ProteinModelPortal; Q9GZU7; -.
DR SMR; Q9GZU7; 77-256.
DR IntAct; Q9GZU7; 2.
DR MINT; MINT-1441843; -.
DR STRING; 9606.ENSP00000273062; -.
DR BindingDB; Q9GZU7; -.
DR ChEMBL; CHEMBL1795098; -.
DR PhosphoSite; Q9GZU7; -.
DR DMDM; 17865510; -.
DR PaxDb; Q9GZU7; -.
DR PRIDE; Q9GZU7; -.
DR DNASU; 58190; -.
DR Ensembl; ENST00000273062; ENSP00000273062; ENSG00000144579.
DR Ensembl; ENST00000443891; ENSP00000392248; ENSG00000144579.
DR GeneID; 58190; -.
DR KEGG; hsa:58190; -.
DR UCSC; uc002vhx.3; human.
DR CTD; 58190; -.
DR GeneCards; GC02P219262; -.
DR HGNC; HGNC:21614; CTDSP1.
DR MIM; 605323; gene.
DR neXtProt; NX_Q9GZU7; -.
DR PharmGKB; PA134938848; -.
DR eggNOG; COG5190; -.
DR HOGENOM; HOG000236379; -.
DR HOVERGEN; HBG053298; -.
DR InParanoid; Q9GZU7; -.
DR KO; K15731; -.
DR OrthoDB; EOG71P2C3; -.
DR PhylomeDB; Q9GZU7; -.
DR SignaLink; Q9GZU7; -.
DR ChiTaRS; CTDSP1; human.
DR EvolutionaryTrace; Q9GZU7; -.
DR GeneWiki; CTDSP1; -.
DR GenomeRNAi; 58190; -.
DR NextBio; 64884; -.
DR PRO; PR:Q9GZU7; -.
DR Bgee; Q9GZU7; -.
DR CleanEx; HS_CTDSP1; -.
DR Genevestigator; Q9GZU7; -.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008420; F:CTD phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR011948; Dullard_phosphatase.
DR InterPro; IPR023214; HAD-like_dom.
DR InterPro; IPR004274; NIF.
DR Pfam; PF03031; NIF; 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; Acetylation; Alternative splicing; Complete proteome;
KW Hydrolase; Metal-binding; Nucleus; Polymorphism; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1 261 Carboxy-terminal domain RNA polymerase II
FT polypeptide A small phosphatase 1.
FT /FTId=PRO_0000212572.
FT DOMAIN 86 244 FCP1 homology.
FT ACT_SITE 96 96 4-aspartylphosphate intermediate.
FT ACT_SITE 98 98 Proton donor.
FT METAL 96 96 Magnesium.
FT METAL 98 98 Magnesium; via carbonyl oxygen.
FT METAL 207 207 Magnesium.
FT SITE 152 152 Transition state stabilizer.
FT SITE 190 190 Transition state stabilizer.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 1 22 MDSSAVITQISKEEARGPLRGK -> MVAAPWATQEQEEGR
FT GIQPGDR (in isoform 3).
FT /FTId=VSP_045865.
FT VAR_SEQ 73 73 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_045866.
FT VARIANT 56 56 A -> T (in dbSNP:rs2227249).
FT /FTId=VAR_049054.
FT MUTAGEN 96 96 D->E: No effect. Completely abolishes
FT phosphatase activity; when associated
FT with N-98.
FT MUTAGEN 98 98 D->N: Completely abolishes phosphatase
FT activity; when associated with E-96.
FT CONFLICT 180 180 S -> F (in Ref. 3; BX446444).
FT HELIX 85 87
FT STRAND 92 95
FT TURN 99 101
FT STRAND 102 107
FT STRAND 113 120
FT STRAND 123 131
FT HELIX 135 145
FT STRAND 146 151
FT HELIX 156 166
FT STRAND 172 176
FT HELIX 178 180
FT STRAND 181 184
FT STRAND 187 189
FT HELIX 192 194
FT STRAND 195 197
FT HELIX 199 201
FT STRAND 202 205
FT HELIX 209 212
FT HELIX 216 218
FT STRAND 219 221
FT HELIX 233 244
FT HELIX 251 254
SQ SEQUENCE 261 AA; 29203 MW; 75A430BCA2748FEA CRC64;
MDSSAVITQI SKEEARGPLR GKGDQKSAAS QKPRSRGILH SLFCCVCRDD GEALPAHSGA
PLLVEENGAI PKQTPVQYLL PEAKAQDSDK ICVVIDLDET LVHSSFKPVN NADFIIPVEI
DGVVHQVYVL KRPHVDEFLQ RMGELFECVL FTASLAKYAD PVADLLDKWG AFRARLFRES
CVFHRGNYVK DLSRLGRDLR RVLILDNSPA SYVFHPDNAV PVASWFDNMS DTELHDLLPF
FEQLSRVDDV YSVLRQPRPG S
//
ID CTDS1_HUMAN Reviewed; 261 AA.
AC Q9GZU7; C9IYG0; Q7Z5Q3; Q7Z5Q4;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 112.
DE RecName: Full=Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1;
DE EC=3.1.3.16;
DE AltName: Full=Nuclear LIM interactor-interacting factor 3;
DE Short=NLI-IF;
DE Short=NLI-interacting factor 3;
DE AltName: Full=Small C-terminal domain phosphatase 1;
DE Short=SCP1;
DE Short=Small CTD phosphatase 1;
GN Name=CTDSP1; Synonyms=NIF3, NLIIF, SCP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=10967134; DOI=10.1007/s003350010151;
RA Marquet S., Lepage P., Hudson T.J., Musser J.M., Schurr E.;
RT "Complete nucleotide sequence and genomic structure of the human
RT NRAMP1 gene region on chromosome region 2q35.";
RL Mamm. Genome 11:755-762(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF
RP 50-260 (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH GTF2F1, AND
RP MUTAGENESIS OF ASP-96 AND ASP-98.
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 [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
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
RT expression.";
RL Science 307:596-600(2005).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 77-261 IN COMPLEX WITH
RP MAGNESIUM AND INHIBITOR.
RX PubMed=15304220; DOI=10.1016/j.molcel.2004.06.035;
RA Kamenski T., Heilmeier S., Meinhart A., Cramer P.;
RT "Structure and mechanism of RNA polymerase II CTD phosphatases.";
RL Mol. Cell 15:399-407(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 77-256 OF MUTANT ASN-96 IN
RP COMPLEX WITH SUBSTRATE PEPTIDES, AND SUBSTRATE SPECIFICITY.
RX PubMed=17157258; DOI=10.1016/j.molcel.2006.10.027;
RA Zhang Y., Kim Y., Genoud N., Gao J., Kelly J.W., Pfaff S.L.,
RA Gill G.N., Dixon J.E., Noel J.P.;
RT "Determinants for dephosphorylation of the RNA polymerase II C-
RT terminal domain by Scp1.";
RL Mol. Cell 24:759-770(2006).
CC -!- FUNCTION: Preferentially catalyzes the dephosphorylation of 'Ser-
CC 5' within the tandem 7 residues repeats in the C-terminal domain
CC (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively
CC regulates RNA polymerase II transcription, possibly by controlling
CC the transition from initiation/capping to processive transcript
CC elongation. Recruited by REST to neuronal genes that contain RE-1
CC elements, leading to neuronal gene silencing in non-neuronal
CC cells.
CC -!- CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein +
CC phosphate.
CC -!- COFACTOR: Binds 1 magnesium ion per monomer.
CC -!- ENZYME REGULATION: Stimulated by GTF2F1. Inhibited by
CC beryllofluoride anions.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5;
CC -!- SUBUNIT: Monomer (By similarity). Interacts with GTF2F1. Interacts
CC with REST.
CC -!- INTERACTION:
CC P58466:Ctdsp1 (xeno); NbExp=2; IntAct=EBI-751587, EBI-7091612;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Colocalizes with RNA
CC polymerase II.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9GZU7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZU7-2; Sequence=VSP_045866;
CC Name=3;
CC IsoId=Q9GZU7-3; Sequence=VSP_045865, VSP_045866;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expression is restricted to non-neuronal
CC tissues. Highest expression in skeletal muscle, spleen, lung and
CC placenta.
CC -!- SIMILARITY: Contains 1 FCP1 homology domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP34398.1; Type=Frameshift; Positions=72;
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DR EMBL; AF229163; AAG15404.1; -; Genomic_DNA.
DR EMBL; AF229162; AAG15402.1; -; mRNA.
DR EMBL; AY279529; AAP34397.1; -; mRNA.
DR EMBL; AY279530; AAP34398.1; ALT_FRAME; mRNA.
DR EMBL; BX446444; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC021016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012977; AAH12977.1; -; mRNA.
DR RefSeq; NP_001193807.1; NM_001206878.1.
DR RefSeq; NP_067021.1; NM_021198.2.
DR RefSeq; NP_872580.1; NM_182642.2.
DR UniGene; Hs.444468; -.
DR PDB; 1T9Z; X-ray; 2.30 A; A=77-261.
DR PDB; 1TA0; X-ray; 2.10 A; A=77-261.
DR PDB; 2GHQ; X-ray; 2.05 A; A/B=77-256.
DR PDB; 2GHT; X-ray; 1.80 A; A/B=77-256.
DR PDB; 3L0B; X-ray; 2.35 A; A/B=77-256.
DR PDB; 3L0C; X-ray; 2.45 A; A/B=77-256.
DR PDB; 3L0Y; X-ray; 2.30 A; A/B=77-256.
DR PDB; 3PGL; X-ray; 2.35 A; A/B=77-256.
DR PDBsum; 1T9Z; -.
DR PDBsum; 1TA0; -.
DR PDBsum; 2GHQ; -.
DR PDBsum; 2GHT; -.
DR PDBsum; 3L0B; -.
DR PDBsum; 3L0C; -.
DR PDBsum; 3L0Y; -.
DR PDBsum; 3PGL; -.
DR ProteinModelPortal; Q9GZU7; -.
DR SMR; Q9GZU7; 77-256.
DR IntAct; Q9GZU7; 2.
DR MINT; MINT-1441843; -.
DR STRING; 9606.ENSP00000273062; -.
DR BindingDB; Q9GZU7; -.
DR ChEMBL; CHEMBL1795098; -.
DR PhosphoSite; Q9GZU7; -.
DR DMDM; 17865510; -.
DR PaxDb; Q9GZU7; -.
DR PRIDE; Q9GZU7; -.
DR DNASU; 58190; -.
DR Ensembl; ENST00000273062; ENSP00000273062; ENSG00000144579.
DR Ensembl; ENST00000443891; ENSP00000392248; ENSG00000144579.
DR GeneID; 58190; -.
DR KEGG; hsa:58190; -.
DR UCSC; uc002vhx.3; human.
DR CTD; 58190; -.
DR GeneCards; GC02P219262; -.
DR HGNC; HGNC:21614; CTDSP1.
DR MIM; 605323; gene.
DR neXtProt; NX_Q9GZU7; -.
DR PharmGKB; PA134938848; -.
DR eggNOG; COG5190; -.
DR HOGENOM; HOG000236379; -.
DR HOVERGEN; HBG053298; -.
DR InParanoid; Q9GZU7; -.
DR KO; K15731; -.
DR OrthoDB; EOG71P2C3; -.
DR PhylomeDB; Q9GZU7; -.
DR SignaLink; Q9GZU7; -.
DR ChiTaRS; CTDSP1; human.
DR EvolutionaryTrace; Q9GZU7; -.
DR GeneWiki; CTDSP1; -.
DR GenomeRNAi; 58190; -.
DR NextBio; 64884; -.
DR PRO; PR:Q9GZU7; -.
DR Bgee; Q9GZU7; -.
DR CleanEx; HS_CTDSP1; -.
DR Genevestigator; Q9GZU7; -.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008420; F:CTD phosphatase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR011948; Dullard_phosphatase.
DR InterPro; IPR023214; HAD-like_dom.
DR InterPro; IPR004274; NIF.
DR Pfam; PF03031; NIF; 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; Acetylation; Alternative splicing; Complete proteome;
KW Hydrolase; Metal-binding; Nucleus; Polymorphism; Protein phosphatase;
KW Reference proteome.
FT CHAIN 1 261 Carboxy-terminal domain RNA polymerase II
FT polypeptide A small phosphatase 1.
FT /FTId=PRO_0000212572.
FT DOMAIN 86 244 FCP1 homology.
FT ACT_SITE 96 96 4-aspartylphosphate intermediate.
FT ACT_SITE 98 98 Proton donor.
FT METAL 96 96 Magnesium.
FT METAL 98 98 Magnesium; via carbonyl oxygen.
FT METAL 207 207 Magnesium.
FT SITE 152 152 Transition state stabilizer.
FT SITE 190 190 Transition state stabilizer.
FT MOD_RES 1 1 N-acetylmethionine.
FT VAR_SEQ 1 22 MDSSAVITQISKEEARGPLRGK -> MVAAPWATQEQEEGR
FT GIQPGDR (in isoform 3).
FT /FTId=VSP_045865.
FT VAR_SEQ 73 73 Missing (in isoform 2 and isoform 3).
FT /FTId=VSP_045866.
FT VARIANT 56 56 A -> T (in dbSNP:rs2227249).
FT /FTId=VAR_049054.
FT MUTAGEN 96 96 D->E: No effect. Completely abolishes
FT phosphatase activity; when associated
FT with N-98.
FT MUTAGEN 98 98 D->N: Completely abolishes phosphatase
FT activity; when associated with E-96.
FT CONFLICT 180 180 S -> F (in Ref. 3; BX446444).
FT HELIX 85 87
FT STRAND 92 95
FT TURN 99 101
FT STRAND 102 107
FT STRAND 113 120
FT STRAND 123 131
FT HELIX 135 145
FT STRAND 146 151
FT HELIX 156 166
FT STRAND 172 176
FT HELIX 178 180
FT STRAND 181 184
FT STRAND 187 189
FT HELIX 192 194
FT STRAND 195 197
FT HELIX 199 201
FT STRAND 202 205
FT HELIX 209 212
FT HELIX 216 218
FT STRAND 219 221
FT HELIX 233 244
FT HELIX 251 254
SQ SEQUENCE 261 AA; 29203 MW; 75A430BCA2748FEA CRC64;
MDSSAVITQI SKEEARGPLR GKGDQKSAAS QKPRSRGILH SLFCCVCRDD GEALPAHSGA
PLLVEENGAI PKQTPVQYLL PEAKAQDSDK ICVVIDLDET LVHSSFKPVN NADFIIPVEI
DGVVHQVYVL KRPHVDEFLQ RMGELFECVL FTASLAKYAD PVADLLDKWG AFRARLFRES
CVFHRGNYVK DLSRLGRDLR RVLILDNSPA SYVFHPDNAV PVASWFDNMS DTELHDLLPF
FEQLSRVDDV YSVLRQPRPG S
//
MIM
605323
*RECORD*
*FIELD* NO
605323
*FIELD* TI
*605323 C-TERMINAL DOMAIN OF RNA POLYMERASE II POLYPEPTIDE A, SMALL PHOSPHATASE
OF, 1; CTDSP1
read more;;CTD SMALL PHOSPHATASE 1;;
SMALL CTD PHOSPHATASE 1; SCP1;;
NUCLEAR LIM INTERACTOR-INTERACTING FACTOR; NLIIF
*FIELD* TX
CLONING
While sequencing genomic DNA surrounding the NRAMP1 gene (600266) on
chromosome 2q34, Marquet et al. (2000) identified a novel gene, which
they termed nuclear LIM interactor-interacting factor (NLIIF) by analogy
to its closest ortholog, chicken NLI-interacting factor. It encodes a
deduced 261-amino acid protein that contains putative regulatory
elements including consensus binding sequences for Sp1 (189906), AP2
(see 107580), NF-kappa-B (see 164011), and PU1 (165170). Analysis of the
predicted amino acid sequence suggested to the authors that NLIIF is a
cytoplasmic protein that may be translocated to the nucleus. Northern
blot analysis revealed ubiquitous expression of a 2.6-kb NLIIF mRNA in
all tissues tested, with highest expression in spleen, lung, and
placenta. A second mRNA of approximately 7 kb was expressed only in
placenta.
By EST database analysis, Yeo et al. (2003) identified a CTDSP1 splice
variant encoding a deduced 214-amino acid protein. This isoform has an
N-terminal truncation but retains the complete CTD phosphatase domain.
The phosphatase domain of CTDSP1 shares more than 90% homology with the
phosphatase domains of CTDSP2 (608711) and CTDSPL (608592), and about
20% homology with the phosphatase domain of CTDP1 (604927).
Immunofluorescence microscopy localized endogenous CTDSP1 in the nucleus
of COS-7 cells.
GENE FUNCTION
Using the synthetic substrate para-nitrophenylphosphate in an in vitro
phosphatase assay, Yeo et al. (2003) determined that both the 261-amino
acid and the 214-amino acid CTDSP1 splice variants had phosphatase
activity. The pH optimum was near 5, and the activity was Mg(2+)
dependent and resistant to the phosphatase inhibitors okadaic acid and
microcystin. By mutating critical asp residues, Yeo et al. (2003)
determined that CTDSP1 is a class 2C phosphatase with activity dependent
on the conserved DxD motif. They also found that the shorter isoform
preferentially dephosphorylated ser5 within the C-terminal domain of the
large subunit of RNA polymerase II (POLR2A; 180660), and activity was
stimulated by the RAP74 (GTF2F1; 189968) subunit of general
transcription factor IIF. Expression of CTDSP1 inhibited activated
transcription from several promoter-reporter gene constructs, but
expression of a mutant lacking phosphatase activity enhanced
transcription.
Neuronal gene transcription is repressed in nonneuronal cells by the
repressor element-1 (RE1)-silencing transcription
factor/neuron-restrictive silencer factor (REST/NRSF; 600571) complex.
To understand how this silencing is achieved, Yeo et al. (2005) examined
CTDSP1, CTDSP2, and CTDSPL, the small CTD phosphatases (SCP), whose
expression is restricted to nonneuronal tissues. Yeo et al. (2005)
showed that REST/NRSF recruits SCPs to neuronal genes that contain RE1
elements, leading to neuronal gene silencing in nonneuronal cells.
Phosphatase-inactive forms of SCP interfere with REST/NRSF function and
promote neuronal differentiation of P19 stem cells. Likewise, small
interfering RNA directed to the single Drosophila SCP unmasks neuronal
gene expression in S2 cells. Thus, Yeo et al. (2005) concluded that SCP
activity is an evolutionarily conserved transcriptional regulator that
acts globally to silence neuronal genes.
GENE STRUCTURE
Marquet et al. (2000) determined that the NLIIF gene contains 7 exons
that vary in size from 57 to 1,644 bp.
Chang et al. (2008) found that intron 4 of CTDSP1 contains the microRNA
MIRN26B (612152).
MAPPING
By genomic sequence analysis, Marquet et al. (2000) mapped the NLIIF
gene to chromosome 2q34. The genomic interval between the end of exon 15
of NRAMP1 and the transcriptional start site of NLIIF is exactly 3,961
bp. NLIIF is transcribed in the same orientation as NRAMP1.
*FIELD* RF
1. Chang, T.-C.; Yu, D.; Lee, Y.-S.; Wentzel, E. A.; Arking, D. E.;
West, K. M.; Dang, C. V.; Thomas-Tikhonenko, A.; Mendell, J. T.:
Widespread microRNA repression by Myc contributes to tumorigenesis. Nature
Genet. 40: 43-50, 2008.
2. Marquet, S.; Lepage, P.; Hudson, T. J.; Musser, J. M.; Schurr,
E.: Complete nucleotide sequence and genomic structure of the human
NRAMP1 gene region on chromosome region 2q35. Mammalian Genome 11:
755-762, 2000.
3. Yeo, M.; Lee, S.-K.; Lee, B.; Ruiz, E. C.; Pfaff, S. L.; Gill,
G. N.: Small CTD phosphatases function in silencing neuronal gene
expression. Science 307: 596-600, 2005.
4. Yeo, M.; Lin, P. S.; Dahmus, M. E.; Gill, G. N.: A novel RNA polymerase
II C-terminal domain phosphatase that preferentially dephosphorylates
serine 5. J. Biol. Chem. 278: 26078-26085, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 5/22/2008
Ada Hamosh - updated: 3/1/2005
Patricia A. Hartz - updated: 6/7/2004
*FIELD* CD
Carol A. Bocchini: 10/9/2000
*FIELD* ED
mgross: 06/30/2008
carol: 5/23/2008
terry: 5/22/2008
wwang: 3/7/2005
terry: 3/1/2005
mgross: 6/7/2004
mgross: 4/19/2004
carol: 10/11/2000
carol: 10/10/2000
mcapotos: 10/10/2000
carol: 10/9/2000
*RECORD*
*FIELD* NO
605323
*FIELD* TI
*605323 C-TERMINAL DOMAIN OF RNA POLYMERASE II POLYPEPTIDE A, SMALL PHOSPHATASE
OF, 1; CTDSP1
read more;;CTD SMALL PHOSPHATASE 1;;
SMALL CTD PHOSPHATASE 1; SCP1;;
NUCLEAR LIM INTERACTOR-INTERACTING FACTOR; NLIIF
*FIELD* TX
CLONING
While sequencing genomic DNA surrounding the NRAMP1 gene (600266) on
chromosome 2q34, Marquet et al. (2000) identified a novel gene, which
they termed nuclear LIM interactor-interacting factor (NLIIF) by analogy
to its closest ortholog, chicken NLI-interacting factor. It encodes a
deduced 261-amino acid protein that contains putative regulatory
elements including consensus binding sequences for Sp1 (189906), AP2
(see 107580), NF-kappa-B (see 164011), and PU1 (165170). Analysis of the
predicted amino acid sequence suggested to the authors that NLIIF is a
cytoplasmic protein that may be translocated to the nucleus. Northern
blot analysis revealed ubiquitous expression of a 2.6-kb NLIIF mRNA in
all tissues tested, with highest expression in spleen, lung, and
placenta. A second mRNA of approximately 7 kb was expressed only in
placenta.
By EST database analysis, Yeo et al. (2003) identified a CTDSP1 splice
variant encoding a deduced 214-amino acid protein. This isoform has an
N-terminal truncation but retains the complete CTD phosphatase domain.
The phosphatase domain of CTDSP1 shares more than 90% homology with the
phosphatase domains of CTDSP2 (608711) and CTDSPL (608592), and about
20% homology with the phosphatase domain of CTDP1 (604927).
Immunofluorescence microscopy localized endogenous CTDSP1 in the nucleus
of COS-7 cells.
GENE FUNCTION
Using the synthetic substrate para-nitrophenylphosphate in an in vitro
phosphatase assay, Yeo et al. (2003) determined that both the 261-amino
acid and the 214-amino acid CTDSP1 splice variants had phosphatase
activity. The pH optimum was near 5, and the activity was Mg(2+)
dependent and resistant to the phosphatase inhibitors okadaic acid and
microcystin. By mutating critical asp residues, Yeo et al. (2003)
determined that CTDSP1 is a class 2C phosphatase with activity dependent
on the conserved DxD motif. They also found that the shorter isoform
preferentially dephosphorylated ser5 within the C-terminal domain of the
large subunit of RNA polymerase II (POLR2A; 180660), and activity was
stimulated by the RAP74 (GTF2F1; 189968) subunit of general
transcription factor IIF. Expression of CTDSP1 inhibited activated
transcription from several promoter-reporter gene constructs, but
expression of a mutant lacking phosphatase activity enhanced
transcription.
Neuronal gene transcription is repressed in nonneuronal cells by the
repressor element-1 (RE1)-silencing transcription
factor/neuron-restrictive silencer factor (REST/NRSF; 600571) complex.
To understand how this silencing is achieved, Yeo et al. (2005) examined
CTDSP1, CTDSP2, and CTDSPL, the small CTD phosphatases (SCP), whose
expression is restricted to nonneuronal tissues. Yeo et al. (2005)
showed that REST/NRSF recruits SCPs to neuronal genes that contain RE1
elements, leading to neuronal gene silencing in nonneuronal cells.
Phosphatase-inactive forms of SCP interfere with REST/NRSF function and
promote neuronal differentiation of P19 stem cells. Likewise, small
interfering RNA directed to the single Drosophila SCP unmasks neuronal
gene expression in S2 cells. Thus, Yeo et al. (2005) concluded that SCP
activity is an evolutionarily conserved transcriptional regulator that
acts globally to silence neuronal genes.
GENE STRUCTURE
Marquet et al. (2000) determined that the NLIIF gene contains 7 exons
that vary in size from 57 to 1,644 bp.
Chang et al. (2008) found that intron 4 of CTDSP1 contains the microRNA
MIRN26B (612152).
MAPPING
By genomic sequence analysis, Marquet et al. (2000) mapped the NLIIF
gene to chromosome 2q34. The genomic interval between the end of exon 15
of NRAMP1 and the transcriptional start site of NLIIF is exactly 3,961
bp. NLIIF is transcribed in the same orientation as NRAMP1.
*FIELD* RF
1. Chang, T.-C.; Yu, D.; Lee, Y.-S.; Wentzel, E. A.; Arking, D. E.;
West, K. M.; Dang, C. V.; Thomas-Tikhonenko, A.; Mendell, J. T.:
Widespread microRNA repression by Myc contributes to tumorigenesis. Nature
Genet. 40: 43-50, 2008.
2. Marquet, S.; Lepage, P.; Hudson, T. J.; Musser, J. M.; Schurr,
E.: Complete nucleotide sequence and genomic structure of the human
NRAMP1 gene region on chromosome region 2q35. Mammalian Genome 11:
755-762, 2000.
3. Yeo, M.; Lee, S.-K.; Lee, B.; Ruiz, E. C.; Pfaff, S. L.; Gill,
G. N.: Small CTD phosphatases function in silencing neuronal gene
expression. Science 307: 596-600, 2005.
4. Yeo, M.; Lin, P. S.; Dahmus, M. E.; Gill, G. N.: A novel RNA polymerase
II C-terminal domain phosphatase that preferentially dephosphorylates
serine 5. J. Biol. Chem. 278: 26078-26085, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 5/22/2008
Ada Hamosh - updated: 3/1/2005
Patricia A. Hartz - updated: 6/7/2004
*FIELD* CD
Carol A. Bocchini: 10/9/2000
*FIELD* ED
mgross: 06/30/2008
carol: 5/23/2008
terry: 5/22/2008
wwang: 3/7/2005
terry: 3/1/2005
mgross: 6/7/2004
mgross: 4/19/2004
carol: 10/11/2000
carol: 10/10/2000
mcapotos: 10/10/2000
carol: 10/9/2000