CTDSL_HUMAN
ID CTDSL_HUMAN Reviewed; 276 AA.
AC O15194; Q3ZTU0; Q70KI4; Q7Z5Q2;
DT 13-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=CTD small phosphatase-like protein;
DE Short=CTDSP-like;
DE EC=3.1.3.16;
DE AltName: Full=Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 3;
DE AltName: Full=NIF-like protein;
DE AltName: Full=Nuclear LIM interactor-interacting factor 1;
DE Short=NLI-interacting factor 1;
DE AltName: Full=Protein YA22;
DE Short=hYA22;
DE AltName: Full=RBSP3;
DE AltName: Full=Small C-terminal domain phosphatase 3;
DE Short=SCP3;
DE Short=Small CTD phosphatase 3;
GN Name=CTDSPL; Synonyms=C3orf8, NIF1, NIFL, SCP3, YA22;
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] (ISOFORM 2).
RC TISSUE=Fetal brain, Lung, and Pancreas;
RX PubMed=9179494; DOI=10.1093/dnares/4.1.35;
RA Ishikawa S., Kai M., Tamari M., Takei Y., Takeuchi K., Bandou H.,
RA Yamane Y., Ogawa M., Nakamura Y.;
RT "Sequence analysis of a 685-kb genomic region on chromosome 3p22-p21.3 that
RT is homozygously deleted in a lung carcinoma cell line.";
RL DNA Res. 4:35-43(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), 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] (ISOFORMS 1 AND 2), AND VARIANTS PRO-121;
RP SER-127 AND GLY-132.
RC TISSUE=Lung;
RX PubMed=15051889; DOI=10.1073/pnas.0401238101;
RA Kashuba V.I., Li J., Wang F., Senchenko V.N., Protopopov A., Malyukova A.,
RA Kutsenko A.S., Kadyrova E., Zabarovska V.I., Muravenko O.V., Zelenin A.V.,
RA Kisselev L.L., Kuzmin I., Minna J.D., Winberg G., Ernberg I., Braga E.,
RA Lerman M.I., Klein G., Zabarovsky E.R.;
RT "RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial
RT malignancies.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4906-4911(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=16533400; DOI=10.1186/1471-2164-7-48;
RA Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P.,
RA Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W.;
RT "NovelFam3000 -- uncharacterized human protein domains conserved across
RT model organisms.";
RL BMC Genomics 7:48-48(2006).
RN [5]
RP TISSUE SPECIFICITY.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 82-265, AND SUBUNIT.
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: Recruited by REST to neuronal genes that contain RE-1
CC elements, leading to neuronal gene silencing in non-neuronal cells (By
CC similarity). 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.
CC {ECO:0000250, ECO:0000269|PubMed:12721286}.
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; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) ion per monomer. {ECO:0000250};
CC -!- SUBUNIT: Interacts with REST (By similarity). Monomer. {ECO:0000250,
CC ECO:0000269|PubMed:18058037}.
CC -!- INTERACTION:
CC O15194; Q15797: SMAD1; NbExp=2; IntAct=EBI-12544034, EBI-1567153;
CC O15194-2; Q99618: CDCA3; NbExp=4; IntAct=EBI-12134515, EBI-739534;
CC O15194-2; P02686-2: MBP; NbExp=3; IntAct=EBI-12134515, EBI-12159027;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=HYA22B;
CC IsoId=O15194-1; Sequence=Displayed;
CC Name=2; Synonyms=HYA22A;
CC IsoId=O15194-2; Sequence=VSP_011541;
CC -!- TISSUE SPECIFICITY: Expression is restricted to non-neuronal tissues.
CC {ECO:0000269|PubMed:15681389}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA21667.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D88153; BAA21667.1; ALT_INIT; mRNA.
DR EMBL; AY279532; AAP34400.1; -; mRNA.
DR EMBL; AJ575644; CAE11804.1; -; mRNA.
DR EMBL; AJ575645; CAE11805.1; -; mRNA.
DR EMBL; AY364238; AAQ76797.1; -; mRNA.
DR CCDS; CCDS33734.1; -. [O15194-1]
DR CCDS; CCDS33735.1; -. [O15194-2]
DR PIR; JC5707; JC5707.
DR RefSeq; NP_001008393.1; NM_001008392.1. [O15194-1]
DR RefSeq; NP_005799.2; NM_005808.2. [O15194-2]
DR PDB; 2HHL; X-ray; 2.10 A; A/B/C/D=82-265.
DR PDBsum; 2HHL; -.
DR AlphaFoldDB; O15194; -.
DR SMR; O15194; -.
DR BioGRID; 115512; 101.
DR DIP; DIP-61247N; -.
DR IntAct; O15194; 82.
DR MINT; O15194; -.
DR STRING; 9606.ENSP00000273179; -.
DR DEPOD; CTDSPL; -.
DR iPTMnet; O15194; -.
DR PhosphoSitePlus; O15194; -.
DR SwissPalm; O15194; -.
DR BioMuta; CTDSPL; -.
DR EPD; O15194; -.
DR jPOST; O15194; -.
DR MassIVE; O15194; -.
DR MaxQB; O15194; -.
DR PaxDb; O15194; -.
DR PeptideAtlas; O15194; -.
DR PRIDE; O15194; -.
DR ProteomicsDB; 48498; -. [O15194-1]
DR ProteomicsDB; 48499; -. [O15194-2]
DR Antibodypedia; 28378; 184 antibodies from 22 providers.
DR DNASU; 10217; -.
DR Ensembl; ENST00000273179.10; ENSP00000273179.5; ENSG00000144677.15. [O15194-1]
DR Ensembl; ENST00000443503.6; ENSP00000398288.2; ENSG00000144677.15. [O15194-2]
DR GeneID; 10217; -.
DR KEGG; hsa:10217; -.
DR MANE-Select; ENST00000273179.10; ENSP00000273179.5; NM_001008392.2; NP_001008393.1.
DR UCSC; uc003chg.4; human. [O15194-1]
DR CTD; 10217; -.
DR DisGeNET; 10217; -.
DR GeneCards; CTDSPL; -.
DR HGNC; HGNC:16890; CTDSPL.
DR HPA; ENSG00000144677; Low tissue specificity.
DR MIM; 608592; gene.
DR neXtProt; NX_O15194; -.
DR OpenTargets; ENSG00000144677; -.
DR PharmGKB; PA128394571; -.
DR VEuPathDB; HostDB:ENSG00000144677; -.
DR eggNOG; KOG1605; Eukaryota.
DR GeneTree; ENSGT01040000240451; -.
DR HOGENOM; CLU_020262_4_0_1; -.
DR InParanoid; O15194; -.
DR OMA; SMRAYCD; -.
DR OrthoDB; 1176152at2759; -.
DR PhylomeDB; O15194; -.
DR TreeFam; TF313556; -.
DR PathwayCommons; O15194; -.
DR SignaLink; O15194; -.
DR SIGNOR; O15194; -.
DR BioGRID-ORCS; 10217; 12 hits in 1086 CRISPR screens.
DR ChiTaRS; CTDSPL; human.
DR EvolutionaryTrace; O15194; -.
DR GeneWiki; CTDSPL; -.
DR GenomeRNAi; 10217; -.
DR Pharos; O15194; Tbio.
DR PRO; PR:O15194; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O15194; protein.
DR Bgee; ENSG00000144677; Expressed in metanephric glomerulus and 208 other tissues.
DR ExpressionAtlas; O15194; baseline and differential.
DR Genevisible; O15194; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
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 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; Alternative splicing; Hydrolase; Magnesium; Metal-binding;
KW Nucleus; Protein phosphatase; Reference proteome.
FT CHAIN 1..276
FT /note="CTD small phosphatase-like protein"
FT /id="PRO_0000212569"
FT DOMAIN 102..260
FT /note="FCP1 homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00336"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 112
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT ACT_SITE 114
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 223
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 168
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 206
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT VAR_SEQ 79..89
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12721286,
FT ECO:0000303|PubMed:15051889, ECO:0000303|PubMed:16533400,
FT ECO:0000303|PubMed:9179494"
FT /id="VSP_011541"
FT VARIANT 121
FT /note="S -> P"
FT /evidence="ECO:0000269|PubMed:15051889"
FT /id="VAR_019683"
FT VARIANT 127
FT /note="N -> S (in dbSNP:rs1341429725)"
FT /evidence="ECO:0000269|PubMed:15051889"
FT /id="VAR_019684"
FT VARIANT 132
FT /note="V -> G"
FT /evidence="ECO:0000269|PubMed:15051889"
FT /id="VAR_019685"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:2HHL"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 151..161
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 162..167
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 194..196
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 218..223
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 225..228
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:2HHL"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:2HHL"
FT HELIX 249..261
FT /evidence="ECO:0007829|PDB:2HHL"
SQ SEQUENCE 276 AA; 31129 MW; 5C7B32A1127B0F59 CRC64;
MDGPAIITQV TNPKEDEGRL PGAGEKASQC NVSLKKQRSR SILSSFFCCF RDYNVEAPPP
SSPSVLPPLV EENGGLQKGD QRQVIPIPSP PAKYLLPEVT VLDYGKKCVV IDLDETLVHS
SFKPISNADF IVPVEIDGTI HQVYVLKRPH VDEFLQRMGQ LFECVLFTAS LAKYADPVAD
LLDRWGVFRA RLFRESCVFH RGNYVKDLSR LGRELSKVII VDNSPASYIF HPENAVPVQS
WFDDMTDTEL LDLIPFFEGL SREDDVYSML HRLCNR
