Q9GZU7 (CTDS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1
EC=3.1.3.16

Alternative name(s):
Nuclear LIM interactor-interacting factor 3
Short name=NLI-IF
Short name=NLI-interacting factor 3
Small C-terminal domain phosphatase 1
Short name=SCP1
Short name=Small CTD phosphatase 1

Gene names

Name:	CTDSP1
Synonyms:	NIF3, NLIIF, SCP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	261 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. Ref.2 Ref.6
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 magnesium ion per monomer.
Enzyme regulation	Stimulated by GTF2F1. Inhibited by beryllofluoride anions. Ref.2
Subunit structure	Monomer By similarity. Interacts with GTF2F1. Interacts with REST. Ref.2 Ref.6
Subcellular location	Nucleus. Note: Colocalizes with RNA polymerase II. Ref.2
Tissue specificity	Expression is restricted to non-neuronal tissues. Highest expression in skeletal muscle, spleen, lung and placenta. Ref.6
Sequence similarities	Contains 1 FCP1 homology domain.
Biophysicochemical properties	pH dependence: Optimum pH is 5. Ref.2
Sequence caution	The sequence AAP34398.1 differs from that shown. Reason: Frameshift at position 72.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of neurogenesis Inferred from electronic annotation. Source: Compara negative regulation of neuron differentiation Inferred from electronic annotation. Source: Compara protein dephosphorylation Inferred from direct assay Ref.2. Source: UniProtKB regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.2. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	CTD phosphatase activity Inferred from direct assay Ref.2. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9GZU7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9GZU7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     73-73: Missing.

Isoform 3 (identifier: Q9GZU7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MDSSAVITQISKEEARGPLRGK → MVAAPWATQEQEEGRGIQPGDR
     73-73: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 261

261

Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 1

PRO_0000212572

Regions

Domain

86 – 244

159

FCP1 homology

Sites

Active site

96

1

4-aspartylphosphate intermediate

Active site

98

1

Proton donor

Metal binding

96

1

Magnesium

Metal binding

98

1

Magnesium; via carbonyl oxygen

Metal binding

207

1

Magnesium

Site

152

1

Transition state stabilizer

Site

190

1

Transition state stabilizer

Natural variations

Alternative sequence

1 – 22

22

MDSSA…PLRGK → MVAAPWATQEQEEGRGIQPG DR in isoform 3.

VSP_045865

Alternative sequence

73

1

Missing in isoform 2 and isoform 3.

VSP_045866

Natural variant

56

1

A → T.
Corresponds to variant rs2227249 [ dbSNP | Ensembl ].

VAR_049054

Experimental info

Mutagenesis

96

1

D → E: No effect. Completely abolishes phosphatase activity; when associated with N-98. Ref.2

Mutagenesis

98

1

D → N: Completely abolishes phosphatase activity; when associated with E-96. Ref.2

Sequence conflict

180

1

S → F in BX446444. Ref.3

Secondary structure

1

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261

Helix Strand Turn

Details...

Helix

85 – 87

3

Beta strand

92 – 95

4

Turn

99 – 101

3

Beta strand

102 – 107

6

Beta strand

113 – 120

8

Beta strand

123 – 131

9

Helix

135 – 145

11

Beta strand

146 – 151

6

Helix

156 – 166

11

Beta strand

172 – 176

5

Helix

178 – 180

3

Beta strand

181 – 184

4

Beta strand

187 – 189

3

Helix

192 – 194

3

Beta strand

195 – 197

3

Helix

199 – 201

3

Beta strand

202 – 205

4

Helix

209 – 212

4

Helix

216 – 218

3

Beta strand

219 – 221

3

Helix

233 – 244

12

Helix

251 – 254

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 75A430BCA2748FEA	FASTA	261	29,203
	10 20 30 40 50 60 MDSSAVITQI SKEEARGPLR GKGDQKSAAS QKPRSRGILH SLFCCVCRDD GEALPAHSGA 70 80 90 100 110 120 PLLVEENGAI PKQTPVQYLL PEAKAQDSDK ICVVIDLDET LVHSSFKPVN NADFIIPVEI 130 140 150 160 170 180 DGVVHQVYVL KRPHVDEFLQ RMGELFECVL FTASLAKYAD PVADLLDKWG AFRARLFRES 190 200 210 220 230 240 CVFHRGNYVK DLSRLGRDLR RVLILDNSPA SYVFHPDNAV PVASWFDNMS DTELHDLLPF 250 260 FEQLSRVDDV YSVLRQPRPG S
	Isoform 2 [UniParc]. Checksum: 30B0CCD745F26DBB	FASTA	260	29,075
	10 20 30 40 50 60 MDSSAVITQI SKEEARGPLR GKGDQKSAAS QKPRSRGILH SLFCCVCRDD GEALPAHSGA 70 80 90 100 110 120 PLLVEENGAI PKTPVQYLLP EAKAQDSDKI CVVIDLDETL VHSSFKPVNN ADFIIPVEID 130 140 150 160 170 180 GVVHQVYVLK RPHVDEFLQR MGELFECVLF TASLAKYADP VADLLDKWGA FRARLFRESC 190 200 210 220 230 240 VFHRGNYVKD LSRLGRDLRR VLILDNSPAS YVFHPDNAVP VASWFDNMSD TELHDLLPFF 250 260 EQLSRVDDVY SVLRQPRPGS
	Isoform 3 [UniParc]. Checksum: D7741284DEE4D3B5	FASTA	260	29,128
	10 20 30 40 50 60 MVAAPWATQE QEEGRGIQPG DRGDQKSAAS QKPRSRGILH SLFCCVCRDD GEALPAHSGA 70 80 90 100 110 120 PLLVEENGAI PKTPVQYLLP EAKAQDSDKI CVVIDLDETL VHSSFKPVNN ADFIIPVEID 130 140 150 160 170 180 GVVHQVYVLK RPHVDEFLQR MGELFECVLF TASLAKYADP VADLLDKWGA FRARLFRESC 190 200 210 220 230 240 VFHRGNYVKD LSRLGRDLRR VLILDNSPAS YVFHPDNAVP VASWFDNMSD TELHDLLPFF 250 260 EQLSRVDDVY SVLRQPRPGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on chromosome region 2q35." Marquet S., Lepage P., Hudson T.J., Musser J.M., Schurr E. Mamm. Genome 11:755-762(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[2]	"A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5." Yeo M., Lin P.S., Dahmus M.E., Gill G.N. J. Biol. Chem. 278:26078-26085(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 50-260 (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH GTF2F1, MUTAGENESIS OF ASP-96 AND ASP-98.
[3]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Placenta.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph.
[6]	"Small CTD phosphatases function in silencing neuronal gene expression." Yeo M., Lee S.-K., Lee B., Ruiz E.C., Pfaff S.L., Gill G.N. Science 307:596-600(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH REST.
[7]	"Structure and mechanism of RNA polymerase II CTD phosphatases." Kamenski T., Heilmeier S., Meinhart A., Cramer P. Mol. Cell 15:399-407(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 77-261 IN COMPLEX WITH MAGNESIUM AND INHIBITOR.
[8]	"Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1." Zhang Y., Kim Y., Genoud N., Gao J., Kelly J.W., Pfaff S.L., Gill G.N., Dixon J.E., Noel J.P. Mol. Cell 24:759-770(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 77-256 OF MUTANT ASN-96 IN COMPLEX WITH SUBSTRATE PEPTIDES, SUBSTRATE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF229163 Genomic DNA. Translation: AAG15404.1.
AF229162 mRNA. Translation: AAG15402.1.
AY279529 mRNA. Translation: AAP34397.1.
AY279530 mRNA. Translation: AAP34398.1. Frameshift.
BX446444 mRNA. No translation available.
AC021016 Genomic DNA. No translation available.
BC012977 mRNA. Translation: AAH12977.1.

IPI

IPI00009633.
IPI00385297.
IPI00927233.

RefSeq

NP_001193807.1. NM_001206878.1.
NP_067021.1. NM_021198.2.
NP_872580.1. NM_182642.2.

UniGene

Hs.444468.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T9Z	X-ray	2.30	A	77-261	[»]
1TA0	X-ray	2.10	A	77-261	[»]
2GHQ	X-ray	2.05	A/B	77-256	[»]
2GHT	X-ray	1.80	A/B	77-256	[»]
3L0B	X-ray	2.35	A/B	77-256	[»]
3L0C	X-ray	2.45	A/B	77-256	[»]
3L0Y	X-ray	2.30	A/B	77-256	[»]
3PGL	X-ray	2.35	A/B	77-256	[»]

ProteinModelPortal

Q9GZU7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9GZU7. 1 interaction.

MINT

MINT-1441843.

STRING

9606.ENSP00000273062.

PTM databases

PhosphoSite

Q9GZU7.

Polymorphism databases

DMDM

17865510.

Proteomic databases

PaxDb

Q9GZU7.

PRIDE

Q9GZU7.

Protocols and materials databases

DNASU

58190.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000273062; ENSP00000273062; ENSG00000144579.
ENST00000443891; ENSP00000392248; ENSG00000144579.

GeneID

58190.

KEGG

hsa:58190.

UCSC

uc002vhx.3. human.
uc002vhy.3. human.
uc002vhz.3. human.

Organism-specific databases

CTD

58190.

GeneCards

GC02P219262.

HGNC

HGNC:21614. CTDSP1.

MIM

605323. gene.

neXtProt

NX_Q9GZU7.

PharmGKB

PA134938848.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5190.

HOGENOM

HOG000236379.

HOVERGEN

HBG053298.

InParanoid

Q9GZU7.

KO

K15731.

OrthoDB

EOG43FGXJ.

PhylomeDB

Q9GZU7.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.
ar_pathway. Coregulation of Androgen receptor activity.
smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling.

SignaLink

Q9GZU7.

Gene expression databases

ArrayExpress

Q9GZU7.

Bgee

Q9GZU7.

CleanEx

HS_CTDSP1.

Genevestigator

Q9GZU7.

GermOnline

ENSG00000144579. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.1000. 1 hit.

InterPro

IPR011948. Dullard_phosphatase.
IPR023214. HAD-like_dom.
IPR004274. NIF.
[Graphical view]

Pfam

PF03031. NIF. 1 hit.
[Graphical view]

SMART

SM00577. CPDc. 1 hit.
[Graphical view]

SUPFAM

SSF56784. HAD-like_dom. 1 hit.

TIGRFAMs

TIGR02251. HIF-SF_euk. 1 hit.

PROSITE

PS50969. FCP1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9GZU7.

ChEMBL

CHEMBL1795098.

ChiTaRS

CTDSP1. human.

EvolutionaryTrace

Q9GZU7.

GenomeRNAi

58190.

NextBio

64884.

SOURCE

Search...

Entry information

Entry name

CTDS1_HUMAN

Accession

Primary (citable) accession number: Q9GZU7
Secondary accession number(s): C9IYG0, Q7Z5Q3, Q7Z5Q4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2001
Last sequence update:	March 1, 2001
Last modified:	May 29, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.