O15194 (CTDSL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CTD small phosphatase-like protein
Short name=CTDSP-like
EC=3.1.3.16

Alternative name(s):
Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 3
NIF-like protein
Nuclear LIM interactor-interacting factor 1
Short name=NLI-interacting factor 1
Protein YA22
Short name=hYA22
RBSP3
Small C-terminal domain phosphatase 3
Short name=SCP3
Short name=Small CTD phosphatase 3

Gene names

Name:	CTDSPL
Synonyms:	C3orf8, NIF1, NIFL, SCP3, YA22

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	276 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 By similarity. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. Ref.5
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 magnesium ion per monomer By similarity.
Subunit structure	Monomer. Interacts with REST. Ref.5 Ref.6
Subcellular location	Nucleus By similarity.
Tissue specificity	Expression is restricted to non-neuronal tissues. Ref.5
Sequence similarities	Contains 1 FCP1 homology domain.
Sequence caution	The sequence BAA21667.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Hydrolase Protein phosphatase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	dephosphorylation Inferred from electronic annotation. Source: GOC
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoprotein phosphatase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O15194-1)

Also known as: HYA22B;

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: O15194-2)

Also known as: HYA22A;

The sequence of this isoform differs from the canonical sequence as follows:
     79-89: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 276

276

CTD small phosphatase-like protein

PRO_0000212569

Regions

Domain

102 – 260

159

FCP1 homology

Sites

Active site

112

1

4-aspartylphosphate intermediate By similarity

Active site

114

1

Proton donor By similarity

Metal binding

112

1

Magnesium By similarity

Metal binding

114

1

Magnesium; via carbonyl oxygen By similarity

Metal binding

223

1

Magnesium By similarity

Site

168

1

Transition state stabilizer By similarity

Site

206

1

Transition state stabilizer By similarity

Natural variations

Alternative sequence

79 – 89

11

Missing in isoform 2.

VSP_011541

Natural variant

121

1

S → P. Ref.3

VAR_019683

Natural variant

127

1

N → S. Ref.3

VAR_019684

Natural variant

132

1

V → G. Ref.3

VAR_019685

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

276

Helix Strand Turn

Details...

Beta strand

93 – 96

4

Helix

101 – 103

3

Beta strand

108 – 111

4

Turn

115 – 117

3

Beta strand

118 – 123

6

Beta strand

129 – 136

8

Beta strand

139 – 147

9

Helix

151 – 161

11

Beta strand

162 – 167

6

Helix

172 – 182

11

Beta strand

188 – 192

5

Helix

194 – 196

3

Beta strand

198 – 200

3

Beta strand

203 – 205

3

Helix

208 – 210

3

Beta strand

211 – 213

3

Helix

215 – 217

3

Beta strand

218 – 223

6

Helix

225 – 228

4

Helix

232 – 234

3

Beta strand

235 – 237

3

Helix

249 – 261

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HYA22B) [UniParc]. Last modified August 31, 2004. Version 2. Checksum: 5C7B32A1127B0F59	FASTA	276	31,129
	10 20 30 40 50 60 MDGPAIITQV TNPKEDEGRL PGAGEKASQC NVSLKKQRSR SILSSFFCCF RDYNVEAPPP 70 80 90 100 110 120 SSPSVLPPLV EENGGLQKGD QRQVIPIPSP PAKYLLPEVT VLDYGKKCVV IDLDETLVHS 130 140 150 160 170 180 SFKPISNADF IVPVEIDGTI HQVYVLKRPH VDEFLQRMGQ LFECVLFTAS LAKYADPVAD 190 200 210 220 230 240 LLDRWGVFRA RLFRESCVFH RGNYVKDLSR LGRELSKVII VDNSPASYIF HPENAVPVQS 250 260 270 WFDDMTDTEL LDLIPFFEGL SREDDVYSML HRLCNR
	Isoform 2 (HYA22A) [UniParc]. Checksum: D19C4461386C1C2F	FASTA	265	29,937
	10 20 30 40 50 60 MDGPAIITQV TNPKEDEGRL PGAGEKASQC NVSLKKQRSR SILSSFFCCF RDYNVEAPPP 70 80 90 100 110 120 SSPSVLPPLV EENGGLQKPP AKYLLPEVTV LDYGKKCVVI DLDETLVHSS FKPISNADFI 130 140 150 160 170 180 VPVEIDGTIH QVYVLKRPHV DEFLQRMGQL FECVLFTASL AKYADPVADL LDRWGVFRAR 190 200 210 220 230 240 LFRESCVFHR GNYVKDLSRL GRELSKVIIV DNSPASYIFH PENAVPVQSW FDDMTDTELL 250 260 DLIPFFEGLS REDDVYSMLH RLCNR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence analysis of a 685-kb genomic region on chromosome 3p22-p21.3 that is homozygously deleted in a lung carcinoma cell line." Ishikawa S., Kai M., Tamari M., Takei Y., Takeuchi K., Bandou H., Yamane Y., Ogawa M., Nakamura Y. DNA Res. 4:35-43(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Fetal brain, Lung and Pancreas.
[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 2).
[3]	"RBSP3 (HYA22) is a tumor suppressor gene implicated in major epithelial malignancies." Kashuba V.I., Li J., Wang F., Senchenko V.N., Protopopov A., Malyukova A., Kutsenko A.S., Kadyrova E., Zabarovska V.I., Muravenko O.V., Zelenin A.V., Kisselev L.L., Kuzmin I., Minna J.D., Winberg G., Ernberg I., Braga E., Lerman M.I., Klein G., Zabarovsky E.R. Proc. Natl. Acad. Sci. U.S.A. 101:4906-4911(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS PRO-121; SER-127 AND GLY-132. Tissue: Lung.
[4]	"NovelFam3000 -- uncharacterized human protein domains conserved across model organisms." Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P., Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W. BMC Genomics 7:48-48(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"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.
[6]	"Structural genomics of protein phosphatases." Almo S.C., Bonanno J.B., Sauder J.M., Emtage S., Dilorenzo T.P., Malashkevich V., Wasserman S.R., Swaminathan S., Eswaramoorthy S., Agarwal R., Kumaran D., Madegowda M., Ragumani S., Patskovsky Y., Alvarado J., Ramagopal U.A., Faber-Barata J., Chance M.R. , Sali A., Fiser A., Zhang Z.Y., Lawrence D.S., Burley S.K. J. Struct. Funct. Genomics 8:121-140(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 82-265, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D88153 mRNA. Translation: BAA21667.1. Different initiation.
AY279532 mRNA. Translation: AAP34400.1.
AJ575644 mRNA. Translation: CAE11804.1.
AJ575645 mRNA. Translation: CAE11805.1.
AY364238 mRNA. Translation: AAQ76797.1.

IPI

IPI00024826.
IPI00454757.

PIR

JC5707.

RefSeq

NP_001008393.1. NM_001008392.1.
NP_005799.2. NM_005808.2.

UniGene

Hs.475963.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HHL	X-ray	2.10	A/B/C/D	82-265	[»]

ProteinModelPortal

O15194.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000273179.

PTM databases

PhosphoSite

O15194.

Proteomic databases

PaxDb

O15194.

PRIDE

O15194.

Protocols and materials databases

DNASU

10217.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000273179; ENSP00000273179; ENSG00000144677.
ENST00000443503; ENSP00000398288; ENSG00000144677.

GeneID

10217.

KEGG

hsa:10217.

UCSC

uc003chg.3. human.
uc003chh.3. human.

Organism-specific databases

CTD

10217.

GeneCards

GC03P037878.

HGNC

HGNC:16890. CTDSPL.

MIM

608592. gene.

neXtProt

NX_O15194.

PharmGKB

PA128394571.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5190.

HOGENOM

HOG000236379.

HOVERGEN

HBG053298.

InParanoid

O15194.

KO

K15731.

OrthoDB

EOG43FGXJ.

Enzyme and pathway databases

Pathway_Interaction_DB

bmppathway. BMP receptor signaling.
smad2_3pathway. Regulation of cytoplasmic and nuclear SMAD2/3 signaling.

Gene expression databases

ArrayExpress

O15194.

Bgee

O15194.

CleanEx

HS_CTDSPL.

Genevestigator

O15194.

GermOnline

ENSG00000144677. 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

EvolutionaryTrace

O15194.

GenomeRNAi

10217.

NextBio

38686.

SOURCE

Search...

Entry information

Entry name

CTDSL_HUMAN

Accession

Primary (citable) accession number: O15194
Secondary accession number(s): Q3ZTU0, Q70KI4, Q7Z5Q2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2001
Last sequence update:	August 31, 2004
Last modified:	May 1, 2013
This is version 98 of the entry and version 2 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.