RNA polymerase II subunit A C-terminal domain phosphatase

Names and origin

Protein names

Recommended name:
    RNA polymerase II subunit A C-terminal domain phosphatase
    EC=3.1.3.16
Alternative name(s):
    TFIIF-associating CTD phosphatase

Gene names

Name:	CTDP1
Synonyms:	FCP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length	961 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	Processively dephosphorylates 'Ser-2' and 'Ser-5' of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. This promotes the activity of RNA polymerase II.
Catalytic activity	A phosphoprotein + H₂O = a protein + phosphate.
Subunit structure	Homodimer. Interacts with GTF2F1. Interacts with WDR77, SNRPB and SNRNP70. Ref.1 Ref.4
Subcellular location	Nucleus.
Tissue specificity	Ubiquitously expressed. Isoform 3 is expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and placenta. Ref.1
Post-translational modification	Phosphorylated. In the presence of TFIIF, the phosphorylated form has an increased CTD phosphatase activity. The phosphorylation is required for the physical interaction with GTF2F1. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9
Involvement in disease	Defects in CTDP1 are a cause of congenital cataracts facial dysmorphism and neuropathy syndrome (CCFDN) [MIM:604168]. CCFDN is an autosomal recessive developmental disorder that occurs in an endogamous group of Vlax Roma (Gypsies). The syndrome is characterized by a complex clinical phenotype with seemingly unrelated features involving multiple organs and systems. Developmental abnormalities include congenital cataracts and microcorneae, hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, facial dysmorphism and hypogonadism. Central nervous system involvement, with cerebral and spinal cord atrophy, may be the result of disrupted development with superimposed degenerative changes. Affected individuals are prone to severe rhabdomyolysis after viral infections and to serious complications related to general anesthesia (such as pulmonary edema and epileptic seizures). Ref.13
Sequence similarities	Contains 1 BRCT domain. Contains 1 FCP1 homology domain.

Hide | Top

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cataract
Molecular function	Hydrolase Protein phosphatase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid dephosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	CTD phosphatase activity Inferred from direct assay. Source: UniProtKB DNA-directed RNA polymerase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Hide | Top

Alternative products

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

Isoform 1 (identifier: Q9Y5B0-1) Also known as: Fcp1; 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: Q9Y5B0-2) Also known as: Fcp1b; The sequence of this isoform differs from the canonical sequence as follows: 807-961: AVPPPQPQMF...ALEAELNDLM → WTTSLEKAAT...AGGPEATRGS

Isoform 3 (identifier: Q9Y5B0-3) Also known as: Fcp1a; The sequence of this isoform differs from the canonical sequence as follows: 1-119: Missing.

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 961

961

RNA polymerase II subunit A C-terminal domain phosphatase

PRO_0000212564

Regions

Domain

178 – 344

167

FCP1 homology

Domain

629 – 728

100

BRCT

Compositional bias

455 – 478

24

Ser-rich

Compositional bias

577 – 582

6

Poly-Glu

Amino acid modifications

Modified residue

674

1

Phosphoserine Ref.8 Ref.9

Modified residue

740

1

Phosphoserine Ref.6 Ref.8 Ref.9

Modified residue

780

1

N6-acetyllysine Ref.11

Modified residue

869

1

Phosphoserine Ref.7

Modified residue

872

1

Phosphoserine Ref.7

Natural variations

Alternative sequence

1 – 119

119

Missing in isoform 3.

VSP_009864

Alternative sequence

807 – 961

155

AVPPP…LNDLM → WTTSLEKAATTATARRGGLR SRRRSPSPGSQGPAGSGRSG HLRPARGARQGAGGPEATRG S in isoform 2.

VSP_009865

Natural variant

282

1

S → F: dbSNP rs4799078.

VAR_060440

Natural variant

340

1

T → M: dbSNP rs2279103.

VAR_018264

Natural variant

519

1

P → H: dbSNP rs557503.

VAR_060441

Natural variant

755

1

L → S: dbSNP rs34967023.

VAR_032763

Experimental info

Sequence conflict

157

1

P → A in AAC64549. Ref.1

Sequence conflict

281

1

F → I in AAH52576. Ref.3

Sequence conflict

305

1

E → K in AAD42088. Ref.2

Sequence conflict

390

1

A → P in AAC64549. Ref.1

Sequence conflict

478

1

S → T in AAC64549. Ref.1

Sequence conflict

486 – 487

2

KP → NA in AAC64549. Ref.1

Sequence conflict

504 – 505

2

EP → DA in AAC64549. Ref.1

Sequence conflict

513

1

L → V in AAC64549. Ref.1

Sequence conflict

656 – 657

2

EH → DD in AAC64549. Ref.1

Sequence conflict

896 – 900

5

GADAR → ERTLG in AAC64549. Ref.1

Sequence conflict

896 – 900

5

GADAR → ERTLG in AAH52576. Ref.3

Secondary structure

1

.

961

Helix Strand Turn

Details...

Hide | Top

Sequences

Sequence		Length	Mass (Da)
Isoform 1 (Fcp1) [UniParc]. Last modified April 13, 2004. Version 2. Checksum: 69B5465A01FE75CE Show »	FASTA	961	104,297
10 20 30 40 50 60 MEVPAAGRVP AEGAPTAAVA EVRCPGPAPL RLLEWRVAAG AAVRIGSVLA VFEAAASAQS 70 80 90 100 110 120 AGASQSRVAS GGCVRPARPE RRLRSERAGV VRELCAQPGQ VVAPGAVLVR LEGCSHPVVM 130 140 150 160 170 180 KGLCAECGQD LTQLQSKNGK QQVPLSTATV SMVHSVPELM VSSEQAEQLG REDQQRLHRN 190 200 210 220 230 240 RKLVLMVDLD QTLIHTTEQH CQQMSNKGIF HFQLGRGEPM LHTRLRPHCK DFLEKIAKLY 250 260 270 280 290 300 ELHVFTFGSR LYAHTIAGFL DPEKKLFSHR ILSRDECIDP FSKTGNLRNL FPCGDSMVCI 310 320 330 340 350 360 IDDREDVWKF APNLITVKKY VYFQGTGDMN APPGSRESQT RKKVNHSRGT EVSEPSPPVR 370 380 390 400 410 420 DPEGVTQAPG VEPSNGLEKP ARELNGSEAA TPRDSPRPGK PDERDIWPPA QAPTSSQELA 430 440 450 460 470 480 GAPEPQGSCA QGGRVAPGQR PAQGATGTDL DFDLSSDSES SSESEGTKSS SSASDGESEG 490 500 510 520 530 540 KRGRQKPKAA PEGAGALAQG SSLEPGRPAA PSLPGEAEPG AHAPDKEPEL GGQEEGERDG 550 560 570 580 590 600 LCGLGNGCAD RKEAETESQN SELSGVTAGE SLDQSMEEEE EEDTDEDDHL IYLEEILVRV 610 620 630 640 650 660 HTDYYAKYDR YLNKEIEEAP DIRKIVPELK SKVLADVAII FSGLHPTNFP IEKTREHYHA 670 680 690 700 710 720 TALGAKILTR LVLSPDAPDR ATHLIAARAG TEKVLQAQEC GHLHVVNPDW LWSCLERWDK 730 740 750 760 770 780 VEEQLFPLRD DHTKAQRENS PAAFPDREGV PPTALFHPMP VLPKAQPGPE VRIYDSNTGK 790 800 810 820 830 840 LIRTGARGPP APSSSLPIRQ EPSSFRAVPP PQPQMFGEEL PDAQDGEQPG PSRRKRQPSM 850 860 870 880 890 900 SETMPLYTLC KEDLESMDKE VDDILGEGSD DSDSEKRRPE EQEEEPQPRK PGTRRGADAR 910 920 930 940 950 960 APASSERSAA GGRGPRGHKR KLNEEDAASE SSRESSNEDE GSSSEADEMA KALEAELNDL M « Hide
Isoform 2 (Fcp1b). Checksum: 1AF59759CECACEF5 Show »	FASTA	867	93,469
10 20 30 40 50 60 MEVPAAGRVP AEGAPTAAVA EVRCPGPAPL RLLEWRVAAG AAVRIGSVLA VFEAAASAQS 70 80 90 100 110 120 AGASQSRVAS GGCVRPARPE RRLRSERAGV VRELCAQPGQ VVAPGAVLVR LEGCSHPVVM 130 140 150 160 170 180 KGLCAECGQD LTQLQSKNGK QQVPLSTATV SMVHSVPELM VSSEQAEQLG REDQQRLHRN 190 200 210 220 230 240 RKLVLMVDLD QTLIHTTEQH CQQMSNKGIF HFQLGRGEPM LHTRLRPHCK DFLEKIAKLY 250 260 270 280 290 300 ELHVFTFGSR LYAHTIAGFL DPEKKLFSHR ILSRDECIDP FSKTGNLRNL FPCGDSMVCI 310 320 330 340 350 360 IDDREDVWKF APNLITVKKY VYFQGTGDMN APPGSRESQT RKKVNHSRGT EVSEPSPPVR 370 380 390 400 410 420 DPEGVTQAPG VEPSNGLEKP ARELNGSEAA TPRDSPRPGK PDERDIWPPA QAPTSSQELA 430 440 450 460 470 480 GAPEPQGSCA QGGRVAPGQR PAQGATGTDL DFDLSSDSES SSESEGTKSS SSASDGESEG 490 500 510 520 530 540 KRGRQKPKAA PEGAGALAQG SSLEPGRPAA PSLPGEAEPG AHAPDKEPEL GGQEEGERDG 550 560 570 580 590 600 LCGLGNGCAD RKEAETESQN SELSGVTAGE SLDQSMEEEE EEDTDEDDHL IYLEEILVRV 610 620 630 640 650 660 HTDYYAKYDR YLNKEIEEAP DIRKIVPELK SKVLADVAII FSGLHPTNFP IEKTREHYHA 670 680 690 700 710 720 TALGAKILTR LVLSPDAPDR ATHLIAARAG TEKVLQAQEC GHLHVVNPDW LWSCLERWDK 730 740 750 760 770 780 VEEQLFPLRD DHTKAQRENS PAAFPDREGV PPTALFHPMP VLPKAQPGPE VRIYDSNTGK 790 800 810 820 830 840 LIRTGARGPP APSSSLPIRQ EPSSFRWTTS LEKAATTATA RRGGLRSRRR SPSPGSQGPA 850 860 GSGRSGHLRP ARGARQGAGG PEATRGS « Hide
Isoform 3 (Fcp1a). Checksum: 25ADF50256DF714A Show »	FASTA	842	92,291
10 20 30 40 50 60 MKGLCAECGQ DLTQLQSKNG KQQVPLSTAT VSMVHSVPEL MVSSEQAEQL GREDQQRLHR 70 80 90 100 110 120 NRKLVLMVDL DQTLIHTTEQ HCQQMSNKGI FHFQLGRGEP MLHTRLRPHC KDFLEKIAKL 130 140 150 160 170 180 YELHVFTFGS RLYAHTIAGF LDPEKKLFSH RILSRDECID PFSKTGNLRN LFPCGDSMVC 190 200 210 220 230 240 IIDDREDVWK FAPNLITVKK YVYFQGTGDM NAPPGSRESQ TRKKVNHSRG TEVSEPSPPV 250 260 270 280 290 300 RDPEGVTQAP GVEPSNGLEK PARELNGSEA ATPRDSPRPG KPDERDIWPP AQAPTSSQEL 310 320 330 340 350 360 AGAPEPQGSC AQGGRVAPGQ RPAQGATGTD LDFDLSSDSE SSSESEGTKS SSSASDGESE 370 380 390 400 410 420 GKRGRQKPKA APEGAGALAQ GSSLEPGRPA APSLPGEAEP GAHAPDKEPE LGGQEEGERD 430 440 450 460 470 480 GLCGLGNGCA DRKEAETESQ NSELSGVTAG ESLDQSMEEE EEEDTDEDDH LIYLEEILVR 490 500 510 520 530 540 VHTDYYAKYD RYLNKEIEEA PDIRKIVPEL KSKVLADVAI IFSGLHPTNF PIEKTREHYH 550 560 570 580 590 600 ATALGAKILT RLVLSPDAPD RATHLIAARA GTEKVLQAQE CGHLHVVNPD WLWSCLERWD 610 620 630 640 650 660 KVEEQLFPLR DDHTKAQREN SPAAFPDREG VPPTALFHPM PVLPKAQPGP EVRIYDSNTG 670 680 690 700 710 720 KLIRTGARGP PAPSSSLPIR QEPSSFRAVP PPQPQMFGEE LPDAQDGEQP GPSRRKRQPS 730 740 750 760 770 780 MSETMPLYTL CKEDLESMDK EVDDILGEGS DDSDSEKRRP EEQEEEPQPR KPGTRRGADA 790 800 810 820 830 840 RAPASSERSA AGGRGPRGHK RKLNEEDAAS ESSRESSNED EGSSSEADEM AKALEAELND LM « Hide

Hide | Top

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FCP1, the RAP74-interacting subunit of a human protein phosphatase that dephosphorylates the carboxyl-terminal domain of RNA polymerase IIO." Archambault J., Pan G., Dahmus G.K., Cartier M., Marshall N., Zhang S., Dahmus M.E., Greenblatt J. J. Biol. Chem. 273:27593-27601(1998) [PubMed: 9765293] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY, INTERACTION WITH GTF2F1. Tissue: Placenta.
[2]	"A protein phosphatase functions to recycle RNA polymerase II." Cho H., Kim T.-K., Mancebo H., Lane W.S., Flores O., Reinberg D. Genes Dev. 13:1540-1552(1999) [PubMed: 10385623] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Cervix carcinoma.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Colon, Lymph and Ovary.
[4]	"The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP." Licciardo P., Amente S., Ruggiero L., Monti M., Pucci P., Lania L., Majello B. Nucleic Acids Res. 31:999-1005(2003) [PubMed: 12560496] [Abstract] Cited for: INTERACTION WITH WDR77; SNRPB AND SNRNP70.
[5]	"The C-terminal domain phosphatase and transcription elongation activities of FCP1 are regulated by phosphorylation." Friedl E.M., Lane W.S., Erdjument-Bromage H., Tempst P., Reinberg D. Proc. Natl. Acad. Sci. U.S.A. 100:2328-2333(2003) [PubMed: 12591939] [Abstract] Cited for: PHOSPHORYLATION.
[6]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-740, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-869 AND SER-872, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-674 AND SER-740, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-674 AND SER-740, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-780, MASS SPECTROMETRY.
[12]	"Molecular mechanism of recruitment of TFIIF-associating RNA polymerase C-terminal domain phosphatase (FCP1) by transcription factor IIF." Kamada K., Roeder R.G., Burley S.K. Proc. Natl. Acad. Sci. U.S.A. 100:2296-2299(2003) [PubMed: 12591941] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 944-961 IN COMPLEX WITH GTF2F1.
[13]	"Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome." Varon R., Gooding R., Steglich C., Marns L., Tang H., Angelicheva D., Yong K.K., Ambrugger P., Reinhold A., Morar B., Baas F., Kwa M., Tournev I., Guerguelcheva V., Kremensky I., Lochmueller H., Muellner-Eidenboeck A., Merlini L. Kalaydjieva L. Nat. Genet. 35:185-189(2003) [PubMed: 14517542] [Abstract] Cited for: INVOLVEMENT IN CCFDN.
+	Additional computationally mapped references.

Hide | Top

Web resources

GeneReviews

Hide | Top

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF081287 mRNA. Translation: AAC64549.1.
AF154115 mRNA. Translation: AAD42088.1.
BC015010 mRNA. Translation: AAH15010.1.
BC052576 mRNA. Translation: AAH52576.1.
BC063447 mRNA. Translation: AAH63447.1.

IPI

IPI00410256.
IPI00410257.
IPI00410258.

RefSeq

NP_004706.3.
NP_430255.2.

UniGene

Hs.465490

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J2X	X-ray	2.00	B	944-961	[»]
1ONV	NMR	-	B	879-961	[»]
2K7L	NMR	-	B	582-600	[»]

SMR

Q9Y5B0. Positions 14-111, 177-321, 618-732.

DisProt

DP00177.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9Y5B0.

PTM databases

PhosphoSite

Q9Y5B0.

Proteomic databases

PRIDE

Q9Y5B0.

Genome annotation databases

Ensembl

ENST00000299543; ENSP00000299543; ENSG00000060069; Homo sapiens. [Genome view]

GeneID

9150.

KEGG

hsa:9150.

UCSC

uc002lnh.1. human.
uc002lni.1. human.

Organism-specific databases

CTD

9150.

GeneCards

GC18P075540.

H-InvDB

HIX0027357.

HGNC

HGNC:2498. CTDP1.

MIM

604168. phenotype.
604927. gene.

Orphanet

48431. Congenital cataracts - facial dysmorphism - neuropathy.

PharmGKB

PA27001.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13967.

HOGENOM

HBG403000.

HOVERGEN

Q9Y5B0.

InParanoid

Q9Y5B0.

Enzyme and pathway databases

BRENDA

3.1.3.16. 247.

Reactome

REACT_1788. Transcription.
REACT_1892. Elongation arrest and recovery.
REACT_6143. Pausing and recovery of Tat-mediated HIV-1 elongation.
REACT_6185. HIV Infection.
REACT_6244. Pausing and recovery of HIV-1 elongation.
REACT_6259. HIV-1 elongation arrest and recovery.
REACT_6344. Tat-mediated HIV-1 elongation arrest and recovery.
REACT_71. Gene Expression.
REACT_769. Pausing and recovery of elongation.

Gene expression databases

ArrayExpress

Q9Y5B0.

Bgee

Q9Y5B0.

CleanEx

HS_CTDP1.

Genevestigator

Q9Y5B0.

GermOnline

ENSG00000060069. Homo sapiens.

Family and domain databases

InterPro

IPR001357. BRCT.
IPR015388. FCP1_C.
IPR011947. FCP1_euk.
IPR004274. NIF.
[Graphical view]

Pfam

PF09309. FCP1_C. 1 hit.
PF03031. NIF. 1 hit.
[Graphical view]

SMART

SM00292. BRCT. 1 hit.
SM00577. CPDc. 1 hit.
[Graphical view]

TIGRFAMs

TIGR02250. FCP1_euk. 1 hit.

PROSITE

PS50172. BRCT. 1 hit.
PS50969. FCP1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

34327.

SOURCE

Search...

Hide | Top

Entry information

Entry name

CTDP1_HUMAN

Accession

Primary (citable) accession number: Q9Y5B0
Secondary accession number(s): Q7Z644, Q96BZ1, Q9Y6F5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 13, 2004
Last sequence update:	April 13, 2004
Last modified:	February 9, 2010
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

Hide | Top