P31384 (CCR4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucose-repressible alcohol dehydrogenase transcriptional effector
EC=3.1.13.4

Alternative name(s):
Carbon catabolite repressor protein 4
Cytoplasmic deadenylase

Gene names

Name:	CCR4
Ordered Locus Names:	YAL021C
ORF Names:	FUN27

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	837 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as catalytic component of the CCR4-NOT core complex, which in the nucleus seems to be a general transcription factor, and in the cytoplasm the major mRNA deadenylase involved in mRNA turnover. CCR4 has 3'-5' RNase activity with a strong preference for polyadenylated substrates and also low exonuclease activity towards single stranded DNA. Discovered because of its role in the control of ADH2 gene expression. It is required for the expression of genes involved in non-fermentative growth and it mediates or is required for the action of the SPT6 and SPT10 genes. Ref.6 Ref.8 Ref.10 Ref.11
Catalytic activity	Exonucleolytic cleavage of poly(A) to 5'-AMP.
Cofactor	Magnesium.
Subunit structure	Subunit of the 1.0 MDa CCR4-NOT core complex that contains CCR4, CAF1, NOT1, NOT2, NOT3, NOT4, NOT5, CAF40 and CAF130. In the complex interacts with NOT1. The core complex probably is part of a less characterized 1.9 MDa CCR4-NOT complex. Ref.6 Ref.7 Ref.9
Subcellular location	Cytoplasm. Nucleus Ref.8.
Domain	The 169 C-terminal residues are important for deadenylase activity.
Miscellaneous	Present with 2780 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the CCR4/nocturin family. Contains 5 LRR (leucine-rich) repeats.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Leucine-rich repeat Repeat
Ligand	Magnesium Metal-binding RNA-binding
Molecular function	Activator Exonuclease Hydrolase Nuclease Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication checkpoint Inferred from genetic interaction PubMed 17158920. Source: SGD nuclear-transcribed mRNA poly(A) tail shortening Inferred from direct assay Ref.11. Source: SGD positive regulation of transcription elongation from RNA polymerase II promoter Inferred from direct assay PubMed 21406554. Source: SGD replication fork protection Inferred from genetic interaction PubMed 17158920. Source: SGD transcription elongation from RNA polymerase II promoter Inferred from mutant phenotype PubMed 11404327. Source: SGD traversing start control point of mitotic cell cycle Inferred from mutant phenotype PubMed 15075273. Source: SGD
Cellular_component	CCR4-NOT core complex Inferred from physical interaction Ref.7. Source: SGD cytoplasmic mRNA processing body Inferred from direct assay PubMed 18611963. Source: SGD nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3'-5'-exoribonuclease activity Inferred from direct assay Ref.11. Source: SGD RNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW poly(A)-specific ribonuclease activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CAF40	P53829	8	EBI-4396,EBI-28306
CDC39	P25655	8	EBI-4396,EBI-12139
MOT2	P34909	4	EBI-4396,EBI-12174
POP2	P39008	9	EBI-4396,EBI-13629

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 837

837

Glucose-repressible alcohol dehydrogenase transcriptional effector

PRO_0000218577

Regions

Repeat

334 – 356

23

LRR 1

Repeat

358 – 379

22

LRR 2

Repeat

381 – 402

22

LRR 3

Repeat

404 – 426

23

LRR 4

Repeat

427 – 447

21

LRR 5

Compositional bias

15 – 24

10

Poly-Gln

Compositional bias

77 – 103

27

Asn-rich

Compositional bias

89 – 103

15

Poly-Asn

Compositional bias

190 – 206

17

Gln-rich

Sites

Metal binding

556

1

Magnesium

Amino acid modifications

Modified residue

266

1

Phosphothreonine Ref.14

Modified residue

276

1

Phosphothreonine Ref.14

Modified residue

278

1

Phosphoserine Ref.14 Ref.15

Modified residue

281

1

Phosphoserine Ref.14

Modified residue

282

1

Phosphothreonine Ref.14

Modified residue

285

1

Phosphothreonine Ref.13 Ref.14

Experimental info

Mutagenesis

556

1

E → A: Loss of activity. Ref.10

Mutagenesis

713

1

D → A: Strongly reduces activity. Ref.10

Mutagenesis

780

1

D → A: Reduces activity. Ref.10

Mutagenesis

818

1

H → A: Loss of activity. Ref.10

Sequence conflict

544

1

I → L in AAB24455. Ref.1

Sequence conflict

803

1

V → E in AAB24455. Ref.1

Secondary structure

1

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837

Helix Strand Turn

Details...

Turn

140 – 142

3

Helix

144 – 146

3

Helix

155 – 169

15

Helix

176 – 186

11

Helix

245 – 258

14

Beta strand

338 – 340

3

Helix

351 – 355

5

Helix

374 – 379

6

Beta strand

384 – 386

3

Helix

399 – 402

4

Beta strand

406 – 409

4

Helix

441 – 460

20

Helix

515 – 517

3

Turn

520 – 522

3

Helix

528 – 531

4

Helix

533 – 546

14

Beta strand

550 – 554

5

Helix

559 – 563

5

Turn

564 – 566

3

Beta strand

600 – 602

3

Helix

800 – 803

4

Beta strand

807 – 811

5

Beta strand

816 – 818

3

Sequences

	Sequence		Length	Mass (Da)
	P31384 [UniParc]. Last modified October 5, 2010. Version 2. Checksum: 5CDB2E8FEDDBEF6F	FASTA	837	94,670
	10 20 30 40 50 60 MNDPSLLGYP NVGPQQQQQQ QQQQHAGLLG KGTPNALQQQ LHMNQLTGIP PPGLMNNSDV 70 80 90 100 110 120 HTSSNNNSRQ LLDQLANGNA NMLNMNMDNN NNNNNNNNNN NNNGGGSGVM MNASTAAVNS 130 140 150 160 170 180 IGMVPTVGTP VNINVNASNP LLHPHLDDPS LLNNPIWKLQ LHLAAVSAQS LGQPNIYARQ 190 200 210 220 230 240 NAMKKYLATQ QAQQAQQQAQ QQAQQQVPGP FGPGPQAAPP ALQPTDFQQS HIAEASKSLV 250 260 270 280 290 300 DCTKQALMEM ADTLTDSKTA KKQQPTGDST PSGTATNSAV STPLTPKIEL FANGKDEANQ 310 320 330 340 350 360 ALLQHKKLSQ YSIDEDDDIE NRMVMPKDSK YDDQLWHALD LSNLQIFNIS ANIFKYDFLT 370 380 390 400 410 420 RLYLNGNSLT ELPAEIKNLS NLRVLDLSHN RLTSLPAELG SCFQLKYFYF FDNMVTTLPW 430 440 450 460 470 480 EFGNLCNLQF LGVEGNPLEK QFLKILTEKS VTGLIFYLRD NRPEIPLPHE RRFIEINTDG 490 500 510 520 530 540 EPQREYDSLQ QSTEHLATDL AKRTFTVLSY NTLCQHYATP KMYRYTPSWA LSWDYRRNKL 550 560 570 580 590 600 KEQILSYDSD LLCLQEVESK TFEEYWVPLL DKHGYTGIFH AKARAKTMHS KDSKKVDGCC 610 620 630 640 650 660 IFFKRDQFKL ITKDAMDFSG AWMKHKKFQR TEDYLNRAMN KDNVALFLKL QHIPSGDTIW 670 680 690 700 710 720 AVTTHLHWDP KFNDVKTFQV GVLLDHLETL LKEETSHNFR QDIKKFPVLI CGDFNSYINS 730 740 750 760 770 780 AVYELINTGR VQIHQEGNGR DFGYMSEKNF SHNLALKSSY NCIGELPFTN FTPSFTDVID 790 800 810 820 830 YIWFSTHALR VRGLLGEVDP EYVSKFIGFP NDKFPSDHIP LLARFEFMKT NTGSKKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression." Malvar T., Biron R.W., Kaback D.B., Denis C.L. Genetics 132:951-962(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Sequencing of chromosome I from Saccharomyces cerevisiae: analysis of a 32 kb region between the LTE1 and SPO7 genes." Ouellette B.F.F., Clark M.W., Keng T., Storms R.K., Zhong W.-W., Zeng B., Fortin N., Delaney S., Barton A.B., Kaback D.B., Bussey H. Genome 36:32-42(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	"Molecular cloning of chromosome I DNA from Saccharomyces cerevisiae: analysis of the genes in the FUN38-MAK16-SPO7 region." Barton A.B., Kaback D.B. J. Bacteriol. 176:1872-1880(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[4]	"The nucleotide sequence of chromosome I from Saccharomyces cerevisiae." Bussey H., Kaback D.B., Zhong W.-W., Vo D.H., Clark M.W., Fortin N., Hall J., Ouellette B.F.F., Keng T., Barton A.B., Su Y., Davies C.J., Storms R.K. Proc. Natl. Acad. Sci. U.S.A. 92:3809-3813(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	"The NOT proteins are part of the CCR4 transcriptional complex and affect gene expression both positively and negatively." Liu H.Y., Badarinarayana V., Audino D.C., Rappsilber J., Mann M., Denis C.L. EMBO J. 17:1096-1106(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE CCR4-NOT CORE COMPLEX, FUNCTION OF THE CCR4-NOT CORE COMPLEX IN TRANSCRIPTIONAL REGULATION.
[7]	"The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5." Bai Y., Salvadore C., Chiang Y.C., Collart M.A., Liu H.Y., Denis C.L. Mol. Cell. Biol. 19:6642-6651(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NOT1.
[8]	"The transcription factor associated Ccr4 and Caf1 proteins are components of the major cytoplasmic mRNA deadenylase in Saccharomyces cerevisiae." Tucker M., Valencia-Sanchez M.A., Staples R.R., Chen J., Denis C.L., Parker R. Cell 104:377-386(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MRNA DEADENYLATION, SUBCELLULAR LOCATION.
[9]	"Purification and characterization of the 1.0 MDa CCR4-NOT complex identifies two novel components of the complex." Chen J., Rappsilber J., Chiang Y.C., Russell P., Mann M., Denis C.L. J. Mol. Biol. 314:683-694(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE CCR4-NOT CORE COMPLEX.
[10]	"CCR4, a 3'-5' poly(A) RNA and ssDNA exonuclease, is the catalytic component of the cytoplasmic deadenylase." Chen J., Chiang Y.-C., Denis C.L. EMBO J. 21:1414-1426(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MRNA DEADENYLATION, MUTAGENESIS OF GLU-556; ASP-713; ASP-780 AND HIS-818.
[11]	"Ccr4p is the catalytic subunit of a Ccr4p/Pop2p/Notp mRNA deadenylase complex in Saccharomyces cerevisiae." Tucker M., Staples R.R., Valencia-Sanchez M.A., Muhlrad D., Parker R. EMBO J. 21:1427-1436(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MRNA DEADENYLATION.
[12]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[13]	"Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae." Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P. J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-285, MASS SPECTROMETRY. Strain: ADR376.
[14]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-266; THR-276; SER-278; SER-281; THR-282 AND THR-285, MASS SPECTROMETRY.
[15]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

S50459 Genomic DNA. Translation: AAB24455.1.
L05146 Genomic DNA. Translation: AAC04936.1.
BK006935 Genomic DNA. Translation: DAA06967.1.

PIR

S36713.

RefSeq

NP_009381.1. NM_001178166.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4B8C	X-ray	3.41	D/J/K/L	111-837	[»]

ProteinModelPortal

P31384.

SMR

P31384. Positions 135-827.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2522N.

IntAct

P31384. 37 interactions.

MINT

MINT-615079.

STRING

4932.YAL021C.

Proteomic databases

PaxDb

P31384.

PeptideAtlas

P31384.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YAL021C; YAL021C; YAL021C.

GeneID

851212.

KEGG

sce:YAL021C.

Organism-specific databases

SGD

S000000019. CCR4.

Phylogenomic databases

eggNOG

COG4886.

GeneTree

ENSGT00550000074364.

HOGENOM

HOG000294222.

KO

K12603.

OMA

CMQEVET.

OrthoDB

EOG4Z39P3.

Gene expression databases

Genevestigator

P31384.

GermOnline

YAL021C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR005135. Endo/exonuclease/phosphatase.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]

Pfam

PF03372. Exo_endo_phos. 1 hit.
PF12799. LRR_4. 1 hit.
[Graphical view]

SMART

SM00369. LRR_TYP. 1 hit.
[Graphical view]

SUPFAM

SSF56219. Exo_endo_phos. 1 hit.

PROSITE

PS51450. LRR. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

968091.

Entry information

Entry name

CCR4_YEAST

Accession

Primary (citable) accession number: P31384
Secondary accession number(s): D6VPJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	October 5, 2010
Last modified:	May 1, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program