Q96LI5 (CNO6L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CCR4-NOT transcription complex subunit 6-like
EC=3.1.-.-

Alternative name(s):
Carbon catabolite repressor protein 4 homolog B

Gene names

Name:	CNOT6L
Synonyms:	CCR4B

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	555 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a role in the deadenylation of mRNAs in the cytoplasm. Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. May be involved in the deadenylation-dependent degradation of mRNAs through the 3'-UTR AU-rich element-mediated mechanism. Involved in deadenylation-dependent degradation of CDKN1B mRNA. Ref.4
Cofactor	Magnesium. Ref.6
Subunit structure	Component of the CCR4-NOT complex at least composed of CNOT1, CNOT2, CNOT3, CNOT8, CNOT9, CNOT10 and TNKS1BP1. Interacts with NANOS2 By similarity. Ref.4
Subcellular location	Cytoplasm Ref.4.
Tissue specificity	Highly expressed in placenta, skeletal muscle, pancreas, testis and leukocytes. Weakly expressed in heart, spleen and thymus. Ref.4
Miscellaneous	Depletion of CNOT6L causes cell growth defect.
Sequence similarities	Belongs to the CCR4/nocturin family. Contains 4 LRR (leucine-rich) repeats.

Ontologies

Keywords
Biological process	mRNA processing
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Leucine-rich repeat Repeat
Ligand	Magnesium Metal-binding
Molecular function	Exonuclease Hydrolase Nuclease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mRNA destabilization Inferred from electronic annotation. Source: Compara nuclear-transcribed mRNA poly(A) tail shortening Traceable author statement. Source: Reactome positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	CCR4-NOT complex Inferred from direct assay PubMed 19558367. Source: UniProtKB cytosol Traceable author statement. Source: Reactome
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW poly(A)-specific ribonuclease activity Traceable author statement. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHAF1B	Q13112	2	EBI-1046635,EBI-1052944
CNOT3	O75175	2	EBI-1046635,EBI-743073
TOB1	P50616	3	EBI-1046635,EBI-723281

Alternative products

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

Isoform 1 (identifier: Q96LI5-1)

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: Q96LI5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     127-153: Missing.
     486-502: GVIDYIFYSKTHMNVLG → VSGSLWAGVEIISDTSM
     503-555: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 555

555

CCR4-NOT transcription complex subunit 6-like

PRO_0000314587

Regions

Repeat

57 – 78

22

LRR 1

Repeat

80 – 101

22

LRR 2

Repeat

103 – 125

23

LRR 3

Repeat

126 – 148

23

LRR 4

Region

158 – 555

398

Nuclease domain

Sites

Active site

240

1

Probable

Active site

489

1

Probable

Active site

529

1

Probable

Metal binding

240

1

Magnesium 1

Metal binding

410

1

Magnesium 2

Metal binding

412

1

Magnesium 2

Metal binding

529

1

Magnesium 2

Natural variations

Alternative sequence

127 – 153

27

Missing in isoform 2.

VSP_030321

Alternative sequence

486 – 502

17

GVIDY…MNVLG → VSGSLWAGVEIISDTSM in isoform 2.

VSP_030322

Alternative sequence

503 – 555

53

Missing in isoform 2.

VSP_030323

Experimental info

Mutagenesis

240

1

E → A: No enzymatic activity. Ref.6

Mutagenesis

410

1

D → A: Loss of deadenylase activity. Ref.4

Mutagenesis

489

1

D → A: Loss of deadenylase activity. Ref.4 Ref.6

Mutagenesis

489

1

D → A: No enzymatic activity. Ref.4 Ref.6

Mutagenesis

529

1

H → A: Loss of deadenylase activity. Ref.4 Ref.6

Mutagenesis

529

1

H → A: No enzymatic activity. Ref.4 Ref.6

Sequence conflict

439

1

R → G in BAB71707. Ref.1

Secondary structure

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555

Helix Strand Turn

Details...

Beta strand

174 – 176

3

Beta strand

187 – 195

9

Helix

199 – 201

3

Turn

204 – 206

3

Helix

212 – 215

4

Helix

217 – 231

15

Beta strand

234 – 242

9

Helix

243 – 248

6

Helix

250 – 256

7

Beta strand

259 – 266

8

Beta strand

268 – 270

3

Helix

274 – 278

5

Beta strand

281 – 288

8

Turn

289 – 291

3

Beta strand

292 – 301

10

Helix

302 – 308

7

Helix

314 – 318

5

Turn

319 – 322

4

Beta strand

326 – 334

9

Helix

336 – 338

3

Beta strand

353 – 360

8

Helix

365 – 367

3

Helix

368 – 386

19

Beta strand

405 – 410

6

Helix

418 – 425

8

Beta strand

427 – 429

3

Helix

433 – 435

3

Helix

443 – 447

5

Beta strand

459 – 461

3

Beta strand

466 – 468

3

Turn

469 – 473

5

Beta strand

474 – 476

3

Beta strand

478 – 480

3

Beta strand

489 – 494

6

Turn

495 – 497

3

Beta strand

498 – 504

7

Helix

509 – 514

6

Beta strand

519 – 522

4

Beta strand

527 – 529

3

Beta strand

532 – 538

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: C6E94F1BAE222241	FASTA	555	63,001
	10 20 30 40 50 60 MRLIGMPKEK YDPPDPRRIY TIMSAEEVAN GKKSHWAELE ISGRVRSLST SLWSLTHLTA 70 80 90 100 110 120 LHLNDNYLSR IPPDIAKLHN LVYLDLSSNK LRSLPAELGN MVSLRELLLN NNLLRVLPYE 130 140 150 160 170 180 LGRLFQLQTL GLKGNPLSQD ILNLYQDPDG TRKLLNFMLD NLAVHPEQLP PRPWITLKER 190 200 210 220 230 240 DQILPSASFT VMCYNVLCDK YATRQLYGYC PSWALNWEYR KKGIMEEIVN CDADIISLQE 250 260 270 280 290 300 VETEQYFTLF LPALKERGYD GFFSPKSRAK IMSEQERKHV DGCAIFFKTE KFTLVQKHTV 310 320 330 340 350 360 EFNQVAMANS DGSEAMLNRV MTKDNIGVAV VLEVHKELFG AGMKPIHAAD KQLLIVANAH 370 380 390 400 410 420 MHWDPEYSDV KLIQTMMFVS EVKNILEKAS SRPGSPTADP NSIPLVLCAD LNSLPDSGVV 430 440 450 460 470 480 EYLSNGGVAD NHKDFKELRY NECLMNFSCN GKNGSSEGRI THGFQLKSAY ENNLMPYTNY 490 500 510 520 530 540 TFDFKGVIDY IFYSKTHMNV LGVLGPLDPQ WLVENNITGC PHPHIPSDHF SLLTQLELHP 550 PLLPLVNGVH LPNRR
	Isoform 2 [UniParc]. Checksum: 6E2E2BB67749C501	FASTA	475	53,891
	10 20 30 40 50 60 MRLIGMPKEK YDPPDPRRIY TIMSAEEVAN GKKSHWAELE ISGRVRSLST SLWSLTHLTA 70 80 90 100 110 120 LHLNDNYLSR IPPDIAKLHN LVYLDLSSNK LRSLPAELGN MVSLRELLLN NNLLRVLPYE 130 140 150 160 170 180 LGRLFQLLNF MLDNLAVHPE QLPPRPWITL KERDQILPSA SFTVMCYNVL CDKYATRQLY 190 200 210 220 230 240 GYCPSWALNW EYRKKGIMEE IVNCDADIIS LQEVETEQYF TLFLPALKER GYDGFFSPKS 250 260 270 280 290 300 RAKIMSEQER KHVDGCAIFF KTEKFTLVQK HTVEFNQVAM ANSDGSEAML NRVMTKDNIG 310 320 330 340 350 360 VAVVLEVHKE LFGAGMKPIH AADKQLLIVA NAHMHWDPEY SDVKLIQTMM FVSEVKNILE 370 380 390 400 410 420 KASSRPGSPT ADPNSIPLVL CADLNSLPDS GVVEYLSNGG VADNHKDFKE LRYNECLMNF 430 440 450 460 470 SCNGKNGSSE GRITHGFQLK SAYENNLMPY TNYTFDFKVS GSLWAGVEII SDTSM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[2]	"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].
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 208-555 (ISOFORM 1). Tissue: Testis.
[4]	"Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth." Morita M., Suzuki T., Nakamura T., Yokoyama K., Miyasaka T., Yamamoto T. Mol. Cell. Biol. 27:4980-4990(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CNOT1; CNOT2; CNOT3; CNOT7; CNOT8; CNOT9 AND CNOT10, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-410; ASP-489 AND HIS-529.
[5]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity." Wang H., Morita M., Yang X., Suzuki T., Yang W., Wang J., Ito K., Wang Q., Zhao C., Bartlam M., Yamamoto T., Rao Z. EMBO J. 29:2566-2576(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 158-555, ALONE AND IN COMPLEX WITH AMP ANALOG AND POLY-A DNA, MUTAGENESIS OF GLU-240; ASP-489 AND HIS-529, COFACTOR, ACTIVE SITE, MAGNESIUM-BINDING SITES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK058188 mRNA. Translation: BAB71707.1.
AC104701 Genomic DNA. No translation available.
AL133112 mRNA. Translation: CAB61415.1.

IPI

IPI00164061.
IPI00878418.

PIR

T42705.

RefSeq

NP_653172.2. NM_144571.2.

UniGene

Hs.592519.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3NGN	X-ray	2.40	A	158-555	[»]
3NGO	X-ray	2.20	A	158-555	[»]
3NGQ	X-ray	1.80	A	158-555	[»]

ProteinModelPortal

Q96LI5.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46837N.

IntAct

Q96LI5. 12 interactions.

STRING

9606.ENSP00000264903.

PTM databases

PhosphoSite

Q96LI5.

Polymorphism databases

DMDM

166216089.

Proteomic databases

PaxDb

Q96LI5.

PRIDE

Q96LI5.

Protocols and materials databases

DNASU

246175.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000264903; ENSP00000264903; ENSG00000138767.
ENST00000504123; ENSP00000424896; ENSG00000138767.

GeneID

246175.

KEGG

hsa:246175.

UCSC

uc003hks.3. human.
uc003hkt.1. human.

Organism-specific databases

CTD

246175.

GeneCards

GC04M078634.

HGNC

HGNC:18042. CNOT6L.

HPA

HPA042688.

neXtProt

NX_Q96LI5.

PharmGKB

PA38480.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4886.

HOGENOM

HOG000294222.

HOVERGEN

HBG052641.

InParanoid

Q96LI5.

KO

K12603.

Enzyme and pathway databases

Reactome

REACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q96LI5.

Bgee

Q96LI5.

CleanEx

HS_CNOT6L.

Genevestigator

Q96LI5.

Family and domain databases

InterPro

IPR005135. Endo/exonuclease/phosphatase.
IPR001611. Leu-rich_rpt.
[Graphical view]

Pfam

PF03372. Exo_endo_phos. 1 hit.
[Graphical view]

SUPFAM

SSF56219. Exo_endo_phos. 1 hit.

PROSITE

PS51450. LRR. 4 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96LI5.

GenomeRNAi

246175.

NextBio

91870.

Entry information

Entry name

CNO6L_HUMAN

Accession

Primary (citable) accession number: Q96LI5
Secondary accession number(s): Q9UF92

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	January 15, 2008
Last modified:	May 1, 2013
This is version 89 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.