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Protein

CCR4-NOT transcription complex subunit 2

Gene

CNOT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specificly involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of emryonic stem (ES) cell identity.4 Publications

GO - Molecular functioni

  • RNA polymerase II transcription cofactor activity Source: UniProtKB
  • RNA polymerase II transcription corepressor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

RNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation

Enzyme and pathway databases

ReactomeiR-HSA-429947. Deadenylation of mRNA.
R-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.

Names & Taxonomyi

Protein namesi
Recommended name:
CCR4-NOT transcription complex subunit 2
Alternative name(s):
CCR4-associated factor 2
Gene namesi
Name:CNOT2
Synonyms:CDC36, NOT2
ORF Names:HSPC131, MSTP046
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:7878. CNOT2.

Subcellular locationi

GO - Cellular componenti

  • CCR4-NOT complex Source: UniProtKB
  • CCR4-NOT core complex Source: GO_Central
  • cytoplasm Source: UniProtKB
  • cytoplasmic mRNA processing body Source: GO_Central
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi4848.
OpenTargetsiENSG00000111596.
PharmGKBiPA26673.

Polymorphism and mutation databases

BioMutaiCNOT2.
DMDMi46396017.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001983311 – 540CCR4-NOT transcription complex subunit 2Add BLAST540

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei93PhosphothreonineCombined sources1
Modified residuei126PhosphoserineCombined sources1
Modified residuei157PhosphoserineBy similarity1
Modified residuei165PhosphoserineCombined sources1
Modified residuei169PhosphoserineBy similarity1
Modified residuei242PhosphoserineCombined sources1
Modified residuei274PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NZN8.
MaxQBiQ9NZN8.
PaxDbiQ9NZN8.
PeptideAtlasiQ9NZN8.
PRIDEiQ9NZN8.

PTM databases

iPTMnetiQ9NZN8.
PhosphoSitePlusiQ9NZN8.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in brain, heart, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood leukocytes.1 Publication

Developmental stagei

Expressed in embryonic stem (ES) cells.1 Publication

Gene expression databases

BgeeiENSG00000111596.
CleanExiHS_CNOT2.
ExpressionAtlasiQ9NZN8. baseline and differential.
GenevisibleiQ9NZN8. HS.

Organism-specific databases

HPAiHPA067711.

Interactioni

Subunit structurei

Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. In the complex interacts directly with CNOT3. Interacts with NCOR1, NCOR2. HDAC3 and GPS2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CNOT1A5YKK65EBI-743033,EBI-1222758
CNOT3O751755EBI-743033,EBI-743073
CNOT6LQ96LI52EBI-743033,EBI-1046635
CNOT8Q9UFF93EBI-743033,EBI-742299
TNRC6CQ9HCJ03EBI-743033,EBI-6507625

GO - Molecular functioni

  • RNA polymerase II transcription corepressor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110910. 58 interactors.
DIPiDIP-42656N.
IntActiQ9NZN8. 50 interactors.
MINTiMINT-1438957.
STRINGi9606.ENSP00000229195.

Structurei

Secondary structure

1540
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi357 – 366Combined sources10
Helixi371 – 373Combined sources3
Turni376 – 378Combined sources3
Helixi382 – 385Combined sources4
Helixi396 – 398Combined sources3
Turni410 – 412Combined sources3
Helixi419 – 421Combined sources3
Helixi424 – 427Combined sources4
Helixi429 – 432Combined sources4
Helixi436 – 438Combined sources3
Helixi441 – 449Combined sources9
Helixi453 – 466Combined sources14
Beta strandi470 – 472Combined sources3
Turni473 – 476Combined sources4
Beta strandi477 – 481Combined sources5
Beta strandi488 – 490Combined sources3
Beta strandi492 – 503Combined sources12
Turni504 – 507Combined sources4
Beta strandi508 – 517Combined sources10
Helixi518 – 520Combined sources3
Helixi537 – 539Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4C0DX-ray3.20B344-540[»]
4C0FX-ray2.40A/B/C/D429-540[»]
5FU6X-ray2.90B/E350-540[»]
5FU7X-ray3.10B/F350-540[»]
ProteinModelPortaliQ9NZN8.
SMRiQ9NZN8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni437 – 540Repressor domainAdd BLAST104

Sequence similaritiesi

Belongs to the CNOT2/3/5 family.Curated

Phylogenomic databases

eggNOGiKOG2151. Eukaryota.
COG5601. LUCA.
GeneTreeiENSGT00390000001285.
HOGENOMiHOG000246523.
HOVERGENiHBG051041.
InParanoidiQ9NZN8.
KOiK12605.
OMAiNIPSGMV.
OrthoDBiEOG091G0C7Y.
PhylomeDBiQ9NZN8.
TreeFamiTF313102.

Family and domain databases

InterProiIPR007282. NOT.
[Graphical view]
PfamiPF04153. NOT2_3_5. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NZN8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVRTDGHTLS EKRNYQVTNS MFGASRKKFV EGVDSDYHDE NMYYSQSSMF
60 70 80 90 100
PHRSEKDMLA SPSTSGQLSQ FGASLYGQQS ALGLPMRGMS NNTPQLNRSL
110 120 130 140 150
SQGTQLPSHV TPTTGVPTMS LHTPPSPSRG ILPMNPRNMM NHSQVGQGIG
160 170 180 190 200
IPSRTNSMSS SGLGSPNRSS PSIICMPKQQ PSRQPFTVNS MSGFGMNRNQ
210 220 230 240 250
AFGMNNSLSS NIFNGTDGSE NVTGLDLSDF PALADRNRRE GSGNPTPLIN
260 270 280 290 300
PLAGRAPYVG MVTKPANEQS QDFSIHNEDF PALPGSSYKD PTSSNDDSKS
310 320 330 340 350
NLNTSGKTTS STDGPKFPGD KSSTTQNNNQ QKKGIQVLPD GRVTNIPQGM
360 370 380 390 400
VTDQFGMIGL LTFIRAAETD PGMVHLALGS DLTTLGLNLN SPENLYPKFA
410 420 430 440 450
SPWASSPCRP QDIDFHVPSE YLTNIHIRDK LAAIKLGRYG EDLLFYLYYM
460 470 480 490 500
NGGDVLQLLA AVELFNRDWR YHKEERVWIT RAPGMEPTMK TNTYERGTYY
510 520 530 540
FFDCLNWRKV AKEFHLEYDK LEERPHLPST FNYNPAQQAF
Length:540
Mass (Da):59,738
Last modified:October 1, 2000 - v1
Checksum:i7183890F033E3B83
GO
Isoform 2 (identifier: Q9NZN8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-175: Missing.

Note: No experimental confirmation available.
Show »
Length:365
Mass (Da):40,818
Checksum:i27FC908ADA1A6201
GO
Isoform 3 (identifier: Q9NZN8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-349: Missing.

Note: May be due to an intron retention. No experimental confirmation available.
Show »
Length:191
Mass (Da):22,254
Checksum:i803037A4A6F670CC
GO
Isoform 4 (identifier: Q9NZN8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     465-475: FNRDWRYHKEE → YVQSILITFVL
     476-540: Missing.

Note: May be due to an intron retention. No experimental confirmation available.
Show »
Length:475
Mass (Da):51,537
Checksum:i5D5C630BB3E89F06
GO
Isoform 5 (identifier: Q9NZN8-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     229-278: Missing.

Note: No experimental confirmation available.
Show »
Length:490
Mass (Da):54,306
Checksum:i7C6A4CC0F0992C9C
GO

Sequence cautioni

The sequence AAF29095 differs from that shown. Reason: Frameshift at position 474.Curated
The sequence AAQ13426 differs from that shown. Reason: Frameshift at positions 71, 76, 84, 98, 123, 370, 384 and 393.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048750460A → T.Corresponds to variant rs11178192dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0099131 – 349Missing in isoform 3. 1 PublicationAdd BLAST349
Alternative sequenceiVSP_0099121 – 175Missing in isoform 2. 1 PublicationAdd BLAST175
Alternative sequenceiVSP_009914229 – 278Missing in isoform 5. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_009915465 – 475FNRDWRYHKEE → YVQSILITFVL in isoform 4. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_009916476 – 540Missing in isoform 4. 1 PublicationAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF180473 mRNA. Translation: AAF29827.1.
AF113226 mRNA. Translation: AAG39297.1.
AF161480 mRNA. Translation: AAF29095.1. Frameshift.
AK000662 mRNA. Translation: BAA91313.1.
AL137674 mRNA. Translation: CAB70869.1.
BX641116 mRNA. Translation: CAE46054.1.
BC002597 mRNA. Translation: AAH02597.1.
BC011826 mRNA. Translation: AAH11826.1.
AF044215 mRNA. Translation: AAQ13426.1. Frameshift.
CCDSiCCDS31857.1. [Q9NZN8-1]
PIRiT46494.
RefSeqiNP_001186231.1. NM_001199302.1. [Q9NZN8-1]
NP_001186232.1. NM_001199303.1. [Q9NZN8-1]
NP_055330.1. NM_014515.5. [Q9NZN8-1]
XP_011536701.1. XM_011538399.1. [Q9NZN8-1]
UniGeneiHs.133350.
Hs.730666.

Genome annotation databases

EnsembliENST00000229195; ENSP00000229195; ENSG00000111596. [Q9NZN8-1]
ENST00000418359; ENSP00000412091; ENSG00000111596. [Q9NZN8-1]
ENST00000551043; ENSP00000449260; ENSG00000111596. [Q9NZN8-1]
ENST00000551483; ENSP00000448883; ENSG00000111596. [Q9NZN8-3]
GeneIDi4848.
KEGGihsa:4848.
UCSCiuc001svv.4. human. [Q9NZN8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF180473 mRNA. Translation: AAF29827.1.
AF113226 mRNA. Translation: AAG39297.1.
AF161480 mRNA. Translation: AAF29095.1. Frameshift.
AK000662 mRNA. Translation: BAA91313.1.
AL137674 mRNA. Translation: CAB70869.1.
BX641116 mRNA. Translation: CAE46054.1.
BC002597 mRNA. Translation: AAH02597.1.
BC011826 mRNA. Translation: AAH11826.1.
AF044215 mRNA. Translation: AAQ13426.1. Frameshift.
CCDSiCCDS31857.1. [Q9NZN8-1]
PIRiT46494.
RefSeqiNP_001186231.1. NM_001199302.1. [Q9NZN8-1]
NP_001186232.1. NM_001199303.1. [Q9NZN8-1]
NP_055330.1. NM_014515.5. [Q9NZN8-1]
XP_011536701.1. XM_011538399.1. [Q9NZN8-1]
UniGeneiHs.133350.
Hs.730666.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4C0DX-ray3.20B344-540[»]
4C0FX-ray2.40A/B/C/D429-540[»]
5FU6X-ray2.90B/E350-540[»]
5FU7X-ray3.10B/F350-540[»]
ProteinModelPortaliQ9NZN8.
SMRiQ9NZN8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110910. 58 interactors.
DIPiDIP-42656N.
IntActiQ9NZN8. 50 interactors.
MINTiMINT-1438957.
STRINGi9606.ENSP00000229195.

PTM databases

iPTMnetiQ9NZN8.
PhosphoSitePlusiQ9NZN8.

Polymorphism and mutation databases

BioMutaiCNOT2.
DMDMi46396017.

Proteomic databases

EPDiQ9NZN8.
MaxQBiQ9NZN8.
PaxDbiQ9NZN8.
PeptideAtlasiQ9NZN8.
PRIDEiQ9NZN8.

Protocols and materials databases

DNASUi4848.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229195; ENSP00000229195; ENSG00000111596. [Q9NZN8-1]
ENST00000418359; ENSP00000412091; ENSG00000111596. [Q9NZN8-1]
ENST00000551043; ENSP00000449260; ENSG00000111596. [Q9NZN8-1]
ENST00000551483; ENSP00000448883; ENSG00000111596. [Q9NZN8-3]
GeneIDi4848.
KEGGihsa:4848.
UCSCiuc001svv.4. human. [Q9NZN8-1]

Organism-specific databases

CTDi4848.
DisGeNETi4848.
GeneCardsiCNOT2.
HGNCiHGNC:7878. CNOT2.
HPAiHPA067711.
MIMi604909. gene.
neXtProtiNX_Q9NZN8.
OpenTargetsiENSG00000111596.
PharmGKBiPA26673.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2151. Eukaryota.
COG5601. LUCA.
GeneTreeiENSGT00390000001285.
HOGENOMiHOG000246523.
HOVERGENiHBG051041.
InParanoidiQ9NZN8.
KOiK12605.
OMAiNIPSGMV.
OrthoDBiEOG091G0C7Y.
PhylomeDBiQ9NZN8.
TreeFamiTF313102.

Enzyme and pathway databases

ReactomeiR-HSA-429947. Deadenylation of mRNA.
R-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.

Miscellaneous databases

ChiTaRSiCNOT2. human.
GeneWikiiCNOT2.
GenomeRNAii4848.
PROiQ9NZN8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111596.
CleanExiHS_CNOT2.
ExpressionAtlasiQ9NZN8. baseline and differential.
GenevisibleiQ9NZN8. HS.

Family and domain databases

InterProiIPR007282. NOT.
[Graphical view]
PfamiPF04153. NOT2_3_5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCNOT2_HUMAN
AccessioniPrimary (citable) accession number: Q9NZN8
Secondary accession number(s): Q9H3E0
, Q9NSX5, Q9NWR6, Q9P028
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.