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Protein

CCR4-NOT transcription complex subunit 3

Gene

CNOT3

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. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of emryonic stem (ES) cell identity.3 Publications

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

BioCyciZFISH:ENSG00000088038-MONOMER.
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.
SIGNORiO75175.

Names & Taxonomyi

Protein namesi
Recommended name:
CCR4-NOT transcription complex subunit 3
Alternative name(s):
CCR4-associated factor 3
Leukocyte receptor cluster member 2
Gene namesi
Name:CNOT3
Synonyms:KIAA0691, LENG2, NOT3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:7879. CNOT3.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi4849.
MalaCardsiCNOT3.
OpenTargetsiENSG00000088038.
ENSG00000273943.
ENSG00000274176.
ENSG00000274616.
ENSG00000274941.
ENSG00000275979.
ENSG00000276082.
ENSG00000277114.
ENSG00000277600.
ENSG00000277615.
Orphaneti99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA26674.

Polymorphism and mutation databases

BioMutaiCNOT3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001983331 – 753CCR4-NOT transcription complex subunit 3Add BLAST753

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei292PhosphothreonineCombined sources1
Modified residuei299PhosphoserineCombined sources1
Modified residuei542PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO75175.
MaxQBiO75175.
PaxDbiO75175.
PeptideAtlasiO75175.
PRIDEiO75175.

PTM databases

iPTMnetiO75175.
PhosphoSitePlusiO75175.

Expressioni

Tissue specificityi

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

Developmental stagei

Expressed in embryonic stem (ES) cells.1 Publication

Gene expression databases

BgeeiENSG00000088038.
CleanExiHS_CNOT3.
ExpressionAtlasiO75175. baseline and differential.
GenevisibleiO75175. HS.

Organism-specific databases

HPAiHPA006408.

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 CNOT2. Interacts with TIP120B and NANOS2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cand2Q6ZQ732EBI-6504867,EBI-6504831From a different organism.
CNOT1A5YKK62EBI-743073,EBI-1222758
CNOT2Q9NZN85EBI-743073,EBI-743033
CNOT6LQ96LI52EBI-743073,EBI-1046635
CNOT8Q9UFF93EBI-743073,EBI-742299
TOB1P506162EBI-743073,EBI-723281

Protein-protein interaction databases

BioGridi110911. 40 interactors.
DIPiDIP-40297N.
IntActiO75175. 25 interactors.
MINTiMINT-1439009.
STRINGi9606.ENSP00000221232.

Structurei

Secondary structure

1753
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi609 – 623Combined sources15
Helixi628 – 631Combined sources4
Beta strandi636 – 638Combined sources3
Turni655 – 658Combined sources4
Helixi660 – 665Combined sources6
Helixi668 – 677Combined sources10
Turni678 – 680Combined sources3
Helixi682 – 693Combined sources12
Beta strandi697 – 699Combined sources3
Turni700 – 703Combined sources4
Beta strandi704 – 710Combined sources7
Beta strandi713 – 715Combined sources3
Beta strandi717 – 728Combined sources12
Turni729 – 732Combined sources4
Beta strandi733 – 743Combined sources11
Helixi744 – 746Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4C0DX-ray3.20C607-753[»]
4C0GX-ray2.40A/B/C/D/E/F656-753[»]
5FU6X-ray2.90C/F607-748[»]
5FU7X-ray3.10C/G607-748[»]
ProteinModelPortaliO75175.
SMRiO75175.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni661 – 753Repressor domainAdd BLAST93

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi314 – 395Pro-richAdd BLAST82
Compositional biasi397 – 425Gly/Ser-richAdd BLAST29
Compositional biasi457 – 655Pro-richAdd BLAST199

Sequence similaritiesi

Belongs to the CNOT2/3/5 family.Curated

Phylogenomic databases

eggNOGiKOG2150. Eukaryota.
COG5665. LUCA.
GeneTreeiENSGT00390000014743.
HOGENOMiHOG000184850.
HOVERGENiHBG051042.
InParanoidiO75175.
KOiK12580.
OMAiRRKWHIN.
OrthoDBiEOG091G040M.
PhylomeDBiO75175.
TreeFamiTF321963.

Family and domain databases

InterProiIPR012270. CCR4-NOT_su3/5.
IPR007282. NOT.
IPR007207. Not_N.
[Graphical view]
PfamiPF04153. NOT2_3_5. 1 hit.
PF04065. Not3. 1 hit.
[Graphical view]
PIRSFiPIRSF005290. NOT_su_3_5. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75175-1) [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
MADKRKLQGE IDRCLKKVSE GVEQFEDIWQ KLHNAANANQ KEKYEADLKK
60 70 80 90 100
EIKKLQRLRD QIKTWVASNE IKDKRQLIDN RKLIETQMER FKVVERETKT
110 120 130 140 150
KAYSKEGLGL AQKVDPAQKE KEEVGQWLTN TIDTLNMQVD QFESEVESLS
160 170 180 190 200
VQTRKKKGDK DKQDRIEGLK RHIEKHRYHV RMLETILRML DNDSILVDAI
210 220 230 240 250
RKIKDDVEYY VDSSQDPDFE ENEFLYDDLD LEDIPQALVA TSPPSHSHME
260 270 280 290 300
DEIFNQSSST PTSTTSSSPI PPSPANCTTE NSEDDKKRGR STDSEVSQSP
310 320 330 340 350
AKNGSKPVHS NQHPQSPAVP PTYPSGPPPA ASALSTTPGN NGVPAPAAPP
360 370 380 390 400
SALGPKASPA PSHNSGTPAP YAQAVAPPAP SGPSTTQPRP PSVQPSGGGG
410 420 430 440 450
GGSGGGGSSS SSNSSAGGGA GKQNGATSYS SVVADSPAEV ALSSSGGNNA
460 470 480 490 500
SSQALGPPSG PHNPPPSTSK EPSAAAPTGA GGVAPGSGNN SGGPSLLVPL
510 520 530 540 550
PVNPPSSPTP SFSDAKAAGA LLNGPPQFST APEIKAPEPL SSLKSMAERA
560 570 580 590 600
AISSGIEDPV PTLHLTERDI ILSSTSAPPA SAQPPLQLSE VNIPLSLGVC
610 620 630 640 650
PLGPVPLTKE QLYQQAMEEA AWHHMPHPSD SERIRQYLPR NPCPTPPYHH
660 670 680 690 700
QMPPPHSDTV EFYQRLSTET LFFIFYYLEG TKAQYLAAKA LKKQSWRFHT
710 720 730 740 750
KYMMWFQRHE EPKTITDEFE QGTYIYFDYE KWGQRKKEGF TFEYRYLEDR

DLQ
Length:753
Mass (Da):81,872
Last modified:November 1, 1998 - v1
Checksum:iC9D4F8B9FEF6CD90
GO
Isoform 2 (identifier: O75175-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     608-609: TK → PR
     610-753: Missing.

Show »
Length:609
Mass (Da):64,053
Checksum:i507FC8AF634B613C
GO
Isoform 3 (identifier: O75175-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-181: Missing.
     680-753: GTKAQYLAAK...YRYLEDRDLQ → PRDVRTAWVD...LSSPLPTPLL

Note: No experimental confirmation available.
Show »
Length:571
Mass (Da):58,841
Checksum:iB21FEF915F2D01F4
GO

Sequence cautioni

The sequence BAA31666 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0099191 – 181Missing in isoform 3. 1 PublicationAdd BLAST181
Alternative sequenceiVSP_009920608 – 609TK → PR in isoform 2. 1 Publication2
Alternative sequenceiVSP_009921610 – 753Missing in isoform 2. 1 PublicationAdd BLAST144
Alternative sequenceiVSP_009922680 – 753GTKAQ…DRDLQ → PRDVRTAWVDSEAGPLRHTS APLPVAHWLTRGPSPALLQQ PQSRPTPLCSSAHSQASLET TGELSSPLPTPLL in isoform 3. 1 PublicationAdd BLAST74

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF180474 mRNA. Translation: AAF29828.1.
AB014591 mRNA. Translation: BAA31666.2. Different initiation.
AL133647 mRNA. Translation: CAB63766.1.
BC016474 mRNA. Translation: AAH16474.1.
CCDSiCCDS12880.1. [O75175-1]
PIRiT43456.
RefSeqiNP_055331.1. NM_014516.3. [O75175-1]
UniGeneiHs.343571.

Genome annotation databases

EnsembliENST00000221232; ENSP00000221232; ENSG00000088038. [O75175-1]
ENST00000358389; ENSP00000351159; ENSG00000088038. [O75175-1]
ENST00000610829; ENSP00000480392; ENSG00000276082. [O75175-3]
ENST00000610883; ENSP00000480258; ENSG00000274941. [O75175-1]
ENST00000611252; ENSP00000483968; ENSG00000275979. [O75175-1]
ENST00000611667; ENSP00000479186; ENSG00000277615. [O75175-3]
ENST00000612924; ENSP00000480585; ENSG00000274176. [O75175-1]
ENST00000613528; ENSP00000483604; ENSG00000277615. [O75175-1]
ENST00000613636; ENSP00000478143; ENSG00000274616. [O75175-3]
ENST00000613752; ENSP00000481681; ENSG00000273943. [O75175-1]
ENST00000614598; ENSP00000483450; ENSG00000274941. [O75175-3]
ENST00000614649; ENSP00000484794; ENSG00000274176. [O75175-1]
ENST00000615030; ENSP00000480697; ENSG00000274616. [O75175-1]
ENST00000616102; ENSP00000477620; ENSG00000277114. [O75175-3]
ENST00000616359; ENSP00000484040; ENSG00000274616. [O75175-1]
ENST00000616910; ENSP00000480876; ENSG00000277615. [O75175-1]
ENST00000617218; ENSP00000481624; ENSG00000274176. [O75175-3]
ENST00000617982; ENSP00000479987; ENSG00000277600. [O75175-1]
ENST00000618405; ENSP00000481924; ENSG00000277114. [O75175-1]
ENST00000619347; ENSP00000477693; ENSG00000273943. [O75175-3]
ENST00000619557; ENSP00000484369; ENSG00000275979. [O75175-3]
ENST00000619567; ENSP00000483882; ENSG00000275979. [O75175-1]
ENST00000619854; ENSP00000483431; ENSG00000273943. [O75175-1]
ENST00000620060; ENSP00000483036; ENSG00000277114. [O75175-1]
ENST00000620419; ENSP00000478956; ENSG00000276082. [O75175-1]
ENST00000620573; ENSP00000480988; ENSG00000276082. [O75175-1]
ENST00000620970; ENSP00000483692; ENSG00000277600. [O75175-1]
ENST00000622131; ENSP00000478280; ENSG00000274941. [O75175-1]
ENST00000622193; ENSP00000478913; ENSG00000277600. [O75175-3]
GeneIDi4849.
KEGGihsa:4849.
UCSCiuc002qdj.3. human. [O75175-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF180474 mRNA. Translation: AAF29828.1.
AB014591 mRNA. Translation: BAA31666.2. Different initiation.
AL133647 mRNA. Translation: CAB63766.1.
BC016474 mRNA. Translation: AAH16474.1.
CCDSiCCDS12880.1. [O75175-1]
PIRiT43456.
RefSeqiNP_055331.1. NM_014516.3. [O75175-1]
UniGeneiHs.343571.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4C0DX-ray3.20C607-753[»]
4C0GX-ray2.40A/B/C/D/E/F656-753[»]
5FU6X-ray2.90C/F607-748[»]
5FU7X-ray3.10C/G607-748[»]
ProteinModelPortaliO75175.
SMRiO75175.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110911. 40 interactors.
DIPiDIP-40297N.
IntActiO75175. 25 interactors.
MINTiMINT-1439009.
STRINGi9606.ENSP00000221232.

PTM databases

iPTMnetiO75175.
PhosphoSitePlusiO75175.

Polymorphism and mutation databases

BioMutaiCNOT3.

Proteomic databases

EPDiO75175.
MaxQBiO75175.
PaxDbiO75175.
PeptideAtlasiO75175.
PRIDEiO75175.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221232; ENSP00000221232; ENSG00000088038. [O75175-1]
ENST00000358389; ENSP00000351159; ENSG00000088038. [O75175-1]
ENST00000610829; ENSP00000480392; ENSG00000276082. [O75175-3]
ENST00000610883; ENSP00000480258; ENSG00000274941. [O75175-1]
ENST00000611252; ENSP00000483968; ENSG00000275979. [O75175-1]
ENST00000611667; ENSP00000479186; ENSG00000277615. [O75175-3]
ENST00000612924; ENSP00000480585; ENSG00000274176. [O75175-1]
ENST00000613528; ENSP00000483604; ENSG00000277615. [O75175-1]
ENST00000613636; ENSP00000478143; ENSG00000274616. [O75175-3]
ENST00000613752; ENSP00000481681; ENSG00000273943. [O75175-1]
ENST00000614598; ENSP00000483450; ENSG00000274941. [O75175-3]
ENST00000614649; ENSP00000484794; ENSG00000274176. [O75175-1]
ENST00000615030; ENSP00000480697; ENSG00000274616. [O75175-1]
ENST00000616102; ENSP00000477620; ENSG00000277114. [O75175-3]
ENST00000616359; ENSP00000484040; ENSG00000274616. [O75175-1]
ENST00000616910; ENSP00000480876; ENSG00000277615. [O75175-1]
ENST00000617218; ENSP00000481624; ENSG00000274176. [O75175-3]
ENST00000617982; ENSP00000479987; ENSG00000277600. [O75175-1]
ENST00000618405; ENSP00000481924; ENSG00000277114. [O75175-1]
ENST00000619347; ENSP00000477693; ENSG00000273943. [O75175-3]
ENST00000619557; ENSP00000484369; ENSG00000275979. [O75175-3]
ENST00000619567; ENSP00000483882; ENSG00000275979. [O75175-1]
ENST00000619854; ENSP00000483431; ENSG00000273943. [O75175-1]
ENST00000620060; ENSP00000483036; ENSG00000277114. [O75175-1]
ENST00000620419; ENSP00000478956; ENSG00000276082. [O75175-1]
ENST00000620573; ENSP00000480988; ENSG00000276082. [O75175-1]
ENST00000620970; ENSP00000483692; ENSG00000277600. [O75175-1]
ENST00000622131; ENSP00000478280; ENSG00000274941. [O75175-1]
ENST00000622193; ENSP00000478913; ENSG00000277600. [O75175-3]
GeneIDi4849.
KEGGihsa:4849.
UCSCiuc002qdj.3. human. [O75175-1]

Organism-specific databases

CTDi4849.
DisGeNETi4849.
GeneCardsiCNOT3.
HGNCiHGNC:7879. CNOT3.
HPAiHPA006408.
MalaCardsiCNOT3.
MIMi604910. gene.
neXtProtiNX_O75175.
OpenTargetsiENSG00000088038.
ENSG00000273943.
ENSG00000274176.
ENSG00000274616.
ENSG00000274941.
ENSG00000275979.
ENSG00000276082.
ENSG00000277114.
ENSG00000277600.
ENSG00000277615.
Orphaneti99861. Precursor T-cell acute lymphoblastic leukemia.
PharmGKBiPA26674.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2150. Eukaryota.
COG5665. LUCA.
GeneTreeiENSGT00390000014743.
HOGENOMiHOG000184850.
HOVERGENiHBG051042.
InParanoidiO75175.
KOiK12580.
OMAiRRKWHIN.
OrthoDBiEOG091G040M.
PhylomeDBiO75175.
TreeFamiTF321963.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000088038-MONOMER.
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.
SIGNORiO75175.

Miscellaneous databases

GeneWikiiCNOT3.
GenomeRNAii4849.
PROiO75175.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000088038.
CleanExiHS_CNOT3.
ExpressionAtlasiO75175. baseline and differential.
GenevisibleiO75175. HS.

Family and domain databases

InterProiIPR012270. CCR4-NOT_su3/5.
IPR007282. NOT.
IPR007207. Not_N.
[Graphical view]
PfamiPF04153. NOT2_3_5. 1 hit.
PF04065. Not3. 1 hit.
[Graphical view]
PIRSFiPIRSF005290. NOT_su_3_5. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCNOT3_HUMAN
AccessioniPrimary (citable) accession number: O75175
Secondary accession number(s): Q9NZN7, Q9UF76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: November 1, 1998
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 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.