Q9NZN8 (CNOT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 108.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: CCR4-NOT transcription complex subunit 2 Alternative name(s): CCR4-associated factor 2 | ||||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||||
| Taxonomic identifier | 9606 [NCBI] | ||||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 540 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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. Ref.8 Ref.9 Ref.16 Ref.18 |
| Subunit structure | 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. Ref.1 Ref.9 Ref.12 Ref.16 |
| Subcellular location | |
| Tissue specificity | Ubiquitous. Highly expressed in brain, heart, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood leukocytes. Ref.1 |
| Developmental stage | Expressed in embryonic stem (ES) cells. Ref.18 |
| Sequence similarities | Belongs to the CNOT2/3/5 family. |
| Sequence caution | The sequence AAF29095.1 differs from that shown. Reason: Frameshift at position 474. The sequence AAQ13426.1 differs from that shown. Reason: Frameshift at positions 71, 76, 84, 98, 123, 370, 384 and 393. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| TNRC6C | Q9HCJ0 | 3 | EBI-743033,EBI-6507625 |
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9NZN8-1) 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: Q9NZN8-2) The sequence of this isoform differs from the canonical sequence as follows: 1-175: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: Q9NZN8-3) 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. | ||||||
| Isoform 4 (identifier: Q9NZN8-4) 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. | ||||||
| Isoform 5 (identifier: Q9NZN8-5) The sequence of this isoform differs from the canonical sequence as follows: 229-278: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 540 | 540 | CCR4-NOT transcription complex subunit 2 | PRO_0000198331 | |||||
Regions | |||||||||
| Region | 437 – 540 | 104 | Repressor domain | ||||||
Amino acid modifications | |||||||||
| Modified residue | 93 | 1 | Phosphothreonine Ref.11 | ||||||
| Modified residue | 126 | 1 | Phosphoserine Ref.11 Ref.13 | ||||||
| Modified residue | 165 | 1 | Phosphoserine Ref.10 Ref.11 Ref.14 Ref.17 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 349 | 349 | Missing in isoform 3. | VSP_009913 | |||||
| Alternative sequence | 1 – 175 | 175 | Missing in isoform 2. | VSP_009912 | |||||
| Alternative sequence | 229 – 278 | 50 | Missing in isoform 5. | VSP_009914 | |||||
| Alternative sequence | 465 – 475 | 11 | FNRDWRYHKEE → YVQSILITFVL in isoform 4. | VSP_009915 | |||||
| Alternative sequence | 476 – 540 | 65 | Missing in isoform 4. | VSP_009916 | |||||
| Natural variant | 460 | 1 | A → T. Corresponds to variant rs11178192 [ dbSNP | Ensembl ]. | VAR_048750 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits." Albert T.K., Lemaire M., van Berkum N.L., Gentz R., Collart M.A., Timmers H.T.M. Nucleic Acids Res. 28:809-817(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH CNOT1, TISSUE SPECIFICITY. |
| [2] | Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y., Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y., Liu L.S., Ding J.F. Hui R.T.Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Heart. |
| [3] | "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. Chen Z.Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Umbilical cord blood. |
| [4] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). |
| [5] | "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] (ISOFORMS 3 AND 4). Tissue: Fetal kidney and Testis. |
| [6] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph and Skin. |
| [7] | "Separation and molecular cloning of a novel human cDNA fragment coding a protein without homologs." Bi A., Yu L., Zhang M., Fan Y., Zhang Q., Zhao Y., Gao J., Zhao S. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-377. |
| [8] | "Repression of promoter activity by CNOT2, a subunit of the transcription regulatory Ccr4-not complex." Zwartjes C.G., Jayne S., van den Berg D.L., Timmers H.T. J. Biol. Chem. 279:10848-10854(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN. |
| [9] | "Involvement of the SMRT/NCoR-HDAC3 complex in transcriptional repression by the CNOT2 subunit of the human Ccr4-Not complex." Jayne S., Zwartjes C.G., van Schaik F.M., Timmers H.T. Biochem. J. 398:461-467(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NCOR1; NCOR2; HDAC3 AND GPS2. |
| [10] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-93; SER-126 AND SER-165, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [12] | "Human Ccr4-Not complexes contain variable deadenylase subunits." Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W., Heck A.J., Timmers H.T. Biochem. J. 422:443-453(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE CCR4-NOT COMPLEX, COMPOSITION OF THE CCR4-NOT COMPLEX. |
| [13] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [14] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [15] | "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]. |
| [16] | "CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death." Ito K., Inoue T., Yokoyama K., Morita M., Suzuki T., Yamamoto T. Genes Cells 16:368-379(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CNOT3, SUBCELLULAR LOCATION. |
| [17] | "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, MASS SPECTROMETRY. |
| [18] | "Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit extraembryonic differentiation." Zheng X., Dumitru R., Lackford B.L., Freudenberg J.M., Singh A.P., Archer T.K., Jothi R., Hu G. Stem Cells 30:910-922(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. |
| IPI | IPI00005011. IPI00017733. IPI00410621. IPI00410622. IPI00410623. |
| PIR | T46494. |
| RefSeq | NP_001186231.1. NM_001199302.1. NP_001186232.1. NM_001199303.1. NP_055330.1. NM_014515.5. |
| UniGene | Hs.133350. Hs.730666. |
3D structure databases | |
| ProteinModelPortal | Q9NZN8. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-42656N. |
| IntAct | Q9NZN8. 13 interactions. |
| MINT | MINT-1438957. |
| STRING | 9606.ENSP00000229195. |
PTM databases | |
| PhosphoSite | Q9NZN8. |
Polymorphism databases | |
| DMDM | 46396017. |
Proteomic databases | |
| PaxDb | Q9NZN8. |
| PRIDE | Q9NZN8. |
Protocols and materials databases | |
| DNASU | 4848. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000229195; ENSP00000229195; ENSG00000111596. ENST00000418359; ENSP00000412091; ENSG00000111596. ENST00000551043; ENSP00000449260; ENSG00000111596. ENST00000551483; ENSP00000448883; ENSG00000111596. |
| GeneID | 4848. |
| KEGG | hsa:4848. |
| UCSC | uc001svv.3. human. uc001svw.1. human. |
Organism-specific databases | |
| CTD | 4848. |
| GeneCards | GC12P070636. |
| HGNC | HGNC:7878. CNOT2. |
| MIM | 604909. gene. |
| neXtProt | NX_Q9NZN8. |
| PharmGKB | PA26673. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | COG5601. |
| HOGENOM | HOG000246523. |
| HOVERGEN | HBG051041. |
| InParanoid | Q9NZN8. |
| KO | K12605. |
| OMA | TQDFSIH. |
| OrthoDB | EOG44MXRV. |
| PhylomeDB | Q9NZN8. |
Enzyme and pathway databases | |
| Reactome | REACT_21257. Metabolism of RNA. REACT_71. Gene Expression. |
Gene expression databases | |
| ArrayExpress | Q9NZN8. |
| Bgee | Q9NZN8. |
| CleanEx | HS_CNOT2. |
| Genevestigator | Q9NZN8. |
| GermOnline | ENSG00000111596. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR007282. NOT. [Graphical view] |
| Pfam | PF04153. NOT2_3_5. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChiTaRS | CNOT2. human. |
| GenomeRNAi | 4848. |
| NextBio | 18670. |
| SOURCE | Search... |
Entry information
| Entry name | CNOT2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9NZN8 Secondary accession number(s): Q9H3E0 Q9P028 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 12 Human chromosome 12: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
