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P22893 (TTP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tristetraprolin

Short name=TTP
Alternative name(s):
Growth factor-inducible nuclear protein NUP475
Protein TIS11A
Short name=TIS11
TPA-induced sequence 11
Zinc finger protein 36
Short name=Zfp-36
Gene names
Name:Zfp36
Synonyms:Tis11, Tis11a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length319 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

mRNA-binding protein involved in post-transcriptional regulation of AU-rich element (ARE)-containing mRNAs. Acts by specifically binding ARE-containing mRNAs and promoting their degradation. Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1. Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF). Ref.10 Ref.12

Subunit structure

Interacts with CNOT1. Ref.12

Subcellular location

Nucleus. Cytoplasm. Note: Localizes to stress granules upon energy starvation. phosphorylation by MAPKAPK2 promotes exclusion from stress granules By similarity. Ref.9

Tissue specificity

Especially abundant in intestine, thymus and regenerating liver, and in macrophage cell line stimulated by gamma-interferon.

Induction

By growth factors and by extracellular signaling agents.

Post-translational modification

Phosphorylation by MAPKAPK2 increases its stability and binding to 14-3-3 proteins, leading to reduce its ARE affinity leading to inhibition of degradation of ARE-containing transcripts. Phosphorylated upon mitogen stimulation. Ref.8 Ref.10

Sequence similarities

Contains 2 C3H1-type zinc fingers.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_process3'-UTR-mediated mRNA stabilization

Inferred from sequence or structural similarity. Source: UniProtKB

RNA destabilization

Inferred from mutant phenotype PubMed 11588035. Source: MGI

intracellular signal transduction

Inferred from direct assay Ref.8. Source: MGI

mRNA catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of inflammatory response

Inferred from mutant phenotype PubMed 21784977. Source: UniProtKB

negative regulation of myeloid cell differentiation

Inferred from mutant phenotype PubMed 11588035. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 21784977. Source: UniProtKB

negative regulation of translation involved in gene silencing by miRNA

Inferred from direct assay Ref.12. Source: UniProtKB

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Inferred from direct assay PubMed 15814898. Source: MGI

nuclear-transcribed mRNA poly(A) tail shortening

Inferred from direct assay PubMed 15814898. Source: MGI

positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of nuclear-transcribed mRNA poly(A) tail shortening

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of mRNA stability

Inferred from direct assay PubMed 15467755. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction PubMed 20410487. Source: MGI

regulation of tumor necrosis factor production

Inferred from sequence or structural similarity. Source: UniProtKB

response to starvation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic stress granule

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 10751406. Source: MGI

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_function14-3-3 protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

AU-rich element binding

Inferred from direct assay PubMed 10330172. Source: UniProtKB

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA 3'-UTR AU-rich region binding

Inferred from direct assay PubMed 20410487. Source: MGI

mRNA binding

Inferred from direct assay PubMed 10751406. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CNOT1A5YKK65EBI-647803,EBI-1222758From a different organism.
CNOT7Q9UIV13EBI-647803,EBI-2105113From a different organism.
YWHABP319465EBI-647803,EBI-359815From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 319319Tristetraprolin
PRO_0000089164

Regions

Repeat63 – 675P-P-P-P-G
Repeat190 – 1945P-P-P-P-G
Repeat211 – 2155P-P-P-P-G
Zinc finger95 – 12329C3H1-type 1
Zinc finger133 – 16129C3H1-type 2
Region305 – 31915Interaction with CNOT1 By similarity

Amino acid modifications

Modified residue521Phosphoserine; by MAPKAPK2 Ref.10
Modified residue581Phosphoserine By similarity
Modified residue801Phosphoserine Ref.10
Modified residue821Phosphoserine Ref.10
Modified residue841Phosphothreonine By similarity
Modified residue851Phosphoserine Ref.10
Modified residue1781Phosphoserine; by MAPKAPK2 Ref.10
Modified residue1891Phosphoserine By similarity
Modified residue2101Phosphoserine By similarity
Modified residue2201Phosphoserine; by MAPK; in vitro Ref.8
Modified residue2501Phosphothreonine Ref.10
Modified residue2691Phosphoserine By similarity
Modified residue2891Phosphoserine By similarity
Modified residue3161Phosphoserine Ref.10

Secondary structure

......... 319
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22893 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 860DD6DDA80386F8

FASTA31933,613
        10         20         30         40         50         60 
MDLSAIYESL QSMSHDLSSD HGGTESLGGL WNINSDSIPS GVTSRLTGRS TSLVEGRSCG 

        70         80         90        100        110        120 
WVPPPPGFAP LAPRPGPELS PSPTSPTATP TTSSRYKTEL CRTYSESGRC RYGAKCQFAH 

       130        140        150        160        170        180 
GLGELRQANR HPKYKTELCH KFYLQGRCPY GSRCHFIHNP TEDLALPGQP HVLRQSISFS 

       190        200        210        220        230        240 
GLPSGRRSSP PPPGFSGPSL SSCSFSPSSS PPPPGDLPLS PSAFSAAPGT PVTRRDPNQA 

       250        260        270        280        290        300 
CCPSCRRSTT PSTIWGPLGG LARSPSAHSL GSDPDDYASS GSSLGGSDSP VFEAGVFGPP 

       310 
QTPAPPRRLP IFNRISVSE 

« Hide

References

« Hide 'large scale' references
[1]"Rapid insulin-stimulated accumulation of an mRNA encoding a proline-rich protein."
Lai W.S., Stumpo D.J., Blackshear P.J.
J. Biol. Chem. 265:16556-16563(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"A growth factor-inducible nuclear protein with a novel cysteine/histidine repetitive sequence."
Dubois R.N., McLane M.W., Ryder K., Lau L.F., Nathans D.
J. Biol. Chem. 265:19185-19191(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Nucleotide sequence of a cDNA encoding TIS11, a message induced in Swiss 3T3 cells by the tumor promoter tetradecanoyl phorbol acetate."
Varnum B.C., Lim R.W., Sukhatme V.P., Herschman H.R.
Oncogene 4:119-120(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Swiss.
[4]"A corrected sequence for the predicted protein from the mitogen-inducible TIS11 primary response gene."
Ma Q., Herschman H.R.
Oncogene 6:1277-1278(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[5]"The TIS11 primary response gene is a member of a gene family that encodes proteins with a highly conserved sequence containing an unusual Cys-His repeat."
Varnum B.C., Ma Q., Chi T., Fletcher B.S., Herschman H.R.
Mol. Cell. Biol. 11:1754-1758(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[6]"Promoter analysis of Zfp-36, the mitogen-inducible gene encoding the zinc finger protein tristetraprolin."
Lai W.S., Thompson M.J., Taylor G.A., Liu Y., Blackshear P.J.
J. Biol. Chem. 270:25266-25272(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: BALB/c.
Tissue: Liver.
[7]"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].
Strain: FVB/N.
Tissue: Liver.
[8]"Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by mitogen-activated protein kinase in vitro."
Taylor G.A., Thompson M.J., Lai W.S., Blackshear P.J.
J. Biol. Chem. 270:13341-13347(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-220.
[9]"Members of the tristetraprolin family of tandem CCCH zinc finger proteins exhibit CRM1-dependent nucleocytoplasmic shuttling."
Phillips R.S., Ramos S.B., Blackshear P.J.
J. Biol. Chem. 277:11606-11613(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding."
Chrestensen C.A., Schroeder M.J., Shabanowitz J., Hunt D.F., Pelo J.W., Worthington M.T., Sturgill T.W.
J. Biol. Chem. 279:10176-10184(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING, PHOSPHORYLATION AT SER-52; SER-80; SER-82; SER-85; SER-178; THR-250 AND SER-316, IDENTIFICATION BY MASS SPECTROMETRY.
[11]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Not1 mediates recruitment of the deadenylase Caf1 to mRNAs targeted for degradation by tristetraprolin."
Sandler H., Kreth J., Timmers H.T., Stoecklin G.
Nucleic Acids Res. 39:4373-4386(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CNOT1.
[13]"A Cys3His zinc-binding domain from Nup475/tristetraprolin: a novel fold with a disklike structure."
Amann B.T., Worthington M.T., Berg J.M.
Biochemistry 42:217-221(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 91-163 IN COMPLEX WITH ZINC.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57422 mRNA. Translation: AAA40498.1.
M58691 mRNA. Translation: AAA39837.1.
X14678 mRNA. Translation: CAA32807.1. Sequence problems.
M58565 mRNA. Translation: AAA72947.1.
L42317 Genomic DNA. Translation: AAC37676.1.
BC021391 mRNA. Translation: AAH21391.1.
PIRA36600.
S04743.
RefSeqNP_035886.1. NM_011756.4.
UniGeneMm.389856.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M9ONMR-A91-163[»]
ProteinModelPortalP22893.
SMRP22893. Positions 91-162.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204658. 3 interactions.
IntActP22893. 34 interactions.
MINTMINT-225240.

PTM databases

PhosphoSiteP22893.

Proteomic databases

PRIDEP22893.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000051241; ENSMUSP00000057815; ENSMUSG00000044786.
GeneID22695.
KEGGmmu:22695.
UCSCuc009fys.1. mouse.

Organism-specific databases

CTD7538.
MGIMGI:99180. Zfp36.

Phylogenomic databases

eggNOGCOG5063.
HOGENOMHOG000233479.
HOVERGENHBG008483.
InParanoidP22893.
KOK15308.
OMARRLPIFN.
OrthoDBEOG76QFJP.
PhylomeDBP22893.
TreeFamTF315463.

Gene expression databases

ArrayExpressP22893.
BgeeP22893.
CleanExMM_ZFP36.
GenevestigatorP22893.

Family and domain databases

Gene3D4.10.1000.10. 2 hits.
InterProIPR000571. Znf_CCCH.
[Graphical view]
PfamPF00642. zf-CCCH. 2 hits.
[Graphical view]
SMARTSM00356. ZnF_C3H1. 2 hits.
[Graphical view]
PROSITEPS50103. ZF_C3H1. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22893.
NextBio303151.
PROP22893.
SOURCESearch...

Entry information

Entry nameTTP_MOUSE
AccessionPrimary (citable) accession number: P22893
Secondary accession number(s): P11520
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot