Tristetraprolin - Mus musculus (Mouse)

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P22893 (TTP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 131. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	319 AA.
Sequence status	Complete.
Protein existence	Evidence 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.9 Ref.10
Subunit structure	Interacts with CNOT1. Ref.10
Subcellular location	Nucleus. Cytoplasm Probable. Note: Localizes to stress granules upon energy starvation. phosphorylation by MAPKAPK2 promotes exclusion from stress granules By similarity.
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.9
Sequence similarities	Contains 2 C3H1-type zinc fingers.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	3'-UTR-mediated mRNA stabilization Inferred from sequence or structural similarity. Source: UniProtKB RNA destabilization Inferred from mutant phenotype PubMed 11588035. Source: MGI intracellular protein kinase cascade Inferred from direct assay Ref.8. Source: MGI 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.10. Source: UniProtKB 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.10. Source: UniProtKB positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Inferred from direct assay Ref.10. Source: UniProtKB regulation of tumor necrosis factor production Inferred from sequence or structural similarity. Source: UniProtKB response to stress Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	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_function	14-3-3 protein binding Inferred from sequence or structural similarity. 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 zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CNOT1	A5YKK6	5	EBI-647803,EBI-1222758	From a different organism.
CNOT7	Q9UIV1	3	EBI-647803,EBI-2105113	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 319

319

Tristetraprolin

PRO_0000089164

Regions

Repeat

63 – 67

P-P-P-P-G

Repeat

190 – 194

P-P-P-P-G

Repeat

211 – 215

P-P-P-P-G

Zinc finger

95 – 123

C3H1-type 1

Zinc finger

133 – 161

C3H1-type 2

Amino acid modifications

Modified residue

Phosphoserine; by MAPKAPK2 Ref.9

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine Ref.9

Modified residue

Phosphoserine Ref.9

Modified residue

Phosphothreonine By similarity

Modified residue

Phosphoserine Ref.9

Modified residue

178

Phosphoserine; by MAPKAPK2 Ref.9

Modified residue

189

Phosphoserine By similarity

Modified residue

210

Phosphoserine By similarity

Modified residue

220

Phosphoserine; by MAPK; in vitro Ref.8

Modified residue

250

Phosphothreonine

Modified residue

269

Phosphoserine By similarity

Modified residue

289

Phosphoserine By similarity

Modified residue

316

Phosphoserine Ref.9

Secondary structure

319

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P22893 [UniParc].

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

FASTA

319

33,613

        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' referencesShow '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]	"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-249 AND SER-316, MASS SPECTROMETRY.
[10]	"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.
+	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.

IPI

IPI00132695.

PIR

A36600.
S04743.

RefSeq

NP_035886.1. NM_011756.4.

UniGene

Mm.389856.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M9O	NMR	-	A	91-163	[»]

ProteinModelPortal

P22893.

SMR

P22893. Positions 91-162.

ModBase

Search...

Protein-protein interaction databases

IntAct

P22893. 34 interactions.

MINT

MINT-225240.

PTM databases

PhosphoSite

P22893.

Proteomic databases

PRIDE

P22893.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000051241; ENSMUSP00000057815; ENSMUSG00000044786.

GeneID

22695.

KEGG

mmu:22695.

UCSC

uc009fys.1. mouse.

Organism-specific databases

CTD

7538.

MGI

MGI:99180. Zfp36.

Phylogenomic databases

eggNOG

COG5063.

HOGENOM

HOG000233479.

HOVERGEN

HBG008483.

InParanoid

P22893.

K15308.

OMA

RRLPIFN.

OrthoDB

EOG4S4PH4.

Gene expression databases

ArrayExpress

P22893.

Bgee

P22893.

CleanEx

MM_ZFP36.

Genevestigator

P22893.

GermOnline

ENSMUSG00000044786. Mus musculus.

Family and domain databases

Gene3D

4.10.1000.10. 2 hits.

InterPro

IPR000571. Znf_CCCH.
[Graphical view]

Pfam

PF00642. zf-CCCH. 2 hits.
[Graphical view]

SMART

SM00356. ZnF_C3H1. 2 hits.
[Graphical view]

PROSITE

PS50103. ZF_C3H1. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P22893.

NextBio

303151.

SOURCE

Search...

Entry information

Entry name

TTP_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents