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P22893

- TTP_MOUSE

UniProt

P22893 - TTP_MOUSE

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Protein

Tristetraprolin

Gene

Zfp36

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri95 – 12329C3H1-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri133 – 16129C3H1-type 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. 14-3-3 protein binding Source: UniProtKB
  2. AU-rich element binding Source: UniProtKB
  3. DNA binding Source: UniProtKB-KW
  4. metal ion binding Source: UniProtKB-KW
  5. mRNA 3'-UTR AU-rich region binding Source: MGI
  6. mRNA binding Source: MGI

GO - Biological processi

  1. 3'-UTR-mediated mRNA stabilization Source: UniProtKB
  2. intracellular signal transduction Source: MGI
  3. mRNA catabolic process Source: UniProtKB
  4. negative regulation of inflammatory response Source: UniProtKB
  5. negative regulation of myeloid cell differentiation Source: MGI
  6. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  7. negative regulation of translation involved in gene silencing by miRNA Source: UniProtKB
  8. nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: MGI
  9. nuclear-transcribed mRNA poly(A) tail shortening Source: MGI
  10. positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay Source: UniProtKB
  11. positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Source: UniProtKB
  12. regulation of mRNA stability Source: MGI
  13. regulation of transcription from RNA polymerase II promoter Source: MGI
  14. regulation of tumor necrosis factor production Source: UniProtKB
  15. response to starvation Source: UniProtKB
  16. RNA destabilization Source: MGI
Complete GO annotation...

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_198689. Tristetraprolin (TTP) destabilizes mRNA.

Names & Taxonomyi

Protein namesi
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 namesi
Name:Zfp36
Synonyms:Tis11, Tis11a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:99180. Zfp36.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication
Note: Localizes to stress granules upon energy starvation. phosphorylation by MAPKAPK2 promotes exclusion from stress granules By similarity.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoplasmic stress granule Source: UniProtKB
  3. cytosol Source: MGI
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 319319TristetraprolinPRO_0000089164Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei52 – 521Phosphoserine; by MAPKAPK21 Publication
Modified residuei58 – 581PhosphoserineBy similarity
Modified residuei80 – 801Phosphoserine1 Publication
Modified residuei82 – 821Phosphoserine1 Publication
Modified residuei84 – 841PhosphothreonineBy similarity
Modified residuei85 – 851Phosphoserine1 Publication
Modified residuei178 – 1781Phosphoserine; by MAPKAPK21 Publication
Modified residuei189 – 1891PhosphoserineBy similarity
Modified residuei210 – 2101PhosphoserineBy similarity
Modified residuei220 – 2201Phosphoserine; by MAPK; in vitro1 Publication
Modified residuei250 – 2501Phosphothreonine1 Publication
Modified residuei269 – 2691PhosphoserineBy similarity
Modified residuei289 – 2891PhosphoserineBy similarity
Modified residuei316 – 3161Phosphoserine1 Publication

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiP22893.

PTM databases

PhosphoSiteiP22893.

Expressioni

Tissue specificityi

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

Inductioni

By growth factors and by extracellular signaling agents.

Gene expression databases

BgeeiP22893.
CleanExiMM_ZFP36.
ExpressionAtlasiP22893. baseline and differential.
GenevestigatoriP22893.

Interactioni

Subunit structurei

Interacts with CNOT1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CNOT1A5YKK65EBI-647803,EBI-1222758From a different organism.
CNOT7Q9UIV13EBI-647803,EBI-2105113From a different organism.
YWHABP319465EBI-647803,EBI-359815From a different organism.

Protein-protein interaction databases

BioGridi204658. 3 interactions.
IntActiP22893. 34 interactions.
MINTiMINT-225240.

Structurei

Secondary structure

1
319
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi103 – 1064
Turni111 – 1155
Beta strandi120 – 1223
Helixi125 – 1273

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M9ONMR-A91-163[»]
ProteinModelPortaliP22893.
SMRiP22893. Positions 91-162.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22893.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati63 – 675P-P-P-P-G
Repeati190 – 1945P-P-P-P-G
Repeati211 – 2155P-P-P-P-G

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni305 – 31915Interaction with CNOT1By similarityAdd
BLAST

Sequence similaritiesi

Contains 2 C3H1-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri95 – 12329C3H1-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri133 – 16129C3H1-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5063.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP22893.
KOiK15308.
OMAiNRISVSE.
OrthoDBiEOG76QFJP.
PhylomeDBiP22893.
TreeFamiTF315463.

Family and domain databases

Gene3Di4.10.1000.10. 2 hits.
InterProiIPR000571. Znf_CCCH.
[Graphical view]
PfamiPF00642. zf-CCCH. 2 hits.
[Graphical view]
SMARTiSM00356. ZnF_C3H1. 2 hits.
[Graphical view]
PROSITEiPS50103. ZF_C3H1. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P22893-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDLSAIYESL QSMSHDLSSD HGGTESLGGL WNINSDSIPS GVTSRLTGRS
60 70 80 90 100
TSLVEGRSCG WVPPPPGFAP LAPRPGPELS PSPTSPTATP TTSSRYKTEL
110 120 130 140 150
CRTYSESGRC RYGAKCQFAH GLGELRQANR HPKYKTELCH KFYLQGRCPY
160 170 180 190 200
GSRCHFIHNP TEDLALPGQP HVLRQSISFS GLPSGRRSSP PPPGFSGPSL
210 220 230 240 250
SSCSFSPSSS PPPPGDLPLS PSAFSAAPGT PVTRRDPNQA CCPSCRRSTT
260 270 280 290 300
PSTIWGPLGG LARSPSAHSL GSDPDDYASS GSSLGGSDSP VFEAGVFGPP
310
QTPAPPRRLP IFNRISVSE
Length:319
Mass (Da):33,613
Last modified:August 1, 1991 - v1
Checksum:i860DD6DDA80386F8
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS21041.1.
PIRiA36600.
S04743.
RefSeqiNP_035886.1. NM_011756.4.
UniGeneiMm.389856.

Genome annotation databases

EnsembliENSMUST00000051241; ENSMUSP00000057815; ENSMUSG00000044786.
GeneIDi22695.
KEGGimmu:22695.
UCSCiuc009fys.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS21041.1.
PIRi A36600.
S04743.
RefSeqi NP_035886.1. NM_011756.4.
UniGenei Mm.389856.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1M9O NMR - A 91-163 [» ]
ProteinModelPortali P22893.
SMRi P22893. Positions 91-162.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204658. 3 interactions.
IntActi P22893. 34 interactions.
MINTi MINT-225240.

PTM databases

PhosphoSitei P22893.

Proteomic databases

PRIDEi P22893.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000051241 ; ENSMUSP00000057815 ; ENSMUSG00000044786 .
GeneIDi 22695.
KEGGi mmu:22695.
UCSCi uc009fys.1. mouse.

Organism-specific databases

CTDi 7538.
MGIi MGI:99180. Zfp36.

Phylogenomic databases

eggNOGi COG5063.
HOGENOMi HOG000233479.
HOVERGENi HBG008483.
InParanoidi P22893.
KOi K15308.
OMAi NRISVSE.
OrthoDBi EOG76QFJP.
PhylomeDBi P22893.
TreeFami TF315463.

Enzyme and pathway databases

Reactomei REACT_198689. Tristetraprolin (TTP) destabilizes mRNA.

Miscellaneous databases

EvolutionaryTracei P22893.
NextBioi 303151.
PROi P22893.
SOURCEi Search...

Gene expression databases

Bgeei P22893.
CleanExi MM_ZFP36.
ExpressionAtlasi P22893. baseline and differential.
Genevestigatori P22893.

Family and domain databases

Gene3Di 4.10.1000.10. 2 hits.
InterProi IPR000571. Znf_CCCH.
[Graphical view ]
Pfami PF00642. zf-CCCH. 2 hits.
[Graphical view ]
SMARTi SM00356. ZnF_C3H1. 2 hits.
[Graphical view ]
PROSITEi PS50103. ZF_C3H1. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiTTP_MOUSE
AccessioniPrimary (citable) accession number: P22893
Secondary accession number(s): P11520
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: October 29, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3