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P26651 (TTP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tristetraprolin

Short name=TTP
Alternative name(s):
G0/G1 switch regulatory protein 24
Growth factor-inducible nuclear protein NUP475
Protein TIS11A
Short name=TIS11
Zinc finger protein 36 homolog
Short name=Zfp-36
Gene names
Name:ZFP36
Synonyms:G0S24, RNF162A, TIS11A, TTP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length326 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). Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF). Ref.5 Ref.10

Subunit structure

Interacts (via C-terminus) with CNOT1. Ref.10

Subcellular location

Nucleus. Cytoplasm. Note: Localizes to stress granules upon energy starvation. phosphorylation by MAPKAPK2 promotes exclusion from stress granules. Ref.5

Induction

By stimulation with various mitogens.

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.5 Ref.6

Sequence similarities

Contains 2 C3H1-type zinc fingers.

Ontologies

Keywords
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   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 direct assay Ref.5. Source: UniProtKB

RNA metabolic process

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

mRNA catabolic process

Inferred from direct assay PubMed 10330172. Source: UniProtKB

mRNA metabolic process

Traceable author statement. Source: Reactome

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 sequence or structural similarity. Source: UniProtKB

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Inferred from direct assay Ref.10. Source: UniProtKB

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

Inferred from sequence or structural similarity. Source: UniProtKB

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

Inferred from direct assay PubMed 10330172. Source: UniProtKB

regulation of tumor necrosis factor production

Inferred from direct assay Ref.5. Source: UniProtKB

response to starvation

Inferred from direct assay Ref.5. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10330172PubMed 21784977. Source: UniProtKB

cytoplasmic stress granule

Inferred from direct assay Ref.5. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 10751406. Source: MGI

nucleus

Inferred from direct assay PubMed 10330172. Source: UniProtKB

   Molecular_function14-3-3 protein binding

Inferred from direct assay Ref.5. Source: UniProtKB

AU-rich element binding

Inferred from direct assay PubMed 10330172Ref.5. Source: UniProtKB

C-C chemokine binding

Inferred from physical interaction PubMed 21784977. Source: UniProtKB

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA binding

Inferred from direct assay PubMed 11782475. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 21784977. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.5. Source: UniProtKB

single-stranded RNA binding

Traceable author statement PubMed 9703499. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DCP1AQ9NPI62EBI-374248,EBI-374238
EDC3Q96F862EBI-374248,EBI-997311

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 326326Tristetraprolin
PRO_0000089163

Regions

Repeat71 – 755P-P-P-P-G
Repeat198 – 2025P-P-P-P-G
Repeat219 – 2235P-P-P-P-G
Zinc finger103 – 13129C3H1-type 1
Zinc finger141 – 16929C3H1-type 2
Region312 – 32615Interaction with CNOT1

Amino acid modifications

Modified residue601Phosphoserine; by MAPKAPK2 Ref.5
Modified residue661Phosphoserine Ref.6
Modified residue881Phosphoserine Ref.6
Modified residue901Phosphoserine By similarity
Modified residue921Phosphothreonine Ref.6
Modified residue931Phosphoserine By similarity
Modified residue1691Phosphoserine Ref.6
Modified residue1861Phosphoserine; by MAPKAPK2 Ref.5 Ref.6 Ref.7
Modified residue1971Phosphoserine Ref.6
Modified residue2181Phosphoserine Ref.6
Modified residue2281Phosphoserine Ref.6
Modified residue2761Phosphoserine Ref.6
Modified residue2961Phosphoserine Ref.6
Modified residue3231Phosphoserine By similarity

Natural variations

Natural variant371P → S. Ref.3
Corresponds to variant rs17878633 [ dbSNP | Ensembl ].
VAR_021064
Natural variant551P → S.
Corresponds to variant rs2229272 [ dbSNP | Ensembl ].
VAR_052324
Natural variant2591I → F. Ref.3
Corresponds to variant rs17886974 [ dbSNP | Ensembl ].
VAR_021065
Natural variant3241V → F. Ref.3
Corresponds to variant rs17884899 [ dbSNP | Ensembl ].
VAR_021066

Experimental info

Mutagenesis601S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-186. Ref.5
Mutagenesis1861S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-60. Ref.5
Mutagenesis3151R → A: Abolishes interaction with CNOT1. Ref.10
Mutagenesis3191F → A: Abolishes interaction with CNOT1 and impairs TNF mRNA deadenylation. Ref.10

Secondary structure

... 326
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P26651 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: DDD9AD950AF7AF98

FASTA32634,003
        10         20         30         40         50         60 
MDLTAIYESL LSLSPDVPVP SDHGGTESSP GWGSSGPWSL SPSDSSPSGV TSRLPGRSTS 

        70         80         90        100        110        120 
LVEGRSCGWV PPPPGFAPLA PRLGPELSPS PTSPTATSTT PSRYKTELCR TFSESGRCRY 

       130        140        150        160        170        180 
GAKCQFAHGL GELRQANRHP KYKTELCHKF YLQGRCPYGS RCHFIHNPSE DLAAPGHPPV 

       190        200        210        220        230        240 
LRQSISFSGL PSGRRTSPPP PGLAGPSLSS SSFSPSSSPP PPGDLPLSPS AFSAAPGTPL 

       250        260        270        280        290        300 
ARRDPTPVCC PSCRRATPIS VWGPLGGLVR TPSVQSLGSD PDEYASSGSS LGGSDSPVFE 

       310        320 
AGVFAPPQPV AAPRRLPIFN RISVSE 

« Hide

References

« Hide 'large scale' references
[1]"The human TTP protein: sequence, alignment with related proteins, and chromosomal localization of the mouse and human genes."
Taylor G.A., Lai W.S., Oakey R.J., Seldin M.F., Shows T.B., Eddy R.L. Jr., Blackshear P.J.
Nucleic Acids Res. 19:3454-3454(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"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. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[3]NIEHS SNPs program
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-37; PHE-259 AND PHE-324.
[4]"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].
Tissue: Pancreas.
[5]"MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay."
Stoecklin G., Stubbs T., Kedersha N., Wax S., Rigby W.F., Blackwell T.K., Anderson P.
EMBO J. 23:1313-1324(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-60 AND SER-186 BY MAPKAPK2, SUBCELLULAR LOCATION, RNA-BINDING, FUNCTION, MUTAGENESIS OF SER-60 AND SER-186.
[6]"Identification of the anti-inflammatory protein tristetraprolin as a hyperphosphorylated protein by mass spectrometry and site-directed mutagenesis."
Cao H., Deterding L.J., Venable J.D., Kennington E.A., Yates J.R. III, Tomer K.B., Blackshear P.J.
Biochem. J. 394:285-297(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-66; SER-88; THR-92; SER-169; SER-186; SER-197; SER-218; SER-228; SER-276 AND SER-296.
[7]"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 SER-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin."
Fabian M.R., Frank F., Rouya C., Siddiqui N., Lai W.S., Karetnikov A., Blackshear P.J., Nagar B., Sonenberg N.
Nat. Struct. Mol. Biol. 20:735-739(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 312-326 IN COMPLEX WITH CNOT1, INTERACTION WITH CNOT1, FUNCTION, MUTAGENESIS OF ARG-315 AND PHE-319.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M92843 mRNA. Translation: AAA58489.1.
M92844 Genomic DNA. Translation: AAC37600.1.
M63625 mRNA. Translation: AAA61240.1.
AK314042 mRNA. Translation: BAG36751.1.
AY771351 Genomic DNA. Translation: AAV28731.1.
BC009693 mRNA. Translation: AAH09693.1.
PIRS34427.
RefSeqNP_003398.2. NM_003407.3.
UniGeneHs.534052.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4J8SX-ray1.55B312-326[»]
ProteinModelPortalP26651.
SMRP26651. Positions 99-170.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113370. 28 interactions.
DIPDIP-29845N.
IntActP26651. 20 interactions.
MINTMINT-1171915.
STRING9606.ENSP00000248673.

PTM databases

PhosphoSiteP26651.

Polymorphism databases

DMDM136471.

Proteomic databases

PaxDbP26651.
PRIDEP26651.

Protocols and materials databases

DNASU7538.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000248673; ENSP00000248673; ENSG00000128016.
GeneID7538.
KEGGhsa:7538.
UCSCuc002olh.2. human.

Organism-specific databases

CTD7538.
GeneCardsGC19P039897.
HGNCHGNC:12862. ZFP36.
HPAHPA006009.
MIM190700. gene.
neXtProtNX_P26651.
PharmGKBPA37451.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5063.
HOGENOMHOG000233479.
HOVERGENHBG008483.
InParanoidP26651.
KOK15308.
OrthoDBEOG76QFJP.
PhylomeDBP26651.
TreeFamTF315463.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.
SignaLinkP26651.

Gene expression databases

ArrayExpressP26651.
BgeeP26651.
CleanExHS_ZFP36.
GenevestigatorP26651.

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

ChiTaRSZFP36. human.
GeneWikiZFP36.
GenomeRNAi7538.
NextBio29497.
PROP26651.
SOURCESearch...

Entry information

Entry nameTTP_HUMAN
AccessionPrimary (citable) accession number: P26651
Secondary accession number(s): B2RA54
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: June 11, 2014
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM