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P26651

- TTP_HUMAN

UniProt

P26651 - TTP_HUMAN

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Protein

Tristetraprolin

Gene

ZFP36

Organism
Homo sapiens (Human)
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). Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF).2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri103 – 13129C3H1-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri141 – 16929C3H1-type 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. 14-3-3 protein binding Source: UniProtKB
  2. AU-rich element binding Source: UniProtKB
  3. C-C chemokine binding Source: UniProtKB
  4. DNA binding Source: UniProtKB-KW
  5. metal ion binding Source: UniProtKB-KW
  6. mRNA 3'-UTR AU-rich region binding Source: Ensembl
  7. mRNA binding Source: MGI
  8. poly(A) RNA binding Source: UniProtKB
  9. protein kinase binding Source: UniProtKB
  10. single-stranded RNA binding Source: ProtInc

GO - Biological processi

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

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_25064. Tristetraprolin (TTP) destabilizes mRNA.
SignaLinkiP26651.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ZFP36
Synonyms:G0S24, RNF162A, TIS11A, TTP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:12862. 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.

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi60 – 601S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-186. 1 Publication
Mutagenesisi186 – 1861S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-60. 1 Publication
Mutagenesisi315 – 3151R → A: Abolishes interaction with CNOT1. 1 Publication
Mutagenesisi319 – 3191F → A: Abolishes interaction with CNOT1 and impairs TNF mRNA deadenylation. 1 Publication

Organism-specific databases

PharmGKBiPA37451.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 326326TristetraprolinPRO_0000089163Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei60 – 601Phosphoserine; by MAPKAPK21 Publication
Modified residuei66 – 661Phosphoserine1 Publication
Modified residuei88 – 881Phosphoserine1 Publication
Modified residuei90 – 901PhosphoserineBy similarity
Modified residuei92 – 921Phosphothreonine1 Publication
Modified residuei93 – 931PhosphoserineBy similarity
Modified residuei169 – 1691Phosphoserine1 Publication
Modified residuei186 – 1861Phosphoserine; by MAPKAPK23 Publications
Modified residuei197 – 1971Phosphoserine1 Publication
Modified residuei218 – 2181Phosphoserine1 Publication
Modified residuei228 – 2281Phosphoserine1 Publication
Modified residuei276 – 2761Phosphoserine1 Publication
Modified residuei296 – 2961Phosphoserine1 Publication
Modified residuei323 – 3231PhosphoserineBy similarity

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.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP26651.
PRIDEiP26651.

PTM databases

PhosphoSiteiP26651.

Expressioni

Inductioni

By stimulation with various mitogens.

Gene expression databases

BgeeiP26651.
CleanExiHS_ZFP36.
ExpressionAtlasiP26651. baseline and differential.
GenevestigatoriP26651.

Organism-specific databases

HPAiHPA006009.

Interactioni

Subunit structurei

Interacts (via C-terminus) with CNOT1.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
DCP1AQ9NPI62EBI-374248,EBI-374238
EDC3Q96F862EBI-374248,EBI-997311

Protein-protein interaction databases

BioGridi113370. 29 interactions.
DIPiDIP-29845N.
IntActiP26651. 20 interactions.
MINTiMINT-1171915.
STRINGi9606.ENSP00000248673.

Structurei

Secondary structure

1
326
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi317 – 3226

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4J8SX-ray1.55B312-326[»]
ProteinModelPortaliP26651.
SMRiP26651. Positions 99-170.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati71 – 755P-P-P-P-G
Repeati198 – 2025P-P-P-P-G
Repeati219 – 2235P-P-P-P-G

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni312 – 32615Interaction with CNOT1Add
BLAST

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri103 – 13129C3H1-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri141 – 16929C3H1-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5063.
HOGENOMiHOG000233479.
HOVERGENiHBG008483.
InParanoidiP26651.
KOiK15308.
OrthoDBiEOG76QFJP.
PhylomeDBiP26651.
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.

P26651-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDLTAIYESL LSLSPDVPVP SDHGGTESSP GWGSSGPWSL SPSDSSPSGV
60 70 80 90 100
TSRLPGRSTS LVEGRSCGWV PPPPGFAPLA PRLGPELSPS PTSPTATSTT
110 120 130 140 150
PSRYKTELCR TFSESGRCRY GAKCQFAHGL GELRQANRHP KYKTELCHKF
160 170 180 190 200
YLQGRCPYGS RCHFIHNPSE DLAAPGHPPV LRQSISFSGL PSGRRTSPPP
210 220 230 240 250
PGLAGPSLSS SSFSPSSSPP PPGDLPLSPS AFSAAPGTPL ARRDPTPVCC
260 270 280 290 300
PSCRRATPIS VWGPLGGLVR TPSVQSLGSD PDEYASSGSS LGGSDSPVFE
310 320
AGVFAPPQPV AAPRRLPIFN RISVSE
Length:326
Mass (Da):34,003
Last modified:August 1, 1992 - v1
Checksum:iDDD9AD950AF7AF98
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti37 – 371P → S.1 Publication
Corresponds to variant rs17878633 [ dbSNP | Ensembl ].
VAR_021064
Natural varianti55 – 551P → S.
Corresponds to variant rs2229272 [ dbSNP | Ensembl ].
VAR_052324
Natural varianti259 – 2591I → F.1 Publication
Corresponds to variant rs17886974 [ dbSNP | Ensembl ].
VAR_021065
Natural varianti324 – 3241V → F.1 Publication
Corresponds to variant rs17884899 [ dbSNP | Ensembl ].
VAR_021066

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
PIRiS34427.
RefSeqiNP_003398.2. NM_003407.3.
UniGeneiHs.534052.

Genome annotation databases

EnsembliENST00000248673; ENSP00000248673; ENSG00000128016.
GeneIDi7538.
KEGGihsa:7538.
UCSCiuc002olh.2. human.

Polymorphism databases

DMDMi136471.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
PIRi S34427.
RefSeqi NP_003398.2. NM_003407.3.
UniGenei Hs.534052.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4J8S X-ray 1.55 B 312-326 [» ]
ProteinModelPortali P26651.
SMRi P26651. Positions 99-170.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113370. 29 interactions.
DIPi DIP-29845N.
IntActi P26651. 20 interactions.
MINTi MINT-1171915.
STRINGi 9606.ENSP00000248673.

PTM databases

PhosphoSitei P26651.

Polymorphism databases

DMDMi 136471.

Proteomic databases

PaxDbi P26651.
PRIDEi P26651.

Protocols and materials databases

DNASUi 7538.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000248673 ; ENSP00000248673 ; ENSG00000128016 .
GeneIDi 7538.
KEGGi hsa:7538.
UCSCi uc002olh.2. human.

Organism-specific databases

CTDi 7538.
GeneCardsi GC19P039897.
HGNCi HGNC:12862. ZFP36.
HPAi HPA006009.
MIMi 190700. gene.
neXtProti NX_P26651.
PharmGKBi PA37451.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5063.
HOGENOMi HOG000233479.
HOVERGENi HBG008483.
InParanoidi P26651.
KOi K15308.
OrthoDBi EOG76QFJP.
PhylomeDBi P26651.
TreeFami TF315463.

Enzyme and pathway databases

Reactomei REACT_25064. Tristetraprolin (TTP) destabilizes mRNA.
SignaLinki P26651.

Miscellaneous databases

ChiTaRSi ZFP36. human.
GeneWikii ZFP36.
GenomeRNAii 7538.
NextBioi 29497.
PROi P26651.
SOURCEi Search...

Gene expression databases

Bgeei P26651.
CleanExi HS_ZFP36.
ExpressionAtlasi P26651. baseline and differential.
Genevestigatori P26651.

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. "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.
    , 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. 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.

Entry informationi

Entry nameiTTP_HUMAN
AccessioniPrimary (citable) accession number: P26651
Secondary accession number(s): B2RA54
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: October 29, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3