P26651 (TTP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ZFP36
Synonyms:	G0S24, RNF162A, TIS11A, TTP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	326 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. Plays a key role in the post-transcriptional regulation of tumor necrosis factor (TNF). Ref.5
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 Ref.7
Sequence similarities	Contains 2 C3H1-type zinc fingers.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of nuclear-transcribed mRNA poly(A) tail shortening Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: MGI nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	AU-rich element binding Inferred from direct assay Ref.5. Source: UniProtKB DNA binding Inferred from electronic annotation. Source: UniProtKB-KW mRNA binding Inferred from direct assay. Source: MGI protein binding Inferred from physical interaction. Source: IntAct single-stranded RNA binding Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DCP1A	Q9NPI6	2	EBI-374248,EBI-374238
EDC3	Q96F86	2	EBI-374248,EBI-997311

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 326	326	Tristetraprolin		PRO_0000089163
Regions
	Repeat	71 – 75	5	P-P-P-P-G
	Repeat	198 – 202	5	P-P-P-P-G
	Repeat	219 – 223	5	P-P-P-P-G
	Zinc finger	103 – 131	29	C3H1-type 1
	Zinc finger	141 – 169	29	C3H1-type 2
Amino acid modifications
	Modified residue	60	1	Phosphoserine; by MAPKAPK2 Ref.5
	Modified residue	88	1	Phosphoserine By similarity
	Modified residue	90	1	Phosphoserine By similarity
	Modified residue	92	1	Phosphothreonine Ref.7
	Modified residue	93	1	Phosphoserine By similarity
	Modified residue	186	1	Phosphoserine; by MAPKAPK2 Ref.5 Ref.6
	Modified residue	257	1	Phosphothreonine By similarity
	Modified residue	323	1	Phosphoserine By similarity
Natural variations
	Natural variant	37	1	P → S. Ref.3 Corresponds to variant rs17878633 [ dbSNP | Ensembl ].		VAR_021064
	Natural variant	55	1	P → S. Corresponds to variant rs2229272 [ dbSNP | Ensembl ].		VAR_052324
	Natural variant	259	1	I → F. Ref.3 Corresponds to variant rs17886974 [ dbSNP | Ensembl ].		VAR_021065
	Natural variant	324	1	V → F. Ref.3 Corresponds to variant rs17884899 [ dbSNP | Ensembl ].		VAR_021066
Experimental info
	Mutagenesis	60	1	S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-186. Ref.5
	Mutagenesis	186	1	S → A: Impairs phosphorylation by MAPKAPK2 and binding to 14-3-3 proteins; when associated with A-60. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P26651 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: DDD9AD950AF7AF98	FASTA	326	34,003
	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

References

	« Hide 'large scale' referencesShow '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: 2062660] [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: 14702039] [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: 15489334] [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: 15014438] [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]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-92, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

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.
IPI	IPI00000893.
PIR	S34427.
RefSeq	NP_003398.1. NM_003407.2.
UniGene	Hs.534052. Hs.728064.
3D structure databases
ProteinModelPortal	P26651.
SMR	P26651. Positions 99-170.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29845N.
IntAct	P26651. 19 interactions.
MINT	MINT-1171915.
STRING	P26651.
PTM databases
PhosphoSite	P26651.
Polymorphism databases
DMDM	136471.
Proteomic databases
PRIDE	P26651.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000248673; ENSP00000248673; ENSG00000128016.
GeneID	7538.
KEGG	hsa:7538.
UCSC	uc002olh.1. human.
Organism-specific databases
CTD	7538.
GeneCards	GC19P039897.
H-InvDB	HIX0015118.
HGNC	HGNC:12862. ZFP36.
HPA	HPA006009.
MIM	190700. gene.
neXtProt	NX_P26651.
PharmGKB	PA37451.
GenAtlas	Search...
Phylogenomic databases
eggNOG	maNOG19044.
GeneTree	ENSGT00530000063262.
HOGENOM	HBG717837.
HOVERGEN	HBG008483.
InParanoid	P26651.
OMA	RRLPIFN.
OrthoDB	EOG4S4PH4.
PhylomeDB	P26651.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P26651.
Bgee	P26651.
CleanEx	HS_ZFP36.
Genevestigator	P26651.
GermOnline	ENSG00000128016. Homo sapiens.
Family and domain databases
InterPro	IPR000571. Znf_CCCH. [Graphical view]
KO	K15308.
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
NextBio	29497.
SOURCE	Search...

Entry information

Entry name

TTP_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.