TISB_RAT
ID TISB_RAT Reviewed; 338 AA.
AC P17431; Q6LAU8;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=mRNA decay activator protein ZFP36L1 {ECO:0000305};
DE AltName: Full=Butyrate response factor 1 {ECO:0000250|UniProtKB:Q07352};
DE AltName: Full=EGF-inducible protein CMG1 {ECO:0000305};
DE AltName: Full=TPA-induced sequence 11b {ECO:0000250|UniProtKB:P23950};
DE AltName: Full=Zinc finger protein 36, C3H1 type-like 1 {ECO:0000312|RGD:62009};
DE Short=ZFP36-like 1 {ECO:0000312|RGD:62009};
GN Name=Zfp36l1 {ECO:0000312|RGD:62009};
GN Synonyms=Brf1 {ECO:0000250|UniProtKB:Q07352},
GN Cmg1 {ECO:0000303|PubMed:7575462}, Tis11b {ECO:0000303|PubMed:7575462};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar;
RX PubMed=1695727;
RA Gomperts M., Pascall J.C., Brown K.D.;
RT "The nucleotide sequence of a cDNA encoding an EGF-inducible gene indicates
RT the existence of a new family of mitogen-induced genes.";
RL Oncogene 5:1081-1083(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-19.
RX PubMed=7575462; DOI=10.1042/bj3110251;
RA Corps A.N., Pascall J.C., Hadfield K.M., Brown K.D.;
RT "Identification of a functional promoter element in the 5'-flanking region
RT of the rat cMG1/TIS11b gene.";
RL Biochem. J. 311:251-258(1995).
RN [3]
RP FUNCTION, RNA-BINDING, AND INDUCTION.
RX PubMed=10751406; DOI=10.1074/jbc.m001696200;
RA Lai W.S., Carballo E., Thorn J.M., Kennington E.A., Blackshear P.J.;
RT "Interactions of CCCH zinc finger proteins with mRNA. Binding of
RT tristetraprolin-related zinc finger proteins to Au-rich elements and
RT destabilization of mRNA.";
RL J. Biol. Chem. 275:17827-17837(2000).
RN [4]
RP FUNCTION.
RX PubMed=11279239; DOI=10.1074/jbc.m100680200;
RA Lai W.S., Blackshear P.J.;
RT "Interactions of CCCH zinc finger proteins with mRNA: tristetraprolin-
RT mediated AU-rich element-dependent mRNA degradation can occur in the
RT absence of a poly(A) tail.";
RL J. Biol. Chem. 276:23144-23154(2001).
RN [5]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=12748283; DOI=10.1128/mcb.23.11.3798-3812.2003;
RA Lai W.S., Kennington E.A., Blackshear P.J.;
RT "Tristetraprolin and its family members can promote the cell-free
RT deadenylation of AU-rich element-containing mRNAs by poly(A)
RT ribonuclease.";
RL Mol. Cell. Biol. 23:3798-3812(2003).
RN [6]
RP PHOSPHORYLATION AT SER-92.
RX PubMed=15538381; DOI=10.1038/sj.emboj.7600477;
RA Schmidlin M., Lu M., Leuenberger S.A., Stoecklin G., Mallaun M., Gross B.,
RA Gherzi R., Hess D., Hemmings B.A., Moroni C.;
RT "The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by
RT protein kinase B.";
RL EMBO J. 23:4760-4769(2004).
CC -!- FUNCTION: Zinc-finger RNA-binding protein that destabilizes several
CC cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by
CC promoting their poly(A) tail removal or deadenylation, and hence
CC provide a mechanism for attenuating protein synthesis (PubMed:10751406,
CC PubMed:12748283). Acts as a 3'-untranslated region (UTR) ARE mRNA-
CC binding adapter protein to communicate signaling events to the mRNA
CC decay machinery (PubMed:12748283). Functions by recruiting the CCR4-NOT
CC deadenylase complex and components of the cytoplasmic RNA decay
CC machinery to the bound ARE-containing mRNAs, and hence promotes ARE-
CC mediated mRNA deadenylation and decay processes (PubMed:12748283).
CC Induces also the degradation of ARE-containing mRNAs even in absence of
CC poly(A) tail (PubMed:11279239). Binds to 3'-UTR ARE of numerous mRNAs
CC (PubMed:10751406). Positively regulates early adipogenesis by promoting
CC ARE-mediated mRNA decay of immediate early genes (IEGs). Promotes ARE-
CC mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in
CC response to hypertonic stress. Negatively regulates
CC hematopoietic/erythroid cell differentiation by promoting ARE-mediated
CC mRNA decay of the transcription factor STAT5B mRNA. Positively
CC regulates monocyte/macrophage cell differentiation by promoting ARE-
CC mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA. Promotes
CC degradation of ARE-containing pluripotency-associated mRNAs in
CC embryonic stem cells (ESCs), such as NANOG, through a fibroblast growth
CC factor (FGF)-induced MAPK-dependent signaling pathway, and hence
CC attenuates ESC self-renewal and positively regulates mesendoderm
CC differentiation. May play a role in mediating pro-apoptotic effects in
CC malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA. In
CC association with ZFP36L2 maintains quiescence on developing B
CC lymphocytes by promoting ARE-mediated decay of several mRNAs encoding
CC cell cycle regulators that help B cells progress through the cell
CC cycle, and hence ensuring accurate variable-diversity-joining (VDJ)
CC recombination and functional immune cell formation. Together with
CC ZFP36L2 is also necessary for thymocyte development and prevention of
CC T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting
CC ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1
CC mRNA. Participates in the delivery of target ARE-mRNAs to processing
CC bodies (PBs). In addition to its cytosolic mRNA-decay function, plays a
CC role in the regulation of nuclear mRNA 3'-end processing; modulates
CC mRNA 3'-end maturation efficiency of the DLL4 mRNA through binding with
CC an ARE embedded in a weak noncanonical polyadenylation (poly(A)) signal
CC in endothelial cells. Also involved in the regulation of stress granule
CC (SG) and P-body (PB) formation and fusion. Plays a role in
CC vasculogenesis and endocardial development. Plays a role in the
CC regulation of keratinocyte proliferation, differentiation and
CC apoptosis. Plays a role in myoblast cell differentiation (By
CC similarity). {ECO:0000250|UniProtKB:P23950,
CC ECO:0000250|UniProtKB:Q07352, ECO:0000269|PubMed:10751406,
CC ECO:0000269|PubMed:11279239, ECO:0000269|PubMed:12748283}.
CC -!- SUBUNIT: Associates with the cytoplasmic CCR4-NOT deadenylase and RNA
CC exosome complexes to trigger ARE-containing mRNA deadenylation and
CC decay processes. Interacts with CNOT1. Interacts (via N-terminus) with
CC CNOT6. Interacts with CNOT7; this interaction is inhibited in response
CC to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-
CC dependent manner. Interacts with DCP1A. Interacts (via N-terminus) with
CC DCP2. Interacts (via N-terminus) with EXOSC2. Interacts with XRN1.
CC Interacts (via phosphorylated form) with YWHAB; this interaction occurs
CC in a protein kinase AKT1-dependent manner. Interacts (via
CC phosphorylated form) with YWHAZ; this interaction occurs in a p38
CC MAPK- and AKT-signaling pathways. {ECO:0000250|UniProtKB:P23950,
CC ECO:0000250|UniProtKB:Q07352}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q07352}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q07352}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q07352}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q07352}. Note=Shuttles between the nucleus and
CC the cytoplasm in a XPO1/CRM1-dependent manner. Component of cytoplasmic
CC stress granules. Localizes in processing bodies (PBs).
CC {ECO:0000250|UniProtKB:P23950, ECO:0000250|UniProtKB:Q07352}.
CC -!- PTM: Phosphorylated. Phosphorylated by RPS6KA1 at Ser-334 upon phorbol
CC 12-myristate 13-acetate (PMA) treatment; this phosphorylation results
CC in dissociation of the CCR4-NOT deadenylase complex and induces p38
CC MAPK-mediated stabilization of the low-density lipoprotein receptor
CC LDLR mRNA. Phosphorylated by protein kinase AKT1 at Ser-92 and Ser-203
CC in response to insulin; these phosphorylations stabilize ZFP36L1,
CC increase the association with 14-3-3 proteins and mediate ARE-
CC containing mRNA stabilization. AKT1-mediated phosphorylation at Ser-92
CC does not impair ARE-containing RNA-binding. Phosphorylated at Ser-54,
CC Ser-92 and Ser-203 by MAPKAPK2; these phosphorylations increase the
CC association with 14-3-3 proteins and mediate ARE-containing mRNA
CC stabilization in a protein kinase AKT1-independent manner. MAPKAPK2-
CC mediated phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair
CC ARE-containing RNA-binding (By similarity). Phosphorylations increase
CC the association with 14-3-3 proteins and mediate ARE-containing mRNA
CC stabilization during early adipogenesis in a p38 MAPK- and AKT-
CC dependent manner (By similarity). Phosphorylated by protein kinase AKT1
CC at Ser-92 (PubMed:15538381). {ECO:0000250|UniProtKB:P23950,
CC ECO:0000250|UniProtKB:Q07352, ECO:0000269|PubMed:15538381}.
CC -!- PTM: Ubiquitinated. Ubiquitination leads to proteasomal degradation, a
CC process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203.
CC {ECO:0000250|UniProtKB:Q07352}.
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DR EMBL; X52590; CAA36826.1; -; mRNA.
DR EMBL; X86571; CAA60379.1; -; Genomic_DNA.
DR PIR; S10471; S10471.
DR RefSeq; NP_058868.1; NM_017172.1.
DR AlphaFoldDB; P17431; -.
DR SMR; P17431; -.
DR MINT; P17431; -.
DR STRING; 10116.ENSRNOP00000051546; -.
DR iPTMnet; P17431; -.
DR PhosphoSitePlus; P17431; -.
DR Ensembl; ENSRNOT00000083677; ENSRNOP00000075412; ENSRNOG00000058646.
DR GeneID; 29344; -.
DR KEGG; rno:29344; -.
DR UCSC; RGD:62009; rat.
DR CTD; 677; -.
DR RGD; 62009; Zfp36l1.
DR eggNOG; KOG1677; Eukaryota.
DR GeneTree; ENSGT00940000155076; -.
DR HOGENOM; CLU_033040_1_0_1; -.
DR InParanoid; P17431; -.
DR OMA; TPYFFRP; -.
DR OrthoDB; 1541140at2759; -.
DR PhylomeDB; P17431; -.
DR Reactome; R-RNO-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR PRO; PR:P17431; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000058646; Expressed in spleen and 19 other tissues.
DR Genevisible; P17431; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:MGI.
DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISO:RGD.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISS:UniProtKB.
DR GO; GO:0097403; P:cellular response to raffinose; ISS:UniProtKB.
DR GO; GO:0071472; P:cellular response to salt stress; ISS:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0060710; P:chorio-allantoic fusion; ISO:RGD.
DR GO; GO:0048568; P:embryonic organ development; ISO:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:0048382; P:mesendoderm development; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:MGI.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0051028; P:mRNA transport; ISS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:1901991; P:negative regulation of mitotic cell cycle phase transition; ISS:UniProtKB.
DR GO; GO:0021915; P:neural tube development; ISO:RGD.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISO:RGD.
DR GO; GO:0031086; P:nuclear-transcribed mRNA catabolic process, deadenylation-independent decay; IDA:UniProtKB.
DR GO; GO:0038066; P:p38MAPK cascade; ISS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:1904582; P:positive regulation of intracellular mRNA localization; ISS:UniProtKB.
DR GO; GO:0045657; P:positive regulation of monocyte differentiation; ISS:UniProtKB.
DR GO; GO:1900153; P:positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:UniProtKB.
DR GO; GO:0003342; P:proepicardium development; ISO:RGD.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
DR GO; GO:1902172; P:regulation of keratinocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0010837; P:regulation of keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:0031440; P:regulation of mRNA 3'-end processing; ISO:RGD.
DR GO; GO:0043488; P:regulation of mRNA stability; IDA:UniProtKB.
DR GO; GO:0045661; P:regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0072091; P:regulation of stem cell proliferation; ISS:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; ISO:RGD.
DR GO; GO:0009611; P:response to wounding; ISS:UniProtKB.
DR GO; GO:0060712; P:spongiotrophoblast layer development; ISO:RGD.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR InterPro; IPR007635; Tis11B_N.
DR InterPro; IPR045877; ZFP36-like.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR PANTHER; PTHR12547; PTHR12547; 1.
DR Pfam; PF04553; Tis11B_N; 1.
DR Pfam; PF00642; zf-CCCH; 2.
DR SMART; SM00356; ZnF_C3H1; 2.
DR SUPFAM; SSF90229; SSF90229; 2.
DR PROSITE; PS50103; ZF_C3H1; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; Developmental protein; DNA-binding; Metal-binding;
KW mRNA processing; mRNA transport; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ribonucleoprotein; RNA-binding; Transport;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..338
FT /note="mRNA decay activator protein ZFP36L1"
FT /id="PRO_0000089169"
FT ZN_FING 114..142
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 152..180
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 1..111
FT /note="Necessary and sufficient for the association with
FT mRNA decay enzymes and mRNA decay activation"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
FT REGION 93..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..338
FT /note="Necessary for mRNA decay activation"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
FT REGION 273..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..338
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 54
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
FT MOD_RES 90
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
FT MOD_RES 92
FT /note="Phosphoserine; by PKB/AKT1 and MAPKAPK2"
FT /evidence="ECO:0000269|PubMed:15538381"
FT MOD_RES 203
FT /note="Phosphoserine; by PKB/AKT1 and MAPKAPK2"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
FT MOD_RES 318
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
FT MOD_RES 334
FT /note="Phosphoserine; by RPS6KA1"
FT /evidence="ECO:0000250|UniProtKB:Q07352"
SQ SEQUENCE 338 AA; 36399 MW; A1547C8BF566196C CRC64;
MTTTLVSATI FDLSEVLCKG NKMLNYSTPS AGGCLLDRKA VGTPAGGGFP RRHSVTLPSS
KFHQNQLLSS LKGEPAPTLS SRDSRFRDRS FSEGGERLLP TQKQPGSGQV NSSRYKTELC
RPFEENGACK YGDKCQFAHG IHELRSLTRH PKYKTELCRT FHTIGFCPYG PRCHFIHNAE
ERRALAGGRD LSADRPRLQH SFSFAGFPSA AATAAATGLL DSPTSITPPP ILSADDLLGS
PTLPDGTNNP FAFSSQELAS LFAPSMGLPG GGSPTTFLFR PMSESPHMFD SPPSPQDSLS
DHEGYLSSSS SSHSGSDSPT LDNSRRLPIF SRLSISDD
