Z36L3_MOUSE
ID Z36L3_MOUSE Reviewed; 725 AA.
AC Q5ISE2;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=mRNA decay activator protein ZFP36L3 {ECO:0000305};
DE AltName: Full=Zinc finger protein 36, C3H1 type-like 3 {ECO:0000312|MGI:MGI:3525151};
DE AltName: Full=zinc finger protein 36-like 3 {ECO:0000303|PubMed:15814898};
GN Name=Zfp36l3 {ECO:0000303|PubMed:15814898, ECO:0000312|MGI:MGI:3525151};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15814898; DOI=10.1095/biolreprod.105.040527;
RA Blackshear P.J., Phillips R.S., Ghosh S., Ramos S.B., Ramos S.V.,
RA Richfield E.K., Lai W.S.;
RT "Zfp36l3, a rodent X chromosome gene encoding a placenta-specific member of
RT the Tristetraprolin family of CCCH tandem zinc finger proteins.";
RL Biol. Reprod. 73:297-307(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP RNA-BINDING, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ARG-153 AND
RP ARG-157.
RX PubMed=18367448; DOI=10.1074/jbc.m801234200;
RA Frederick E.D., Ramos S.B., Blackshear P.J.;
RT "A unique C-terminal repeat domain maintains the cytosolic localization of
RT the placenta-specific tristetraprolin family member ZFP36L3.";
RL J. Biol. Chem. 283:14792-14800(2008).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=26952984; DOI=10.1242/dev.130369;
RA Stumpo D.J., Trempus C.S., Tucker C.J., Huang W., Li L., Kluckman K.,
RA Bortner D.M., Blackshear P.J.;
RT "Deficiency of the placenta- and yolk sac-specific tristetraprolin family
RT member ZFP36L3 identifies likely mRNA targets and an unexpected link to
RT placental iron metabolism.";
RL Development 143:1424-1433(2016).
RN [5]
RP SUBCELLULAR LOCATION, GENE EVOLUTION, AND RETROGENE.
RX PubMed=26493225; DOI=10.1016/j.ympev.2015.10.016;
RA Gingerich T.J., Stumpo D.J., Lai W.S., Randall T.A., Steppan S.J.,
RA Blackshear P.J.;
RT "Emergence and evolution of Zfp36l3.";
RL Mol. Phylogenet. Evol. 94:518-530(2016).
CC -!- FUNCTION: Placenta-specific zinc-finger RNA-binding protein that
CC destabilizes cytoplasmic AU-rich element (ARE)-containing mRNA
CC transcripts by promoting their poly(A) tail removal or deadenylation,
CC and hence provide a mechanism for attenuating protein synthesis
CC (PubMed:15814898, PubMed:26952984). Binds to the 3'-UTR ARE of
CC placental target mRNAs, such as TNF, HBEGF and LIPG (PubMed:15814898,
CC PubMed:18367448, PubMed:26952984). Involved in placental expression of
CC many genes important for normal placental physiology (PubMed:26952984).
CC {ECO:0000269|PubMed:15814898, ECO:0000269|PubMed:18367448,
CC ECO:0000269|PubMed:26952984}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15814898,
CC ECO:0000269|PubMed:18367448, ECO:0000269|PubMed:26493225}. Membrane
CC {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.
CC Note=Localizes exlusively in the cytoplasm (PubMed:18367448,
CC PubMed:15814898). Not detected in the nucleus despite the presence of a
CC nuclear localization signal (NLS) in the zinc finger regions; a C-
CC terminal alanine-rich repeat domain is able to override the activity of
CC the nuclear localization signal and prevent import into the nucleus
CC (PubMed:18367448, PubMed:26493225). {ECO:0000269|PubMed:15814898,
CC ECO:0000269|PubMed:18367448, ECO:0000269|PubMed:26493225}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta and extraembryonic tissues
CC (at protein level). Not detected in embryos and fetus (PubMed:15814898,
CC PubMed:26952984). {ECO:0000269|PubMed:15814898,
CC ECO:0000269|PubMed:26952984}.
CC -!- DEVELOPMENTAL STAGE: Expressed in placenta at 14.5 dpc. Expressed in
CC the single layer of endodermal epithelial cells of the visceral yolk
CC sac at 15.5 dpc (PubMed:26952984). Expressed in syncytiotrophoblast and
CC trophoblast giant cells of the labyrinth region of the placenta at 17.5
CC dpc (PubMed:15814898, PubMed:26952984) (at protein level). Expressed
CC specifically in extraembryonic structures, in placenta from 9.5 to 18.5
CC and yolk sac/amnion from 12.5 to 18.5 (PubMed:15814898,
CC PubMed:26952984). Expressed in the labyrinthine layer of the
CC trophoblastic placenta at 10.5, 12.5 and 14.5 dpc (PubMed:15814898).
CC Expressed in syncytiotrophoblast and trophoblast giant cells, less in
CC spongiotrophoblast cells, and not detected in maternal decidua or in
CC allantois at 17.5 dpc (PubMed:26952984). {ECO:0000269|PubMed:15814898,
CC ECO:0000269|PubMed:26952984}.
CC -!- DOMAIN: Contains long series of C-terminal alanine-rich repeats that
CC serve to maintain the protein in the cytoplasm.
CC {ECO:0000269|PubMed:18367448}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile, without apparent
CC morphological or histological abnormalities in the placenta, but
CC display a decrease in the numbers of surviving offspring. Display an
CC abnormal accumulation of placental 3'UTR ARE-containing mRNAs. Exhibit
CC also a decrease in ARE-containing mRNA decay in differentiated
CC trophoblast stem cells. {ECO:0000269|PubMed:26952984}.
CC -!- MISCELLANEOUS: Rodent-specific retrogene derived apparently from its
CC related family member ZFP36L2 mRNA (PubMed:15814898, PubMed:26493225).
CC {ECO:0000269|PubMed:15814898, ECO:0000269|PubMed:26493225}.
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DR EMBL; AY661338; AAV74249.1; -; mRNA.
DR EMBL; AL691513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS30138.1; -.
DR RefSeq; NP_001009549.1; NM_001009549.2.
DR AlphaFoldDB; Q5ISE2; -.
DR SMR; Q5ISE2; -.
DR CORUM; Q5ISE2; -.
DR STRING; 10090.ENSMUSP00000071630; -.
DR iPTMnet; Q5ISE2; -.
DR PhosphoSitePlus; Q5ISE2; -.
DR PaxDb; Q5ISE2; -.
DR PeptideAtlas; Q5ISE2; -.
DR PRIDE; Q5ISE2; -.
DR DNASU; 333473; -.
DR Ensembl; ENSMUST00000071711; ENSMUSP00000071630; ENSMUSG00000059334.
DR GeneID; 333473; -.
DR KEGG; mmu:333473; -.
DR UCSC; uc009tfk.1; mouse.
DR CTD; 333473; -.
DR MGI; MGI:3525151; Zfp36l3.
DR VEuPathDB; HostDB:ENSMUSG00000059334; -.
DR eggNOG; KOG1677; Eukaryota.
DR GeneTree; ENSGT00940000155076; -.
DR HOGENOM; CLU_383066_0_0_1; -.
DR InParanoid; Q5ISE2; -.
DR OMA; ASAQFQM; -.
DR OrthoDB; 1541140at2759; -.
DR TreeFam; TF315463; -.
DR BioGRID-ORCS; 333473; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q5ISE2; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q5ISE2; protein.
DR Bgee; ENSMUSG00000059334; Expressed in placenta and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:MGI.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IDA:MGI.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IDA:MGI.
DR InterPro; IPR011004; Trimer_LpxA-like_sf.
DR InterPro; IPR045877; ZFP36-like.
DR InterPro; IPR000571; Znf_CCCH.
DR InterPro; IPR036855; Znf_CCCH_sf.
DR PANTHER; PTHR12547; PTHR12547; 1.
DR Pfam; PF00642; zf-CCCH; 2.
DR SMART; SM00356; ZnF_C3H1; 2.
DR SUPFAM; SSF51161; SSF51161; 1.
DR SUPFAM; SSF90229; SSF90229; 2.
DR PROSITE; PS50103; ZF_C3H1; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Membrane; Metal-binding; Reference proteome;
KW Repeat; RNA-binding; Transmembrane; Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..725
FT /note="mRNA decay activator protein ZFP36L3"
FT /id="PRO_0000423554"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 420..440
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 441..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 468..488
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ZN_FING 122..150
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 160..188
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT REGION 1..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..711
FT /note="Necessary for cytoplasmic localization"
FT /evidence="ECO:0000269|PubMed:18367448"
FT REGION 276..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 686..709
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..119
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 278..295
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 694..709
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 153
FT /note="R->A: Reduces ARE-containing RNA-binding. Loss of
FT ARE-containing RNA-binding; when associated with A-157."
FT /evidence="ECO:0000269|PubMed:18367448"
FT MUTAGEN 157
FT /note="R->A: Reduces ARE-containing RNA-binding. Loss of
FT ARE-containing RNA-binding; when associated with A-153."
FT /evidence="ECO:0000269|PubMed:18367448"
SQ SEQUENCE 725 AA; 72346 MW; D6FC9F4F92BAC37E CRC64;
MANNNLNRPL NTNVADSSNS SSTPGTAPPP SSSDPQVLGH QAPSSSASSL TEDCSSSFAR
DLNSYNNGQS GATGAVSWEA PHEPSEANAV SQIHPRNGEH SLQQKPKPQK VSGSSSLATS
ERYKTELCRP FEESGICKYG HKCQFAHGYR ELRTLSRHPK YKTEPCRTFH SVGFCPYGTR
CHFIHNQPEQ QPVLSESTLE EPSSFNGSNV LHLGVNGEQQ PGLQSDSPSG FLSVNSQALQ
APLQLNQQAL SSGGVMPSSH PAAANLRMMC CRTSSSTTAH DADKDPDKDA DKDPSNNSAN
DALAFPQEPG DFSPVAFQNP NTATTTPTAF YNNQQQMGLA ASAQFQMPLA RPLPSATIFG
QASVGPALTP GAAMAPGAAL APAAALTPAA ALAPGAAMAL GAAMATGAAM ATGAALTPGA
ALALGAAMAA GAALAPGAAM APGAAMATGA ALAFGAAMAT GTTLTPGAAM ALGAAMATGA
ALAPGAAVAP RAALAPRAAF APGAAALAPR AALPPGAALT PGAALAPGAA LAPRAALPPG
ATLRPGAALI PRAALAPGAA LAPGAALTPG AALAPGATLA PRAALAPGAA LAPRITITSR
AAITPGVAIA PGVATASTGI LAPGAATATV GNTSSTTITA ATAAEGAAPH FTFQLPDVES
ESESESLEFD VVTSTLDSLL VSDDEDEDDF LRRSSSSSSL NESEFDNTNS SRRLPIFSRF
SDSEK
