LN28A_DANRE
ID LN28A_DANRE Reviewed; 202 AA.
AC Q803L0; Q1LXL3;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Protein lin-28 homolog A;
DE Short=Lin-28A;
GN Name=lin28a; Synonyms=lin28; ORFNames=si:ch211-232d9.4, zgc:55584;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18307296; DOI=10.1021/pr700667w;
RA Lemeer S., Pinkse M.W.H., Mohammed S., van Breukelen B., den Hertog J.,
RA Slijper M., Heck A.J.R.;
RT "Online automated in vivo zebrafish phosphoproteomics: from large-scale
RT analysis down to a single embryo.";
RL J. Proteome Res. 7:1555-1564(2008).
CC -!- FUNCTION: RNA-binding protein that inhibits processing of pre-let-7
CC miRNAs and regulates translation of mRNAs that control developmental
CC timing, pluripotency and metabolism. Seems to recognize a common
CC structural G-quartet (G4) feature in its miRNA and mRNA targets (By
CC similarity). 'Translational enhancer' that drives specific mRNAs to
CC polysomes and increases the efficiency of protein synthesis. Its
CC association with the translational machinery and target mRNAs results
CC in an increased number of initiation events per molecule of mRNA and,
CC indirectly, in mRNA stabilization. Suppressor of microRNA (miRNA)
CC biogenesis, including that of let-7. Binds specific target miRNA
CC precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in their
CC terminal loop, and recruits uridylyltransferase. This results in the
CC terminal uridylation of target pre-miRNAs. Uridylated pre-miRNAs fail
CC to be processed by Dicer and undergo degradation (By similarity).
CC Localized to the periendoplasmic reticulum area, binds to a large
CC number of spliced mRNAs and inhibits the translation of mRNAs destined
CC for the ER, reducing the synthesis of transmembrane proteins, ER or
CC Golgi lumen proteins, and secretory proteins. Binds to and enhances the
CC translation of mRNAs for several metabolic enzymes, increasing
CC glycolysis and oxidative phosphorylation. Which, with the let-7
CC repression may enhance tissue repair in adult tissue (By similarity).
CC {ECO:0000250|UniProtKB:Q8K3Y3, ECO:0000250|UniProtKB:Q9H9Z2}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q8K3Y3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8K3Y3}. Rough
CC endoplasmic reticulum {ECO:0000250|UniProtKB:Q8K3Y3}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q9H9Z2}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q8K3Y3}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q8K3Y3}. Note=Predominantly cytoplasmic. In the
CC cytoplasm, localizes to peri-endoplasmic reticulum regions and may be
CC bound to the cytosolic surface of rough endoplasmic reticulum (ER) on
CC which ER-associated mRNAs are translated. Shuttle from the nucleus to
CC the cytoplasm requires RNA-binding. {ECO:0000250|UniProtKB:Q8K3Y3}.
CC -!- DOMAIN: The CCHC zinc fingers interact with the GGAG motif at the 3'
CC end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-
CC 3' consensus motif with micromolar affinity. The CSD domain recognizes
CC the loop at the 5' end. The flexible linker allows accommodating
CC variable sequences and lengths among let-7 family members (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the lin-28 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAK04626.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; BX322664; CAK04625.1; -; Genomic_DNA.
DR EMBL; BX322664; CAK04626.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC044433; AAH44433.1; -; mRNA.
DR RefSeq; NP_957385.1; NM_201091.1.
DR AlphaFoldDB; Q803L0; -.
DR SMR; Q803L0; -.
DR STRING; 7955.ENSDARP00000089741; -.
DR iPTMnet; Q803L0; -.
DR PaxDb; Q803L0; -.
DR Ensembl; ENSDART00000098970; ENSDARP00000089741; ENSDARG00000016999.
DR GeneID; 394066; -.
DR KEGG; dre:394066; -.
DR CTD; 394066; -.
DR ZFIN; ZDB-GENE-040426-747; lin28ab.
DR eggNOG; KOG3070; Eukaryota.
DR GeneTree; ENSGT00940000153295; -.
DR InParanoid; Q803L0; -.
DR PhylomeDB; Q803L0; -.
DR TreeFam; TF316240; -.
DR PRO; PR:Q803L0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000016999; Expressed in presomitic mesoderm and 38 other tissues.
DR ExpressionAtlas; Q803L0; baseline.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0005844; C:polysome; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1905538; F:polysome binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043009; P:chordate embryonic development; IMP:ZFIN.
DR GO; GO:0010587; P:miRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ZFIN.
DR GO; GO:2000767; P:positive regulation of cytoplasmic translation; ISS:UniProtKB.
DR GO; GO:0031054; P:pre-miRNA processing; ISS:UniProtKB.
DR GO; GO:0031099; P:regeneration; IMP:ZFIN.
DR GO; GO:0031123; P:RNA 3'-end processing; ISS:UniProtKB.
DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR CDD; cd04458; CSP_CDS; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR011129; CSD.
DR InterPro; IPR002059; CSP_DNA-bd.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR001878; Znf_CCHC.
DR InterPro; IPR036875; Znf_CCHC_sf.
DR Pfam; PF00313; CSD; 1.
DR Pfam; PF00098; zf-CCHC; 1.
DR PRINTS; PR00050; COLDSHOCK.
DR SMART; SM00357; CSP; 1.
DR SMART; SM00343; ZnF_C2HC; 2.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF57756; SSF57756; 1.
DR PROSITE; PS51857; CSD_2; 1.
DR PROSITE; PS50158; ZF_CCHC; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endoplasmic reticulum; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing; Zinc;
KW Zinc-finger.
FT CHAIN 1..202
FT /note="Protein lin-28 homolog A"
FT /id="PRO_0000253790"
FT DOMAIN 33..106
FT /note="CSD"
FT ZN_FING 129..146
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 151..168
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 107..130
FT /note="Flexible linker"
FT /evidence="ECO:0000250"
FT REGION 170..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 161
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18307296"
SQ SEQUENCE 202 AA; 21886 MW; 830E89B418F3AF1C CRC64;
MPPANPHLNH TGGCTKTEEE EAASSEEDSG SFHGSGVCKW FNVRMGFGFL SMTHREGICL
DSPVDVFVHQ SKLHMEGFRS LKEGEAVEFT FKRSSKGLES LQVTGPGGAP CVGSEKKPKG
TQKRRSKGDR CFNCGGPNHH AKECQLPPQP KKCHFCQSIS HMVANCPIKA QQLSPGSQGK
STTSTGEEED MSHTPLLPES TD
