LN28A_HUMAN
ID LN28A_HUMAN Reviewed; 209 AA.
AC Q9H9Z2;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Protein lin-28 homolog A;
DE Short=Lin-28A;
DE AltName: Full=Zinc finger CCHC domain-containing protein 1;
GN Name=LIN28A; Synonyms=CSDD1, LIN28, ZCCHC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12798299; DOI=10.1016/s0012-1606(03)00126-x;
RA Moss E.G., Tang L.;
RT "Conservation of the heterochronic regulator Lin-28, its developmental
RT expression and microRNA complementary sites.";
RL Dev. Biol. 258:432-442(2003).
RN [2]
RP ERRATUM OF PUBMED:12798299.
RA Moss E.G., Tang L.;
RL Dev. Biol. 262:361-361(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INDUCTION.
RX PubMed=15003116; DOI=10.1186/gb-2004-5-3-r13;
RA Sempere L.F., Freemantle S., Pitha-Rowe I., Moss E.G., Dmitrovsky E.,
RA Ambros V.;
RT "Expression profiling of mammalian microRNAs uncovers a subset of brain-
RT expressed microRNAs with possible roles in murine and human neuronal
RT differentiation.";
RL Genome Biol. 5:R13.1-R13.11(2004).
RN [7]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14688391; DOI=10.1634/stemcells.22-1-51;
RA Richards M., Tan S.-P., Tan J.-H., Chan W.-K., Bongso A.;
RT "The transcriptome profile of human embryonic stem cells as defined by
RT SAGE.";
RL Stem Cells 22:51-64(2004).
RN [8]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15614775; DOI=10.1002/dvdy.20247;
RA Gerecht-Nir S., Dazard J.-E., Golan-Mashiach M., Osenberg S., Botvinnik A.,
RA Amariglio N., Domany E., Rechavi G., Givol D., Itskovitz-Eldor J.;
RT "Vascular gene expression and phenotypic correlation during differentiation
RT of human embryonic stem cells.";
RL Dev. Dyn. 232:487-497(2005).
RN [9]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15722555; DOI=10.1074/jbc.m412247200;
RA Lee Y.S., Kim H.K., Chung S., Kim K.-S., Dutta A.;
RT "Depletion of human micro-RNA miR-125b reveals that it is critical for the
RT proliferation of differentiated cells but not for the down-regulation of
RT putative targets during differentiation.";
RL J. Biol. Chem. 280:16635-16641(2005).
RN [10]
RP INDUCTION.
RX PubMed=16227573; DOI=10.1128/mcb.25.21.9198-9208.2005;
RA Wu L., Belasco J.G.;
RT "Micro-RNA regulation of the mammalian lin-28 gene during neuronal
RT differentiation of embryonal carcinoma cells.";
RL Mol. Cell. Biol. 25:9198-9208(2005).
RN [11]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-46; PHE-55; PHE-73; HIS-147
RP AND HIS-169.
RX PubMed=17617744; DOI=10.4161/rna.4.1.4364;
RA Balzer E., Moss E.G.;
RT "Localization of the developmental timing regulator Lin28 to mRNP
RT complexes, P-bodies and stress granules.";
RL RNA Biol. 4:16-25(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING, AND MUTAGENESIS OF HIS-147 AND
RP HIS-169.
RX PubMed=18951094; DOI=10.1016/j.molcel.2008.09.014;
RA Heo I., Joo C., Cho J., Ha M., Han J., Kim V.N.;
RT "Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.";
RL Mol. Cell 32:276-284(2008).
RN [13]
RP FUNCTION IN PRE-MIRNA URIDYLATION, RNA-BINDING, AND INTERACTION WITH
RP ZCCHC11.
RX PubMed=19703396; DOI=10.1016/j.cell.2009.08.002;
RA Heo I., Joo C., Kim Y.-K., Ha M., Yoon M.-J., Cho J., Yeom K.-H., Han J.,
RA Kim V.N.;
RT "TUT4 in concert with Lin28 suppresses MicroRNA biogenesis through pre-
RT microRNA uridylation.";
RL Cell 138:696-708(2009).
RN [14]
RP POSSIBLE INVOLVEMENT IN CANCERS.
RX PubMed=19483683; DOI=10.1038/ng.392;
RA Viswanathan S.R., Powers J.T., Einhorn W., Hoshida Y., Ng T.L.,
RA Toffanin S., O'Sullivan M., Lu J., Phillips L.A., Lockhart V.L., Shah S.P.,
RA Tanwar P.S., Mermel C.H., Beroukhim R., Azam M., Teixeira J., Meyerson M.,
RA Hughes T.P., Llovet J.M., Radich J., Mullighan C.G., Golub T.R.,
RA Sorensen P.H., Daley G.Q.;
RT "Lin28 promotes transformation and is associated with advanced human
RT malignancies.";
RL Nat. Genet. 41:843-848(2009).
RN [15]
RP FUNCTION IN PRE-LET-7 URIDYLATION, INTERACTION WITH ZCCHC11, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22118463; DOI=10.1016/j.cell.2011.10.039;
RA Piskounova E., Polytarchou C., Thornton J.E., LaPierre R.J.,
RA Pothoulakis C., Hagan J.P., Iliopoulos D., Gregory R.I.;
RT "Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct
RT mechanisms.";
RL Cell 147:1066-1079(2011).
RN [16]
RP FUNCTION IN MRNA TRANSLATION, AND INTERACTION WITH DHX9.
RX PubMed=21247876; DOI=10.1093/nar/gkq1350;
RA Jin J., Jing W., Lei X.X., Feng C., Peng S., Boris-Lawrie K., Huang Y.;
RT "Evidence that Lin28 stimulates translation by recruiting RNA helicase A to
RT polysomes.";
RL Nucleic Acids Res. 39:3724-3734(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-3; SER-120 AND SER-200, CLEAVAGE OF INITIATOR METHIONINE
RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [19]
RP FUNCTION IN PRE-LET-7 URIDYLATION.
RX PubMed=22898984; DOI=10.1261/rna.034538.112;
RA Thornton J.E., Chang H.M., Piskounova E., Gregory R.I.;
RT "Lin28-mediated control of let-7 microRNA expression by alternative TUTases
RT Zcchc11 (TUT4) and Zcchc6 (TUT7).";
RL RNA 18:1875-1885(2012).
RN [20]
RP STRUCTURE BY NMR OF 134-186.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the zinc-finger domain in LIN-28.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [21]
RP STRUCTURE BY NMR OF 124-186 IN COMPLEX WITH SHORT RNA, AND CONSENSUS MOTIF.
RX PubMed=22157959; DOI=10.1038/nsmb.2202;
RA Loughlin F.E., Gebert L.F., Towbin H., Brunschweiger A., Hall J.,
RA Allain F.H.;
RT "Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of
RT pluripotency factor Lin28.";
RL Nat. Struct. Mol. Biol. 19:84-89(2012).
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 (PubMed:21247876). Seems to
CC recognize a common structural G-quartet (G4) feature in its miRNA and
CC mRNA targets (Probable). 'Translational enhancer' that drives specific
CC mRNAs to polysomes and increases the efficiency of protein synthesis.
CC Its association with the translational machinery and target mRNAs
CC results in an increased number of initiation events per molecule of
CC mRNA and, indirectly, in mRNA stabilization. Binds IGF2 mRNA, MYOD1
CC mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for
CC skeletal muscle differentiation program through the translational up-
CC regulation of IGF2 expression. Suppressor of microRNA (miRNA)
CC biogenesis, including that of let-7, miR107, miR-143 and miR-200c.
CC Specifically binds the miRNA precursors (pre-miRNAs), recognizing an
CC 5'-GGAG-3' motif found in pre-miRNA terminal loop, and recruits TUT4
CC and TUT7 uridylyltransferases (PubMed:18951094, PubMed:19703396,
CC PubMed:22118463, PubMed:22898984). This results in the terminal
CC uridylation of target pre-miRNAs (PubMed:18951094, PubMed:19703396,
CC PubMed:22118463, PubMed:22898984). Uridylated pre-miRNAs fail to be
CC processed by Dicer and undergo degradation. The repression of let-7
CC expression is required for normal development and contributes to
CC maintain the pluripotent state by preventing let-7-mediated
CC differentiation of embryonic stem cells (PubMed:18951094,
CC PubMed:19703396, PubMed:22118463, PubMed:22898984). Localized to the
CC periendoplasmic reticulum area, binds to a large number of spliced
CC mRNAs and inhibits the translation of mRNAs destined for the ER,
CC reducing the synthesis of transmembrane proteins, ER or Golgi lumen
CC proteins, and secretory proteins. Binds to and enhances the translation
CC of mRNAs for several metabolic enzymes, such as PFKP, PDHA1 or SDHA,
CC increasing glycolysis and oxidative phosphorylation. Which, with the
CC let-7 repression may enhance tissue repair in adult tissue (By
CC similarity). {ECO:0000250|UniProtKB:Q8K3Y3,
CC ECO:0000269|PubMed:18951094, ECO:0000269|PubMed:19703396,
CC ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:22118463,
CC ECO:0000269|PubMed:22898984, ECO:0000305}.
CC -!- SUBUNIT: Monomer (By similarity). During skeletal muscle
CC differentiation, associated with translation initiation complexes in
CC the polysomal compartment (PubMed:21247876). Directly interacts with
CC EIF3S2 (By similarity). Interacts with NCL in an RNA-dependent manner
CC (By similarity). Interacts (via C-terminus) with DHX9 (via N- and C-
CC terminus); this interaction occurs in a RNA-independent manner
CC (PubMed:21247876). Interacts with TUT4 in the presence of pre-let-7 RNA
CC (PubMed:19703396, PubMed:22118463). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q8K3Y3, ECO:0000269|PubMed:19703396,
CC ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:22118463,
CC ECO:0000269|PubMed:22157959}.
CC -!- INTERACTION:
CC Q9H9Z2; P42858: HTT; NbExp=18; IntAct=EBI-2462365, EBI-466029;
CC Q9H9Z2; Q9NSD4: ZNF275; NbExp=3; IntAct=EBI-2462365, EBI-17263125;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18951094,
CC ECO:0000269|PubMed:22118463}. Rough endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8K3Y3}. Cytoplasm, P-body
CC {ECO:0000269|PubMed:17617744}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:17617744}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q8K3Y3}. Note=Predominantly cytoplasmic
CC (PubMed:22118463). In the cytoplasm, localizes to peri-endoplasmic
CC reticulum regions and detected in the microsomal fraction derived from
CC rough endoplasmic reticulum (RER) following subcellular fractionation.
CC May be bound to the cytosolic surface of RER on which ER-associated
CC mRNAs are translated (By similarity). Shuttle from the nucleus to the
CC cytoplasm requires RNA-binding (PubMed:17617744). Nucleolar
CC localization is observed in 10-15% of the nuclei in differentiated
CC myotubes (By similarity). {ECO:0000250|UniProtKB:Q8K3Y3,
CC ECO:0000269|PubMed:17617744, ECO:0000269|PubMed:22118463}.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic stem cells, placenta and
CC testis. Tends to be up-regulated in HER2-overexpressing breast tumors.
CC {ECO:0000269|PubMed:14688391, ECO:0000269|PubMed:15614775,
CC ECO:0000269|PubMed:15722555, ECO:0000269|PubMed:22118463}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver. Expression decreases
CC during differentiation of ES cells or upon induction of neuronal
CC differentiation by retinoic acid. {ECO:0000269|PubMed:14688391,
CC ECO:0000269|PubMed:15614775, ECO:0000269|PubMed:15722555}.
CC -!- INDUCTION: Can be negatively regulated by the interaction of microRNAs
CC miR-125a and miR-125b with at least two miRNA responsive elements
CC (miREs) in the 3'-UTR of this gene. These interactions may reduce both
CC translation efficiency and mRNA abundance. Negatively regulated by
CC retinoic acid. {ECO:0000269|PubMed:15003116,
CC ECO:0000269|PubMed:16227573}.
CC -!- DOMAIN: The CSD domain is required for function in muscle
CC differentiation. {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.
CC {ECO:0000250|UniProtKB:Q8K3Y3}.
CC -!- MISCELLANEOUS: Overexpressed in primary tumors (overall frequency
CC approximately 15%), overexpression being linked to repression of let-7
CC family miRNAs and derepression of let-7 targets. Facilitates cellular
CC transformation in vitro, and overexpression is associated with advanced
CC disease across multiple tumor types. {ECO:0000269|PubMed:19483683}.
CC -!- MISCELLANEOUS: Reactivation of LIN28A expression enhances tissue repair
CC in some adult tissues by reprogramming cellular bioenergetics. Improves
CC hair regrowth by promoting anagen in hair follicle and accelerates
CC regrowth of cartilage, bone and mesenchyme after ear and digit
CC injuries. {ECO:0000250|UniProtKB:Q8K3Y3}.
CC -!- SIMILARITY: Belongs to the lin-28 family. {ECO:0000305}.
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DR EMBL; AF521099; AAM77751.1; -; mRNA.
DR EMBL; AK022519; BAB14075.1; -; mRNA.
DR EMBL; AL513365; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028566; AAH28566.1; -; mRNA.
DR CCDS; CCDS280.1; -.
DR RefSeq; NP_078950.1; NM_024674.5.
DR RefSeq; XP_011540450.1; XM_011542148.1.
DR PDB; 2CQF; NMR; -; A=137-186.
DR PDB; 2LI8; NMR; -; A=124-186.
DR PDB; 5UDZ; X-ray; 2.00 A; A/B=31-187.
DR PDBsum; 2CQF; -.
DR PDBsum; 2LI8; -.
DR PDBsum; 5UDZ; -.
DR AlphaFoldDB; Q9H9Z2; -.
DR BMRB; Q9H9Z2; -.
DR SMR; Q9H9Z2; -.
DR BioGRID; 122842; 430.
DR IntAct; Q9H9Z2; 25.
DR MINT; Q9H9Z2; -.
DR STRING; 9606.ENSP00000363314; -.
DR BindingDB; Q9H9Z2; -.
DR ChEMBL; CHEMBL4523458; -.
DR GlyGen; Q9H9Z2; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q9H9Z2; -.
DR PhosphoSitePlus; Q9H9Z2; -.
DR SwissPalm; Q9H9Z2; -.
DR BioMuta; LIN28A; -.
DR DMDM; 74752750; -.
DR EPD; Q9H9Z2; -.
DR jPOST; Q9H9Z2; -.
DR MassIVE; Q9H9Z2; -.
DR PaxDb; Q9H9Z2; -.
DR PeptideAtlas; Q9H9Z2; -.
DR PRIDE; Q9H9Z2; -.
DR ProteomicsDB; 81371; -.
DR Antibodypedia; 30634; 736 antibodies from 43 providers.
DR CPTC; Q9H9Z2; 1 antibody.
DR DNASU; 79727; -.
DR Ensembl; ENST00000254231.4; ENSP00000254231.4; ENSG00000131914.11.
DR Ensembl; ENST00000326279.11; ENSP00000363314.3; ENSG00000131914.11.
DR GeneID; 79727; -.
DR KEGG; hsa:79727; -.
DR MANE-Select; ENST00000326279.11; ENSP00000363314.3; NM_024674.6; NP_078950.1.
DR UCSC; uc001bmj.4; human.
DR CTD; 79727; -.
DR DisGeNET; 79727; -.
DR GeneCards; LIN28A; -.
DR HGNC; HGNC:15986; LIN28A.
DR HPA; ENSG00000131914; Tissue enriched (testis).
DR MIM; 611043; gene.
DR neXtProt; NX_Q9H9Z2; -.
DR OpenTargets; ENSG00000131914; -.
DR PharmGKB; PA165751523; -.
DR VEuPathDB; HostDB:ENSG00000131914; -.
DR eggNOG; KOG3070; Eukaryota.
DR GeneTree; ENSGT00940000153295; -.
DR HOGENOM; CLU_089169_4_0_1; -.
DR InParanoid; Q9H9Z2; -.
DR OMA; ANCPVKT; -.
DR OrthoDB; 1604809at2759; -.
DR PhylomeDB; Q9H9Z2; -.
DR TreeFam; TF316240; -.
DR PathwayCommons; Q9H9Z2; -.
DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells.
DR SignaLink; Q9H9Z2; -.
DR BioGRID-ORCS; 79727; 20 hits in 1083 CRISPR screens.
DR EvolutionaryTrace; Q9H9Z2; -.
DR GeneWiki; LIN28; -.
DR GenomeRNAi; 79727; -.
DR Pharos; Q9H9Z2; Tbio.
DR PRO; PR:Q9H9Z2; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H9Z2; protein.
DR Bgee; ENSG00000131914; Expressed in oocyte and 21 other tissues.
DR Genevisible; Q9H9Z2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0002151; F:G-quadruplex RNA binding; ISS:UniProtKB.
DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1905538; F:polysome binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:1990825; F:sequence-specific mRNA binding; ISS:UniProtKB.
DR GO; GO:0031369; F:translation initiation factor binding; IEA:Ensembl.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:BHF-UCL.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0010587; P:miRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0045686; P:negative regulation of glial cell differentiation; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:1901724; P:positive regulation of cell proliferation involved in kidney development; IEA:Ensembl.
DR GO; GO:2000767; P:positive regulation of cytoplasmic translation; IMP:UniProtKB.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; ISS:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:BHF-UCL.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:BHF-UCL.
DR GO; GO:0031054; P:pre-miRNA processing; IMP:UniProtKB.
DR GO; GO:0071076; P:RNA 3' uridylation; IEA:Ensembl.
DR GO; GO:0031123; P:RNA 3'-end processing; IMP:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR GO; GO:0019827; P:stem cell population maintenance; IMP: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 3D-structure; Acetylation; Cytoplasm; Endoplasmic reticulum; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW RNA-mediated gene silencing; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895"
FT CHAIN 2..209
FT /note="Protein lin-28 homolog A"
FT /id="PRO_0000253787"
FT DOMAIN 39..112
FT /note="CSD"
FT ZN_FING 137..154
FT /note="CCHC-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT ZN_FING 159..176
FT /note="CCHC-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 113..136
FT /note="Flexible linker"
FT REGION 178..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MUTAGEN 46
FT /note="W->A: Does not affect localization to P-bodies; when
FT associated with A-55 and A-73."
FT /evidence="ECO:0000269|PubMed:17617744"
FT MUTAGEN 55
FT /note="F->A: Does not affect localization to P-bodies; when
FT associated with A-46 and A-73."
FT /evidence="ECO:0000269|PubMed:17617744"
FT MUTAGEN 73
FT /note="F->A: Does not affect localization to P-bodies; when
FT associated with A-46 and A-55."
FT /evidence="ECO:0000269|PubMed:17617744"
FT MUTAGEN 147
FT /note="H->A: Abolishes ability to suppress pre-let-7
FT biogenesis and localization to P-bodies without affecting
FT pre-let-7 binding; when associated with A-169."
FT /evidence="ECO:0000269|PubMed:17617744,
FT ECO:0000269|PubMed:18951094"
FT MUTAGEN 169
FT /note="H->A: Abolishes ability to suppress pre-let-7
FT biogenesis and localization to P-bodies without affecting
FT pre-let-7 binding; when associated with A-147."
FT /evidence="ECO:0000269|PubMed:17617744,
FT ECO:0000269|PubMed:18951094"
FT STRAND 36..48
FT /evidence="ECO:0007829|PDB:5UDZ"
FT TURN 49..52
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 53..61
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 64..75
FT /evidence="ECO:0007829|PDB:5UDZ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 92..100
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 103..111
FT /evidence="ECO:0007829|PDB:5UDZ"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:5UDZ"
FT TURN 124..126
FT /evidence="ECO:0007829|PDB:5UDZ"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2CQF"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:5UDZ"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:5UDZ"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:2CQF"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:5UDZ"
FT HELIX 175..178
FT /evidence="ECO:0007829|PDB:5UDZ"
SQ SEQUENCE 209 AA; 22743 MW; FA5EF6DD33FABF54 CRC64;
MGSVSNQQFA GGCAKAAEEA PEEAPEDAAR AADEPQLLHG AGICKWFNVR MGFGFLSMTA
RAGVALDPPV DVFVHQSKLH MEGFRSLKEG EAVEFTFKKS AKGLESIRVT GPGGVFCIGS
ERRPKGKSMQ KRRSKGDRCY NCGGLDHHAK ECKLPPQPKK CHFCQSISHM VASCPLKAQQ
GPSAQGKPTY FREEEEEIHS PTLLPEAQN
