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LIN28_CAEEL
ID   LIN28_CAEEL             Reviewed;         227 AA.
AC   P92186; Q9U3K6;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   03-AUG-2022, entry version 166.
DE   RecName: Full=Protein lin-28 {ECO:0000305};
DE   AltName: Full=Abnormal cell lineage protein 28 {ECO:0000312|WormBase:F02E9.2a};
GN   Name=lin-28 {ECO:0000312|WormBase:F02E9.2a};
GN   ORFNames=F02E9.2 {ECO:0000312|WormBase:F02E9.2a};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR
RP   LOCATION, DEVELOPMENTAL STAGE, INDUCTION, AND MUTAGENESIS OF GLY-55;
RP   MET-87; ARG-91; GLY-128 AND PRO-133.
RC   STRAIN=Bristol N2;
RX   PubMed=9054503; DOI=10.1016/s0092-8674(00)81906-6;
RA   Moss E.G., Lee R.C., Ambros V.;
RT   "The cold shock domain protein LIN-28 controls developmental timing in C.
RT   elegans and is regulated by the lin-4 RNA.";
RL   Cell 88:637-646(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [3]
RP   FUNCTION.
RX   PubMed=6494891; DOI=10.1126/science.6494891;
RA   Ambros V., Horvitz H.R.;
RT   "Heterochronic mutants of the nematode Caenorhabditis elegans.";
RL   Science 226:409-416(1984).
RN   [4]
RP   FUNCTION.
RX   PubMed=2702689; DOI=10.1016/0092-8674(89)90171-2;
RA   Ambros V.;
RT   "A hierarchy of regulatory genes controls a larva-to-adult developmental
RT   switch in C. elegans.";
RL   Cell 57:49-57(1989).
RN   [5]
RP   FUNCTION.
RX   PubMed=2628162; DOI=10.1101/gad.3.12b.2039;
RA   Liu Z.C., Ambros V.;
RT   "Heterochronic genes control the stage-specific initiation and expression
RT   of the dauer larva developmental program in Caenorhabditis elegans.";
RL   Genes Dev. 3:2039-2049(1989).
RN   [6]
RP   FUNCTION.
RX   PubMed=1916265; DOI=10.1101/gad.5.10.1825;
RA   Arasu P., Wightman B., Ruvkun G.;
RT   "Temporal regulation of lin-14 by the antagonistic action of two other
RT   heterochronic genes, lin-4 and lin-28.";
RL   Genes Dev. 5:1825-1833(1991).
RN   [7]
RP   FUNCTION.
RX   PubMed=7671811; DOI=10.1242/dev.121.8.2471;
RA   Liu Z.C., Kirch S., Ambros V.;
RT   "The Caenorhabditis elegans heterochronic gene pathway controls stage-
RT   specific transcription of collagen genes.";
RL   Development 121:2471-2478(1995).
RN   [8]
RP   FUNCTION.
RX   PubMed=8625405; DOI=10.1016/s0092-8674(00)81045-4;
RA   Euling S., Ambros V.;
RT   "Heterochronic genes control cell cycle progress and developmental
RT   competence of C. elegans vulva precursor cells.";
RL   Cell 84:667-676(1996).
RN   [9]
RP   FUNCTION.
RX   PubMed=8756295; DOI=10.1242/dev.122.8.2507;
RA   Euling S., Ambros V.;
RT   "Reversal of cell fate determination in Caenorhabditis elegans vulval
RT   development.";
RL   Development 122:2507-2515(1996).
RN   [10]
RP   FUNCTION.
RX   PubMed=8756296; DOI=10.1242/dev.122.8.2517;
RA   Bettinger J.C., Lee K., Rougvie A.E.;
RT   "Stage-specific accumulation of the terminal differentiation factor LIN-29
RT   during Caenorhabditis elegans development.";
RL   Development 122:2517-2527(1996).
RN   [11]
RP   FUNCTION.
RX   PubMed=9477318; DOI=10.1242/dev.125.7.1191;
RA   Antebi A., Culotti J.G., Hedgecock E.M.;
RT   "daf-12 regulates developmental age and the dauer alternative in
RT   Caenorhabditis elegans.";
RL   Development 125:1191-1205(1998).
RN   [12]
RP   FUNCTION.
RX   PubMed=9649524; DOI=10.1093/genetics/149.3.1335;
RA   Abrahante J.E., Miller E.A., Rougvie A.E.;
RT   "Identification of heterochronic mutants in Caenorhabditis elegans.
RT   Temporal misexpression of a collagen::green fluorescent protein fusion
RT   gene.";
RL   Genetics 149:1335-1351(1998).
RN   [13]
RP   FUNCTION.
RX   PubMed=10706289; DOI=10.1038/35002607;
RA   Reinhart B.J., Slack F.J., Basson M., Pasquinelli A.E., Bettinger J.C.,
RA   Rougvie A.E., Horvitz H.R., Ruvkun G.;
RT   "The 21-nucleotide let-7 RNA regulates developmental timing in
RT   Caenorhabditis elegans.";
RL   Nature 403:901-906(2000).
RN   [14]
RP   DEVELOPMENTAL STAGE, AND INDUCTION.
RX   PubMed=11884032; DOI=10.1006/dbio.2001.0563;
RA   Seggerson K., Tang L., Moss E.G.;
RT   "Two genetic circuits repress the Caenorhabditis elegans heterochronic gene
RT   lin-28 after translation initiation.";
RL   Dev. Biol. 243:215-225(2002).
RN   [15]
RP   FUNCTION.
RX   PubMed=12871707; DOI=10.1016/s0012-1606(03)00202-1;
RA   Johnson S.M., Lin S.-Y., Slack F.J.;
RT   "The time of appearance of the C. elegans let-7 microRNA is
RT   transcriptionally controlled utilizing a temporal regulatory element in its
RT   promoter.";
RL   Dev. Biol. 259:364-379(2003).
RN   [16]
RP   INDUCTION.
RX   PubMed=15380030; DOI=10.1186/1471-213x-4-11;
RA   Liu T., Zimmerman K.K., Patterson G.I.;
RT   "Regulation of signaling genes by TGFbeta during entry into dauer diapause
RT   in C. elegans.";
RL   BMC Dev. Biol. 4:11-11(2004).
RN   [17]
RP   FUNCTION.
RX   PubMed=15073154; DOI=10.1242/dev.01098;
RA   Pepper A.-S., McCane J.E., Kemper K., Yeung D.A., Lee R.C., Ambros V.,
RA   Moss E.G.;
RT   "The C. elegans heterochronic gene lin-46 affects developmental timing at
RT   two larval stages and encodes a relative of the scaffolding protein
RT   gephyrin.";
RL   Development 131:2049-2059(2004).
RN   [18]
RP   DEVELOPMENTAL STAGE, AND INDUCTION.
RX   PubMed=16122423; DOI=10.1016/j.cell.2005.07.031;
RA   Bagga S., Bracht J., Hunter S., Massirer K., Holtz J., Eachus R.,
RA   Pasquinelli A.E.;
RT   "Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation.";
RL   Cell 122:553-563(2005).
RN   [19]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=16139228; DOI=10.1016/j.devcel.2005.07.009;
RA   Abbott A.L., Alvarez-Saavedra E., Miska E.A., Lau N.C., Bartel D.P.,
RA   Horvitz H.R., Ambros V.;
RT   "The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function
RT   together to regulate developmental timing in Caenorhabditis elegans.";
RL   Dev. Cell 9:403-414(2005).
RN   [20]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=21471153; DOI=10.1242/dev.057109;
RA   Huang X., Zhang H., Zhang H.;
RT   "The zinc-finger protein SEA-2 regulates larval developmental timing and
RT   adult lifespan in C. elegans.";
RL   Development 138:2059-2068(2011).
RN   [21]
RP   PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-11;
RP   GLU-23; ASP-24 AND ASP-31.
RX   PubMed=25432023; DOI=10.7554/elife.04265;
RA   Weaver B.P., Zabinsky R., Weaver Y.M., Lee E.S., Xue D., Han M.;
RT   "CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression
RT   dynamics for robust development in C. elegans.";
RL   Elife 3:E04265-E04265(2014).
RN   [22]
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=26811380; DOI=10.1242/dev.132738;
RA   Herrera R.A., Kiontke K., Fitch D.H.;
RT   "Makorin ortholog LEP-2 regulates LIN-28 stability to promote the juvenile-
RT   to-adult transition in Caenorhabditis elegans.";
RL   Development 143:799-809(2016).
RN   [23]
RP   FUNCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF 2-SER--ASN-32; ASP-31
RP   AND ASN-32.
RX   PubMed=28602583; DOI=10.1016/j.devcel.2017.05.013;
RA   Weaver B.P., Weaver Y.M., Mitani S., Han M.;
RT   "Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and
RT   Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic
RT   Development.";
RL   Dev. Cell 41:665-673(2017).
RN   [24]
RP   FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=31264582; DOI=10.7554/elife.43660;
RA   Lawson H., Vuong E., Miller R.M., Kiontke K., Fitch D.H., Portman D.S.;
RT   "The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual
RT   maturation of the C. elegans nervous system.";
RL   Elife 8:0-0(2019).
RN   [25]
RP   FUNCTION, IDENTIFICATION IN COMPLEX WITH LEP-2, DEVELOPMENTAL STAGE, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=30956008; DOI=10.1016/j.devcel.2019.03.003;
RA   Kiontke K.C., Herrera R.A., Vuong E., Luo J., Schwarz E.M., Fitch D.H.A.,
RA   Portman D.S.;
RT   "The Long Non-Coding RNA lep-5 Promotes the Juvenile-to-Adult Transition by
RT   Destabilizing LIN-28.";
RL   Dev. Cell 49:542-555(2019).
CC   -!- FUNCTION: Heterochronic protein which controls the choice of stage
CC       specific cell fates (PubMed:9054503, PubMed:6494891, PubMed:2702689,
CC       PubMed:2628162, PubMed:1916265, PubMed:7671811, PubMed:8625405,
CC       PubMed:8756295, PubMed:8756296, PubMed:9477318, PubMed:9649524,
CC       PubMed:10706289, PubMed:12871707, PubMed:15073154, PubMed:16139228).
CC       Regulates the timing of the second larval stage events (L2 events) in
CC       the hypodermis (PubMed:2702689, PubMed:2628162). May negatively
CC       regulate the larval to adult transition via the suppression of the
CC       microRNA (miRNA) let-7 during L3 (PubMed:10706289, PubMed:12871707,
CC       PubMed:16139228). Through this regulatory role, controls the timing of
CC       the sexual maturation of the nervous system (PubMed:31264582). Also has
CC       a role in the fox-1-sex-1-mediated determination of sexual fate
CC       (PubMed:21471153). Plays a role in governing the developmental timing
CC       of male tail tip morphogenesis (PubMed:26811380, PubMed:30956008).
CC       Plays a role in controlling the seam cell number during larval stages
CC       (PubMed:21471153, PubMed:28602583). Plays a role in vulval development
CC       (PubMed:28602583). {ECO:0000269|PubMed:10706289,
CC       ECO:0000269|PubMed:12871707, ECO:0000269|PubMed:15073154,
CC       ECO:0000269|PubMed:16139228, ECO:0000269|PubMed:1916265,
CC       ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:2628162,
CC       ECO:0000269|PubMed:26811380, ECO:0000269|PubMed:2702689,
CC       ECO:0000269|PubMed:28602583, ECO:0000269|PubMed:30956008,
CC       ECO:0000269|PubMed:31264582, ECO:0000269|PubMed:6494891,
CC       ECO:0000269|PubMed:7671811, ECO:0000269|PubMed:8625405,
CC       ECO:0000269|PubMed:8756295, ECO:0000269|PubMed:8756296,
CC       ECO:0000269|PubMed:9054503, ECO:0000269|PubMed:9477318,
CC       ECO:0000269|PubMed:9649524}.
CC   -!- SUBUNIT: Component of a complex at least containing lep-2, lin-28 and
CC       the long non-coding RNA lep-5, which mediates the degradation of lin-
CC       28. {ECO:0000269|PubMed:30956008}.
CC   -!- INTERACTION:
CC       P92186-2; Q09408: pup-2; NbExp=2; IntAct=EBI-15801711, EBI-15801698;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26811380,
CC       ECO:0000269|PubMed:9054503}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=a {ECO:0000312|WormBase:F02E9.2a};
CC         IsoId=P92186-1; Sequence=Displayed;
CC       Name=b {ECO:0000312|WormBase:F02E9.2b};
CC         IsoId=P92186-2; Sequence=VSP_021122, VSP_021123;
CC   -!- DEVELOPMENTAL STAGE: Expressed at the first larval stage (L1) in
CC       several cell types including hypodermis, muscle, neurons and seam cells
CC       (PubMed:9054503, PubMed:11884032, PubMed:16122423, PubMed:16139228,
CC       PubMed:26811380, PubMed:31264582, PubMed:30956008, PubMed:21471153).
CC       Also expressed in the tail tip and pharynx at the L1 stage
CC       (PubMed:26811380). Down-regulated at L2, and absent from L3 and L4
CC       (PubMed:9054503, PubMed:11884032, PubMed:16122423, PubMed:16139228,
CC       PubMed:26811380, PubMed:31264582, PubMed:30956008, PubMed:21471153).
CC       {ECO:0000269|PubMed:11884032, ECO:0000269|PubMed:16122423,
CC       ECO:0000269|PubMed:16139228, ECO:0000269|PubMed:21471153,
CC       ECO:0000269|PubMed:26811380, ECO:0000269|PubMed:30956008,
CC       ECO:0000269|PubMed:31264582, ECO:0000269|PubMed:9054503}.
CC   -!- INDUCTION: Negatively regulated by the miRNA lin-4 which causes
CC       degradation of the mRNA encoding this protein. This requires a lin-4
CC       complementary element (LCE) in the 3'-UTR of the mRNA encoding this
CC       protein. Also negatively regulated independent of lin-4 and this is
CC       counteracted by the action of lin-14. Positively regulated by TGF-beta
CC       signaling. {ECO:0000269|PubMed:11884032, ECO:0000269|PubMed:15380030,
CC       ECO:0000269|PubMed:16122423, ECO:0000269|PubMed:9054503}.
CC   -!- PTM: Cleavage by caspase ced-3 during larval development probably
CC       induces lin-28 degradation. {ECO:0000269|PubMed:25432023,
CC       ECO:0000269|PubMed:28602583}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in a ced-3 and ain-1
CC       double mutant background reduces the percentage of animals with
CC       developmental defects including impaired egg-laying and production of
CC       ectopic seam cells. RNAi-mediated knockdown results in the precocious
CC       onset of tail tip retraction at the L3 larval stage resulting in over-
CC       retracted and shortened adult male tails (also known as the Ore
CC       phenotype) (PubMed:26811380, PubMed:30956008). RNAi-mediated knockdown
CC       suppresses the male tail tip morphogenesis defects of mutants for the
CC       long non-coding RNA lep-5 (PubMed:30956008).
CC       {ECO:0000269|PubMed:25432023, ECO:0000269|PubMed:26811380,
CC       ECO:0000269|PubMed:30956008}.
CC   -!- SIMILARITY: Belongs to the lin-28 family. {ECO:0000305}.
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DR   EMBL; U75912; AAC47476.1; -; mRNA.
DR   EMBL; U75915; AAB49759.1; -; Genomic_DNA.
DR   EMBL; BX284601; CAB61008.1; -; Genomic_DNA.
DR   EMBL; BX284601; CAB61009.1; -; Genomic_DNA.
DR   RefSeq; NP_001021085.1; NM_001025914.4. [P92186-1]
DR   RefSeq; NP_492281.2; NM_059880.5. [P92186-2]
DR   AlphaFoldDB; P92186; -.
DR   SMR; P92186; -.
DR   BioGRID; 38059; 6.
DR   ComplexPortal; CPX-5081; lep-2-lep-5-lin-28 ubiquitin ligase complex.
DR   DIP; DIP-40151N; -.
DR   IntAct; P92186; 4.
DR   STRING; 6239.F02E9.2a; -.
DR   iPTMnet; P92186; -.
DR   EPD; P92186; -.
DR   PaxDb; P92186; -.
DR   PeptideAtlas; P92186; -.
DR   EnsemblMetazoa; F02E9.2a.1; F02E9.2a.1; WBGene00003014. [P92186-1]
DR   EnsemblMetazoa; F02E9.2b.1; F02E9.2b.1; WBGene00003014. [P92186-2]
DR   GeneID; 172626; -.
DR   KEGG; cel:CELE_F02E9.2; -.
DR   UCSC; F02E9.2a; c. elegans. [P92186-1]
DR   CTD; 38639; -.
DR   WormBase; F02E9.2a; CE24879; WBGene00003014; lin-28. [P92186-1]
DR   WormBase; F02E9.2b; CE24880; WBGene00003014; lin-28. [P92186-2]
DR   eggNOG; KOG3070; Eukaryota.
DR   InParanoid; P92186; -.
DR   OMA; EPPQSHC; -.
DR   OrthoDB; 1604809at2759; -.
DR   PhylomeDB; P92186; -.
DR   PRO; PR:P92186; -.
DR   Proteomes; UP000001940; Chromosome I.
DR   Bgee; WBGene00003014; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IC:ComplexPortal.
DR   GO; GO:0019899; F:enzyme binding; IPI:WormBase.
DR   GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:WormBase.
DR   GO; GO:0003729; F:mRNA binding; IDA:WormBase.
DR   GO; GO:1990715; F:mRNA CDS binding; IDA:WormBase.
DR   GO; GO:0070883; F:pre-miRNA binding; IPI:WormBase.
DR   GO; GO:0070878; F:primary miRNA binding; IDA:WormBase.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0001708; P:cell fate specification; IMP:UniProtKB.
DR   GO; GO:0007549; P:dosage compensation; IGI:WormBase.
DR   GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:2000635; P:negative regulation of primary miRNA processing; IMP:WormBase.
DR   GO; GO:0002119; P:nematode larval development; IC:ComplexPortal.
DR   GO; GO:0042551; P:neuron maturation; IC:ComplexPortal.
DR   GO; GO:0031054; P:pre-miRNA processing; IDA:WormBase.
DR   GO; GO:0042659; P:regulation of cell fate specification; IGI:UniProtKB.
DR   GO; GO:0040034; P:regulation of development, heterochronic; IMP:WormBase.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IC:ComplexPortal.
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   Alternative splicing; Cytoplasm; Developmental protein; Metal-binding;
KW   Reference proteome; Repeat; Zinc; Zinc-finger.
FT   CHAIN           1..227
FT                   /note="Protein lin-28"
FT                   /id="PRO_0000253799"
FT   DOMAIN          52..120
FT                   /note="CSD"
FT   ZN_FING         143..160
FT                   /note="CCHC-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   ZN_FING         166..183
FT                   /note="CCHC-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   REGION          1..27
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          181..227
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         144
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         147
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="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         158
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         168
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         171
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         176
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         181
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   SITE            31..32
FT                   /note="Cleavage; by ced-3"
FT                   /evidence="ECO:0000269|PubMed:25432023,
FT                   ECO:0000269|PubMed:28602583"
FT   VAR_SEQ         1..16
FT                   /note="MSTVVSEGRNDGNNRY -> MIEAALENPVPIKSQL (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_021122"
FT   VAR_SEQ         17..47
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_021123"
FT   MUTAGEN         2..32
FT                   /note="Missing: Constitutively active and results in
FT                   reduced lin-28 protein levels. Rescues the seam cell number
FT                   and vulval developmental defects of the lin-28 n719 loss of
FT                   function mutant."
FT                   /evidence="ECO:0000269|PubMed:28602583"
FT   MUTAGEN         11
FT                   /note="D->A: Reduced ced-3-mediated cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:25432023"
FT   MUTAGEN         23
FT                   /note="E->A: Reduced ced-3-mediated cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:25432023"
FT   MUTAGEN         24
FT                   /note="D->A: Reduced ced-3-mediated cleavage in vitro."
FT                   /evidence="ECO:0000269|PubMed:25432023"
FT   MUTAGEN         31
FT                   /note="D->A: Loss of ced-3-mediated cleavage in vitro.
FT                   Partially prevents reduction of lin-28 protein levels in
FT                   vivo. About 20 percent of mutants fail to reach adulthood.
FT                   Defects in alae morphology."
FT                   /evidence="ECO:0000269|PubMed:25432023,
FT                   ECO:0000269|PubMed:28602583"
FT   MUTAGEN         32
FT                   /note="N->M: Loss of ced-3-mediated cleavage in vitro.
FT                   Prevents reduction of lin-28 protein levels in vitro."
FT                   /evidence="ECO:0000269|PubMed:28602583"
FT   MUTAGEN         55
FT                   /note="G->S: In n1119; loss of function."
FT                   /evidence="ECO:0000269|PubMed:9054503"
FT   MUTAGEN         87
FT                   /note="M->I: In ga73; when associated with Q-91."
FT                   /evidence="ECO:0000269|PubMed:9054503"
FT   MUTAGEN         91
FT                   /note="R->Q: In ga73; when associated with I-87."
FT                   /evidence="ECO:0000269|PubMed:9054503"
FT   MUTAGEN         128
FT                   /note="G->E: In ma157."
FT                   /evidence="ECO:0000269|PubMed:9054503"
FT   MUTAGEN         128
FT                   /note="G->R: In sy283."
FT                   /evidence="ECO:0000269|PubMed:9054503"
FT   MUTAGEN         133
FT                   /note="P->S: In ve9."
FT                   /evidence="ECO:0000269|PubMed:9054503"
SQ   SEQUENCE   227 AA;  25465 MW;  5E4AE901AD8BAEBC CRC64;
     MSTVVSEGRN DGNNRYSPQD EVEDRLPDVV DNRLTENMRV PSFERLPSPT PRYFGSCKWF
     NVSKGYGFVI DDITGEDLFV HQSNLNMQGF RSLDEGERVS YYIQERSNGK GREAYAVSGE
     VEGQGLKGSR IHPLGRKKAV SLRCFRCGKF ATHKAKSCPN VKTDAKVCYT CGSEEHVSSI
     CPERRRKHRP EQVAAEEAEA ARMAAEKSSP TTSDDDIREK NSNSSDE
 
 
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