PER_CAEEL
ID PER_CAEEL Reviewed; 597 AA.
AC Q65ZG8; H2L053; P91313;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Period protein homolog lin-42 {ECO:0000305};
DE AltName: Full=Abnormal cell lineage protein 42 {ECO:0000312|WormBase:F47F6.1b};
GN Name=lin-42 {ECO:0000312|WormBase:F47F6.1b};
GN ORFNames=F47F6.1 {ECO:0000312|WormBase:F47F6.1b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:CCD71436.1};
RN [1] {ECO:0000312|EMBL:AAF13188.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM C), FUNCTION, SUBCELLULAR
RP LOCATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAF13188.1};
RX PubMed=10550049; DOI=10.1126/science.286.5442.1141;
RA Jeon M., Gardner H.F., Miller E.A., Deshler J., Rougvie A.E.;
RT "Similarity of the C. elegans developmental timing protein LIN-42 to
RT circadian rhythm proteins.";
RL Science 286:1141-1146(1999).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15691769; DOI=10.1016/j.devcel.2004.12.006;
RA Banerjee D., Kwok A., Lin S.-Y., Slack F.J.;
RT "Developmental timing in C. elegans is regulated by kin-20 and tim-1,
RT homologs of core circadian clock genes.";
RL Dev. Cell 8:287-295(2005).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND ALTERNATIVE SPLICING.
RX PubMed=16300753; DOI=10.1016/j.ydbio.2005.09.044;
RA Tennessen J.M., Gardner H.F., Volk M.L., Rougvie A.E.;
RT "Novel heterochronic functions of the Caenorhabditis elegans period-related
RT protein LIN-42.";
RL Dev. Biol. 289:30-43(2006).
RN [5]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=20843862; DOI=10.1242/dev.048850;
RA Tennessen J.M., Opperman K.J., Rougvie A.E.;
RT "The C. elegans developmental timing protein LIN-42 regulates diapause in
RT response to environmental cues.";
RL Development 137:3501-3511(2010).
RN [6]
RP FUNCTION (ISOFORM A), DEVELOPMENTAL STAGE, AND ALTERNATIVE SPLICING.
RX PubMed=22137474; DOI=10.1016/j.cub.2011.10.054;
RA Monsalve G.C., Van Buskirk C., Frand A.R.;
RT "LIN-42/PERIOD controls cyclical and developmental progression of C.
RT elegans molts.";
RL Curr. Biol. 21:2033-2045(2011).
RN [7]
RP FUNCTION.
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 [8]
RP FUNCTION.
RX PubMed=24699545; DOI=10.1016/j.ydbio.2014.03.017;
RA Van Wynsberghe P.M., Finnegan E.F., Stark T., Angelus E.P., Homan K.E.,
RA Yeo G.W., Pasquinelli A.E.;
RT "The Period protein homolog LIN-42 negatively regulates microRNA biogenesis
RT in C. elegans.";
RL Dev. Biol. 390:126-135(2014).
RN [9]
RP FUNCTION.
RX PubMed=25032706; DOI=10.1371/journal.pgen.1004486;
RA Perales R., King D.M., Aguirre-Chen C., Hammell C.M.;
RT "LIN-42, the Caenorhabditis elegans PERIOD homolog, negatively regulates
RT microRNA transcription.";
RL PLoS Genet. 10:E1004486-E1004486(2014).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25319259; DOI=10.1073/pnas.1414856111;
RA McCulloch K.A., Rougvie A.E.;
RT "Caenorhabditis elegans period homolog lin-42 regulates the timing of
RT heterochronic miRNA expression.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:15450-15455(2014).
RN [11]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=29880558; DOI=10.1534/g3.118.200392;
RA Rhodehouse K., Cascino K., Aseltine L., Padula A., Weinstein R.,
RA Spina J.S., Olivero C.E., Van Wynsberghe P.M.;
RT "The Doubletime Homolog KIN-20 Mainly Regulates let-7 Independently of Its
RT Effects on the Period Homolog LIN-42 in Caenorhabditis elegans.";
RL G3 (Bethesda) 8:2617-2629(2018).
CC -!- FUNCTION: Transcriptional repressor which interacts with the promoter
CC region of target genes (PubMed:25032706). Has a specific role in
CC developmental timing where it regulates temporal expression of a number
CC of miRNAs and mRNAs (PubMed:16300753, PubMed:25032706, PubMed:25319259,
CC PubMed:15691769, PubMed:29880558). Controls temporal cell fate
CC transition during embryonic and early larval development by restricting
CC the expression of specific miRNAs, including let-7, miR-48, lin-4, miR-
CC 35 and miR-58 (PubMed:24699545, PubMed:25032706, PubMed:25319259,
CC PubMed:15691769, PubMed:29880558). Restricts the accumulation of lin-29
CC in the hypodermis to the larval L4 stage, thus controlling terminal
CC differentiation of seam cells (PubMed:10550049, PubMed:21471153). Has a
CC role in the miRNA-mediated specification of asymmetric gene expression
CC patterns in gustatory neurons (PubMed:25032706). May also regulate
CC genes involved in other biological processes including transport, small
CC molecule metabolism, and growth (PubMed:25032706). Inhibits dauer
CC formation, by antagonizing daf-12 (PubMed:20843862).
CC {ECO:0000269|PubMed:10550049, ECO:0000269|PubMed:15691769,
CC ECO:0000269|PubMed:16300753, ECO:0000269|PubMed:20843862,
CC ECO:0000269|PubMed:21471153, ECO:0000269|PubMed:24699545,
CC ECO:0000269|PubMed:25032706, ECO:0000269|PubMed:25319259,
CC ECO:0000269|PubMed:29880558}.
CC -!- FUNCTION: [Isoform a]: Specifically required for maintaining the timing
CC of larval development and molting cycle rhythms.
CC {ECO:0000269|PubMed:22137474}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10550049,
CC ECO:0000269|PubMed:16300753}. Cytoplasm {ECO:0000269|PubMed:10550049}.
CC Note=Expression is generally more enriched in the nuclei than the
CC cytoplasm (PubMed:10550049). Cytoplasmic expression is enhanced in
CC lateral seam cells during the molt periods of larval development
CC (PubMed:16300753). {ECO:0000269|PubMed:10550049,
CC ECO:0000269|PubMed:16300753}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.
CC {ECO:0000303|PubMed:16300753};
CC Name=b {ECO:0000312|WormBase:F47F6.1b}; Synonyms=c
CC {ECO:0000303|PubMed:16300753};
CC IsoId=Q65ZG8-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F47F6.1a}; Synonyms=d
CC {ECO:0000303|PubMed:16300753};
CC IsoId=Q65ZG8-2; Sequence=VSP_057503;
CC Name=c {ECO:0000312|WormBase:F47F6.1c}; Synonyms=a
CC {ECO:0000303|PubMed:16300753};
CC IsoId=Q65ZG8-3; Sequence=VSP_057504, VSP_057505;
CC -!- DEVELOPMENTAL STAGE: Expressed from late embryonic stage onwards
CC (PubMed:10550049, PubMed:16300753). Shows oscillating expression levels
CC during larval stages, with peak levels in intermolt periods and minimal
CC levels during ecdysis (PubMed:16300753, PubMed:20843862,
CC PubMed:22137474, PubMed:29880558). Expressed in hypodermis, vulva,
CC intestine, muscle, neurons and somatic gonad throughout larval
CC development, in an oscillating pattern (PubMed:16300753,
CC PubMed:22137474). Expressed in sex myoblasts during larval stages L1,
CC L2 and L3, in an oscillating pattern (PubMed:16300753). Expressed in
CC gonad distal tip cells (DTC) during the L2 and L3 stages, in an
CC oscillating pattern (PubMed:16300753). {ECO:0000269|PubMed:10550049,
CC ECO:0000269|PubMed:16300753, ECO:0000269|PubMed:20843862,
CC ECO:0000269|PubMed:22137474, ECO:0000269|PubMed:29880558}.
CC -!- DEVELOPMENTAL STAGE: [Isoform a]: Expressed in the pharyngeal
CC myoepithelium, the major body hypodermal syncytium and lateral seam
CC cells from the mid L1 stage. Expression in the hypodermis rises and
CC falls at the start and end of every molt, respectively.
CC {ECO:0000269|PubMed:22137474}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit a delay in development
CC characterized by a strong molting defect, resulting in a prolonged L1
CC stage followed by an arrest in development in the L2 stage in most
CC animals (PubMed:25319259). There is increased expression of the
CC heterochronic miRNAs, lin-4 and miR-48, in late L1 (PubMed:25319259).
CC In addition, there is increased expression of the heterochronic miRNA
CC let-7 at the L3 and L4 larval stages (PubMed:29880558). Seam cell shape
CC and connectivity is severely abnormal during the molt stages
CC (PubMed:22137474). Animals display a precocious alae phenotype, with
CC the early formation of either full or partial alae in the adult cuticle
CC (PubMed:25319259, PubMed:29880558). The precocious alae phenotype is
CC suppressed in the double lin-42 and let-7 mutant and lin-42 and miR-48
CC mutant (PubMed:25319259). The quadruple lin-42, miR-48, miR-241 and
CC let-7 mutant has a retarded phenotype at L4, with many animals having
CC few full and partial alae or none (PubMed:25319259). The number of
CC animals displaying a squat body statue, referred to as a dumpy
CC phenotype, is increased, the incomplete alae formation defect is
CC rescued and increased let-7 levels are reduced in a kin-20 RNAi-
CC mediated knockdown mutant background (PubMed:29880558). RNAi-mediated
CC knockdown leads to a severe hypodermal phenotype, premature execution
CC of developmental events in vulval precursor cells, DTC and sex
CC myoblasts (PubMed:16300753). Furthermore, seam cell terminal
CC differentiation is only partially initiated at the L4 larval stage
CC (PubMed:15691769). RNAi-mediated knockdown increases the survival rate
CC and partially restores alae formation of let-7 n2853 mutants at 20
CC degrees Celsius (PubMed:15691769). {ECO:0000269|PubMed:15691769,
CC ECO:0000269|PubMed:16300753, ECO:0000269|PubMed:25319259,
CC ECO:0000269|PubMed:29880558}.
CC -!- MISCELLANEOUS: [Isoform a]: Produced by alternative promoter usage.
CC {ECO:0000303|PubMed:10550049, ECO:0000303|PubMed:22137474}.
CC -!- MISCELLANEOUS: [Isoform c]: Produced by alternative splicing.
CC {ECO:0000303|PubMed:22137474}.
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DR EMBL; AF183400; AAF13188.1; -; mRNA.
DR EMBL; BX284602; CCD71436.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD71435.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD71437.1; -; Genomic_DNA.
DR PIR; B88040; B88040.
DR RefSeq; NP_001022176.1; NM_001027005.3. [Q65ZG8-2]
DR RefSeq; NP_001022177.1; NM_001027006.4. [Q65ZG8-1]
DR RefSeq; NP_001022178.1; NM_001027007.2. [Q65ZG8-3]
DR AlphaFoldDB; Q65ZG8; -.
DR SMR; Q65ZG8; -.
DR DIP; DIP-25313N; -.
DR IntAct; Q65ZG8; 1.
DR STRING; 6239.F47F6.1b; -.
DR EPD; Q65ZG8; -.
DR PaxDb; Q65ZG8; -.
DR PeptideAtlas; Q65ZG8; -.
DR EnsemblMetazoa; F47F6.1a.1; F47F6.1a.1; WBGene00018572. [Q65ZG8-2]
DR EnsemblMetazoa; F47F6.1b.1; F47F6.1b.1; WBGene00018572. [Q65ZG8-1]
DR EnsemblMetazoa; F47F6.1c.1; F47F6.1c.1; WBGene00018572. [Q65ZG8-3]
DR GeneID; 173503; -.
DR UCSC; F47F6.1b; c. elegans.
DR CTD; 173503; -.
DR WormBase; F47F6.1a; CE29325; WBGene00018572; lin-42. [Q65ZG8-2]
DR WormBase; F47F6.1b; CE37237; WBGene00018572; lin-42. [Q65ZG8-1]
DR WormBase; F47F6.1c; CE10706; WBGene00018572; lin-42. [Q65ZG8-3]
DR eggNOG; KOG3753; Eukaryota.
DR GeneTree; ENSGT00940000174107; -.
DR HOGENOM; CLU_432276_0_0_1; -.
DR InParanoid; Q65ZG8; -.
DR OMA; APIAHQK; -.
DR SignaLink; Q65ZG8; -.
DR PRO; PR:Q65ZG8; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00018572; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; Q65ZG8; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:WormBase.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0001222; F:transcription corepressor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; IBA:GO_Central.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0061067; P:negative regulation of dauer larval development; IMP:WormBase.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0040034; P:regulation of development, heterochronic; IMP:WormBase.
DR CDD; cd00130; PAS; 1.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR SMART; SM00091; PAS; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
PE 2: Evidence at transcript level;
KW Alternative promoter usage; Alternative splicing; Cytoplasm;
KW Developmental protein; Differentiation; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..597
FT /note="Period protein homolog lin-42"
FT /id="PRO_0000432385"
FT DOMAIN 155..223
FT /note="PAS"
FT /evidence="ECO:0000305"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 418..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..441
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..499
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 564..597
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..312
FT /note="MEPAGHSSATHNIVVPNANPTQPQPLAPAMREEGATLSPPNTWSSSSVEFLD
FT DADDNRLLFTCTFTLPHGTVLSSATYADGFHEQYLTIGDNFLARLEPKGQSFILSAAAA
FT SVKQRIFARVTMPDGALRACELLCEFETDRAKITVLALRSAFSLQASHVSSNFHVFTFI
FT TKHSSTCALTHIDYASIPYLGLLPTDLIGKSLLAFVYSPDVHVVRQAHIDLHNSRGKIV
FT KSIADLRLVAHNGSILRCQTEWSAYVNPWTRKMELVVARHRICSLPIGDSDVISSPPPG
FT IQSNTLPPVMAKTFEDELRTIMNK -> MDILSYLYDLAE (in isoform a)"
FT /id="VSP_057503"
FT VAR_SEQ 313..453
FT /note="PVPSTSRHSHHHHHSSLKDQNQGFPANIDLGAYIDKIVEQLVVNSTAQQQQK
FT VAVAAAAAAQAAQAAVVATAQIRKVASAPPTTSTDPPLSYTQINCLENVHRLLKSQSRP
FT ESPAKQDEPFDEKKYPPQTPLTREALTLHT -> VSSAISSVTFLSSGDGASHRLSSSS
FT VLLVLTLHFYLCASLRRDTRLARRIRRRESGQQRHLSEQKVHMLALRSMAPCQEKECKN
FT DALAGGAVSGTTDELIPRRTFLEFAWNGECNFIGGPVLYGSRRDMVQVLQKPTKLKS
FT (in isoform c)"
FT /id="VSP_057504"
FT VAR_SEQ 454..597
FT /note="Missing (in isoform c)"
FT /id="VSP_057505"
SQ SEQUENCE 597 AA; 65255 MW; 26ED5D4061A5CA43 CRC64;
MEPAGHSSAT HNIVVPNANP TQPQPLAPAM REEGATLSPP NTWSSSSVEF LDDADDNRLL
FTCTFTLPHG TVLSSATYAD GFHEQYLTIG DNFLARLEPK GQSFILSAAA ASVKQRIFAR
VTMPDGALRA CELLCEFETD RAKITVLALR SAFSLQASHV SSNFHVFTFI TKHSSTCALT
HIDYASIPYL GLLPTDLIGK SLLAFVYSPD VHVVRQAHID LHNSRGKIVK SIADLRLVAH
NGSILRCQTE WSAYVNPWTR KMELVVARHR ICSLPIGDSD VISSPPPGIQ SNTLPPVMAK
TFEDELRTIM NKPVPSTSRH SHHHHHSSLK DQNQGFPANI DLGAYIDKIV EQLVVNSTAQ
QQQKVAVAAA AAAQAAQAAV VATAQIRKVA SAPPTTSTDP PLSYTQINCL ENVHRLLKSQ
SRPESPAKQD EPFDEKKYPP QTPLTREALT LHTKRFEDEY KDTWCRRLKR LSDDVPSSPP
AKRTTPIHWT SSSQNHYRTM APAPPPPPGK NYQITYTPLD DLTDQKSTNT KSDVENVAYP
ISGSKFSTPM RLSIDGLLPR GATSTGGASP TSGTNSPPVF PKTSSSSSLL MLRDSQN
