LIN41_CAEEL
ID LIN41_CAEEL Reviewed; 1147 AA.
AC Q9U489; Q9U490;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Protein lin-41;
DE AltName: Full=Abnormal cell lineage protein 41;
GN Name=lin-41 {ECO:0000312|WormBase:C12C8.3a};
GN ORFNames=C12C8.3 {ECO:0000312|WormBase:C12C8.3a};
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 [MRNA] (ISOFORMS A AND B), FUNCTION, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND DOWN-REGULATION BY LET-7.
RX PubMed=10882102; DOI=10.1016/s1097-2765(00)80245-2;
RA Slack F.J., Basson M., Liu Z., Ambros V., Horvitz H.R., Ruvkun G.;
RT "The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between
RT the let-7 regulatory RNA and the LIN-29 transcription factor.";
RL Mol. Cell 5:659-669(2000).
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 DEVELOPMENTAL STAGE, AND DOWN-REGULATION BY LET-7.
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 [4]
RP FUNCTION, AND MUTAGENESIS OF 1-MET--SER-38 AND GLY-34.
RX PubMed=16806150; DOI=10.1016/j.ydbio.2006.04.472;
RA Del Rio-Albrechtsen T., Kiontke K., Chiou S.-Y., Fitch D.H.A.;
RT "Novel gain-of-function alleles demonstrate a role for the heterochronic
RT gene lin-41 in C. elegans male tail tip morphogenesis.";
RL Dev. Biol. 297:74-86(2006).
RN [5]
RP FUNCTION.
RX PubMed=18550714; DOI=10.1242/dev.017046;
RA Mason D.A., Rabinowitz J.S., Portman D.S.;
RT "dmd-3, a doublesex-related gene regulated by tra-1, governs sex-specific
RT morphogenesis in C. elegans.";
RL Development 135:2373-2382(2008).
RN [6]
RP FUNCTION, AND DISRUPTION 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 [7]
RP FUNCTION.
RX PubMed=28933985; DOI=10.1080/15384101.2017.1344798;
RA Metheetrairut C., Ahuja Y., Slack F.J.;
RT "acn-1, a C. elegans homologue of ACE, genetically interacts with the let-7
RT microRNA and other heterochronic genes.";
RL Cell Cycle 16:1800-1809(2017).
RN [8]
RP COMMENT ON FUNCTION.
RX PubMed=28157501; DOI=10.1016/j.molcel.2017.01.018;
RA Hand J.M., Bazzini A.A.;
RT "When LIN41 comes to a fork in the road, it takes BOTH paths: translational
RT repression OR mRNA decay, depending on the target site position.";
RL Mol. Cell 65:375-377(2017).
RN [9]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=28111013; DOI=10.1016/j.molcel.2016.12.010;
RA Aeschimann F., Kumari P., Bartake H., Gaidatzis D., Xu L., Ciosk R.,
RA Grosshans H.;
RT "LIN41 post-transcriptionally silences mRNAs by two distinct and position-
RT dependent mechanisms.";
RL Mol. Cell 65:476-489(2017).
RN [10]
RP FUNCTION, AND 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).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF 1-MET--SER-38.
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 [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 1-MET--SER-38 AND
RP GLY-34.
RX PubMed=30910805; DOI=10.26508/lsa.201900335;
RA Aeschimann F., Neagu A., Rausch M., Grosshans H.;
RT "let-7 coordinates the transition to adulthood through a single primary and
RT four secondary targets.";
RL Life. Sci Alliance 2:0-0(2019).
CC -!- FUNCTION: Heterochronic protein which acts downstream of let-7 in
CC temporal patterning (PubMed:10882102, PubMed:30910805). Plays a role in
CC the developmental timing of postembryonic hypodermal seam cell division
CC and fusion events and adult alae production (PubMed:28933985).
CC Represses lin-29 during late larval stages, which prevents terminal
CC differentiation of hypodermal seam cells and promotes their division
CC (PubMed:10882102). Involved in post-transcriptional gene regulation,
CC uses two independent pathways (PubMed:28157501). Has direct and
CC specific RNA-binding activity and, depending on the location (5'UTR or
CC 3'UTR) of the target site, triggers either mRNA decay or repression of
CC translation (PubMed:28111013, PubMed:30910805). Degrades the mRNA of
CC transcription factor dmd-3 to govern the timing and extent of male tail
CC tip morphogenesis (PubMed:16806150, PubMed:18550714, PubMed:28111013,
CC PubMed:30910805, PubMed:26811380, PubMed:30956008). Plays a role in the
CC sexual maturation of the nervous system (PubMed:31264582).
CC {ECO:0000269|PubMed:10882102, ECO:0000269|PubMed:16806150,
CC ECO:0000269|PubMed:18550714, ECO:0000269|PubMed:26811380,
CC ECO:0000269|PubMed:28111013, ECO:0000269|PubMed:28157501,
CC ECO:0000269|PubMed:28933985, ECO:0000269|PubMed:30910805,
CC ECO:0000269|PubMed:30956008, ECO:0000269|PubMed:31264582}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10882102}.
CC Cytoplasm, P-body {ECO:0000250|UniProtKB:Q2Q1W2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:C12C8.3a};
CC IsoId=Q9U489-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C12C8.3b};
CC IsoId=Q9U489-2; Sequence=VSP_023468;
CC -!- DEVELOPMENTAL STAGE: Expressed in body wall muscles, pharyngeal muscles
CC and most neurons at all stages from late embryogenesis until adulthood.
CC Expressed in hypodermal seam cells until the L4 stage.
CC {ECO:0000269|PubMed:10882102, ECO:0000269|PubMed:16122423}.
CC -!- INDUCTION: Negatively regulated by the microRNA (miRNA) let-7 which
CC causes degradation of the mRNA encoding this protein. This requires a
CC let-7 complementary site (LCS) in the 3'-UTR of the mRNA encoding this
CC protein. {ECO:0000269|PubMed:10882102, ECO:0000269|PubMed:16122423}.
CC -!- DOMAIN: The NHL domain, containing the 6 NHL repeats, is necessary and
CC sufficient to target RNA but not to repress mRNA. The minimal region
CC needed to execute repression consists of the coiled coil domain and the
CC Filamin repeat. The RING-type domain is dispensable for mRNA
CC repression. {ECO:0000250|UniProtKB:Q2Q1W2}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in the precocious
CC onset of tail tip retraction resulting in over-retracted and shortened
CC adult male tails (also known as the Ore phenotype) (PubMed:26811380,
CC PubMed:30956008). RNAi-mediated knockdown results in increased
CC expression of dmd-3. {ECO:0000269|PubMed:26811380,
CC ECO:0000269|PubMed:30910805, ECO:0000269|PubMed:30956008}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
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DR EMBL; AF195610; AAF15529.1; -; mRNA.
DR EMBL; AF195611; AAF15530.1; -; mRNA.
DR EMBL; BX284601; CAC42255.1; -; Genomic_DNA.
DR EMBL; BX284601; CAC42254.1; -; Genomic_DNA.
DR RefSeq; NP_001020998.1; NM_001025827.4. [Q9U489-1]
DR RefSeq; NP_001020999.1; NM_001025828.4. [Q9U489-2]
DR PDB; 4UMG; X-ray; 1.68 A; A=691-821.
DR PDBsum; 4UMG; -.
DR AlphaFoldDB; Q9U489; -.
DR SMR; Q9U489; -.
DR BioGRID; 38191; 96.
DR IntAct; Q9U489; 13.
DR STRING; 6239.C12C8.3a.1; -.
DR EPD; Q9U489; -.
DR PaxDb; Q9U489; -.
DR PeptideAtlas; Q9U489; -.
DR EnsemblMetazoa; C12C8.3a.1; C12C8.3a.1; WBGene00003026. [Q9U489-1]
DR EnsemblMetazoa; C12C8.3a.2; C12C8.3a.2; WBGene00003026. [Q9U489-1]
DR EnsemblMetazoa; C12C8.3b.1; C12C8.3b.1; WBGene00003026. [Q9U489-2]
DR EnsemblMetazoa; C12C8.3b.2; C12C8.3b.2; WBGene00003026. [Q9U489-2]
DR GeneID; 172760; -.
DR KEGG; cel:CELE_C12C8.3; -.
DR UCSC; C12C8.3b; c. elegans. [Q9U489-1]
DR CTD; 172760; -.
DR WormBase; C12C8.3a; CE27062; WBGene00003026; lin-41. [Q9U489-2]
DR WormBase; C12C8.3b; CE27063; WBGene00003026; lin-41. [Q9U489-1]
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00980000198821; -.
DR InParanoid; Q9U489; -.
DR OMA; ESGPCAK; -.
DR OrthoDB; 489543at2759; -.
DR PhylomeDB; Q9U489; -.
DR PRO; PR:Q9U489; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003026; Expressed in larva and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:1990124; C:messenger ribonucleoprotein complex; IDA:WormBase.
DR GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR GO; GO:0035198; F:miRNA binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IMP:UniProtKB.
DR GO; GO:0030371; F:translation repressor activity; IMP:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:WormBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009957; P:epidermal cell fate specification; IMP:UniProtKB.
DR GO; GO:0007276; P:gamete generation; IMP:WormBase.
DR GO; GO:0006402; P:mRNA catabolic process; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; IMP:UniProtKB.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:UniProtKB.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:0060282; P:positive regulation of oocyte development; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:WormBase.
DR GO; GO:0019538; P:protein metabolic process; IMP:WormBase.
DR GO; GO:0040034; P:regulation of development, heterochronic; IMP:WormBase.
DR GO; GO:0045604; P:regulation of epidermal cell differentiation; IMP:WormBase.
DR GO; GO:0110037; P:regulation of nematode male tail tip morphogenesis; IMP:UniProtKB.
DR DisProt; DP02990; -.
DR Gene3D; 2.120.10.30; -; 2.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR003649; Bbox_C.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR001298; Filamin/ABP280_rpt.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR001258; NHL_repeat.
DR InterPro; IPR000315; Znf_B-box.
DR Pfam; PF00630; Filamin; 1.
DR Pfam; PF01436; NHL; 6.
DR SMART; SM00502; BBC; 1.
DR SMART; SM00336; BBOX; 2.
DR SMART; SM00557; IG_FLMN; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR PROSITE; PS51125; NHL; 6.
DR PROSITE; PS50119; ZF_BBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Developmental protein; Metal-binding; Reference proteome; Repeat;
KW RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..1147
FT /note="Protein lin-41"
FT /id="PRO_0000279514"
FT REPEAT 723..817
FT /note="Filamin"
FT REPEAT 832..875
FT /note="NHL 1"
FT REPEAT 879..922
FT /note="NHL 2"
FT REPEAT 926..969
FT /note="NHL 3"
FT REPEAT 974..1017
FT /note="NHL 4"
FT REPEAT 1022..1065
FT /note="NHL 5"
FT REPEAT 1107..1147
FT /note="NHL 6"
FT ZN_FING 114..155
FT /note="RING-type"
FT ZN_FING 366..412
FT /note="B box-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 1..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1104..1123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 565..618
FT /evidence="ECO:0000255"
FT COMPBIAS 28..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 398
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT VAR_SEQ 452..455
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_023468"
FT MUTAGEN 1..38
FT /note="Missing: In bx42; disrupts tail tip morphogenesis
FT resulting in retention of the pointed larval tail tip in
FT 33% of adult males (also known as the Lep phenotype).
FT Defective sexual maturation of AIM, CEM and AWA neurons in
FT males."
FT /evidence="ECO:0000269|PubMed:16806150,
FT ECO:0000269|PubMed:30910805, ECO:0000269|PubMed:31264582"
FT MUTAGEN 34
FT /note="G->R: In bx37; disrupts tail tip morphogenesis
FT resulting in retention of the pointed larval tail tip in
FT 33% of adult males (also known as the Lep phenotype)."
FT /evidence="ECO:0000269|PubMed:16806150,
FT ECO:0000269|PubMed:30910805"
FT HELIX 695..697
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 699..703
FT /evidence="ECO:0007829|PDB:4UMG"
FT HELIX 704..706
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 707..709
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 714..719
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 761..766
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 776..779
FT /evidence="ECO:0007829|PDB:4UMG"
FT HELIX 781..783
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 784..789
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 795..803
FT /evidence="ECO:0007829|PDB:4UMG"
FT STRAND 812..818
FT /evidence="ECO:0007829|PDB:4UMG"
SQ SEQUENCE 1147 AA; 124232 MW; 2B94B8AD81C4DD8A CRC64;
MATIVPCSLE KEEGAPSGPR RLQTEIDVDA NDSGNELSMG GSSSEGDSMS HHRGEHSPNH
HHQDNHLGSG PPPPQFTGSL FDTPPSMIQS PQQQPQFQFN TGFGLGLPQD SFRCSVCSKS
STIGVLPFVC AHKTCQSCYQ MTPSSYDRRA CKLCGAVSTA TANFTSQMYL SPTLPSPPRG
ALMSDCSTPT MNNHINSSTP LHQPRAFSFS LSGMPGSPSP VMGARMPSSA GGLMMRPIGF
PDSDSSLTSW SPLQQPSQLS INNLSSIGGH QQQSPMLMQN VFDSLAVNDD TPVFSPLSPT
NTSMHMPPSL MASPDVPKHS ATIAPPRNSM CSTPRLQLAT PMSSQSQQTF PIPSPLGSQP
QQQQPMGPIQ CQGCESKISF AYCMQCQEAL CIHCVQAHQR VRATKQHAFV ELQQLMATLM
SRAVQPQQAQ QYTQNVGGSV RQALGSVGSG DVFFSGHVSG VENDSIGSGE SSPRSSSVCG
THDSVIIGIC ENCPHSVLLC AICVAQHPGK HRVQPLGDIR VAVGEVVNES QLLQWQCEKT
GDTIKQIIDG IVTNATTAEN EIRAAFDTHV NALEERRKEL LKRVETVKNL KLSVLISQAE
SLQSKQIDLQ QAIQTATKLM DSSDCDEMVL RQVFEKLASC QMGNEGTEPN NNILNVLMLA
CQVNEDDRLK FTAPQDGILL NKARQFGNIE SGPCAKNSSI VGDSFKKAIR ERQTVIYVQL
RDACGDLLSS SIAATQPTSQ ALLPHQEPHS HLEQAMPTSD VQAFVISPDG STVEVTMTPR
ENGIVALSYY PSIEGSYTLN ILVKGTPISG CPTTMDIRRG RNYDEIAAKG PILTFGKEGS
GDGELCRPWG ICVDQRGRVI VADRSNNRVQ IFDKDGNFIS KFGTSGNRPG QFDRPAGITT
NSLNNIVVAD KDNHRVQVFD ENGMFLLKFG DRGRAVGYFN YPWGVATNSH NAIAVSDTRN
HRVQIFTPQG QFVRKCGFDS AYFFKNLDSP RGLCYLPDGQ LLITDFNNHR LAVLSPRNMS
EMKVYGSEGD GDGMFVRPQG VVIDPEGHIL VCDSRNNRVQ VFASDDMRFI GSFGLGPVPN
SGFQMPQELP APYSSLGGPF GAPAFSSAPT PLTPSPRQLL DRPTDLAVGP DGRIYVVDFG
NNCIRVF
