LIN41_MOUSE
ID LIN41_MOUSE Reviewed; 855 AA.
AC Q1PSW8;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=E3 ubiquitin-protein ligase TRIM71;
DE EC=2.3.2.27;
DE AltName: Full=Protein lin-41 homolog;
DE Short=mLin41;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM71 {ECO:0000305};
DE AltName: Full=Tripartite motif-containing protein 71;
GN Name=Trim71; Synonyms=Gm1127, Lin41;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=16477647; DOI=10.1002/dvdy.20712;
RA Kanamoto T., Terada K., Yoshikawa H., Furukawa T.;
RT "Cloning and regulation of the vertebrate homologue of lin-41 that
RT functions as a heterochronic gene in Caenorhabditis elegans.";
RL Dev. Dyn. 235:1142-1149(2006).
RN [2]
RP IDENTIFICATION.
RX PubMed=16245339; DOI=10.1002/dvdy.20591;
RA Lancman J.J., Caruccio N.C., Harfe B.D., Pasquinelli A.E., Schageman J.J.,
RA Pertsemlidis A., Fallon J.F.;
RT "Analysis of the regulation of lin-41 during chick and mouse limb
RT development.";
RL Dev. Dyn. 234:948-960(2005).
RN [3]
RP IDENTIFICATION, AND DEVELOPMENTAL STAGE.
RX PubMed=16247770; DOI=10.1002/dvdy.20599;
RA Maller Schulman B.R., Esquela-Kerscher A., Slack F.J.;
RT "Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during
RT mouse embryogenesis.";
RL Dev. Dyn. 234:1046-1054(2005).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=19098426; DOI=10.4161/cc.7.24.7397;
RA Maller Schulman B.R., Liang X., Stahlhut C., DelConte C., Stefani G.,
RA Slack F.J.;
RT "The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse
RT embryonic survival and neural tube closure.";
RL Cell Cycle 7:3935-3942(2008).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH AGO2,
RP AND MUTAGENESIS OF CYS-12 AND CYS-15.
RX PubMed=19898466; DOI=10.1038/ncb1987;
RA Rybak A., Fuchs H., Hadian K., Smirnova L., Wulczyn E.A., Michel G.,
RA Nitsch R., Krappmann D., Wulczyn F.G.;
RT "The let-7 target gene mouse lin-41 is a stem cell specific E3 ubiquitin
RT ligase for the miRNA pathway protein Ago2.";
RL Nat. Cell Biol. 11:1411-1420(2009).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AUTOUBIQUITINATION, AND INTERACTION WITH AGO2 AND SHCBP1.
RX PubMed=22508726; DOI=10.1101/gad.187641.112;
RA Chen J., Lai F., Niswander L.;
RT "The ubiquitin ligase mLin41 temporally promotes neural progenitor cell
RT maintenance through FGF signaling.";
RL Genes Dev. 26:803-815(2012).
RN [7]
RP FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, INTERACTION WITH AGO2, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=22735451; DOI=10.1038/ncomms1909;
RA Chang H.M., Martinez N.J., Thornton J.E., Hagan J.P., Nguyen K.D.,
RA Gregory R.I.;
RT "Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote
RT embryonic stem cell proliferation.";
RL Nat. Commun. 3:923-923(2012).
RN [8]
RP FUNCTION.
RX PubMed=23125361; DOI=10.1093/nar/gks1032;
RA Loedige I., Gaidatzis D., Sack R., Meister G., Filipowicz W.;
RT "The mammalian TRIM-NHL protein TRIM71/LIN-41 is a repressor of mRNA
RT function.";
RL Nucleic Acids Res. 41:518-532(2013).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=25883935; DOI=10.3389/fcell.2015.00020;
RA Cuevas E., Rybak-Wolf A., Rohde A.M., Nguyen D.T., Wulczyn F.G.;
RT "Lin41/Trim71 is essential for mouse development and specifically expressed
RT in postnatal ependymal cells of the brain.";
RL Front. Cell Dev. Biol. 3:20-20(2015).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that cooperates with the
CC microRNAs (miRNAs) machinery and promotes embryonic stem cells
CC proliferation and maintenance (PubMed:19898466). Binds to miRNAs and
CC associates with AGO2, participating in post-transcriptional repression
CC of transcripts such as CDKN1A. Facilitates the G1-S transition to
CC promote rapid embryonic stem cell self-renewal by repressing CDKN1A
CC expression (PubMed:22735451). In addition, participates in post-
CC transcriptional mRNA repression in a miRNA independent mechanism
CC (PubMed:23125361). Required to maintain proliferation and prevent
CC premature differentiation of neural progenitor cells during early
CC neural development: positively regulates FGF signaling by controlling
CC the stability of SHCBP1 (PubMed:22735451). Specific regulator of miRNA
CC biogenesis. miRNA Binds MIR29A hairpin and postranscriptionally
CC modulates MIR29A levels, which indirectly regulates TET proteins
CC expression (By similarity). {ECO:0000250|UniProtKB:Q2Q1W2,
CC ECO:0000269|PubMed:19898466, ECO:0000269|PubMed:22735451,
CC ECO:0000269|PubMed:23125361}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts (via NHL repeats) with AGO2; the interaction
CC increases in presence of RNA (PubMed:19898466, PubMed:22508726,
CC PubMed:22735451). Interacts with HSP90AA1. Interacts (via NHL repeats)
CC with MOV10, PABPC1, PUM1, PUM2, STAU2, XRN1 and XRN2 in an RNA-
CC dependent manner (By similarity). Interacts with SHCBP1; leading to
CC enhance its stability (PubMed:22508726). {ECO:0000250|UniProtKB:Q2Q1W2,
CC ECO:0000269|PubMed:19898466, ECO:0000269|PubMed:22508726,
CC ECO:0000269|PubMed:22735451}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:19898466,
CC ECO:0000269|PubMed:22508726, ECO:0000269|PubMed:22735451}.
CC -!- TISSUE SPECIFICITY: Highly expressed in undifferentiated embryonic stem
CC cells (ESCs). Expressed in the epiblast and in interfollicular
CC epidermal stem cells during early development. Also expressed in male
CC germ cells and in the reproductive tract. Highly expressed in
CC neuroepithelial cells, and its expression declines as neurogenesis
CC proceeds (at protein level). Expressed in ependymal cells of the brain
CC (PubMed:25883935). {ECO:0000269|PubMed:19898466,
CC ECO:0000269|PubMed:22508726, ECO:0000269|PubMed:22735451,
CC ECO:0000269|PubMed:25883935}.
CC -!- DEVELOPMENTAL STAGE: Expression is first detected at 8.5 dpc, increases
CC to highest levels at 14.5 dpc and remains elevated through the newborn
CC stage. Expressed in developing limb buds and tail buds starting from
CC 9.5 dpc. At 9.5 dpc, expression is prominent in the entire embryo, with
CC the exception of the primordial cardiac sac. At 10.5 dpc, expression
CC reduces to the neuroepithelium, branchial arches, spinal cord, somites,
CC limb, and tail buds. At the onset of central nervous system
CC development, the neuroepithelium shows a prominent staining between 9.5
CC dpc and 10.5 dpc. Thereafter, expression is unevenly distributed in a
CC progressively thinner layer along the inner surface of the ventricle.
CC Expression is intense at the bumps corresponding to the nascent limb
CC buds around 10.5 dpc. Shortly thereafter, as the limb buds emerge from
CC the body and expand, expression declines and is limited to the most
CC distal surface at 12.5 dpc. At 13.5 dpc it is no longer possible to
CC identify expression in either the developing nervous system, the limb
CC or the tail buds. From postnatal day 10 (P10) to the adulthood,
CC expressed in cells lining the wall of the four ventricles of the
CC postnatal brain (PubMed:25883935). {ECO:0000269|PubMed:16247770,
CC ECO:0000269|PubMed:16477647, ECO:0000269|PubMed:25883935}.
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:22735451}.
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 -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:22508726}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality at 9.5 dpc, due to a neural
CC tube closure defect in the anterior craniofacial region of the neural
CC tube, corresponding to the forebrain/midbrain boundary. Reduced cell
CC proliferation in the neuroepithelium. {ECO:0000269|PubMed:19098426,
CC ECO:0000269|PubMed:22508726, ECO:0000269|PubMed:25883935}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC -!- CAUTION: Reported to mediate ubiquitination and subsequent degradation
CC of AGO2 (PubMed:19898466). However, this result is subject to
CC discussion and later reports suggest that, while it interacts with
CC AGO2, it is not involved in AGO2 ubiquitination (PubMed:22508726,
CC PubMed:22735451). {ECO:0000305|PubMed:19898466,
CC ECO:0000305|PubMed:22508726, ECO:0000305|PubMed:22735451}.
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DR EMBL; DQ005956; AAY55947.1; -; mRNA.
DR CCDS; CCDS40793.1; -.
DR RefSeq; NP_001035968.1; NM_001042503.2.
DR AlphaFoldDB; Q1PSW8; -.
DR SMR; Q1PSW8; -.
DR BioGRID; 561929; 10.
DR STRING; 10090.ENSMUSP00000107447; -.
DR iPTMnet; Q1PSW8; -.
DR PhosphoSitePlus; Q1PSW8; -.
DR PaxDb; Q1PSW8; -.
DR PeptideAtlas; Q1PSW8; -.
DR PRIDE; Q1PSW8; -.
DR ProteomicsDB; 292260; -.
DR Antibodypedia; 45336; 190 antibodies from 33 providers.
DR Ensembl; ENSMUST00000111816; ENSMUSP00000107447; ENSMUSG00000079259.
DR GeneID; 636931; -.
DR KEGG; mmu:636931; -.
DR UCSC; uc009rxp.1; mouse.
DR CTD; 131405; -.
DR MGI; MGI:2685973; Trim71.
DR VEuPathDB; HostDB:ENSMUSG00000079259; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000159099; -.
DR HOGENOM; CLU_008645_4_1_1; -.
DR InParanoid; Q1PSW8; -.
DR OMA; QGEPRCS; -.
DR OrthoDB; 489543at2759; -.
DR PhylomeDB; Q1PSW8; -.
DR TreeFam; TF331018; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 636931; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Trim71; mouse.
DR PRO; PR:Q1PSW8; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q1PSW8; protein.
DR Bgee; ENSMUSG00000079259; Expressed in primitive streak and 68 other tissues.
DR Genevisible; Q1PSW8; MM.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB.
DR GO; GO:0030371; F:translation repressor activity; ISO:MGI.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0061158; P:3'-UTR-mediated mRNA destabilization; ISO:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0010586; P:miRNA metabolic process; IDA:UniProtKB.
DR GO; GO:0035196; P:miRNA processing; ISS:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IMP:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0021915; P:neural tube development; IDA:UniProtKB.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IDA:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0060964; P:regulation of miRNA-mediated gene silencing; IMP:UniProtKB.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; IMP:UniProtKB.
DR GO; GO:0051246; P:regulation of protein metabolic process; IDA:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:UniProtKB.
DR Gene3D; 2.120.10.30; -; 3.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
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 InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00630; Filamin; 1.
DR Pfam; PF01436; NHL; 6.
DR Pfam; PF00643; zf-B_box; 1.
DR SMART; SM00336; BBOX; 2.
DR SMART; SM00557; IG_FLMN; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR PROSITE; PS51125; NHL; 6.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Coiled coil; Cytoplasm; Developmental protein; Metal-binding;
KW Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q2Q1W2"
FT CHAIN 2..855
FT /note="E3 ubiquitin-protein ligase TRIM71"
FT /id="PRO_0000279512"
FT REPEAT 466..567
FT /note="Filamin"
FT REPEAT 580..623
FT /note="NHL 1"
FT REPEAT 627..670
FT /note="NHL 2"
FT REPEAT 674..717
FT /note="NHL 3"
FT REPEAT 721..764
FT /note="NHL 4"
FT REPEAT 768..811
FT /note="NHL 5"
FT REPEAT 815..855
FT /note="NHL 6"
FT ZN_FING 12..94
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 181..228
FT /note="B box-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT ZN_FING 260..301
FT /note="B box-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 26..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 314..352
FT /evidence="ECO:0000255"
FT COILED 378..411
FT /evidence="ECO:0000255"
FT COMPBIAS 26..45
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 265
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 288
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q2Q1W2"
FT MUTAGEN 12
FT /note="C->L: Abolishes E3 ubiquitin-protein ligase
FT activity; when associated with A-15."
FT /evidence="ECO:0000269|PubMed:19898466"
FT MUTAGEN 15
FT /note="C->A: Abolishes E3 ubiquitin-protein ligase
FT activity; when associated with L-12."
FT /evidence="ECO:0000269|PubMed:19898466"
SQ SEQUENCE 855 AA; 92054 MW; 151BA48E28C34904 CRC64;
MASFPETDFQ ICLLCKEMCG SPAPLSSNSS ASSSSSQTST SSAGGGGPGA AARRLHVLPC
LHAFCRPCLE AHRLPAPGGA GPAEALKLRC PVCDQKVVLA EAAGMDALPS SAFLLSNLLD
AVVATAEEPP PKNGRAGGGP GGAGGHSNHR HHAHHPAQRA AAPAPQPPPG PAASPGSLLM
RRPHGCSSCD EGNAASSRCL DCQEHLCDNC VRAHQRVRLT KDHYIERGPP GPAAASAAQQ
LGLGPPFAGA PFSILSVFPE RLGFCQHHDD EVLHLYCDTC SVPICRECTL GRHGGHSFAY
LQDALQDSRA LTIQLLADAQ QGRQALQLSI EQAQTVAEQV EMKAKVVQSE VKAVTARHKK
ALEDRECELL WKVEKIRQVK AKSLFLQVEK LRQSLSKLES TISAVQQVLE EGRALDILLA
RDRMLAQVQE LKTIRGLLQP QEDDRIMFTP PDQALYLALK SIGFVSSGAF APLTKATGDG
IKRALQGKVA SFTVMGYDHD GEPRHSGGDL MSVVVLGPDG NLFGAEVSDQ QNGTYIVSYR
PQLEGEHLVS VTLYNQHIEN SPFKVVVKSG RSYVGIGLPG LSFGSEGDGE GKLCRPWGVS
VDKEGFIIVA DRSNNRIQVF KPCGSFHHKF GTLGSRPGQF DRPAGVACDA SRRIIVADKD
NHRIQIFTFE GQFLLKFGEK GTKNGQFNYP WDVAVNSEGK ILVSDTRNHR IQLFGPDGVF
LNKYGFEGSL WKHFDSPRGV AFNNEGHLVV TDFNNHRLLV IHPDCQSARF LGSEGSGNGQ
FLRPQGVAVD QEGRIIVADS RNHRVQMFEA NGSFLCKFGA QGSGFGQMDR PSGIAVTPDG
LIVVVDFGNN RILIF
