NEMF_DROME
ID NEMF_DROME Reviewed; 992 AA.
AC Q9VBX1; A8E6Q0;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Ribosome quality control complex subunit NEMF homolog {ECO:0000305};
DE AltName: Full=Protein Caliban {ECO:0000303|PubMed:16103875};
GN Name=Clbn {ECO:0000303|PubMed:16103875, ECO:0000312|FlyBase:FBgn0259152};
GN ORFNames=CG11847 {ECO:0000312|FlyBase:FBgn0259152};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000312|EMBL:AAF56406.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000305}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:ABV82224.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J., Frise E., Kapadia B., Park S., Wan K., Yu C.,
RA Celniker S.;
RL Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH PROS AND EMB, DEVELOPMENTAL STAGE, DOMAIN, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16103875; DOI=10.1038/sj.onc.1208962;
RA Bi X., Jones T., Abbasi F., Lee H., Stultz B., Hursh D.A., Mortin M.A.;
RT "Drosophila caliban, a nuclear export mediator, can function as a tumor
RT suppressor in human lung cancer cells.";
RL Oncogene 24:8229-8239(2005).
RN [5]
RP FUNCTION, INDUCTION BY DNA DAMAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=22964637; DOI=10.1038/onc.2012.395;
RA Wang Y., Wang Z., Joshi B.H., Puri R.K., Stultz B., Yuan Q., Bai Y.,
RA Zhou P., Yuan Z., Hursh D.A., Bi X.;
RT "The tumor suppressor Caliban regulates DNA damage-induced apoptosis
RT through p53-dependent and -independent activity.";
RL Oncogene 32:3857-3866(2013).
RN [6]
RP FUNCTION, INDUCTION BY DNA DAMAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=30231800; DOI=10.1080/15384101.2018.1524237;
RA Song F., Li D., Wang Y., Bi X.;
RT "Drosophila Caliban mediates G1-S transition and ionizing radiation induced
RT S phase checkpoint.";
RL Cell Cycle 17:2256-2267(2018).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31378462; DOI=10.1016/j.molcel.2019.06.031;
RA Wu Z., Tantray I., Lim J., Chen S., Li Y., Davis Z., Sitron C., Dong J.,
RA Gispert S., Auburger G., Brandman O., Bi X., Snyder M., Lu B.;
RT "MISTERMINATE Mechanistically Links Mitochondrial Dysfunction with
RT Proteostasis Failure.";
RL Mol. Cell 75:835-848.e8(2019).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=33057338; DOI=10.1371/journal.pgen.1009140;
RA Dai Z., Li D., Du X., Ge Y., Hursh D.A., Bi X.;
RT "Drosophila Caliban preserves intestinal homeostasis and lifespan through
RT regulating mitochondrial dynamics and redox state in enterocytes.";
RL PLoS Genet. 16:e1009140-e1009140(2020).
CC -!- FUNCTION: As part of the ribosome quality control complex (RQC), a
CC ribosome-associated complex, mediates the extraction of incompletely
CC synthesized nascent chains from stalled ribosomes as well as their
CC ubiquitin-mediated proteasomal degradation. Thereby, frees ribosomes
CC from the stalled translation complex and prevents the accumulation of
CC nascent polypeptide chains that are potentially toxic for the cell (By
CC similarity). Responsible for selective recognition of stalled 60S
CC subunits by recognizing an exposed, nascent chain-conjugated tRNA
CC moiety (PubMed:31378462). Binds to Ala- and Thr-tRNAs and, to a lesser
CC extent, Ser-tRNA (PubMed:31378462). On mitochondrial surface, plays a
CC role in mitochondrial-stress induced translational termination
CC impairment and protein carboxyl terminal extension (MISTERMINATE)
CC (PubMed:31378462). Important for the stable association of
CC l(3)76BDr/LTN1 to the complex (By similarity). Plays a role in
CC regulating nuclear transport possibly through directly binding to both
CC emb and cargo proteins (PubMed:16103875). Plays a role in the
CC regulation of G1-to-S cell cycle transition (PubMed:30231800).
CC Regulates S phase checkpoint by antagonizing E2F1 activity
CC (PubMed:30231800). Together with hid and tefu/ATM, plays a role in DNA
CC damage-induced apoptosis through both p53-dependent and -independent
CC activity (PubMed:22964637). Plays an essential role in the regulation
CC of mitochondrial structure and redox state in enterocytes which is
CC essential for the control of intestinal stem cells proliferation and
CC intestinal homeostasis (PubMed:33057338).
CC {ECO:0000250|UniProtKB:O60524, ECO:0000269|PubMed:16103875,
CC ECO:0000269|PubMed:22964637, ECO:0000269|PubMed:30231800,
CC ECO:0000269|PubMed:31378462, ECO:0000269|PubMed:33057338}.
CC -!- SUBUNIT: Component of the ribosome quality control complex (RQC),
CC composed of at least the E3 ubiquitin ligase l(3)76BDr/LTN1 and
CC Clbn/NEMF associated with the 60S ribosomal subunit. The complex
CC probably also contains TCF25 as well as TER94/VCP and its ubiquitin-
CC binding cofactors (By similarity). Interacts (via its C-terminus) with
CC pros (via its homeobox) (PubMed:16103875). Interacts (via its N-
CC terminus) with emb (PubMed:16103875). {ECO:0000250|UniProtKB:O60524,
CC ECO:0000250|UniProtKB:Q12532, ECO:0000269|PubMed:16103875}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:33057338}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:33057338}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in enterocytes (at protein level).
CC {ECO:0000269|PubMed:33057338}.
CC -!- DEVELOPMENTAL STAGE: Expressed ubiquitously throughout embryonic
CC development. {ECO:0000269|PubMed:16103875}.
CC -!- INDUCTION: Up-regulated in response to DNA-damage induced by ionizing
CC radiation. {ECO:0000269|PubMed:22964637, ECO:0000269|PubMed:30231800}.
CC -!- DOMAIN: The N-terminal domain contains a nuclear export signal. The C-
CC terminal domain may interact with cargo proteins.
CC {ECO:0000269|PubMed:16103875}.
CC -!- DISRUPTION PHENOTYPE: Mutant flies are viable and fertile
CC (PubMed:16103875). Shows small, developmental delays and shortened
CC lifespans (PubMed:22964637, PubMed:33057338). Shows dysfunctional
CC intestinal barrier with increased number of intestinal stem cells (ISC)
CC and enteroblasts (EB) (PubMed:33057338). Results in enterocytes (EC)
CC with fragmented mitochondria and defective depolarization
CC (PubMed:33057338). Results in aberrant activation of JAK-STAT signaling
CC pathway (PubMed:33057338). Shows hypersensitization to ionizing
CC irradiation with melanotic masses, defective S phase checkpoint and
CC decreased cell death by apoptosis (PubMed:22964637, PubMed:30231800).
CC In neuroblasts, pros protein does not show relocalization to the
CC nucleus (PubMed:16103875). After ionizing irradiation, simultaneous
CC knockout of Clbn/NEMF and p53 shows similar number of DNA breaks per
CC nucleus but absence of irradiation-induced cell death compared to
CC single knockout (PubMed:22964637). Simultaneous knockout of Clbn/NEMF
CC and hid has similar disregulation of apoptosis to single mutants upon
CC ionizing irradiation (PubMed:22964637). Simultaneous knockout Clbn/NEMF
CC and tefu increases the formation of spontaneous tumors
CC (PubMed:22964637). Simultaneous knockout of Clbn and Pink1 rescues ATP
CC levels, wing posture defects and impaired neuronal numbers observed in
CC Pink1 single mutants (PubMed:31378462). RNAi-mediated knockdown results
CC in reduced lifespan (PubMed:33057338). RNAi-mediated knockdown in EC
CC results in increased number of progenitor cells and EE cells
CC (PubMed:33057338). RNAi-mediated knockdown in ISC and EB, or EE cells,
CC has no significant effect on the number of ISC, EB and EE cells
CC (PubMed:33057338). RNAi-mediated knockdown in the smooth muscle
CC surrounding the gut has no effect on the number of ISC, EB and EE cells
CC (PubMed:33057338). Simultaneous RNAi-mediated knockdown of Clbn and
CC Pink1 rescues muscular and mitochondrial morphology defects present in
CC Pink1 knockdown single mutants (PubMed:31378462).
CC {ECO:0000269|PubMed:16103875, ECO:0000269|PubMed:22964637,
CC ECO:0000269|PubMed:30231800, ECO:0000269|PubMed:31378462,
CC ECO:0000269|PubMed:33057338}.
CC -!- SIMILARITY: Belongs to the NEMF family. {ECO:0000269|PubMed:16103875}.
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DR EMBL; AE014297; AAF56406.2; -; Genomic_DNA.
DR EMBL; AE014297; ACZ95015.1; -; Genomic_DNA.
DR EMBL; BT030842; ABV82224.1; -; mRNA.
DR RefSeq; NP_001163721.1; NM_001170250.1.
DR RefSeq; NP_651341.2; NM_143084.2.
DR AlphaFoldDB; Q9VBX1; -.
DR SMR; Q9VBX1; -.
DR BioGRID; 67938; 10.
DR IntAct; Q9VBX1; 2.
DR STRING; 7227.FBpp0290493; -.
DR PaxDb; Q9VBX1; -.
DR PRIDE; Q9VBX1; -.
DR DNASU; 43018; -.
DR EnsemblMetazoa; FBtr0301277; FBpp0290492; FBgn0259152.
DR EnsemblMetazoa; FBtr0301278; FBpp0290493; FBgn0259152.
DR GeneID; 43018; -.
DR KEGG; dme:Dmel_CG11847; -.
DR UCSC; CG11847-RA; d. melanogaster.
DR CTD; 43018; -.
DR FlyBase; FBgn0259152; Clbn.
DR VEuPathDB; VectorBase:FBgn0259152; -.
DR eggNOG; KOG2030; Eukaryota.
DR GeneTree; ENSGT00390000018516; -.
DR HOGENOM; CLU_003612_1_0_1; -.
DR InParanoid; Q9VBX1; -.
DR OMA; MGAWWVN; -.
DR OrthoDB; 131285at2759; -.
DR PhylomeDB; Q9VBX1; -.
DR SignaLink; Q9VBX1; -.
DR BioGRID-ORCS; 43018; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43018; -.
DR PRO; PR:Q9VBX1; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0259152; Expressed in eye disc (Drosophila) and 28 other tissues.
DR ExpressionAtlas; Q9VBX1; baseline and differential.
DR Genevisible; Q9VBX1; DM.
DR GO; GO:0032473; C:cytoplasmic side of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:1990112; C:RQC complex; IBA:GO_Central.
DR GO; GO:0043023; F:ribosomal large subunit binding; IBA:GO_Central.
DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR GO; GO:0140708; P:CAT tailing; ISS:UniProtKB.
DR GO; GO:1902231; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IMP:FlyBase.
DR GO; GO:1902167; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:FlyBase.
DR GO; GO:0006611; P:protein export from nucleus; IMP:FlyBase.
DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB.
DR GO; GO:1990116; P:ribosome-associated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR InterPro; IPR021846; NFACT-C.
DR InterPro; IPR008532; NFACT_RNA-bd.
DR Pfam; PF11923; NFACT-C; 1.
DR Pfam; PF05670; NFACT-R_1; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleus; Reference proteome.
FT CHAIN 1..992
FT /note="Ribosome quality control complex subunit NEMF
FT homolog"
FT /id="PRO_0000408362"
FT REGION 214..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 688..715
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 771..895
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 331..370
FT /evidence="ECO:0000255"
FT COILED 481..514
FT /evidence="ECO:0000255"
FT COILED 774..839
FT /evidence="ECO:0000255"
FT COMPBIAS 214..243
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 699..715
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..794
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 824..884
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 992 AA; 112616 MW; 4F44719E1E54CBD4 CRC64;
MKTRFNTFDI ICGVAELQKL VGWRVNQIYD VDNKTYLFRM QGTGAVEKVT LLIESGTRFH
TTRFEWPKNM APSGFSMKLR KHLKNKRLEK VQQMGSDRIV DFQFGTGDAA YHVILELYDR
GNVILTDYEL TTLYILRPHT EGENLRFAMR EKYPVERAKQ PTKELELEAL VKLLENARNG
DYLRQILTPN LDCGPAVIEH VLLSHGLDNH VIKKETTEET PEAEDKPEKG GKKQRKKQQN
TKLEQKPFDM VNDLPILQQA VKDAQELIAE GNSGKSKGYI IQVKEEKPTE NGTVEFFFRN
IEFHPYLFIQ FKNFEKATFE SFMEAVDEFY STQESQKIDM KTLQQEREAL KKLSNVKNDH
AKRLEELTKV QDVDRKKAEL ITSNQSLVDN AIRAVQSAIA SQLSWPDIHE LVKEAQANGD
AVASSIKQLK LETNHISLML SDPYDNDEDD DLKDPEVTVV DVDLALSAWA NARRYYDMKR
SAAQKEKKTV DASQKALKSA ERKTQQTLKE VRTISNIVKA RKVFWFEKFY WFISSENYLV
IGGRDAQQNE LIVKRYMRPK DIYVHAEIQG ASSVIIQNPT GEEIPPKTLL EAGSMAISYS
VAWDAKVVTN SYWVTSDQVS KTAPTGEYLA TGSFMIRGKK NFLPSCHLTM GLSLLFKLED
SFIERHLGER KVRSLEDDQI DPNVKENEVE HDLLSDNEDA DSNINLSEPS SNTEITAFPN
TEVKIEHDTG RIIVRSDSVN PEIEETKESE VVLDKILKKT DDEETTIILA GPSRKKQVSA
KKTKEDKARA KQEAAKQEVP PVSSEPKNPS QVKRGQKGKL KKMKQKYKDQ DDEEREIRMM
ILKSSGKEKP QASADKVVEK SESTKEYVKP EKSAAPKNPV ELDDADEVPV GGDVDVLNSL
TGQPHEGDEL LFAIPVVAPY QALQNYKFKV KLTPGTGKRG KAAKLALNIF AKEKSCSARE
KDLLKSIKEE SLARNIPGKV KLSAPQLQKY HK
