UFD1_CAEEL
ID UFD1_CAEEL Reviewed; 342 AA.
AC Q19584;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Ubiquitin fusion degradation protein 1 homolog;
DE Short=UB fusion protein 1;
GN Name=ufd-1; ORFNames=F19B6.2;
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 [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 [2]
RP FUNCTION, INTERACTION WITH CDC-48.1; CDC-48.2 AND NPL-4, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16647269; DOI=10.1016/j.jsb.2006.02.015;
RA Mouysset J., Kaehler C., Hoppe T.;
RT "A conserved role of Caenorhabditis elegans CDC-48 in ER-associated protein
RT degradation.";
RL J. Struct. Biol. 156:41-49(2006).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=18728180; DOI=10.1073/pnas.0805944105;
RA Mouysset J., Deichsel A., Moser S., Hoege C., Hyman A.A., Gartner A.,
RA Hoppe T.;
RT "Cell cycle progression requires the CDC-48UFD-1/NPL-4 complex for
RT efficient DNA replication.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12879-12884(2008).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH UBXN-3; UFD-1 AND NPL-4.1, INTERACTION
RP WITH CDC-48.1, AND DISRUPTION PHENOTYPE.
RX PubMed=20977550; DOI=10.1111/j.1365-2443.2010.01454.x;
RA Sasagawa Y., Yamanaka K., Saito-Sasagawa Y., Ogura T.;
RT "Caenorhabditis elegans UBX cofactors for CDC-48/p97 control
RT spermatogenesis.";
RL Genes Cells 15:1201-1215(2010).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21981920; DOI=10.1016/j.molcel.2011.08.028;
RA Franz A., Orth M., Pirson P.A., Sonneville R., Blow J.J., Gartner A.,
RA Stemmann O., Hoppe T.;
RT "CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation
RT to ensure faithful DNA replication.";
RL Mol. Cell 44:85-96(2011).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22768338; DOI=10.1371/journal.pone.0040145;
RA Miedel M.T., Graf N.J., Stephen K.E., Long O.S., Pak S.C., Perlmutter D.H.,
RA Silverman G.A., Luke C.J.;
RT "A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-
RT associated degradation in C. elegans.";
RL PLoS ONE 7:E40145-E40145(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26842564; DOI=10.1038/ncomms10612;
RA Franz A., Pirson P.A., Pilger D., Halder S., Achuthankutty D., Kashkar H.,
RA Ramadan K., Hoppe T.;
RT "Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard
RT DNA replication fork progression.";
RL Nat. Commun. 7:10612-10612(2016).
CC -!- FUNCTION: Functions at a post-ubiquitination step in the ubiquitin
CC fusion degradation (UFD) pathway (By similarity). In association with
CC npl-4.1 and/or npl-4.2 and ATPase cdc-48.1 and/or cdc-48.2, involved in
CC the cytoplasmic elimination of misfolded proteins exported from the ER
CC (PubMed:16647269, PubMed:22768338). This pathway, known as ERAD,
CC prevents the activation of the unfolded protein response (UPR) caused
CC by the accumulation of misfolded proteins in the ER (PubMed:16647269,
CC PubMed:22768338). During S phase and in association with npl-4.1 and/or
CC npl-4.2, cdc-48.1 and/or cdc-48.2 and ubxn-3, ensures the degradation
CC of DNA licensing factor cdt-1 after the initiation of DNA replication
CC and thus the disassembly of the DNA replication CMG helicase complex by
CC promoting the dissociation from chromatin of several of its components
CC including cdc-45 and sld-5 (PubMed:18728180, PubMed:21981920,
CC PubMed:26842564). Regulates ubxn-3 nuclear localization during S phase
CC (PubMed:26842564). {ECO:0000250|UniProtKB:P53044,
CC ECO:0000269|PubMed:16647269, ECO:0000269|PubMed:18728180,
CC ECO:0000269|PubMed:21981920, ECO:0000269|PubMed:22768338,
CC ECO:0000269|PubMed:26842564}.
CC -!- SUBUNIT: Forms a complex composed of ubxn-3, ufd-1, npl-4.1 and cdc-
CC 48.1; within the complex interacts with cdc-48.1 (PubMed:20977550,
CC PubMed:16647269). Interacts with cdc-48.2 (PubMed:16647269). Interacts
CC with npl-4.1 and/or npl-4.2 (PubMed:16647269).
CC {ECO:0000269|PubMed:16647269, ECO:0000269|PubMed:20977550}.
CC -!- INTERACTION:
CC Q19584; Q95QZ9: npl-4.2; NbExp=3; IntAct=EBI-319945, EBI-319957;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18728180}. Nucleus
CC {ECO:0000269|PubMed:18728180}. Note=Localizes to the cytoplasm during
CC mitosis. Nuclear localization upon nuclear membrane re-assembly is cdc-
CC 48-dependent. {ECO:0000269|PubMed:18728180}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes embryonic
CC lethality (PubMed:16647269, PubMed:18728180). In embryos, DNA
CC replication is partially impaired causing a delay in S phase
CC progression in P0, AB and P1 cells; simultaneous RNAi-mediated
CC knockdown of DNA replication checkpoint kinases chk-1 or atl-1
CC suppresses the delay in S phase (PubMed:18728180). Prevents DNA
CC replication licensing factor cdt-1 down-regulation and causes cdt-1
CC accumulation on mitotic chromosomes (PubMed:21981920). Impairs
CC dissociation from the chromatin of components of the DNA replication
CC machinery, including cdc-45 and GINS complex component sld-5, resulting
CC in their persistent association with chromatin throughout embryonic
CC mitosis (PubMed:21981920, PubMed:26842564, PubMed:18728180). Abnormal
CC ubxn-3 localization into punctate structures in the nucleus
CC (PubMed:26842564). Reduces npl-4 expression in embryos
CC (PubMed:21981920, PubMed:26842564). RNAi-mediated knockdown in adults
CC causes defects in germline development, induces the unfolded protein
CC response, and causes the accumulation of misfolded protein cpl-1 in the
CC ER (PubMed:16647269, PubMed:20977550, PubMed:22768338).
CC {ECO:0000269|PubMed:16647269, ECO:0000269|PubMed:18728180,
CC ECO:0000269|PubMed:20977550, ECO:0000269|PubMed:21981920,
CC ECO:0000269|PubMed:22768338, ECO:0000269|PubMed:26842564}.
CC -!- SIMILARITY: Belongs to the UFD1 family. {ECO:0000305}.
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DR EMBL; Z69635; CAA93460.1; -; Genomic_DNA.
DR PIR; T21108; T21108.
DR RefSeq; NP_502348.1; NM_069947.3.
DR AlphaFoldDB; Q19584; -.
DR SMR; Q19584; -.
DR BioGRID; 533178; 6.
DR DIP; DIP-26847N; -.
DR IntAct; Q19584; 3.
DR STRING; 6239.F19B6.2a; -.
DR iPTMnet; Q19584; -.
DR EPD; Q19584; -.
DR PaxDb; Q19584; -.
DR PeptideAtlas; Q19584; -.
DR EnsemblMetazoa; F19B6.2a.1; F19B6.2a.1; WBGene00006733.
DR GeneID; 3565860; -.
DR KEGG; cel:CELE_F19B6.2; -.
DR UCSC; F19B6.2b; c. elegans.
DR CTD; 3565860; -.
DR WormBase; F19B6.2a; CE05667; WBGene00006733; ufd-1.
DR eggNOG; KOG1816; Eukaryota.
DR InParanoid; Q19584; -.
DR OMA; KDHSETQ; -.
DR OrthoDB; 1134444at2759; -.
DR PhylomeDB; Q19584; -.
DR Reactome; R-CEL-110320; Translesion Synthesis by POLH.
DR Reactome; R-CEL-8951664; Neddylation.
DR Reactome; R-CEL-9755511; KEAP1-NFE2L2 pathway.
DR PRO; PR:Q19584; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006733; Expressed in germ line (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q19584; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0034098; C:VCP-NPL4-UFD1 AAA ATPase complex; IDA:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IMP:WormBase.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IBA:GO_Central.
DR Gene3D; 2.40.40.50; -; 1.
DR InterPro; IPR004854; Ufd1-like.
DR InterPro; IPR042299; Ufd1-like_Nn.
DR PANTHER; PTHR12555; PTHR12555; 1.
DR Pfam; PF03152; UFD1; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..342
FT /note="Ubiquitin fusion degradation protein 1 homolog"
FT /id="PRO_0000194986"
FT REGION 245..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 342 AA; 36904 MW; 4D809C9DE97C0F15 CRC64;
MQAWIQQGLH GMQMGGRVGN YDQTFVVYGP VFLPNATQSK ISEINYGGKI LLPSSALNLL
MQYNIPMPML FKLTNMAVQR VTHCGVLEFS APEGQAILPL WMMQQLGLDD GDTIRIESAT
LPKATFAKLK PMSLEFLNIT NPKAVLEVEL RKYACLTKND RIPTSYAGQT LEFLVVDLKP
ANSVCIIECD VNLDFDPPEG YVEQPRQVTP AVTAKPPAPD ASAFIGAGQK AGGSGGTGQN
ATSVFGGAGR RLDGKKKPSS SVSLSDGTGV STSNAAPVAN DLPAIPPVVV NEDYKPGRVS
FLRYDYKRVD VLEKELREKE ASKAGQPSNV FRGGNRTLRG AR
