UBQL_CAEEL
ID UBQL_CAEEL Reviewed; 502 AA.
AC G5EFF7; G5EC78; G5EG66;
DT 23-MAY-2018, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Ubiquilin {ECO:0000312|WormBase:F15C11.2a};
GN Name=ubql-1 {ECO:0000312|WormBase:F15C11.2a};
GN ORFNames=F15C11.2 {ECO:0000312|WormBase:F15C11.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {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 [2] {ECO:0000305}
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19822669; DOI=10.1083/jcb.200903024;
RA Lim P.J., Danner R., Liang J., Doong H., Harman C., Srinivasan D.,
RA Rothenberg C., Wang H., Ye Y., Fang S., Monteiro M.J.;
RT "Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD.";
RL J. Cell Biol. 187:201-217(2009).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29666234; DOI=10.1073/pnas.1711017115;
RA Hirayama S., Sugihara M., Morito D., Iemura S.I., Natsume T., Murata S.,
RA Nagata K.;
RT "Nuclear export of ubiquitinated proteins via the UBIN-POST system.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E4199-E4208(2018).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30612738; DOI=10.1016/j.cell.2018.11.024;
RA Jachimowicz R.D., Beleggia F., Isensee J., Velpula B.B., Goergens J.,
RA Bustos M.A., Doll M.A., Shenoy A., Checa-Rodriguez C., Wiederstein J.L.,
RA Baranes-Bachar K., Bartenhagen C., Hertwig F., Teper N., Nishi T.,
RA Schmitt A., Distelmaier F., Luedecke H.J., Albrecht B., Krueger M.,
RA Schumacher B., Geiger T., Hoon D.S.B., Huertas P., Fischer M., Hucho T.,
RA Peifer M., Ziv Y., Reinhardt H.C., Wieczorek D., Shiloh Y.;
RT "UBQLN4 represses homologous recombination and is overexpressed in
RT aggressive tumors.";
RL Cell 0:0-0(2019).
CC -!- FUNCTION: May play a role in the ER-associated protein degradation
CC pathway (ERAD) possibly via its interaction with ER-localized proteins
CC ubxn-4 and cdc-48.1 and/or cdc48.2, providing a link between the
CC polyubiquitinated ERAD substrates and the proteasome (PubMed:19822669).
CC Also plays an important role in the regulation of other protein
CC degradation mechanisms and pathways including ubiquitin-proteasome
CC system (UPS) and autophagy (By similarity). Mediates the proteasomal
CC targeting of misfolded or accumulated proteins for degradation by
CC binding (via UBA domain) to their polyubiquitin chains and by
CC interacting (via ubiquitin-like domain) with the subunits of the
CC proteasome (By similarity). Collaborates with POST (F36D4.5) in the
CC export of ubiquitinated proteins from the nucleus to the cytoplasm
CC (PubMed:29666234). Also acts as a regulator of DNA repair by inhibiting
CC homologous recombination repair, thereby redirecting double-strand
CC break repair toward non-homologous end joining (NHEJ)
CC (PubMed:30612738). {ECO:0000250|UniProtKB:Q9UMX0,
CC ECO:0000269|PubMed:19822669, ECO:0000269|PubMed:29666234,
CC ECO:0000269|PubMed:30612738}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:F15C11.2a};
CC IsoId=G5EFF7-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F15C11.2b};
CC IsoId=G5EFF7-2; Sequence=VSP_059588;
CC Name=c {ECO:0000312|WormBase:F15C11.2c};
CC IsoId=G5EFF7-3; Sequence=VSP_059589, VSP_059590;
CC -!- TISSUE SPECIFICITY: Expressed in the pharynx, hypodermis, intestine and
CC head neurons (PubMed:29666234). Upon ER stress, expressed predominantly
CC in pharyngeal muscle, hypodermis and intestine (PubMed:19822669).
CC {ECO:0000269|PubMed:19822669, ECO:0000269|PubMed:29666234}.
CC -!- INDUCTION: Induced upon ER stress. {ECO:0000269|PubMed:19822669}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a reduction in
CC lifespan (PubMed:19822669). Induces ER stress characterized by the
CC expression of hsp-4, the accumulation of ubiquitinated proteins and an
CC increase in ubxn-4 expression (PubMed:19822669). Mutants display
CC increased homologous recombination repair in response to DNA damage
CC compared to wild-type worms (PubMed:30612738). Worms lacking both POST
CC (F36D4.5) and ubql-1 have a shorter lifespan and display an
CC accumulation of ubiquitinated proteins in the nucleus
CC (PubMed:29666234). {ECO:0000269|PubMed:19822669,
CC ECO:0000269|PubMed:29666234, ECO:0000269|PubMed:30612738}.
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DR EMBL; BX284601; CAA95799.1; -; Genomic_DNA.
DR EMBL; BX284601; CAD44115.1; -; Genomic_DNA.
DR EMBL; BX284601; CAD44116.1; -; Genomic_DNA.
DR PIR; T18584; T18584.
DR RefSeq; NP_740883.1; NM_170894.3. [G5EFF7-1]
DR RefSeq; NP_740884.1; NM_171839.1. [G5EFF7-2]
DR RefSeq; NP_740885.1; NM_170895.3. [G5EFF7-3]
DR AlphaFoldDB; G5EFF7; -.
DR SMR; G5EFF7; -.
DR IntAct; G5EFF7; 4.
DR STRING; 6239.F15C11.2a; -.
DR EPD; G5EFF7; -.
DR PaxDb; G5EFF7; -.
DR EnsemblMetazoa; F15C11.2a.1; F15C11.2a.1; WBGene00008852. [G5EFF7-1]
DR EnsemblMetazoa; F15C11.2b.1; F15C11.2b.1; WBGene00008852. [G5EFF7-2]
DR EnsemblMetazoa; F15C11.2c.1; F15C11.2c.1; WBGene00008852. [G5EFF7-3]
DR GeneID; 172434; -.
DR KEGG; cel:CELE_F15C11.2; -.
DR CTD; 172434; -.
DR WormBase; F15C11.2a; CE09413; WBGene00008852; ubql-1. [G5EFF7-1]
DR WormBase; F15C11.2b; CE31479; WBGene00008852; ubql-1. [G5EFF7-2]
DR WormBase; F15C11.2c; CE31480; WBGene00008852; ubql-1. [G5EFF7-3]
DR eggNOG; KOG0010; Eukaryota.
DR GeneTree; ENSGT00940000156437; -.
DR HOGENOM; CLU_024293_4_0_1; -.
DR InParanoid; G5EFF7; -.
DR OMA; QMMNNPD; -.
DR OrthoDB; 1553668at2759; -.
DR PhylomeDB; G5EFF7; -.
DR Reactome; R-CEL-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR SignaLink; G5EFF7; -.
DR PRO; PR:G5EFF7; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00008852; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; IEA:InterPro.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IGI:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR036353; XPC-bd_sf.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00727; STI1; 4.
DR SMART; SM00165; UBA; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF101238; SSF101238; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; DNA damage; DNA repair; Reference proteome; Repeat.
FT CHAIN 1..502
FT /note="Ubiquilin"
FT /id="PRO_0000444369"
FT DOMAIN 8..83
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 124..157
FT /note="STI1 1"
FT /evidence="ECO:0000255"
FT DOMAIN 161..200
FT /note="STI1 2"
FT /evidence="ECO:0000255"
FT DOMAIN 289..327
FT /note="STI1 3"
FT /evidence="ECO:0000255"
FT DOMAIN 351..387
FT /note="STI1 4"
FT /evidence="ECO:0000255"
FT DOMAIN 455..501
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 84..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 235..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 100..118
FT /note="SSNPTPSSQPNPTNNPFAA -> T (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_059588"
FT VAR_SEQ 449..454
FT /note="PSSTAA -> VSILNI (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059589"
FT VAR_SEQ 455..502
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059590"
SQ SEQUENCE 502 AA; 54086 MW; BD4E36944FDB45BC CRC64;
MATESALIKV HVKSPSNKYD VEIAADASVS ELKDKVLVFV PTANKEQVCI IYTGKILKDE
ETLTQHKIAD GHTVHLVIRN QARPTPAPAA ATPTASSAPS SNPTPSSQPN PTNNPFAAMG
GMGSPADILN NPDAMRSVMD NPITQQLLGN PEFMRTIIQS NPQFQALIER NPEVGHILND
PNVMRQTMEM IRNPNMFQEM MRNHDQAIRN LQGIPGGEAA LERLYNDVQE PLLNSATNSL
SGNPFASLRG DQSSEPRVDR AGQENNEALP NPWASNANQA TNNQSNNRSA DFNSLLDSPG
ISSLMEQMMS NPSMQASMFS PEVINSIRQN MSNNPGLIDS IVGQIPSARD NPQISEGIRR
SFPQMLNMMS DPSVMEAMRN PRVSEAFRQI QEGFSTLRRE APQLLNLFQA GAMGGGAFGS
DANASSAGAN SANGLADLFN SMNMGGGRPS STAAPVNPEQ TYASQLEQLQ SMGFSDRARN
VAALTATFGD LNAAVERLLN SP
