ID UBQL1_RAT Reviewed; 582 AA. AC Q9JJP9; Q6IN34; DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 03-MAY-2023, entry version 145. DE RecName: Full=Ubiquilin-1; DE AltName: Full=Protein linking IAP with cytoskeleton 1; DE Short=PLIC-1; GN Name=Ubqln1; Synonyms=Da41, Plic1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH NBL1. RX PubMed=9303440; DOI=10.1089/dna.1997.16.985; RA Ozaki T., Hishiki T., Toyama Y., Yuasa S., Nakagawara A., Sakiyama S.; RT "Identification of a new cellular protein that can interact specifically RT with DAN."; RL DNA Cell Biol. 16:985-991(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PROTEIN SEQUENCE OF 37-53; 62-74; 198-212; 245-263 AND 540-575, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus; RA Lubec G., Chen W.-Q., Diao W.; RL Submitted (APR-2007) to UniProtKB. RN [4] RP FUNCTION, INTERACTION WITH GABRA1; GABRA2; GABRA3; GABRA6; GABRB1; GABRB2 RP AND GABRB3, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11528422; DOI=10.1038/nn0901-908; RA Bedford F.K., Kittler J.T., Muller E., Thomas P., Uren J.M., Merlo D., RA Wisden W., Triller A., Smart T.G., Moss S.J.; RT "GABA(A) receptor cell surface number and subunit stability are regulated RT by the ubiquitin-like protein Plic-1."; RL Nat. Neurosci. 4:908-916(2001). RN [5] RP FUNCTION. RX PubMed=22847417; DOI=10.1073/pnas.1206786109; RA El Ayadi A., Stieren E.S., Barral J.M., Boehning D.; RT "Ubiquilin-1 regulates amyloid precursor protein maturation and degradation RT by stimulating K63-linked polyubiquitination of lysine 688."; RL Proc. Natl. Acad. Sci. U.S.A. 109:13416-13421(2012). RN [6] RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 450-458 IN COMPLEX WITH MHC I. RX PubMed=12470953; DOI=10.1016/s0022-2836(02)01095-1; RA Rudolph M.G., Stevens J., Speir J.A., Trowsdale J., Butcher G.W., Joly E., RA Wilson I.A.; RT "Crystal structures of two rat MHC class Ia (RT1-A) molecules that are RT associated differentially with peptide transporter alleles TAP-A and TAP- RT B."; RL J. Mol. Biol. 324:975-990(2002). CC -!- FUNCTION: Plays an important role in the regulation of different CC protein degradation mechanisms and pathways including ubiquitin- CC proteasome system (UPS), autophagy and endoplasmic reticulum-associated CC protein degradation (ERAD) pathway. Mediates the proteasomal targeting CC of misfolded or accumulated proteins for degradation by binding (via CC UBA domain) to their polyubiquitin chains and by interacting (via CC ubiquitin-like domain) with the subunits of the proteasome. Plays a CC role in the ERAD pathway via its interaction with ER-localized proteins CC UBXN4, VCP and HERPUD1 and may form a link between the CC polyubiquitinated ERAD substrates and the proteasome. Plays a role in CC unfolded protein response (UPR) by attenuating the induction of UPR- CC inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress. Involved CC in the regulation of macroautophagy and autophagosome formation; CC required for maturation of autophagy-related protein LC3 from the CC cytosolic form LC3-I to the membrane-bound form LC3-II and may assist CC in the maturation of autophagosomes to autolysosomes by mediating CC autophagosome-lysosome fusion. Negatively regulates the TICAM1/TRIF- CC dependent toll-like receptor signaling pathway by decreasing the CC abundance of TICAM1 via the autophagic pathway. Promotes the CC ubiquitination and lysosomal degradation of ORAI1, consequently down- CC regulating the ORAI1-mediated Ca2+ mobilization (By similarity). CC Suppresses the maturation and proteasomal degradation of amyloid beta CC A4 protein (A4) by stimulating the lysine 63 (K63)-linked CC polyubiquitination. Delays the maturation of A4 by sequestering it in CC the Golgi apparatus and preventing its transport to the cell surface CC for subsequent processing (PubMed:22847417). Promotes the surface CC expression of GABA-A receptors (PubMed:11528422). Ubiquitinates BCL2L10 CC and thereby stabilizes protein abundance (By similarity). CC {ECO:0000250|UniProtKB:Q9UMX0, ECO:0000269|PubMed:11528422, CC ECO:0000269|PubMed:22847417}. CC -!- SUBUNIT: Monomer and homodimer. Heterodimer with UBQLN2. Binds CD47 (By CC similarity). Binds NBL1 (PubMed:9303440). Binds GABRA1, GABRA2, GABRA3, CC GABRA6, GABRB1, GABRB2 and GABRB3 (PubMed:11528422). Binds UBE3A, BTRC, CC P4HB and MTOR. Interacts with the proteasome 19S subunit. Interacts CC (via ubiquitin-like domain) with TREX1; the interaction is direct and CC may control TREX1 subcellular location. Forms a complex with UBXN4 and CC VCP. Interacts (via UBA domain) with UBQLN4 (via ubiquitin-like CC domain). Found in a complex with UBQLN2 and MAP1LC3A/B/C. The monomeric CC form interacts with PSEN1 and PSEN2. Interacts with ORAI1. Interacts CC (via UBA domain) with TICAM1. Interacts with EPS15. Interacts (via UBA CC domain) with UBA52 and (via ubiquitin-like domain) with PSMD3 and CC PSMD4. Interacts with HERPUD1. Interacts with MAP1LC3A/B/C in the CC presence of UBQLN4. Interacts (via ubiquitin-like domain) with EPS15 CC (via UIM domains) and both the ubiquitinated and non-ubiquitinated CC forms can interact with EPS15. Interacts (via ubiquitin-like domain) CC with EPS15L1, HGS (via UIM domain) and STAM2 (via UIM domain) (By CC similarity). Interacts with BCL2L10/BCL-B; in the cytoplasm (By CC similarity). {ECO:0000250|UniProtKB:Q8R317, CC ECO:0000250|UniProtKB:Q9UMX0, ECO:0000269|PubMed:11528422, CC ECO:0000269|PubMed:9303440}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UMX0}. Cytoplasm CC {ECO:0000269|PubMed:11528422}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:Q9UMX0}. Cytoplasmic vesicle, autophagosome CC {ECO:0000250|UniProtKB:Q9UMX0}. Cell membrane CC {ECO:0000250|UniProtKB:Q9UMX0}. Note=Recruited to the ER during ER- CC associated protein degradation (ERAD). Colocalizes with PSEN1 in the CC cell membrane and in cytoplasmic juxtanuclear structures called CC aggresomes. Colocalizes with ORAI1 and TICAM1 in the autophagosome. CC Colocalizes with EPS15 and HGS in ubiquitin-rich cytoplasmic aggregates CC that are not endocytic compartments and with EPS15 also in aggresomes CC (By similarity). Detected in neuronal processes and synapses CC (PubMed:11528422). {ECO:0000250|UniProtKB:Q9UMX0, CC ECO:0000269|PubMed:11528422}. CC -!- DOMAIN: The UBA domain mediates binding to PSEN1 and PSEN2. It also CC binds ubiquitin with micromolar affinity, independently of CC polyubiquitin linkage type. Essential for its association with CC microtubule-associated protein 1 light chain 3 (MAP1LC3). CC {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- DOMAIN: The ubiquitin-like domain mediates its association with the CC subunits of the proteasome. {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- DOMAIN: Dimerization is dependent upon the central region of the CC protein containing the STI1 domains and is independent of its CC ubiquitin-like and UBA domains. {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- PTM: Degraded during both macroautophagy and during chaperone-mediated CC autophagy (CMA). {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q9UMX0}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D87950; BAA92267.1; -; mRNA. DR EMBL; BC072477; AAH72477.1; -; mRNA. DR RefSeq; NP_446199.2; NM_053747.2. DR PDB; 1KJV; X-ray; 1.48 A; P=450-458. DR PDBsum; 1KJV; -. DR AlphaFoldDB; Q9JJP9; -. DR SMR; Q9JJP9; -. DR BioGRID; 250384; 4. DR IntAct; Q9JJP9; 1. DR STRING; 10116.ENSRNOP00000057944; -. DR GlyGen; Q9JJP9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9JJP9; -. DR PhosphoSitePlus; Q9JJP9; -. DR jPOST; Q9JJP9; -. DR PaxDb; Q9JJP9; -. DR GeneID; 114590; -. DR KEGG; rno:114590; -. DR UCSC; RGD:620745; rat. DR AGR; RGD:620745; -. DR CTD; 29979; -. DR RGD; 620745; Ubqln1. DR eggNOG; KOG0010; Eukaryota. DR InParanoid; Q9JJP9; -. DR OrthoDB; 5491123at2759; -. DR PhylomeDB; Q9JJP9; -. DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis. DR EvolutionaryTrace; Q9JJP9; -. DR PRO; PR:Q9JJP9; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0016235; C:aggresome; ISS:UniProtKB. DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:RGD. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:HGNC-UCL. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:HGNC-UCL. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0019900; F:kinase binding; ISO:RGD. DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD. DR GO; GO:0035973; P:aggrephagy; ISS:UniProtKB. DR GO; GO:0000045; P:autophagosome assembly; ISO:RGD. DR GO; GO:0097352; P:autophagosome maturation; ISO:RGD. DR GO; GO:0071456; P:cellular response to hypoxia; ISS:HGNC. DR GO; GO:0016236; P:macroautophagy; ISO:RGD. DR GO; GO:1901340; P:negative regulation of store-operated calcium channel activity; ISS:UniProtKB. DR GO; GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; ISO:RGD. DR GO; GO:1903071; P:positive regulation of ER-associated ubiquitin-dependent protein catabolic process; ISS:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB. DR GO; GO:0016241; P:regulation of macroautophagy; IBA:GO_Central. DR GO; GO:1902175; P:regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISS:HGNC. DR GO; GO:0031396; P:regulation of protein ubiquitination; ISS:HGNC-UCL. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:RGD. DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB. DR CDD; cd14399; UBA_PLICs; 1. DR CDD; cd01808; Ubl_PLICs; 1. DR Gene3D; 1.10.260.100; -; 2. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR015940; UBA. DR InterPro; IPR009060; UBA-like_sf. DR InterPro; IPR015496; Ubiquilin. DR InterPro; IPR000626; Ubiquitin-like_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR10677; UBIQUILIN; 1. DR PANTHER; PTHR10677:SF16; UBIQUILIN-1; 1. 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; SSF46934; UBA-like; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS50030; UBA; 1. DR PROSITE; PS50053; UBIQUITIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Autophagy; Cell membrane; Cytoplasm; KW Cytoplasmic vesicle; Direct protein sequencing; Endoplasmic reticulum; KW Membrane; Nucleus; Proteasome; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q9UMX0" FT CHAIN 2..582 FT /note="Ubiquilin-1" FT /id="PRO_0000211010" FT DOMAIN 28..102 FT /note="Ubiquitin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214" FT DOMAIN 173..201 FT /note="STI1 1" FT /evidence="ECO:0000255" FT DOMAIN 203..242 FT /note="STI1 2" FT /evidence="ECO:0000255" FT DOMAIN 381..428 FT /note="STI1 3" FT /evidence="ECO:0000255" FT DOMAIN 432..464 FT /note="STI1 4" FT /evidence="ECO:0000255" FT DOMAIN 539..579 FT /note="UBA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212" FT REGION 1..26 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 102..136 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 169..422 FT /note="Interaction with UBXN4" FT /evidence="ECO:0000250|UniProtKB:Q9UMX0" FT REGION 285..365 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 481..513 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 285..308 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 320..353 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 490..504 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q9UMX0" FT CONFLICT 63..64 FT /note="HI -> QT (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="N -> D (in Ref. 2; AAH72477)" FT /evidence="ECO:0000305" FT CONFLICT 247..249 FT /note="ERD -> DRA (in Ref. 2; AAH72477)" FT /evidence="ECO:0000305" SQ SEQUENCE 582 AA; 62072 MW; 6651E95B09071E5B CRC64; MAESAESGGP PGAQDSAADS GPAEPKIMKV TVKTPKEKEE FAVPENSSVQ QFKEEISKRF KSHIDQLVLI FAGKILKDQD TLSQHGIHDG LTVHLVIKTQ NRPQDNSAQQ TNTTGNSVTS SPAPDSNPTS GPAANSSFGL GGLGGLAGLS SLGLNTTNFS ELQSQMQRQL LSNPEMMVQI MENPFVQSML SNPDLMRQLI MANPQMQQLI QRNPEISHML NNPNIMRQTL ELARNPAMMQ EMMRNQERDL SNLESIPGGY NALRRMYTDI QEPMLNAAQE QFGGNPFASL VSSPSSAEGT QPSRTENRDP LPNPWAPQTP QSSPASGSTG STTNTVSTSA GNATSTPAGQ GTSGPNLVPG AGASMFNTPG MQSLLQQITE NPQLMQNMLS APYMRSMMQS LSQNPDLAAQ MMLNNPLFAG NPQLQEQMRQ QLPTFLQQMQ NPDTLSAMSN PRAMQALLQI QQGLQTLATE APGLIPGFTP GLAAGNSGGP AGTTAPSTAP GEDTNPQGGA AEPGHQQFIQ QMLQALAGVN PQLQSPEVRF QQQLEQLSAM GFLNREANLQ ALIATGGDIN AAIERLLGSQ PS //