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 02-NOV-2016, entry version 115. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; 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 RT specifically 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 RT project: 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; RP GABRB2 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 RT regulated 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 RT degradation by stimulating K63-linked polyubiquitination of lysine RT 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 RP 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., RA Joly E., 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 RT TAP-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- CC associated protein degradation (ERAD) pathway. Mediates the CC proteasomal targeting of misfolded or accumulated proteins for CC degradation by binding (via UBA domain) to their polyubiquitin CC chains and by interacting (via ubiquitin-like domain) with the CC subunits of the proteasome. Plays a role in the ERAD pathway via CC its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 CC and may form a link between the polyubiquitinated ERAD substrates CC and the proteasome. Plays a role in unfolded protein response CC (UPR) by attenuating the induction of UPR-inducible genes, CC DDTI3/CHOP, HSPA5 and PDIA2 during ER stress. Involved in the CC regulation of macroautophagy and autophagosome formation; required CC for maturation of autophagy-related protein LC3 from the cytosolic CC form LC3-I to the membrane-bound form LC3-II and may assist in the CC maturation of autophagosomes to autolysosomes by mediating CC autophagosome-lysosome fusion. Negatively regulates the CC TICAM1/TRIF-dependent toll-like receptor signaling pathway by CC decreasing the abundance of TICAM1 via the autophagic pathway. CC Plays a key role in the regulation of the levels of PSEN1 by CC targeting its accumulation to aggresomes which may then be removed CC from cells by autophagocytosis. Promotes the ubiquitination and CC lysosomal degradation of ORAI1, consequently downregulating the CC ORAI1-mediated Ca2+ mobilization (By similarity). Suppresses the CC maturation and proteasomal degradation of amyloid beta A4 protein CC (A4) by stimulating the lysine 63 (K63)-linked polyubiquitination. CC Delays the maturation of A4 by sequestering it in the Golgi CC apparatus and preventing its transport to the cell surface for CC subsequent processing (PubMed:22847417). Promotes the surface CC expression of GABA-A receptors (PubMed:11528422). CC {ECO:0000250|UniProtKB:Q9UMX0, ECO:0000269|PubMed:11528422, CC ECO:0000269|PubMed:22847417}. CC -!- SUBUNIT: Monomer and homodimer. Heterodimer with UBQLN2. Binds CC CD47 (By similarity). Binds NBL1 (PubMed:9303440). Binds GABRA1, CC GABRA2, GABRA3, GABRA6, GABRB1, GABRB2 and GABRB3 CC (PubMed:11528422). Binds UBE3A, BTRC, P4HB and MTOR. Interacts CC with the proteasome 19S subunit. Interacts (via ubiquitin-like CC domain) with TREX1; the interaction is direct and may control CC TREX1 subcellular location. Forms a complex with UBXN4 and VCP. CC Interacts (via UBA domain) with UBQLN4 (via ubiquitin-like CC domain). Found in a complex with UBQLN2 and MAP1LC3A/B/C. The CC monomeric form interacts with PSEN1 and PSEN2. Interacts with CC ORAI1. Interacts (via UBA domain) with TICAM1. Interacts with CC EPS15. Interacts (via UBA domain) with UBA52 and (via ubiquitin- CC like domain) with PSMD3 and PSMD4. Interacts with HERPUD1. CC Interacts with MAP1LC3A/B/C in the presence of UBQLN4. Interacts CC (via ubiquitin-like domain) with EPS15 (via UIM domains) and both CC the ubiquitinated and non-ubiquitinated forms can interact with CC EPS15. Interacts (via ubiquitin-like domain) with EPS15L1, HGS CC (via UIM domain) and STAM2 (via UIM domain) (By similarity). CC {ECO:0000250|UniProtKB:Q8R317, ECO:0000250|UniProtKB:Q9UMX0, CC ECO:0000269|PubMed:11528422, ECO:0000269|PubMed:9303440}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UMX0}. CC Cytoplasm {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 CC ER-associated protein degradation (ERAD). Colocalizes with PSEN1 CC in the cell membrane and in cytoplasmic juxtanuclear structures CC called aggresomes. Colocalizes with ORAI1 and TICAM1 in the CC autophagosome. Colocalizes with EPS15 and HGS in ubiquitin-rich CC cytoplasmic aggregates that are not endocytic compartments and CC with EPS15 also in aggresomes (By similarity). Detected in CC neuronal processes and synapses (PubMed:11528422). CC {ECO:0000250|UniProtKB:Q9JJP9, ECO:0000250|UniProtKB:Q9UMX0, CC ECO:0000269|PubMed:11528422}. CC -!- DOMAIN: The UBA domain mediates binding to PSEN1 and PSEN2. It CC also 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 CC the 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- CC mediated autophagy (CMA). {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q9UMX0}. CC -!- SIMILARITY: Contains 4 STI1 domains. {ECO:0000255}. CC -!- SIMILARITY: Contains 1 UBA domain. {ECO:0000255|PROSITE- CC ProRule:PRU00212}. CC -!- SIMILARITY: Contains 1 ubiquitin-like domain. CC {ECO:0000255|PROSITE-ProRule:PRU00214}. 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 UniGene; Rn.94864; -. DR PDB; 1KJV; X-ray; 1.48 A; P=450-458. DR PDBsum; 1KJV; -. DR ProteinModelPortal; Q9JJP9; -. DR BioGrid; 250384; 3. DR IntAct; Q9JJP9; 1. DR STRING; 10116.ENSRNOP00000057944; -. DR iPTMnet; Q9JJP9; -. DR PhosphoSitePlus; Q9JJP9; -. DR PaxDb; Q9JJP9; -. DR PRIDE; Q9JJP9; -. DR GeneID; 114590; -. DR KEGG; rno:114590; -. DR UCSC; RGD:620745; rat. DR CTD; 29979; -. DR RGD; 620745; Ubqln1. DR eggNOG; KOG0010; Eukaryota. DR eggNOG; COG5272; LUCA. DR HOGENOM; HOG000234878; -. DR HOVERGEN; HBG064537; -. DR InParanoid; Q9JJP9; -. DR KO; K04523; -. DR PhylomeDB; Q9JJP9; -. DR EvolutionaryTrace; Q9JJP9; -. DR PRO; PR:Q9JJP9; -. DR Proteomes; UP000002494; Unplaced. DR Bgee; ENSRNOG00000019282; -. DR GO; GO:0016235; C:aggresome; ISS:UniProtKB. DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:HGNC. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:HGNC. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:HGNC. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW. DR GO; GO:0031593; F:polyubiquitin 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:0071456; P:cellular response to hypoxia; ISS:BHF-UCL. DR GO; GO:0030433; P:ER-associated ubiquitin-dependent protein catabolic process; ISS:UniProtKB. DR GO; GO:1901340; P:negative regulation of store-operated calcium channel activity; ISS:UniProtKB. 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:1902175; P:regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0031396; P:regulation of protein ubiquitination; ISS:HGNC. DR InterPro; IPR006636; STI1_HS-bd. DR InterPro; IPR015940; UBA. DR InterPro; IPR009060; UBA-like. DR InterPro; IPR015496; Ubiquilin. DR InterPro; IPR028430; Ubiquilin-1/2. DR InterPro; IPR029071; Ubiquitin-rel_dom. DR InterPro; IPR000626; Ubiquitin_dom. DR PANTHER; PTHR10677; PTHR10677; 1. DR PANTHER; PTHR10677:SF5; PTHR10677:SF5; 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; SSF46934; 1. DR SUPFAM; SSF54236; SSF54236; 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; KW Complete proteome; Cytoplasm; Cytoplasmic vesicle; KW Direct protein sequencing; Endoplasmic reticulum; Membrane; Nucleus; KW Proteasome; Reference proteome; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:Q9UMX0}. FT CHAIN 2 582 Ubiquilin-1. FT /FTId=PRO_0000211010. FT DOMAIN 28 102 Ubiquitin-like. {ECO:0000255|PROSITE- FT ProRule:PRU00214}. FT DOMAIN 173 201 STI1 1. {ECO:0000255}. FT DOMAIN 203 242 STI1 2. {ECO:0000255}. FT DOMAIN 381 428 STI1 3. {ECO:0000255}. FT DOMAIN 432 464 STI1 4. {ECO:0000255}. FT DOMAIN 539 579 UBA. {ECO:0000255|PROSITE- FT ProRule:PRU00212}. FT REGION 169 422 Interaction with UBXN4. FT {ECO:0000250|UniProtKB:Q9UMX0}. FT COMPBIAS 372 546 Gln-rich. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000250|UniProtKB:Q9UMX0}. FT CONFLICT 63 64 HI -> QT (in Ref. 3; AA sequence). FT {ECO:0000305}. FT CONFLICT 224 224 N -> D (in Ref. 2; AAH72477). FT {ECO:0000305}. FT CONFLICT 247 249 ERD -> DRA (in Ref. 2; AAH72477). FT {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 //