UBQL1_RAT
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-AUG-2022, entry version 142.
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}.
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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 iPTMnet; Q9JJP9; -.
DR PhosphoSitePlus; Q9JJP9; -.
DR jPOST; 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 InParanoid; Q9JJP9; -.
DR OrthoDB; 1553668at2759; -.
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 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; IPR028430; Ubiquilin-1/2.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10677:SF5; PTHR10677:SF5; 2.
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; 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
