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 08-JUN-2016, entry version 111.
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}.
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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 UniGene; Rn.94864; -.
DR PDB; 1KJV; X-ray; 1.48 A; P=450-458.
DR PDBsum; 1KJV; -.
DR ProteinModelPortal; Q9JJP9; -.
DR SMR; Q9JJP9; 1-98, 530-579.
DR BioGrid; 250384; 3.
DR IntAct; Q9JJP9; 1.
DR STRING; 10116.ENSRNOP00000057944; -.
DR iPTMnet; 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 OrthoDB; EOG7HF1J8; -.
DR PhylomeDB; Q9JJP9; -.
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; 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:2000785; P:regulation of autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; 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
//