ID UBQL1_PONAB Reviewed; 589 AA.
AC Q5R684;
DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 22-FEB-2023, entry version 98.
DE RecName: Full=Ubiquilin-1;
GN Name=UBQLN1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. Suppresses the
CC maturation and proteasomal degradation of amyloid beta A4 protein (A4)
CC by stimulating the lysine 63 (K63)-linked polyubiquitination. Delays
CC the maturation of A4 by sequestering it in the Golgi apparatus and
CC preventing its transport to the cell surface for subsequent processing.
CC Ubiquitinates BCL2L10 and thereby stabilizes protein abundance (By
CC similarity). {ECO:0000250|UniProtKB:Q9JJP9,
CC ECO:0000250|UniProtKB:Q9UMX0}.
CC -!- SUBUNIT: Monomer and homodimer. Heterodimer with UBQLN2. Binds CD47,
CC NBL1, GABRA1, GABRA2, GABRA3, GABRA6, GABRB1, GABRB2 and GABRB3. Binds
CC UBE3A, BTRC, P4HB and MTOR. Interacts with the proteasome 19S subunit.
CC Interacts (via ubiquitin-like domain) with TREX1; the interaction is
CC direct and may control TREX1 subcellular location. Forms a complex with
CC UBXN4 and VCP. Interacts (via UBA domain) with UBQLN4 (via ubiquitin-
CC like domain). Found in a complex with UBQLN2 and MAP1LC3A/B/C. The
CC monomeric form interacts with PSEN1 and PSEN2. Interacts with ORAI1.
CC Interacts (via UBA domain) with TICAM1. Interacts with EPS15. Interacts
CC (via UBA domain) with UBA52 and (via ubiquitin-like domain) with PSMD3
CC and 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:Q9JJP9, ECO:0000250|UniProtKB:Q9UMX0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UMX0}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UMX0}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9UMX0}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q9UMX0}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9UMX0}. Note=Detected in neuronal processes and
CC at synapses. Recruited to the ER during ER-associated protein
CC degradation (ERAD). Colocalizes with PSEN1 in the cell membrane and in
CC cytoplasmic juxtanuclear structures called aggresomes. Colocalizes with
CC ORAI1 and TICAM1 in the autophagosome. Colocalizes with EPS15 and HGS
CC in ubiquitin-rich cytoplasmic aggregates that are not endocytic
CC compartments and with EPS15 also in aggresomes.
CC {ECO:0000250|UniProtKB:Q9JJP9, ECO:0000250|UniProtKB:Q9UMX0}.
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; CR860611; CAH92732.1; -; mRNA.
DR RefSeq; NP_001127579.1; NM_001134107.1.
DR AlphaFoldDB; Q5R684; -.
DR BMRB; Q5R684; -.
DR SMR; Q5R684; -.
DR STRING; 9601.ENSPPYP00000021651; -.
DR GeneID; 100174657; -.
DR KEGG; pon:100174657; -.
DR CTD; 29979; -.
DR eggNOG; KOG0010; Eukaryota.
DR InParanoid; Q5R684; -.
DR OrthoDB; 5491123at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0016235; C:aggresome; ISS:UniProtKB.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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 modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0035973; P:aggrephagy; 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: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; 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 2: Evidence at transcript level;
KW Acetylation; Autophagy; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Membrane; Nucleus; Phosphoprotein; Proteasome;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UMX0"
FT CHAIN 2..589
FT /note="Ubiquilin-1"
FT /id="PRO_0000290337"
FT DOMAIN 37..111
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 182..210
FT /note="STI1 1"
FT /evidence="ECO:0000255"
FT DOMAIN 212..251
FT /note="STI1 2"
FT /evidence="ECO:0000255"
FT DOMAIN 387..434
FT /note="STI1 3"
FT /evidence="ECO:0000255"
FT DOMAIN 438..470
FT /note="STI1 4"
FT /evidence="ECO:0000255"
FT DOMAIN 546..586
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 110..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..428
FT /note="Interaction with UBXN4"
FT /evidence="ECO:0000250|UniProtKB:Q9UMX0"
FT REGION 295..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..364
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 491..520
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"
SQ SEQUENCE 589 AA; 62503 MW; 8B4756A7542F3025 CRC64;
MAESGESGGP PGSQDSAAGA EGAGAPAAAA SAEPKIMKVT VKTPKEKEEF AVPENSSVQQ
FKEEISKRFK SHTDQLVLIF AGKILKDQDT LSQHGIHDGL TVHLVIKTQN RPQDHSAQQT
NTAGSNVTTS STPNSNSTSG SATSNPFGLG GLGGLAGLSS LGLNTTNFSE LQSQMQRQLL
SNPEMMVQIM ENPFVQSMLS NPDLMRQLIM ANPQMQQLIQ RNPEISHMLN NPDIMRQTLE
LARNPAMMQE MMRNQDRALS NLESIPGGYN ALRRMYTDIQ EPMLSAAQEQ FGGNPFASLV
SNTSSGEGSQ PSRTENRDPL PNPWAPQTSQ SSSASSGTAS TVGGTTGSTA SGTSGQSTTA
PNLVPGVGAS MFNTPGMQSL LQQITENPQL MQNMLSAPYM RSMMQSLSQN PDLAAQMMLN
NPLFAGNPQL QEQMRQQLPT FLQQMQNPDT LSAMSNPRAM QALLQIQQGL QTLATEAPGL
IPGFTPGLGA LGSTGGSSGT NGSNATPSEN TSPTAGTTEP GHQQFIQQML QALAGVNPQL
QNPEVRFQQQ LEQPSAMGFL NREANLQALI ATGGDINAAI ERLLGSQPS
//
