Tbio UBQLN1 Ubiquilin-1

Protein Summary

Description

Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (PubMed:15147878). Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:19822669, PubMed:18307982). Isoform 1, isoform 2 and isoform 3 play a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress (PubMed:18953672). Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (PubMed:19148225, PubMed:20529957, PubMed:23459205). Negatively regulates the TICAM1/TRIF-dependent toll-like receptor signaling pathway by decreasing the abundance of TICAM1 via the autophagic pathway (PubMed:21695056). Isoform 1 and isoform 3 play a key role in the regulation of the levels of PSEN1 by targeting its accumulation to aggresomes which may then be removed from cells by autophagocytosis (PubMed:21143716). Promotes the ubiquitination and lysosomal degradation of ORAI1, consequently downregulating the ORAI1-mediated Ca2+ mobilization (PubMed:23307288). Suppresses the maturation and proteasomal degradation of amyloid beta A4 protein (A4) by stimulating the lysine 63 (K63)-linked polyubiquitination. Delays the maturation of A4 by sequestering it in the Golgi apparatus and preventing its transport to the cell surface for subsequent processing (By similarity). This gene encodes an ubiquitin-like protein (ubiquilin) that shares a high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and thus are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to modulate accumulation of presenilin proteins, and it is found in lesions associated with Alzheimer's and Parkinson's disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9UMX0
• A0A024R284
• Q5T6J5
• Q5T6J9
• Q8IXS9
• Q8N2Q3
• Q9H0T8
• Q9H3R4
• Q9HAZ5

Gene Name

• UBQLN1

Ensembl ID

• ENST00000257468
• ENSP00000257468
• ENSG00000135018
• ENST00000376395
• ENSP00000365576

Symbol

• DA41
• PLIC1
• DA41
• DSK2
• UBQN
• XDRP1
• PLIC-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.99
protein domain	0.97
transcription factor binding site profile	0.86
interacting protein	0.82
kinase perturbation	0.81

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 113.29   (req: < 5)

Gene RIFs: 54   (req: <= 3)

Antibodies: 327   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 113.29   (req: >= 5)

Gene RIFs: 54   (req: > 3)

Antibodies: 327   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	ubiquilin 1	VGNC:4898	464550
Mouse	ubiquilin 1	MGI:1860276	56085
Rat	ubiquilin 1	RGD:620745	114590
Dog	ubiquilin 1	VGNC:48084	476312
Horse	ubiquilin 1	VGNC:24744	100052573

Species	Name	OMA	EggNOG	Inparanoid
Chimp	ubiquilin 1
Mouse	ubiquilin 1
Rat	ubiquilin 1
Dog	ubiquilin 1
Horse	ubiquilin 1

Protein Structure (3 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q9UMX0-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 3 of 3

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (6)

Reactome (4)

KEGG (1)

PathwayCommons (1)

Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

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Items per page:

5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Reactome	Clathrin-mediated endocytosis	143 targets	R-HSA-8856828
Reactome	Membrane Trafficking	612 targets	R-HSA-199991
Reactome	Vesicle-mediated transport	725 targets	R-HSA-5653656

Name	Explore in Pharos	Explore in Source
Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Clathrin-mediated endocytosis	143 targets	R-HSA-8856828
Membrane Trafficking	612 targets	R-HSA-199991
Vesicle-mediated transport	725 targets	R-HSA-5653656

Gene Ontology Terms (27)

Functions (3)

Components (11)

Processes (13)

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Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
polyubiquitin modification-dependent protein binding	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB

Protein-Protein Interactions (357)

Explore Interacting Targets

1 – 10 of 357

• See Interactions on String-DB

TMEM31

Tdark

Novelty: 0.65381391

p_int: 0.999936835

p_ni: 0.000063165

Data Source: BioPlex

KDELR1

Tbio

Novelty: 0.0036468

p_int: 0.821175619

p_ni: 0.178824381

Score: 0.426

Data Source: BioPlex,STRINGDB

UBE4B

Tbio

Novelty: 0.01396546

Score: 0.99

Data Source: STRINGDB

PSMD4

Tbio

Family: Enzyme

Novelty: 0.00614538

Score: 0.986

Data Source: STRINGDB

EPS15

Tbio

Novelty: 0.00451447

Score: 0.967

Data Source: STRINGDB

GABARAP

Tbio

Novelty: 0.00444901

Score: 0.96

Data Source: STRINGDB

UBL7

Tdark

Novelty: 0.20935024

Score: 0.954

Data Source: STRINGDB

UBE4A

Tbio

Novelty: 0.02576018

Score: 0.953

Data Source: STRINGDB

GABRA6

Tclin

Family: IC

Novelty: 0.02894664

Score: 0.951

Data Source: STRINGDB

GNB1

Tbio

Novelty: 0.02477955

Score: 0.943

Data Source: STRINGDB

Publication Statistics

PubMed Score  113.29

PubMed score by year

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PubTator Score  62.69

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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3D-structure
Acetylation
Alternative splicing
Autophagy
Cell membrane
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Direct protein sequencing
Endoplasmic reticulum

MGI Phenotype Find Similar Targets

cellular phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
nervous system phenotype