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UBQLN4 ubiquilin 4 [ Homo sapiens (human) ]

Gene ID: 56893, updated on 7-Apr-2024

Summary

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Official Symbol
UBQLN4provided by HGNC
Official Full Name
ubiquilin 4provided by HGNC
Primary source
HGNC:HGNC:1237
See related
Ensembl:ENSG00000160803 MIM:605440; AllianceGenome:HGNC:1237
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
A1U; A1Up; UBIN; CIP75; C1orf6
Summary
Enables K48-linked polyubiquitin modification-dependent protein binding activity and identical protein binding activity. Involved in cellular response to DNA damage stimulus; negative regulation of double-strand break repair via homologous recombination; and regulation of cellular catabolic process. Located in several cellular components, including autophagosome; nucleoplasm; and site of DNA damage. Part of protein-containing complex. Colocalizes with cytosolic proteasome complex and nuclear proteasome complex. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in brain (RPKM 15.5), endometrium (RPKM 13.7) and 25 other tissues See more
Orthologs
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Genomic context

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See UBQLN4 in Genome Data Viewer
Location:
1q22
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (156031247..156053798, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (155169709..155192264, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (156005090..156023589, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ARHGEF2 antisense RNA 1 Neighboring gene signal sequence receptor subunit 2 Neighboring gene uncharacterized LOC105371729 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1414 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:156022535-156023256 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1415 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1417 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1835 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1836 Neighboring gene late endosomal/lysosomal adaptor, MAPK and MTOR activator 2 Neighboring gene RAB25, member RAS oncogene family

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor. Kobayashi Y, et al. Cells, 2022 Oct 21. PMID 36291176, Free PMC Article
  2. Ubqln4 Facilitates Endoplasmic Reticulum-to-Cytosol Escape of a Nonenveloped Virus during Infection. Liu X, et al. J Virol, 2020 May 18. PMID 32161173, Free PMC Article
  3. Overexpression of the Ubiquilin-4 (UBQLN4) is Associated with Cell Cycle Arrest and Apoptosis in Human Normal Gastric Epithelial Cell Lines GES-1 Cells by Activation of the ERK Signaling Pathway. Huang S, et al. Med Sci Monit, 2018 May 28. PMID 29807370, Free PMC Article
  4. A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis. Edens BM, et al. Elife, 2017 May 2. PMID 28463112, Free PMC Article
  5. Albendazole induces immunotherapy response by facilitating ubiquitin-mediated PD-L1 degradation. Zhu L, et al. J Immunother Cancer, 2022 May. PMID 35577504, Free PMC Article

See all (60) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Ubiquilin-4 induces immune escape in gastric cancer by activating the notch signaling pathway.
    Title: Ubiquilin-4 induces immune escape in gastric cancer by activating the notch signaling pathway.
  2. Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor.
    Title: Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor.
  3. Regulation of MRE11A by UBQLN4 leads to cisplatin resistance in patients with esophageal squamous cell carcinoma.
    Title: Regulation of MRE11A by UBQLN4 leads to cisplatin resistance in patients with esophageal squamous cell carcinoma.
  4. Angiogenesis-Centered Molecular Cross-Talk in Amyotrophic Lateral Sclerosis Survival: Mechanistic Insights.
    Title: Angiogenesis-Centered Molecular Cross-Talk in Amyotrophic Lateral Sclerosis Survival: Mechanistic Insights.
  5. Ubqln4 Facilitates Endoplasmic Reticulum-to-Cytosol Escape of a Nonenveloped Virus during Infection.
    Title: Ubqln4 Facilitates Endoplasmic Reticulum-to-Cytosol Escape of a Nonenveloped Virus during Infection.
  6. Findings not only establish the anti-tumor potential of Ubqln4 in gastric cancer but also reveal a role for Ubqln4 in regulation of the cell cycle and cellular senescence via stabilizing p21.
    Title: The UbL-UBA Ubiquilin4 protein functions as a tumor suppressor in gastric cancer by p53-dependent and p53-independent regulation of p21.
  7. UBQLN4 therefore curtails HRR activity through removal of MRE11 from damaged chromatin.
    Title: UBQLN4 Represses Homologous Recombination and Is Overexpressed in Aggressive Tumors.
  8. UBQLN4 may induce cell cycle arrest and apoptosis via activation of the ERK pathway and upregulation of cyclin D1 in GES-1 cells.
    Title: Overexpression of the Ubiquilin-4 (UBQLN4) is Associated with Cell Cycle Arrest and Apoptosis in Human Normal Gastric Epithelial Cell Lines GES-1 Cells by Activation of the ERK Signaling Pathway.
  9. results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis.
    Title: Nuclear export of ubiquitinated proteins via the UBIN-POST system.
  10. Here, the authors present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish.
    Title: A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis.
Submit: New GeneRIF Correction See all GeneRIFs (17)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of ubiquilin 4 (UBQLN4) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables K48-linked polyubiquitin modification-dependent protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables polyubiquitin modification-dependent protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables polyubiquitin modification-dependent protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables polyubiquitin modification-dependent protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA damage response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in DNA repair IEA
Inferred from Electronic Annotation
more info
  
involved_in autophagy IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of autophagosome maturation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of double-strand break repair via homologous recombination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in autophagosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasmic vesicle IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol ISS
Inferred from Sequence or Structural Similarity
more info
  
part_of cytosolic proteasome complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
part_of nuclear proteasome complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
  
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in site of DNA damage IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
ubiquilin-4
Names
Cx43-interacting protein of 75 kDa
ataxin-1 interacting ubiquitin-like protein
ataxin-1 ubiquitin-like interacting protein
ataxin-1 ubiquitin-like-interacting protein A1U
connexin43-interacting protein of 75 kDa

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001304342.2 → NP_001291271.1  ubiquilin-4 isoform 2

    See identical proteins and their annotated locations for NP_001291271.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
    Source sequence(s)
    AB209566, AI074831, AK302895, BC063841, DC334851, HY061664
    UniProtKB/TrEMBL
    B4DZF6, Q59F94
    Conserved Domains (4) summary
    smart00727
    Location:172 → 209
    STI1; Heat shock chaperonin-binding motif
    cd01808
    Location:13 → 83
    hPLIC_N; Ubiquitin-like domain of hPLIC-1 and hPLIC2
    smart00213
    Location:13 → 83
    UBQ; Ubiquitin homologues
    cd14399
    Location:538 → 577
    UBA_PLICs; UBA domain of eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins

  2. NM_020131.5 → NP_064516.2  ubiquilin-4 isoform 1

    See identical proteins and their annotated locations for NP_064516.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AI074831, AL355388, BC063841, DC334851, HY061664
    Consensus CDS
    CCDS1127.1
    UniProtKB/Swiss-Prot
    A6ND44, B2RAY7, Q5VYA0, Q5VYA1, Q9BR98, Q9NRR5, Q9UHX4
    UniProtKB/TrEMBL
    Q59F94
    Related
    ENSP00000357292.3, ENST00000368309.4
    Conserved Domains (4) summary
    smart00727
    Location:192 → 229
    STI1; Heat shock chaperonin-binding motif
    cd01808
    Location:13 → 83
    hPLIC_N; Ubiquitin-like domain of hPLIC-1 and hPLIC2
    smart00213
    Location:13 → 83
    UBQ; Ubiquitin homologues
    cd14399
    Location:558 → 597
    UBA_PLICs; UBA domain of eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    156031247..156053798 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024448469.2 → XP_024304237.1  ubiquilin-4 isoform X1

    UniProtKB/TrEMBL
    Q59F94
    Conserved Domains (3) summary
    smart00727
    Location:393 → 424
    STI1; Heat shock chaperonin-binding motif
    cd01808
    Location:13 → 83
    hPLIC_N; Ubiquitin-like domain of hPLIC-1 and hPLIC2
    cl28408
    Location:13 → 291
    UBQ; Ubiquitin homologues

  2. XM_047425666.1 → XP_047281622.1  ubiquilin-4 isoform X3

  3. XM_005245348.5 → XP_005245405.1  ubiquilin-4 isoform X2

    Conserved Domains (3) summary
    smart00727
    Location:192 → 229
    STI1; Heat shock chaperonin-binding motif
    cd01808
    Location:13 → 83
    hPLIC_N; Ubiquitin-like domain of hPLIC-1 and hPLIC2
    smart00213
    Location:13 → 83
    UBQ; Ubiquitin homologues

RNA

  1. XR_007061984.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    155169709..155192264 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054337752.1 → XP_054193727.1  ubiquilin-4 isoform X1

  2. XM_054337754.1 → XP_054193729.1  ubiquilin-4 isoform X3

  3. XM_054337753.1 → XP_054193728.1  ubiquilin-4 isoform X2

RNA

  1. XR_008486114.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NRR5.2 GenPept UniProtKB/Swiss-Prot:Q9NRR5

Gene LinkOut

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