UBQLN4 ubiquilin 4 [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor.
Title: Genomic Amplification of UBQLN4 Is a Prognostic and Treatment Resistance Factor.
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.
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.
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.
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.
UBQLN4 therefore curtails HRR activity through removal of MRE11 from damaged chromatin.
Title: UBQLN4 Represses Homologous Recombination and Is Overexpressed in Aggressive Tumors.
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.
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.
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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH12747 (e-PCR)
- UniSTS:86809

RH41451 (e-PCR)
- UniSTS:7749

RH70381 (e-PCR)
- UniSTS:11730

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)

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
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

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

156031247..156053798 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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