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    UBL4A ubiquitin like 4A [ Homo sapiens (human) ]

    Gene ID: 8266, updated on 7-Apr-2024

    Summary

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    Official Symbol
    UBL4Aprovided by HGNC
    Official Full Name
    ubiquitin like 4Aprovided by HGNC
    Primary source
    HGNC:HGNC:12505
    See related
    Ensembl:ENSG00000102178 MIM:312070; AllianceGenome:HGNC:12505
    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
    GDX; G6PD; GET5; MDY2; UBL4; TMA24; DX254E; DXS254E
    Summary
    Enables chaperone binding activity. Involved in tail-anchored membrane protein insertion into ER membrane. Located in cytosol; membrane; and nucleoplasm. Part of BAT3 complex. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in heart (RPKM 16.9), brain (RPKM 12.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    Xq28
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (154483717..154486615, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (152720226..152723124, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (153712056..153714954, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 50 member A Neighboring gene microRNA 6858 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30062 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21106 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21107 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21108 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:153687524-153688076 Neighboring gene plexin A3 Neighboring gene Sharpr-MPRA regulatory region 3405 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21109 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:153707495-153707994 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30063 Neighboring gene L antigen family member 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:153713643-153714401 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:153714402-153715160 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30064 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21112 Neighboring gene solute carrier family 10 member 3 Neighboring gene RNA, 7SL, cytoplasmic 697, pseudogene

    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. Partial purification and characterization of the messenger RNA for human glucose-6-phosphate dehydrogenase. Toniolo D, et al. Mol Biol Med, 1984 Apr. PMID 6533418
    2. A "housekeeping" gene on the X chromosome encodes a protein similar to ubiquitin. Toniolo D, et al. Proc Natl Acad Sci U S A, 1988 Feb. PMID 2829204, Free PMC Article
    3. miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A. He SY, et al. Kaohsiung J Med Sci, 2020 Oct. PMID 32609950
    4. UBL4A inhibits autophagy-mediated proliferation and metastasis of pancreatic ductal adenocarcinoma via targeting LAMP1. Chen H, et al. J Exp Clin Cancer Res, 2019 Jul 9. PMID 31288830, Free PMC Article
    5. The C-terminus of Ubl4A is critical for pro-death activity and association with the Arp2/3 complex. Yao Q, et al. Biochem Biophys Res Commun, 2018 Sep 18. PMID 30146258, Free PMC Article

    See all (109) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A.
      Title: miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A.
    2. a novel positive feedback regulation of UBL4A in innate immune response combating virus invasion by enhancing the K63-linked ubiquitination of TRAF6.
      Title: UBL4A Augments Innate Immunity by Promoting the K63-Linked Ubiquitination of TRAF6.
    3. UBL4A is a novel autophagy inhibitor and tumor suppressor in PDAC. Mechanistically, UBL4A is involved in late stage autophagy, particularly in lysosomal dysfunction, causing impaired degradation of autophagosomes.
      Title: UBL4A inhibits autophagy-mediated proliferation and metastasis of pancreatic ductal adenocarcinoma via targeting LAMP1.
    4. The single point mutation of an aspartic acid to alanine (D122A) in the Ubl4A C-terminus abolishes its ability to bind the Arp2/3 complex. This mutation also destabilizes Ubl4A proteins susceptible to protease degradation. Importantly, ectopic expression of wild-type Ubl4A can induce cell death in colon cancer cells, but such pro-death activity is diminished in the D122A mutant.
      Title: The C-terminus of Ubl4A is critical for pro-death activity and association with the Arp2/3 complex.
    5. The authors identify USP13 as a gp78-associated deubiquitinase that eliminates ubiquitin conjugates from Ubl4A to maintain the functionality of Bag6.
      Title: USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation.
    6. Data show that molecular chaperone BAG6_ubiquitin-like domain (UBL) and ubiquitin-like 4A UBL4A_UBL compete for the same binding site on N-terminal dimerisation domain of SGTA protein (SGTA_NT).
      Title: Solution structure of the SGTA dimerisation domain and investigation of its interactions with the ubiquitin-like domains of BAG6 and UBL4A.
    7. Both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex.
      Title: Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain.
    8. Data indicate that BCL2-associated athanogene 6 (BAG6) appears to be the central component for the process, as depletion of BAG6 leads to the loss of both UBL4A and GET4 proteins and resistance to cell killing by DNA-damaging agents.
      Title: Nuclear BAG6-UBL4A-GET4 complex mediates DNA damage signaling and cell death.
    9. Data indicate that the Bag6-Ubl4A-Trc35 complex is localized to the endoplasmic reticulum (ER) membrane to regulate ER-associated degradation (ERAD).
      Title: A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation complex in endoplasmic reticulum-associated degradation.
    10. SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation.
      Title: SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35 complex to promote endoplasmic reticulum-associated degradation.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    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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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif is identified to have a physical interaction with ubiquitin-like 4A (UBL4A) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses 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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-folding chaperone binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein-folding chaperone binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin-like protein transferase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in post-translational protein targeting to endoplasmic reticulum membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in post-translational protein targeting to endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein modification process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of protein stability IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tail-anchored membrane protein insertion into ER membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in tail-anchored membrane protein insertion into ER membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tail-anchored membrane protein insertion into ER membrane IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of BAT3 complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of BAT3 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of BAT3 complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in membrane 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 

    General protein information

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    Preferred Names
    ubiquitin-like protein 4A
    Names
    ubiquitin-like 4
    ubiquitin-like protein GDX

    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_014235.5 → NP_055050.1  ubiquitin-like protein 4A

      See identical proteins and their annotated locations for NP_055050.1

      Status: VALIDATED

      Source sequence(s)
      BC043346, BM711450, CK826435, DA012854, DR003955
      Consensus CDS
      CCDS14754.1
      UniProtKB/Swiss-Prot
      P11441, Q5HY80
      Related
      ENSP00000358674.4, ENST00000369660.9
      Conserved Domains (2) summary
      cd01807
      Location:1 → 72
      Ubl_UBL4A_like; ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins
      pfam17840
      Location:96 → 142
      Tugs; Tethering Ubl4a to BAGS domain

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      154483717..154486615 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      152720226..152723124 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P11441.1 GenPept UniProtKB/Swiss-Prot:P11441

    Gene LinkOut

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