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    UFD1 ubiquitin recognition factor in ER associated degradation 1 [ Homo sapiens (human) ]

    Gene ID: 7353, updated on 11-Apr-2024

    Summary

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    Official Symbol
    UFD1provided by HGNC
    Official Full Name
    ubiquitin recognition factor in ER associated degradation 1provided by HGNC
    Primary source
    HGNC:HGNC:12520
    See related
    Ensembl:ENSG00000070010 MIM:601754; AllianceGenome:HGNC:12520
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    UFD1L
    Summary
    The protein encoded by this gene forms a complex with two other proteins, nuclear protein localization-4 and valosin-containing protein, and this complex is necessary for the degradation of ubiquitinated proteins. In addition, this complex controls the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. Mutations in this gene have been associated with Catch 22 syndrome as well as cardiac and craniofacial defects. Alternative splicing results in multiple transcript variants encoding different isoforms. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Jun 2009]
    Expression
    Ubiquitous expression in bone marrow (RPKM 14.2), testis (RPKM 13.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    22q11.21
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (19449911..19479193, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (19826739..19856026, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (19437434..19466716, complement)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13460 Neighboring gene mitochondrial ribosomal protein L40 Neighboring gene chromosome 22 open reading frame 39 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr22:19434430-19435332 Neighboring gene UFD1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13462 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18660 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13463 Neighboring gene cell division cycle 45 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:19486137-19486353 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19493394-19493894 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19493895-19494395 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19502006-19502506 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19502507-19503007 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19509616-19510548 Neighboring gene claudin 5

    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. Polymorphisms in schizophrenia candidate gene UFD1L may contribute to cognitive deficits. Ota VK, et al. Psychiatry Res, 2013 Aug 30. PMID 23623450
    2. The UFD1L rs5992403 polymorphism is associated with age at onset of schizophrenia. Ota VK, et al. J Psychiatr Res, 2010 Nov. PMID 20471029
    3. A family- and population-based study of the UFD1L gene for schizophrenia. Xie L, et al. Am J Med Genet B Neuropsychiatr Genet, 2008 Oct 5. PMID 18270977
    4. Analysis of intracellular distribution and apoptosis involvement of the Ufd1l gene product by over-expression studies. Amati F, et al. Cell Biochem Funct, 2003 Sep. PMID 12910480
    5. Functional characterization of the 5' flanking region of human ubiquitin fusion degradation 1 like gene (UFD1L). Amati F, et al. Cell Biochem Funct, 2002 Jun. PMID 11979512

    See all (141) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural basis for the interaction between human Npl4 and Npl4-binding motif of human Ufd1.
      Title: Structural basis for the interaction between human Npl4 and Npl4-binding motif of human Ufd1.
    2. Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.
      Title: Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.
    3. PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E.
      Title: PCBP2 Posttranscriptional Modifications Induce Breast Cancer Progression via Upregulation of UFD1 and NT5E.
    4. Involvement of VCP/UFD1/Nucleolin in the viral entry of Enterovirus A species.
      Title: Involvement of VCP/UFD1/Nucleolin in the viral entry of Enterovirus A species.
    5. Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative.
      Title: Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative.
    6. Multisystem proteinopathy mutations in VCP/p97 increase NPLOC4-UFD1L binding and substrate processing.
      Title: Multisystem Proteinopathy Mutations in VCP/p97 Increase NPLOC4·UFD1L Binding and Substrate Processing.
    7. results support that Ufd1 S229 phosphorylation status mediated by PKA serves as a key regulatory point for the VCP-Ufd1 interaction and functional ERAD.
      Title: Ufd1 phosphorylation at serine 229 negatively regulates endoplasmic reticulum-associated degradation by inhibiting the interaction of Ufd1 with VCP.
    8. CHOP inactivation or BCL2 overexpression is sufficient to rescue tumor cell apoptosis induced by UFD1 knockdown.
      Title: UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response.
    9. We demonstrate that WT p97 can unfold proteins and that this activity is dependent on the p97 adaptor NPLOC4-UFD1L, ATP hydrolysis, and substrate ubiquitination, with branched chains providing maximal stimulation.
      Title: Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP•NPLOC4•UFD1L is enhanced by a mutation that causes multisystem proteinopathy.
    10. The study revealed a regulatory role of the p97-Npl4-Ufd1 complex in regulating a partial degradation of the NF-kappaB subunit p100.
      Title: The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-κB Signaling via Partial Degradation of the NF-κB Subunit p100.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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
    Vpu vpu The VCP-UFD1L-NPL4 complex is required for HIV-1 Vpu-induced CD4 degradation in the ER-associated degradation pathway. The ATPase activity of VCP and ubiquitin binding to UFD1L are important for CD4 degradation by Vpu 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 IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cysteine-type deubiquitinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables polyubiquitin modification-dependent protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ERAD pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ERAD pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to misfolded protein IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of RIG-I signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of type I interferon production IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in retrograde protein transport, ER to cytosol IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in retrograde protein transport, ER to cytosol ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in skeletal system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of UFD1-NPL4 complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of VCP-NPL4-UFD1 AAA ATPase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of VCP-NPL4-UFD1 AAA ATPase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of VCP-NPL4-UFD1 AAA ATPase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of VCP-NPL4-UFD1 AAA ATPase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus HDA PubMed 

    General protein information

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    Preferred Names
    ubiquitin recognition factor in ER-associated degradation protein 1
    Names
    UB fusion protein 1
    ubiquitin fusion degradation 1 like
    ubiquitin fusion degradation protein 1 homolog

    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_001035247.3 → NP_001030324.2  ubiquitin recognition factor in ER-associated degradation protein 1 isoform B

      See identical proteins and their annotated locations for NP_001030324.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region that results in a frameshift, compared to variant 1. The encoded isoform (B) has a distinct C-terminus and is shorter than isoform A.
      Source sequence(s)
      AC000068, AK225877, AW131352, CB128364, DB496066, DB570679
      Consensus CDS
      CCDS33600.2
      UniProtKB/TrEMBL
      B7Z9N3
      Related
      ENSP00000382439.1, ENST00000399523.5
      Conserved Domains (1) summary
      pfam03152
      Location:19 → 193
      UFD1; Ubiquitin fusion degradation protein UFD1

    2. NM_001362910.2 → NP_001349839.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform C

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 5' region and is predicted to use a downstream start codon compared to variant 1. The encoded isoform (C) has a shorter N-terminus compared to isoform A.
      Source sequence(s)
      AC000068, AC000087
      UniProtKB/TrEMBL
      B7Z9N3
      Conserved Domains (1) summary
      pfam03152
      Location:14 → 188
      UFD1; Ubiquitin fusion degradation protein UFD1

    3. NM_005659.7 → NP_005650.2  ubiquitin recognition factor in ER-associated degradation protein 1 isoform A

      See identical proteins and their annotated locations for NP_005650.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1)encodes the longest isoform (A).
      Source sequence(s)
      AC000068, AW131352, BC005087, CB128364, DB570679
      Consensus CDS
      CCDS13761.1
      UniProtKB/Swiss-Prot
      A8MW31, Q92890, Q9Y5N0
      UniProtKB/TrEMBL
      B7Z9N3, Q541A5
      Related
      ENSP00000263202.9, ENST00000263202.15
      Conserved Domains (1) summary
      pfam03152
      Location:19 → 193
      UFD1; Ubiquitin fusion degradation protein UFD1

    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_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      19449911..19479193 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047441488.1 → XP_047297444.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform X3

    2. XM_047441487.1 → XP_047297443.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform X2

    3. XM_047441486.1 → XP_047297442.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      19826739..19856026 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054325901.1 → XP_054181876.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform X3

    2. XM_054325900.1 → XP_054181875.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform X2

    3. XM_054325899.1 → XP_054181874.1  ubiquitin recognition factor in ER-associated degradation protein 1 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q92890.3 GenPept UniProtKB/Swiss-Prot:Q92890

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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