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    HERPUD1 homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1 [ Homo sapiens ]

    Gene ID: 9709, updated on 11-May-2012
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    Summary

    Official Symbol
    HERPUD1provided by HGNC
    Official Full Name
    homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1provided by HGNC
    Primary source
    HGNC:13744
    See related
    Ensembl:ENSG00000051108; HPRD:07456; MIM:608070; Vega:OTTHUMG00000133276
    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
    SUP; HERP; Mif1; KIAA0025
    Summary
    The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. The full-length nature of all transcript variants has not been determined. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    16q13
    Sequence :
    Chromosome: 16; NC_000016.9 (56965748..56977793)
    See HERPUD1 in Epigenomics, MapViewer

    Chromosome 16 - NC_000016.9Genomic Context describing neighboring genes Neighboring gene microRNA 138-2 Neighboring gene solute carrier family 12 (sodium/chloride transporters), member 3 Neighboring gene ribosomal protein S24 pseudogene 17 Neighboring gene cholesteryl ester transfer protein, plasma Neighboring gene NLR family, CARD domain containing 5 Neighboring gene chromosome 7 open reading frame 63 pseudogene

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. E3 ligases determine ubiquitination site and conjugate type by enforcing specificity on E2 enzymes. David Y, et al. J Biol Chem, 2011 Dec 23. PMID 21965653.
    2. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    3. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    4. Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner. Kny M, et al. J Biol Chem, 2011 Feb 18. PMID 21149444.
    5. Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Danielsen JM, et al. Mol Cell Proteomics, 2011 Mar. PMID 21139048.

    See all (40) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. binding of Herp to Hrd1-containing ERAD complexes positively regulates the ubiquitylation activity of these complexes, thus permitting survival of the cell during ER stress.
      Title: Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner.
    2. The results suggest that ERAD molecule Herp may delay the degradation of cytosolic proteins at the ubiquitination step.
      Title: Deletion of Herp facilitates degradation of cytosolic proteins.
    3. Herp mimics structural determinants of DNA immunologically and can be immunogenic in vivo. Thus, Herp represents a candidate autoantigen for anti-DNA antibodies.
      Title: The endoplasmic reticulum stress-inducible protein, Herp, is a potential triggering antigen for anti-DNA response.
    4. Data show that that 4-trifluoromethyl-celecoxib can inhibit secretion but not transcription of IL-12 (p35/p40) and IL-23 (p40/p19 heterodimers), and that this is associated with HERP function in the endoplasmic reticulum.
      Title: Inhibition of secretion of interleukin (IL)-12/IL-23 family cytokines by 4-trifluoromethyl-celecoxib is coupled to degradation via the endoplasmic reticulum stress protein HERP.
    5. the underlying molecular mechanism(s) whereby Herp counteracts Ca(2+) disturbances will provide insights into the molecular cascade of cell death in dopaminergic neurons
      Title: The homocysteine-inducible endoplasmic reticulum stress protein counteracts calcium store depletion and induction of CCAAT enhancer-binding protein homologous protein in a neurotoxin model of Parkinson disease.
    6. Herp may play a role in the initiation of the well-known inflammation-like changes in Parkinson disease substantia nigra and serve as a molecular link between degeneration and neuroinflammation in Parkinson disease
      Title: Homocysteine-induced endoplasmic reticulum protein (herp) is up-regulated in parkinsonian substantia nigra and present in the core of Lewy bodies.
    7. Type II alcoholic patients had a statistically significant higher expression of Herp mRNA due to upregulation of the expression of this neuroprotective cell non-chaperone by toxic effects of ethanol.
      Title: Herp mRNA expression in patients classified according to Lesch's typology.
    8. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates.
      Title: Herp enhances ER-associated protein degradation by recruiting ubiquilins.
    9. Herp is in a complex with ubiquitinated proteins and with the 26S proteasome, suggesting that it plays a role in linking substrates with the proteasome.
      Title: Characterization of an ERAD pathway for nonglycosylated BiP substrates, which require Herp.
    10. enhances presnilin-mediated generation of amyloid beta protein
      Title: Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein.
    Submit: New GeneRIF Correction See all (16)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    A genome-wide association study of the metabolic syndrome in Indian Asian men.

    Longitudinal genome-wide association of cardiovascular disease risk factors in the Bogalusa heart study.

    Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: Genomewide analysis among 18 245 initially healthy women from the Women's Genome Health Study.

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q15011 P19256 CD58    HPRD  PubMed  
    Q15011 Q01844 EWSR1    HPRD  PubMed  
    Q15011 O14732 IMPA2    HPRD  PubMed  
    Q15011 P49768 PSEN1    HPRD  PubMed  
    Q15011 P15927 RPA2    HPRD  PubMed  
    Q15011 Q9P2P6 STARD9    HPRD  PubMed  
    Q15011 Q93009 USP7    HPRD  PubMed  
    BioGRID:115060 BioGRID:106764 AMFR    BioGRID  PubMed Biochemical Activity 
    BioGRID:115060 BioGRID:106889 ARHGDIA    BioGRID  PubMed Two-hybrid 
    BioGRID:115060 BioGRID:107403 CD58    BioGRID  PubMed Two-hybrid 
    BioGRID:115060 BioGRID:122559 DERL1    BioGRID  PubMed Affinity Capture-Western; Co-fractionation 
    BioGRID:115060 BioGRID:108431 EWSR1    BioGRID  PubMed Two-hybrid 
    BioGRID:115060 BioGRID:111642 PSEN1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:111681 PSMD2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:112038 RPA2    BioGRID  PubMed Two-hybrid 
    BioGRID:115060 BioGRID:120934 SELS    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:112372 SIAH1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:112506 SNCA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:114986 SNCAIP    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:121580 STARD9    BioGRID  PubMed Two-hybrid 
    BioGRID:115060 BioGRID:124085 SYVN1    BioGRID  PubMed Affinity Capture-Western; Co-fractionation; Reconstituted Complex 
    BioGRID:115060 BioGRID:119978 TOLLIP    BioGRID  PubMed Two-hybrid 
    BioGRID:115060 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:115060 BioGRID:119007 UBQLN1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:119006 UBQLN2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:121223 UBQLN4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115060 BioGRID:113258 VCP    BioGRID  PubMed Affinity Capture-Western; Co-fractionation; Reconstituted Complex 
    BioGRID:115060 BioGRID:108822 XRCC6    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Activation of Genes by ATF4, organism-specific biosystem (from REACTOME)
      Activation of Genes by ATF4, organism-specific biosystemATF4 is a transcription factor and activates expression of IL-8, MCP1, IGFBP-1, CHOP, HERP1 and ATF3.
    • Diabetes pathways, organism-specific biosystem (from REACTOME)
      Diabetes pathways, organism-specific biosystemThis module groups several normal processes that have key roles in the synthesis and function of insulin, insulin-like growth factors and ghrelin, and whose derangement is thus central to the pathoge...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diurnally regulated genes with circadian orthologs, organism-specific biosystem (from WikiPathways)
      Diurnally regulated genes with circadian orthologs, organism-specific biosystemHuman genes regulated in the diurnal comparison with orthologues that display circadian regulation in mouse heart and liver (Panda 2002, Storch 2002), and SCN (Panda 2002). The 608 significantly regu...
    • HRD1/SEL1 ERAD complex, organism-specific biosystem (from KEGG)
      HRD1/SEL1 ERAD complex, organism-specific biosystemStructural complex; Genetic information processing; Protein processing
    • HRD1/SEL1 ERAD complex, conserved biosystem (from KEGG)
      HRD1/SEL1 ERAD complex, conserved biosystemStructural complex; Genetic information processing; Protein processing
    • PERK regulated gene expression, organism-specific biosystem (from REACTOME)
      PERK regulated gene expression, organism-specific biosystemPERK is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintained in an in...
    • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
      Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
    • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
      Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
    • Unfolded Protein Response, organism-specific biosystem (from REACTOME)
      Unfolded Protein Response, organism-specific biosystemThe Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER d...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    molecular_function ND
    No biological Data available
    more info
    		  
    Process Evidence Code Pubs
    activation of signaling protein activity involved in unfolded protein response TAS
    Traceable Author Statement
    more info
    		  
    cellular calcium ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoplasmic reticulum unfolded protein response TAS
    Traceable Author Statement
    more info
    		  
    negative regulation of cysteine-type endopeptidase activity involved in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to unfolded protein IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    Component Evidence Code Pubs
    endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein
    Names
    homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein
    MMS-inducible
    methyl methanesulfonate (MMF)-inducible fragment protein 1
    homocysteine-inducible endoplasmic reticulum stress-inducible ubiquitin-like domain member 1 protein
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    NCBI Reference Sequences (RefSeq)

    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_001010989.1 → NP_001010989.1  homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in a shorter protein (isoform 2).
      Source sequence(s)
      AB034989, AF055003, BI520043, CD358537
      Consensus CDS
      CCDS45492.1
      UniProtKB/Swiss-Prot
      Q15011
      Related
      ENSP00000300302, OTTHUMP00000254434, ENST00000300302, OTTHUMT00000432314
      Conserved Domains (2) summary
      smart00213
      Location:10 – 85
      Blast Score: 121
      UBQ; Ubiquitin homologues
      cl00155
      Location:9 – 86
      Blast Score: 302
      UBQ; Ubiquitin-like proteins

    2. NM_001010990.1 → NP_001010990.1  homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon, compared to variant 1, resulting in a shorter protein (isoform 3) that has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AB034989, AF055003, BG685245, BI520043, CD358537
      Consensus CDS
      CCDS32457.1
      UniProtKB/TrEMBL
      E9PGD1
      UniProtKB/Swiss-Prot
      Q15011
      Related
      ENSP00000369118, OTTHUMP00000254433, ENST00000379792, OTTHUMT00000432313
      Conserved Domains (1) summary
      cl00155
      Location:9 – 61
      Blast Score: 263
      UBQ; Ubiquitin-like proteins

    3. NM_014685.2 → NP_055500.1  homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AB034989, AF055001, BI520043, CD358537
      Consensus CDS
      CCDS10771.1
      UniProtKB/Swiss-Prot
      Q15011
      Related
      ENSP00000409555, OTTHUMP00000164377, ENST00000439977, OTTHUMT00000257056
      Conserved Domains (2) summary
      cd01790
      Location:9 – 87
      Blast Score: 319
      Herp_N; Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain protein
      smart00213
      Location:10 – 86
      Blast Score: 122
      UBQ; Ubiquitin homologues

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000016.9 Reference GRCh37.p5 Primary Assembly

      Range
      56965748..56977793
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000148.1 Alternate HuRef

      Range
      42835065..42847282
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AB034990.1 BAB19010.1
    genomic AC012181.8 (24011..36056) None
    genomic CH471092.1 EAW82892.1
      EAW82893.1
      EAW82894.1
    mRNA AB034989.1 BAB07891.1
    mRNA AF055001.1 AAC09355.1
    mRNA AF055003.1 AAC09357.1
    mRNA AF217990.1 AAG17233.1
    mRNA AK223233.1 BAD96953.1
    mRNA AK291565.1 BAF84254.1
    mRNA AK292088.1 BAF84777.1
    mRNA AK302167.1 BAG63534.1
    mRNA AK304800.1 BAG65550.1
    mRNA BC000086.1 AAH00086.1
    mRNA BC008320.1 AAH08320.1
    mRNA BC009739.1 AAH09739.1
    mRNA BC032673.1 AAH32673.1
    mRNA BG685245.1 None
    mRNA BI520043.1 None
    mRNA CD358537.1 None
    mRNA CR457116.1 CAG33397.1
    mRNA D14695.1 BAA03521.1
    mRNA DQ837586.1 ABI18163.1
    other-genetic DQ891867.2 ABM82793.1
    other-genetic EU176642.1 ABW03443.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q15011.1 GenPept UniProtKB/Swiss-Prot:Q15011
    Q53FP9 GenPept UniProtKB/TrEMBL:Q53FP9
    Q9HBR2 GenPept UniProtKB/TrEMBL:Q9HBR2
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    Additional Links

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
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