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    HERC3 HECT and RLD domain containing E3 ubiquitin protein ligase 3 [ Homo sapiens (human) ]

    Gene ID: 8916, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HERC3provided by HGNC
    Official Full Name
    HECT and RLD domain containing E3 ubiquitin protein ligase 3provided by HGNC
    Primary source
    HGNC:HGNC:4876
    See related
    Ensembl:ENSG00000138641 MIM:605200; AllianceGenome:HGNC:4876
    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
    Summary
    This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]
    Expression
    Ubiquitous expression in prostate (RPKM 6.4), thyroid (RPKM 5.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HERC3 in Genome Data Viewer
    Location:
    4q22.1
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (88523843..88708539)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (91855488..92040225)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (89444994..89629690)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21716 Neighboring gene CD53 molecule pseudogene Neighboring gene nuclear receptor coactivator 4 pseudogene 2 Neighboring gene PIGY divergent transcript Neighboring gene PIGY upstream open reading frame Neighboring gene phosphatidylinositol glycan anchor biosynthesis class Y Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15564 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15565 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15566 Neighboring gene NANOG hESC enhancer GRCh37_chr4:89522262-89522952 Neighboring gene RN7SK pseudogene 244 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:89555405-89555907 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:89554901-89555404 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:89585126-89586325 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21717 Neighboring gene RNA, U6 small nuclear 33, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:89642061-89642562 Neighboring gene FAM13A antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 7691 Neighboring gene nucleosome assembly protein 1 like 5 Neighboring gene HNF1 motif-containing MPRA enhancer 87 Neighboring gene family with sequence similarity 13 member A Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:89743767-89744454 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:89744455-89745141 Neighboring gene uncharacterized LOC124900732

    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. HERC3 facilitates ERAD of select membrane proteins by recognizing membrane-spanning domains. Kamada Y, et al. J Cell Biol, 2024 Jul 1. PMID 38722278, Free PMC Article
    2. The human HERC3 gene maps to chromosome 4q21 by fluorescence in situ hybridization. Cruz C, et al. Cytogenet Cell Genet, 1999. PMID 10702688
    3. HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer. Zhang Z, et al. Cell Death Dis, 2022 Jan 21. PMID 35064108, Free PMC Article
    4. HERC3-Mediated SMAD7 Ubiquitination Degradation Promotes Autophagy-Induced EMT and Chemoresistance in Glioblastoma. Li H, et al. Clin Cancer Res, 2019 Jun 15. PMID 30862693
    5. ΔNp63α down-regulates c-Myc modulator MM1 via E3 ligase HERC3 in the regulation of cell senescence. Chen Y, et al. Cell Death Differ, 2018 Dec. PMID 29880857, Free PMC Article

    See all (35) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HERC3 facilitates ERAD of select membrane proteins by recognizing membrane-spanning domains.
      Title: HERC3 facilitates ERAD of select membrane proteins by recognizing membrane-spanning domains.
    2. HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.
      Title: HERC3 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity.
    3. HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle.
      Title: HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle.
    4. HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer.
      Title: HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer.
    5. The increased expression of HERC3 in glioblastoma associated with poor clinical outcome. In experimental models, autophagy inducers upregulated HERC3.
      Title: HERC3-Mediated SMAD7 Ubiquitination Degradation Promotes Autophagy-Induced EMT and Chemoresistance in Glioblastoma.
    6. The data illuminate a novel axis regulating cell senescence: DeltaNp63alpha stimulates transcription of E3 ligase HERC3, which mediates ubiquitination of c-Myc modulator MM1 and targets it to proteasomal degradation; subsequently, c-Myc is derepressed by DeltaNp63alpha, thereby cell senescence is modulated by this axis.
      Title: ΔNp63α down-regulates c-Myc modulator MM1 via E3 ligase HERC3 in the regulation of cell senescence.
    7. HERC3 negatively regulates NF-kappaB signaling by enhancing RelA subunit degradation.
      Title: The ubiquitin ligase HERC3 attenuates NF-κB-dependent transcription independently of its enzymatic activity by delivering the RelA subunit for degradation.
    8. we found somatic mutations of HERC2, HERC3, TRIP12, UBE2Q1 and UBE4B genes in gastric carcinoma and colorectal carcinomas with microsatellite instability
      Title: Frameshift mutations of ubiquitination-related genes HERC2, HERC3, TRIP12, UBE2Q1 and UBE4B in gastric and colorectal carcinomas with microsatellite instability.
    9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    Submit: New GeneRIF Correction

    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0032

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasmic vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    probable E3 ubiquitin-protein ligase HERC3
    Names
    HECT domain and RCC1-like domain-containing protein 3
    HECT-type E3 ubiquitin transferase HERC3
    hect domain and RLD 3
    NP_001258531.1
    NP_001305434.1
    NP_001362406.1
    NP_001362407.1
    NP_001362408.1
    NP_001362409.1
    NP_001362410.1
    NP_001362411.1
    NP_001362412.1
    NP_055421.1

    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_001271602.2 → NP_001258531.1  probable E3 ubiquitin-protein ligase HERC3 isoform 2

      See identical proteins and their annotated locations for NP_001258531.1

      Status: REVIEWED

      Source sequence(s)
      AC098582, AC108065
      UniProtKB/TrEMBL
      B4DK41
      Conserved Domains (5) summary
      smart00119
      Location:608 → 929
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      COG5184
      Location:134 → 383
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:584 → 930
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:90 → 139
      RCC1; Regulator of chromosome condensation (RCC1) repeat
      pfam13540
      Location:21 → 50
      RCC1_2; Regulator of chromosome condensation (RCC1) repeat

    2. NM_001318505.2 → NP_001305434.1  probable E3 ubiquitin-protein ligase HERC3 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AK289990, BC038960, CA427366, DA333248
      Consensus CDS
      CCDS82939.1
      UniProtKB/TrEMBL
      Q4W5H5
      Related
      ENSP00000384005.1, ENST00000407637.5
      Conserved Domains (1) summary
      cl27697
      Location:2 → 331
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    3. NM_001375477.1 → NP_001362406.1  probable E3 ubiquitin-protein ligase HERC3 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC098582, AC108065
      Conserved Domains (2) summary
      COG5184
      Location:9 → 237
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:576 → 922
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

    4. NM_001375478.1 → NP_001362407.1  probable E3 ubiquitin-protein ligase HERC3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC098582, AC108065
      Consensus CDS
      CCDS93559.1
      UniProtKB/TrEMBL
      H0Y8G9
      Conserved Domains (3) summary
      COG5184
      Location:2 → 331
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:694 → 1040
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:313 → 377
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    5. NM_001375479.1 → NP_001362408.1  probable E3 ubiquitin-protein ligase HERC3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC098582, AC108065
      Consensus CDS
      CCDS93559.1
      UniProtKB/TrEMBL
      H0Y8G9
      Conserved Domains (3) summary
      COG5184
      Location:2 → 331
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:694 → 1040
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:313 → 377
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    6. NM_001375480.1 → NP_001362409.1  probable E3 ubiquitin-protein ligase HERC3 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC098582, AC108065
      Conserved Domains (3) summary
      COG5184
      Location:2 → 331
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:701 → 1047
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:313 → 377
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    7. NM_001375481.1 → NP_001362410.1  probable E3 ubiquitin-protein ligase HERC3 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC098582, AC108065
      Conserved Domains (2) summary
      COG5184
      Location:4 → 277
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:522 → 868
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

    8. NM_001375482.1 → NP_001362411.1  probable E3 ubiquitin-protein ligase HERC3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC083829, AC098582, AC108065
      UniProtKB/TrEMBL
      H0Y8G9
      Conserved Domains (3) summary
      COG5184
      Location:2 → 331
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:694 → 1040
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:313 → 377
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    9. NM_001375483.1 → NP_001362412.1  probable E3 ubiquitin-protein ligase HERC3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC083829, AC098582, AC108065
      UniProtKB/TrEMBL
      H0Y8G9
      Conserved Domains (3) summary
      COG5184
      Location:2 → 331
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:694 → 1040
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:313 → 377
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    10. NM_014606.3 → NP_055421.1  probable E3 ubiquitin-protein ligase HERC3 isoform 1

      See identical proteins and their annotated locations for NP_055421.1

      Status: REVIEWED

      Source sequence(s)
      AK289990, BE044624, D25215, DA333248
      Consensus CDS
      CCDS34028.1
      UniProtKB/Swiss-Prot
      A8K1S5, Q15034, Q8IXX3
      Related
      ENSP00000385684.1, ENST00000402738.6
      Conserved Domains (3) summary
      COG5184
      Location:2 → 331
      ATS1; Alpha-tubulin suppressor and related RCC1 domain-containing proteins [Cell cycle control, cell division, chromosome partitioning, Cytoskeleton]
      cd00078
      Location:702 → 1048
      HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...
      pfam00415
      Location:313 → 377
      RCC1; Regulator of chromosome condensation (RCC1) repeat

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      88523843..88708539
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      91855488..92040225
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q15034.1 GenPept UniProtKB/Swiss-Prot:Q15034

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