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

Gene ID: 8916, updated on 5-Mar-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
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Genomic context

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Location:
4q22.1
Exon count:
28
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (88523843..88708539)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (91855488..92040225)
105.20220307 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 promotes YAP/TAZ stability and tumorigenesis independently of its ubiquitin ligase activity. Yuan B, et al. EMBO J, 2023 Feb 15. PMID 36598329, 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 (34) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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)

Genotypes

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 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_2023_10

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

Gene LinkOut

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