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HACE1 HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 [ Homo sapiens (human) ]

Gene ID: 57531, updated on 10-Mar-2024

Summary

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Official Symbol
HACE1provided by HGNC
Official Full Name
HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1provided by HGNC
Primary source
HGNC:HGNC:21033
See related
Ensembl:ENSG00000085382 MIM:610876; AllianceGenome:HGNC:21033
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
SPPRS
Summary
This gene encodes a HECT domain and ankyrin repeat-containing ubiquitin ligase. The encoded protein is involved in specific tagging of target proteins, leading to their subcellular localization or proteasomal degradation. The protein is a potential tumor suppressor and is involved in the pathophysiology of several tumors, including Wilm's tumor. [provided by RefSeq, Mar 2016]
Expression
Broad expression in placenta (RPKM 13.5), testis (RPKM 6.0) and 22 other tissues See more
Orthologs
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Genomic context

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Location:
6q16.3
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (104728094..104859919, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (105904367..106035941, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (105175969..105307794, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102724443 Neighboring gene Sharpr-MPRA regulatory region 11207 Neighboring gene uncharacterized LOC105377918 Neighboring gene MPRA-validated peak5987 silencer Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:104919911-104920484 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:104937517-104938123 Neighboring gene VISTA enhancer hs1452 Neighboring gene Sharpr-MPRA regulatory region 1651 Neighboring gene MPRA-validated peak5988 silencer Neighboring gene RNA, U6 small nuclear 897, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:105307475-105307974 Neighboring gene poly(A) binding protein cytoplasmic 4 pseudogene Neighboring gene MPRA-validated peak5989 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:105384704-105385204 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:105385205-105385705 Neighboring gene LIN28B antisense RNA 1 Neighboring gene lin-28 homolog B

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. Correlations of HACE1 expression with pathological stages, CT features and prognosis of hepatocellular carcinoma patients. Zhang Z, et al. J BUON, 2020 Nov-Dec. PMID 33455098
  2. Loss of the Tumor Suppressor HACE1 Contributes to Cancer Progression. Li JC, et al. Curr Drug Targets, 2019. PMID 30827236
  3. HACE1 is a potential tumor suppressor in osteosarcoma. El-Naggar AM, et al. Cell Death Dis, 2019 Jan 8. PMID 30622235, Free PMC Article
  4. Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration. Chen YL, et al. Cancer Med, 2018 Jun. PMID 29673126, Free PMC Article
  5. Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells. El-Hachem N, et al. Cell Death Differ, 2018 Nov. PMID 29515254, Free PMC Article

See all (74) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.
    Title: Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.
  2. HACE1 expression in heart failure patients might promote mitochondrial oxidative stress and ferroptosis by targeting NRF2.
    Title: HACE1 expression in heart failure patients might promote mitochondrial oxidative stress and ferroptosis by targeting NRF2.
  3. Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.
    Title: Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.
  4. HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.
    Title: HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.
  5. HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models.
    Title: HACE1 negatively regulates neuroinflammation through ubiquitylating and degrading Rac1 in Parkinson's disease models.
  6. HACE1 blocks HIF1alpha accumulation under hypoxia in a RAC1 dependent manner.
    Title: HACE1 blocks HIF1α accumulation under hypoxia in a RAC1 dependent manner.
  7. Correlations of HACE1 expression with pathological stages, CT features and prognosis of hepatocellular carcinoma patients.
    Title: Correlations of HACE1 expression with pathological stages, CT features and prognosis of hepatocellular carcinoma patients.
  8. meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.
    Title: meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.
  9. Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion.
    Title: Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion.
  10. Loss of the Tumor Suppressor HACE1 Contributes to Cancer Progression.
    Title: Loss of the Tumor Suppressor HACE1 Contributes to Cancer Progression.
Submit: New GeneRIF Correction See all GeneRIFs (42)

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

Associated conditions

Description Tests
Spastic paraplegia-severe developmental delay-epilepsy syndrome
MedGen: C4225215 OMIM: 616756 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study.
EBI GWAS Catalog
A genome-wide association study of brain lesion distribution in multiple sclerosis.
EBI GWAS Catalog
Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma.
EBI GWAS Catalog
Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche.
EBI GWAS Catalog
Genome-wide association study of obsessive-compulsive disorder.
EBI GWAS Catalog
Many sequence variants affecting diversity of adult human height.
EBI GWAS Catalog

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

  • FLJ42274

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables small GTPase binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables small GTPase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in Golgi organization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in Golgi organization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in Rac protein signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in cell cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in membrane fusion IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in membrane fusion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein polyubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi cisterna membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in Golgi membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in Golgi membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
  
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
E3 ubiquitin-protein ligase HACE1
Names
HECT-type E3 ubiquitin transferase HACE1
NP_001308009.1
NP_001308012.1
NP_001308013.1
NP_001337483.1
NP_001337484.1
NP_001337485.1
NP_001337486.1
NP_001337487.1
NP_001337488.1
NP_001337489.1
NP_065822.2

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.

Genomic

  1. NG_046782.1 RefSeqGene

    Range
    5001..136826
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001321080.2 → NP_001308009.1  E3 ubiquitin-protein ligase HACE1 isoform b

    Status: REVIEWED

    Source sequence(s)
    AK131207, AL513472, AL590402, BC034982
    UniProtKB/Swiss-Prot
    Q8IYU2
    Conserved Domains (4) summary
    cd00078
    Location:510 → 859
    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 ...
    sd00045
    Location:66 → 95
    ANK; ANK repeat [structural motif]
    pfam12796
    Location:69 → 179
    Ank_2; Ankyrin repeats (3 copies)
    cl39094
    Location:157 → 207
    Ank_2; Ankyrin repeats (3 copies)

  2. NM_001321083.2 → NP_001308012.1  E3 ubiquitin-protein ligase HACE1 isoform c

    Status: REVIEWED

    Source sequence(s)
    AL513472, AL590402, BC034982, CN288032, DB094058
    UniProtKB/Swiss-Prot
    Q8IYU2
    Conserved Domains (5) summary
    cd00078
    Location:520 → 869
    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 ...
    cd00204
    Location:58 → 183
    ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
    sd00045
    Location:63 → 94
    ANK; ANK repeat [structural motif]
    pfam12796
    Location:4 → 92
    Ank_2; Ankyrin repeats (3 copies)
    pfam13637
    Location:165 → 215
    Ank_4; Ankyrin repeats (many copies)

  3. NM_001321084.2 → NP_001308013.1  E3 ubiquitin-protein ligase HACE1 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variants 9 and 10, encodes isoform d.
    Source sequence(s)
    AL513472, AL590402, BC034982, DB094058
    UniProtKB/Swiss-Prot
    Q8IYU2
    Conserved Domains (2) summary
    cd00078
    Location:386 → 735
    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 ...
    cl39094
    Location:38 → 83
    Ank_2; Ankyrin repeats (3 copies)

  4. NM_001350554.2 → NP_001337483.1  E3 ubiquitin-protein ligase HACE1 isoform e

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (4) summary
    cd00078
    Location:476 → 825
    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 ...
    sd00045
    Location:32 → 61
    ANK; ANK repeat [structural motif]
    pfam12796
    Location:35 → 145
    Ank_2; Ankyrin repeats (3 copies)
    cl39094
    Location:123 → 173
    Ank_2; Ankyrin repeats (3 copies)

  5. NM_001350555.2 → NP_001337484.1  E3 ubiquitin-protein ligase HACE1 isoform f

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (3) summary
    cd00078
    Location:457 → 806
    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 ...
    cd00204
    Location:25 → 152
    ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
    sd00045
    Location:66 → 95
    ANK; ANK repeat [structural motif]

  6. NM_001350556.2 → NP_001337485.1  E3 ubiquitin-protein ligase HACE1 isoform g

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (3) summary
    cd00078
    Location:392 → 741
    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 ...
    sd00045
    Location:1 → 32
    ANK; ANK repeat [structural motif]
    pfam12796
    Location:6 → 89
    Ank_2; Ankyrin repeats (3 copies)

  7. NM_001350557.2 → NP_001337486.1  E3 ubiquitin-protein ligase HACE1 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 5 and 10, encodes isoform d.
    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (2) summary
    cd00078
    Location:386 → 735
    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 ...
    cl39094
    Location:38 → 83
    Ank_2; Ankyrin repeats (3 copies)

  8. NM_001350558.2 → NP_001337487.1  E3 ubiquitin-protein ligase HACE1 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 5 and 9, encodes isoform d.
    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (2) summary
    cd00078
    Location:386 → 735
    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 ...
    cl39094
    Location:38 → 83
    Ank_2; Ankyrin repeats (3 copies)

  9. NM_001350559.2 → NP_001337488.1  E3 ubiquitin-protein ligase HACE1 isoform h

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (2) summary
    cd00078
    Location:360 → 709
    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 ...
    cd00204
    Location:12 → 58
    ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

  10. NM_001350560.2 → NP_001337489.1  E3 ubiquitin-protein ligase HACE1 isoform i

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402
    Conserved Domains (1) summary
    cd00078
    Location:293 → 642
    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 ...

  11. NM_020771.4 → NP_065822.2  E3 ubiquitin-protein ligase HACE1 isoform a

    See identical proteins and their annotated locations for NP_065822.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AJ420474, AK131207, BC034982, BC038119
    Consensus CDS
    CCDS5050.1
    UniProtKB/Swiss-Prot
    A8K6U5, B3KY89, B4DFM6, B4DTQ4, B7Z9X6, E9PGP0, Q5VU99, Q5VUA0, Q8IYU2, Q8ND12, Q9P2M6
    Related
    ENSP00000262903.4, ENST00000262903.9
    Conserved Domains (4) summary
    cd00078
    Location:554 → 903
    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 ...
    cd00204
    Location:92 → 217
    ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
    sd00045
    Location:97 → 128
    ANK; ANK repeat [structural motif]
    cl26073
    Location:27 → 283
    Ank_2; Ankyrin repeats (3 copies)

RNA

  1. NR_104424.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) includes an additional exon in both the 5' and central regions, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    BC034982, BC038119, DA651352
    Related
    ENST00000416605.6

  2. NR_146787.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402

  3. NR_146788.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402

  4. NR_146789.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402

  5. NR_146790.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402

  6. NR_146791.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402

  7. NR_146792.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AL357315, AL513472, AL590402

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_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    104728094..104859919 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    105904367..106035941 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IYU2.2 GenPept UniProtKB/Swiss-Prot:Q8IYU2

Gene LinkOut

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

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