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

Summary

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: mouse all
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Genomic context

Location:: 6q16.3

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (104728094..104859919, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (105904367..106035941, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (105175969..105307794, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.
Title: A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.
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.
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.
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.
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.
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.
HACE1 blocks HIF1alpha accumulation under hypoxia in a RAC1 dependent manner.
Title: HACE1 blocks HIF1α accumulation under hypoxia in a RAC1 dependent manner.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (43)

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 EBI GWAS CatalogPubMed
A genome-wide association study of brain lesion distribution in multiple sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of obsessive-compulsive disorder. EBI GWAS Catalog EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

RH104260 (e-PCR)
- UniSTS:98585

RH36005 (e-PCR)
- UniSTS:27173

SHGC-68696 (e-PCR)
- UniSTS:95550

RH92023 (e-PCR)
- UniSTS:87991

SHGC-53557 (e-PCR)
- UniSTS:52919

D6S2180 (e-PCR)
- UniSTS:46527

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 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 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

EC 2.3.2.26

NP_001308012.1

EC 2.3.2.26

NP_001308013.1

EC 2.3.2.26

NP_001337483.1

EC 2.3.2.26

NP_001337484.1

EC 2.3.2.26

NP_001337485.1

EC 2.3.2.26

NP_001337486.1

EC 2.3.2.26

NP_001337487.1

EC 2.3.2.26

NP_001337488.1

EC 2.3.2.26

NP_001337489.1

EC 2.3.2.26

NP_065822.2

EC 2.3.2.26

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

NG_046782.1 RefSeqGene

Range

5001..136826

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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)
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)
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)
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)
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]
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)
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)
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)
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 ...
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 ...
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

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
NR_146787.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL357315, AL513472, AL590402
NR_146788.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL357315, AL513472, AL590402
NR_146789.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL357315, AL513472, AL590402
NR_146790.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL357315, AL513472, AL590402
NR_146791.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL357315, AL513472, AL590402
NR_146792.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL357315, AL513472, AL590402