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FLASH GENE

Symbol

HACE1

contributors: mct - updated : 08-11-2017

HGNC name	HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1
HGNC id	21033

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Lymphoid/Immune thymus       highly Reproductive male system testis       Respiratory respiratory tract trachea     highly Urinary kidney       moderately

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	brain, kidney

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six N-terminal ankyrin protein–protein interaction repeats with sequence similarity to those of INKA
	a middle (MID) domain, with a role in conferring the specificity of association of HACE1 to the active form of RAC1
	a C- terminus homologous to E6-associating protein carboxy terminus ubiquitin-protein ligase domain and HECT domain (Slade 2010)

HOMOLOGY

interspecies

ortholog to murine Hace1

Homologene

FAMILY

HECT family of E3 ubiqutin protein ligase

CATEGORY

enzyme , regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus

basic FUNCTION	involved in protein modification, ubiquitin cycle
	possessing intrinsic ubiquitin ligase activity
	having tumor-suppressor function dependent on its E3 ligase activity and controling adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1
	involved in repression of RAR-regulated transcription which is due to its ability to inhibit the RA-dependent degradation of RARs (Zhao 2010)
	play a role in the regulation of cell cycle progression during cellular stress by influencing cyclin D1 degradation (Slade 2010)
	role of the HACE1 E3 ubiquitin-ligase in controlling RAC1 ubiquitylation and activity
	is an antagonist of cell migration through its ability to degrade active RAC1
	protects the heart under pressure stress by controlling protein degradation
	has a protective function in the heart in response to haemodynamic stress, suggesting that HACE1 may be a potential diagnostic and therapeutic target for heart disease
	critical role for HACE1 in breast cancer progression
	can act as a haploinsufficient tumor suppressor gene in most B-cell lymphomas
	HACE1 controls TNF-elicited cell fate decisions and exerts tumor suppressor and anti-inflammatory activities via a TNFRSF1A-RIPK3 kinase-necroptosis pathway
	E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase RAC1 to target it to proteasomal degradation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells

INTERACTION

DNA

RNA

small molecule

protein	interacting with UBCH7
	HACE1 plays a role in the NFE2L2 antioxidative stress response pathway and in neurodegeneration
	ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux
	HACE1 is a specific E3 ligase that polyubiquitinates YBX1 through non-canonical K27 linked ubiquitin chains
	HACE1 is a central gatekeeper of TNFRSF1A-induced cell fate
	is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic CASP8 effector complex
	STX5 is monoubiquitinated by the ubiquitin ligase HACE1 in early mitosis and deubiquitinated by the deubiquitinase VCPIP1 in late mitosis

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

SPPRS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in sporadic Wilms tumor (by hypermethylation) tumoral     --low   in multiple human tumor type tumoral     --low   by hyper methylation in gastric carcinoma (Sakata 2009) constitutional     --low   associated with a significant decrease in apoptosis and an accumulation of cells in the S and G2/M phases constitutional     --over   in the serum of patients with heart failure constitutional     --low   reduction of HACE1 levels in the striatum of Huntington disease patients, implicating HACE1 in the pathology of Huntington disease tumoral     --low   by hypermethylation in hepatocellular carcinoma

Susceptibility

to neuroblastoma

Variant & Polymorphism other	common variants in HACE1 and LIN28B influence neuroblastoma susceptibility

Candidate gene
Marker	may be a valuable prognostic biomarker for hepatocellular carcinoma
Therapy target
	System Type Disorder Pubmed cancer digestive liver potential therapeutic target for hepatocellular carcinoma treatment

ANIMAL & CELL MODELS