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Details on Person UniProt:Q8IYU2-2 HACE1

Class:IdReferenceIsoform:231496
_chainChangeLogchain:1-909 added on Fri February 6 2015
_displayNameUniProt:Q8IYU2-2 HACE1
_timestamp2025-02-21 18:57:11
chainchain:1-909
checksum8AEC09D9D29DC1D8
commentFUNCTION E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases (PubMed:15254018, PubMed:21988917, PubMed:22036506, PubMed:37537642, PubMed:38332367). Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion (PubMed:21988917). Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division (PubMed:21988917). Specifically binds GTP-bound RAC1, mediating ubiquitination and subsequent degradation of active RAC1, thereby playing a role in host defense against pathogens (PubMed:22036506, PubMed:37537642, PubMed:38332367). May also act as a transcription regulator via its interaction with RARB (By similarity).CATALYTIC ACTIVITY S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.ACTIVITY REGULATION Sterically autoinhibited in its dimeric state.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Homodimer (PubMed:37537642, PubMed:38332367). The homodimer is autoinhibited and stabilized by its N-terminal helix (PubMed:37537642, PubMed:38332367). Interacts with RAB1 (RAB1A, RAB1B or RAB1C), RAB4 (RAB4A or RAB4B) and RAB11 (RAB11A or RAB11B); in a GTP-dependent manner (PubMed:21988917). Interacts with the 26S proteasomal complex through the 20S core proteasomal subunit (PubMed:15254018). Interacts with RARB (By similarity).INTERACTION A significant portion localizes to the endoplasmic reticulum. Targeted to Golgi membrane via its interaction with Rab proteins.ALTERNATIVE PRODUCTS Expressed in multiple tissues including heart, brain and kidney.DEVELOPMENTAL STAGE Expressed in fetal and pediatric kidney cells.INDUCTION Down-regulated in sporadic Wilms tumor.DOMAIN The N-terminal lobe of the HECT domain is important for interaction with E2 ubiquitin-conjugating enzymes.DOMAIN The ANK repeats ANK 3, ANK 4 and ANK 5 are important for recognizing the RAC1 substrate.PTM Autoubiquitinated.DISEASE Defects in HACE1 are a cause of Wilms tumor (WT). WT is a pediatric malignancy of kidney and one of the most common solid cancers in childhood. HACE1 is epigenetically down-regulated in sporadic Wilms tumor. Moreover, a t(5;6)(q21;q21) translocation that truncates HACE1 has been found in a child with bilateral, young-onset Wilms tumor (PubMed:19948536).DISEASE The disease is caused by variants affecting the gene represented in this entry.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.
created[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
descriptionrecommendedName: E3 ubiquitin-protein ligase HACE1 ecNumber evidence="12 13"2.3.2.26 alternativeName: HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1 alternativeName: fullName evidence="17 18"HECT-type E3 ubiquitin transferase HACE1
geneNameHACE1
KIAA1320
identifierQ8IYU2
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
ANK repeat
Cell cycle
Chromosomal rearrangement
Cytoplasm
Disease variant
Endoplasmic reticulum
Golgi apparatus
Hereditary spastic paraplegia
Membrane
Neurodegeneration
Proteomics identification
Reference proteome
Repeat
Transcription
Transcription regulation
Transferase
Ubl conjugation
Ubl conjugation pathway
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameHACE1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8993659] ENSEMBL:ENSG00000085382 HACE1 [Homo sapiens]
secondaryIdentifierHACE1_HUMAN
A8K6U5
B3KY89
B4DFM6
B4DTQ4
B7Z9X6
E9PGP0
Q5VU99
Q5VUA0
Q8ND12
Q9P2M6
sequenceLength909
species[Species:48887] Homo sapiens
variantIdentifierQ8IYU2-2
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