HACE1
entrez
57531
canonical
uniprot
Q8IYU2
canonical
ensembl
ENSG00000085382
resolver
ensp
ENSP00000262903
resolver
ensp
ENSP00000521466
resolver
ensp
ENSP00000521467
resolver
genesymbol
HACE1
resolver
genesymbol_syn
KIAA1320
resolver
hgnc
HGNC:21033
resolver
uniprot
A8K6U5
resolver
uniprot
B3KY89
resolver
uniprot
B4DFM6
resolver
uniprot
B4DTQ4
resolver
uniprot
B7Z9X6
resolver
uniprot
E9PGP0
resolver
uniprot
Q5VU99
resolver
uniprot
Q5VUA0
resolver
uniprot
Q8ND12
resolver
uniprot
Q9P2M6
resolver
uniprot_entry
HACE1_HUMAN
resolver
uniprot_sec
A8K6U5
resolver
uniprot_sec
B3KY89
resolver
uniprot_sec
B4DFM6
resolver
uniprot_sec
B4DTQ4
resolver
uniprot_sec
B7Z9X6
resolver
uniprot_sec
E9PGP0
resolver
uniprot_sec
Q5VU99
resolver
uniprot_sec
Q5VUA0
resolver
uniprot_sec
Q8ND12
resolver
uniprot_sec
Q9P2M6
resolver
activity_regulation
ACTIVITY REGULATION: Sterically autoinhibited in its dimeric state. {ECO:0000269|PubMed:37537642, ECO:0000269|PubMed:38332367}.
uniprot
proteins
amino_acid_sequence
MERAMEQLNRLTRSLRRARTVELPEDNETAVYTLMPMVMADQHRSVSELLSNSKFDVNYAFGRVKRSLLHIAANCGSVECLVLLLKKGANPNYQDISGCTPLHLAARNGQKKCMSKLLEYSADVNICNNEGLTAIHWLAVNGRTELLHDLVQHVSDVDVEDAMGQTALHVACQNGHKTTVQCLLDSGADINRPNVSGATPLYFACSHGQRDTAQILLLRGAKYLPDKNGVTPLDLCVQGGYGETCEVLIQYHPRLFQTIIQMTQNEDLRENMLRQVLEHLSQQSESQYLKILTSLAEVATTNGHKLLSLSSNYDAQMKSLLRIVRMFCHVFRIGPSSPSNGIDMGYNGNKTPRSQVFKPLELLWHSLDEWLVLIATELMKNKRDSTEITSILLKQKGQDQDAASIPPFEPPGPGSYENLSTGTRESKPDALAGRQEASADCQDVISMTANRLSAVIQAFYMCCSCQMPPGMTSPRFIEFVCKHDEVLKCFVNRNPKIIFDHFHFLLECPELMSRFMHIIKAQPFKDRCEWFYEHLHSGQPDSDMVHRPVNENDILLVHRDSIFRSSCEVVSKANCAKLKQGIAVRFHGEEGMGQGVVREWFDILSNEIVNPDYALFTQSADGTTFQPNSNSYVNPDHLNYFRFAGQILGLALNHRQLVNIYFTRSFYKHILGIPVNYQDVASIDPEYAKNLQWILDNDISDLGLELTFSVETDVFGAMEEVPLKPGGGSILVTQNNKAEYVQLVTELRMTRAIQPQINAFLQGFHMFIPPSLIQLFDEYELELLLSGMPEIDVSDWIKNTEYTSGYEREDPVIQWFWEVVEDITQEERVLLLQFVTGSSRVPHGGFANIMGGSGLQNFTIAAVPYTPNLLPTSSTCINMLKLPEYPSKEILKDRLLVALHCGSYGYTMA
uniprot
proteins
disease_involvement
DISEASE: Note=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). {ECO:0000269|PubMed:17694067, ECO:0000269|PubMed:19948536}.; DISEASE: Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) [MIM:616756]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPPRS is an autosomal recessive neurodevelopmental disorder manifesting in infancy. Affected individuals show hypotonia and psychomotor retardation. Most develop seizures. {ECO:0000269|PubMed:26424145, ECO:0000269|PubMed:26437029}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.26
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:Q3U0D9, ECO:0000269|PubMed:15254018, ECO:0000269|PubMed:21988917, ECO:0000269|PubMed:22036506, ECO:0000269|PubMed:37537642, ECO:0000269|PubMed:38332367}.
uniprot
proteins
mass_dalton
102342
uniprot
proteins
mutagenesis
MUTAGEN 8; /note="L->A,D: Exists as a mixture of monomer and dimer; promotes autoubiquitination and ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 11; /note="L->A: Exists as a mixture of monomer and dimer; promotes autoubiquitination and ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 11; /note="L->D: Monomeric; promotes autoubiquitination and ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 14; /note="S->E: Monomeric; promotes autoubiquitination and ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 15; /note="L->A,D: Monomeric; promotes autoubiquitination and ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 20; /note="T->E: Monomeric; promotes autoubiquitination and ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 140; /note="V->A: Promotes ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 173; /note="Q->A: Impairs ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 174; /note="N->A: Impairs ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 175; /note="G->S: Impairs ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 204; /note="A->T: Impairs ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 332; /note="R->A: Promotes ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 353; /note="R->A: Promotes ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 694; /note="I->D: Monomeric; loss of E3 ubiquitin ligase activity."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 704; /note="L->D: Dimeric; loss of E3 ubiquitin ligase activity."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 706; /note="L->D: Monomeric; loss of E3 ubiquitin ligase activity."; /evidence="ECO:0000269|PubMed:38332367"; MUTAGEN 876; /note="C->A,S: Loss of E3 ubiquitin ligase activity."; /evidence="ECO:0000269|PubMed:15254018, ECO:0000269|PubMed:21988917, ECO:0000269|PubMed:22036506"; MUTAGEN 906; /note="Y->A: Abolishes ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642"; MUTAGEN 907..909; /note="Missing: Abolishes ubiquitination of RAC1."; /evidence="ECO:0000269|PubMed:37537642
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:37537642, ECO:0000269|PubMed:38332367}.
uniprot
proteins
post_translational_modification
PTM: Autoubiquitinated. {ECO:0000269|PubMed:37537642, ECO:0000269|PubMed:38332367}.
uniprot
proteins
pubmed
10718198
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15254018
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17694067
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19948536
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21988917
uniprot
proteins
pubmed
22036506
uniprot
proteins
pubmed
26424145
uniprot
proteins
pubmed
26437029
uniprot
proteins
pubmed
37537642
uniprot
proteins
pubmed
38332367
uniprot
proteins
sequence_length
909
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane {ECO:0000269|PubMed:21988917}. Cytoplasm {ECO:0000269|PubMed:21988917}. Endoplasmic reticulum {ECO:0000269|PubMed:21988917}. Note=A significant portion localizes to the endoplasmic reticulum. Targeted to Golgi membrane via its interaction with Rab proteins. {ECO:0000269|PubMed:21988917}.
uniprot
proteins