Mouse Anti-HUWE1 Recombinant Antibody (AX8D1) (CBMAB-C3560-CN)

HECT, UBA And WWE Domain Containing 1, E3 Ubiquitin Protein Ligase

This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]

HECT, UBA And WWE Domain Containing 1, E3 Ubiquitin Protein Ligase; Homologous To E6AP Carboxyl Terminus Homologous Protein 9; Upstream Regulatory Element-Binding Protein 1; HECT-Type E3 Ubiquitin Transferase HUWE1; Mcl-1 Ubiquitin Ligase E3; Large Structure Of UREB1; ARF-Binding Protein 1; URE-Binding Protein 1; ARF-BP1; HECTH9; URE-B1; LASU1; UREB1; MULE;

E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15989957, PubMed:19713937, PubMed:15567145, PubMed:15767685, PubMed:18488021, PubMed:17567951, PubMed:19037095, PubMed:20534529, PubMed:30217973).

Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957).

Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937).

Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956).

Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738).

Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973).

Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021).

May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951).

Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095).

Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529).

Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity).

Base-excision repair Source: UniProtKB
Cell differentiation Source: UniProtKB-KW
Circadian regulation of gene expression Source: UniProtKB
Golgi organization Source: GO_Central
Histone ubiquitination Source: UniProtKB
Membrane fusion Source: GO_Central
Negative regulation of mitochondrial fusion Source: UniProtKB
Positive regulation of mitophagy in response to mitochondrial depolarization Source: CACAO
Positive regulation of protein catabolic process Source: GO_Central
Positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
Positive regulation of protein ubiquitination Source: UniProtKB
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
Protein monoubiquitination Source: UniProtKB
Protein polyubiquitination Source: UniProtKB
Protein ubiquitination Source: GO_Central

Cytoplasm; Mitochondrion; Nucleus. Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells (By similarity). Recruited to mitochondria following interaction with AMBRA1 (PubMed:30217973).

Intellectual developmental disorder, X-linked, syndromic, Turner type (MRXST):
An X-linked neurodevelopmental disorder with highly variable clinical manifestations. Common features consist of moderate to profound intellectual disability, delayed or absent speech, short stature with small hands and feet, and non-specific but recurrent dysmorphic facial features such as macrocephaly, microcephaly, a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures and a short philtrum. Patients may manifest other features, such as hypotonia, seizures and delayed bone age.

Phosphorylated on tyrosine; phosphorylation is probably required for its ability to inhibit TP53 transactivation.