HECW2

This gene encodes a member of a family of E3 ubiquitin ligases which plays an important role in the proliferation, migration and differentiation of neural crest cells as a regulator of glial cell line-derived neurotrophic factor (GDNF)/Ret signaling. This gene also plays an important role in angiogenesis through stabilization of endothelial cell-to-cell junctions as a regulator of angiomotin-like 1 stability. The encoded protein contains an N-terminal calcium/lipid-binding (C2) domain involved in membrane targeting, two-four WW domains responsible for cellular localization and substrate recognition, and a C-terminal homologous with E6-associated protein C-terminus (HECT) catalytic domain. Naturally occurring mutations in this gene are associated with neurodevelopmental delay, hypotonia, and epilepsy. The decreased expression of this gene in the aganglionic colon is associated with Hirschsprung's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

Full Name

HECT, C2 And WW Domain Containing E3 Ubiquitin Protein Ligase 2

Function

E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487).

Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370).

Biological Process

Negative regulation of sodium ion transmembrane transporter activity Source: GO_Central
Positive regulation of protein catabolic process Source: GO_Central
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
Protein polyubiquitination Source: GO_Central
Protein ubiquitination Source: GO_Central
Regulation of dendrite morphogenesis Source: GO_Central
Regulation of mitotic metaphase/anaphase transition Source: UniProtKB

Cellular Location

Spindle; Cytoplasm

Involvement in disease

Neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL):
A neurodevelopmental disorder characterized by severely delayed psychomotor development, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly. Brain imaging show cerebral atrophy, enlarged ventricles, and white matter abnormalities.

PTM

Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.