FEATURES

DESCRIPTION

Also known as KLH12_HUMAN, KLHL12, C3IP1. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins (PubMed:18303015, PubMed:20100572, PubMed:27716508). Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1 (PubMed:22358839). This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A (PubMed:16547521). Interacts with DRD4, KLHL2 and SEC31A (PubMed:15383316, PubMed:18303015, PubMed:22358839). Interacts with PEF1 and PDCD6/ALG-2; interaction takes place in response to cytosolic calcium increase and leads to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B) (PubMed:27716508).

EXTERNAL LINKS

KLHL12

Mutations

Mutation(s) distribution

Mutations table