Summary

Name KLHL12
Full Name Kelch-like protein 12
Synonyms CUL3-interacting protein 1, DKIR homolog, hDKIR | C3IP1
Primary ID Q53G59
Links - -
Type protein
Relations 6
Function 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).

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Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png binding Cullin 3-RBX1-Skp1 0.525
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding SEC31A 0.59
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding SEC31B 0.534
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding LNPK 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding DVL1 0.601
Publications: 1 Organism: Homo Sapiens