background:
KLHL12 is a 568 amino acid protein that is a component of an ubiquitin-protein E3 ligase complex, which includes at least CUL-3. KLHL12 is a substrate-specific adapter for the complex, which negatively regulates the Wnt signaling pathway via the targeted ubiquitination and subsequent proteolysis of Dvl-3. KLHL12 contains six Kelch repeats and one BTB (POZ) domain, which is required for interaction with CUL-3. KLHL12 has highest expression in testis, with lower levels found in the submandibular salivary gland. The gene that encodes KLHL12 maps to human chromosome 1q32.1
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. 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). 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. The BCR(KLHL12) complex also mediates polyubiquitination of DRD4, without leading to degradation of DRD4.
Subunit:
Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A. Interacts with DRD4, KLHL12 and SEC31A.
Subcellular Location:
Cytoplasmic vesicle, COPII-coated vesicle.
Tissue Specificity:
Ubiquitously expressed. Highly expressed in testis and at lower levels in the submandibular salivary gland.
Similarity:
Contains 1 BACK (BTB/Kelch associated) domain.
Contains 1 BTB (POZ) domain.
Contains 6 Kelch repeats.
Database links:
Entrez Gene: 713668 Cow
Entrez Gene: 59349 Human
Entrez Gene: 48756 Mouse
Entrez Gene: 266772 Rat
Entrez Gene: 431860 Xenopus laevis
Entrez Gene: 492362 Zebrafish
Omim: 614522 Human
SwissProt: E1B932 Cow
SwissProt: Q53G59 Human
SwissProt: Q8BZM0 Mouse
SwissProt: Q8R2H4 Rat
SwissProt: Q6NRH0 Xenopus laevis
SwissProt: Q5U374 Zebrafish
Unigene: 706793 Human
Unigene: 478061 Mouse
Unigene: 87398 Mouse
Unigene: 15513 Rat
Unigene: 32296 Xenopus laevis
Unigene: 81655 Zebrafish
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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