Human Gene KLHL12 (uc001gyo.1) Description and Page Index
Description: Homo sapiens kelch-like family member 12 (KLHL12), mRNA. RefSeq Summary (NM_021633): This gene encodes a member of the KLHL (Kelch-like) family of proteins. This protein has been identified as an autoantigen in the autoimmune disease Sjogren's syndrome and as a potential biomarker in primary biliary cirrhosis. This protein may act as a substrate adaptor of the Cullin-3 ubiquitin ligase complex to promote substrate-specific ubiquitylation. Ubiquitylation by this complex has been shown to regulate the Wnt signaling pathway as well as COPII vesicle coat size. A pseudogene has been identified on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]. Transcript (Including UTRs) Position: hg19 chr1:202,860,230-202,896,371 Size: 36,142 Total Exon Count: 12 Strand: - Coding Region Position: hg19 chr1:202,861,661-202,894,290 Size: 32,630 Coding Exon Count: 11
ID:KLH12_HUMAN DESCRIPTION: RecName: Full=Kelch-like protein 12; AltName: Full=CUL3-interacting protein 1; AltName: Full=DKIR homolog; Short=hDKIR; 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. PATHWAY: Protein modification; protein ubiquitination. 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. INTERACTION: P54253:ATXN1; NbExp=2; IntAct=EBI-740929, EBI-930964; Q9UBV8:PEF1; NbExp=2; IntAct=EBI-740929, EBI-724639; SUBCELLULAR LOCATION: Cytoplasmic vesicle, COPII-coated vesicle. TISSUE SPECIFICITY: Ubiquitously expressed. Highly expressed in testis and at lower levels in the submandibular salivary gland. DOMAIN: The BTB domain is required for interaction with CUL3. SIMILARITY: Contains 1 BACK (BTB/Kelch associated) domain. SIMILARITY: Contains 1 BTB (POZ) domain. SIMILARITY: Contains 6 Kelch repeats.
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): KLHL12 CDC HuGE Published Literature: KLHL12
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q53G59
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.