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 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:202,860,230-202,896,371)mRNA (may differ from genome)Protein (568 aa)
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Wikipedia

-  Comments and Description Text from UniProtKB
  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

-  MalaCards Disease Associations
  MalaCards Gene Search: KLHL12
Diseases sorted by gene-association score: primary biliary cirrhosis (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 29.68 RPKM in Testis
Total median expression: 521.69 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -108.10200-0.540 Picture PostScript Text
3' UTR -408.631431-0.286 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011705 - BACK
IPR000210 - BTB/POZ-like
IPR011333 - BTB/POZ_fold
IPR013069 - BTB_POZ
IPR015916 - Gal_Oxidase_b-propeller
IPR017096 - Kelch-like_gigaxonin
IPR006652 - Kelch_1

Pfam Domains:
PF00651 - BTB/POZ domain
PF01344 - Kelch motif
PF07646 - Kelch motif
PF07707 - BTB And C-terminal Kelch
PF13415 - Galactose oxidase, central domain
PF13964 - Kelch motif

SCOP Domains:
101898 - NHL repeat
50965 - Galactose oxidase, central domain
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50978 - WD40 repeat-like
54695 - POZ domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2VPJ
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q53G59
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0004842 ubiquitin-protein transferase activity

Biological Process:
GO:0006513 protein monoubiquitination
GO:0006888 ER to Golgi vesicle-mediated transport
GO:0014029 neural crest formation
GO:0014032 neural crest cell development
GO:0016055 Wnt signaling pathway
GO:0016192 vesicle-mediated transport
GO:0016567 protein ubiquitination
GO:0048208 COPII vesicle coating
GO:0090090 negative regulation of canonical Wnt signaling pathway

Cellular Component:
GO:0000139 Golgi membrane
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0030127 COPII vesicle coat
GO:0030134 ER to Golgi transport vesicle
GO:0031410 cytoplasmic vesicle
GO:0031463 Cul3-RING ubiquitin ligase complex
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  AK130662 - Homo sapiens cDNA FLJ27152 fis, clone SYN00618, highly similar to Homo sapiens kelch-like protein C3IP1 (C3IP1).
AK027656 - Homo sapiens cDNA FLJ14750 fis, clone NT2RP3002948, weakly similar to RING CANAL PROTEIN.
AK024412 - Homo sapiens cDNA FLJ14350 fis, clone THYRO1001721, weakly similar to RING CANAL PROTEIN.
AF306688 - Homo sapiens clone O19r mRNA sequence.
JD307346 - Sequence 288370 from Patent EP1572962.
JD049399 - Sequence 30423 from Patent EP1572962.
JD081767 - Sequence 62791 from Patent EP1572962.
JD301196 - Sequence 282220 from Patent EP1572962.
JD433471 - Sequence 414495 from Patent EP1572962.
JD232208 - Sequence 213232 from Patent EP1572962.
JD557010 - Sequence 538034 from Patent EP1572962.
JD294555 - Sequence 275579 from Patent EP1572962.
JD326479 - Sequence 307503 from Patent EP1572962.
JD139946 - Sequence 120970 from Patent EP1572962.
JD239111 - Sequence 220135 from Patent EP1572962.
JD185562 - Sequence 166586 from Patent EP1572962.
JD306196 - Sequence 287220 from Patent EP1572962.
AK223072 - Homo sapiens mRNA for kelch-like 12 variant, clone: KAT02609.
JD053928 - Sequence 34952 from Patent EP1572962.
JD279646 - Sequence 260670 from Patent EP1572962.
AF190900 - Homo sapiens kelch-like protein C3IP1 mRNA, complete cds.
BC003183 - Homo sapiens kelch-like 12 (Drosophila), mRNA (cDNA clone MGC:4435 IMAGE:2958852), complete cds.
BC004175 - Homo sapiens kelch-like 12 (Drosophila), mRNA (cDNA clone MGC:2770 IMAGE:2958852), complete cds.
AF306687 - Homo sapiens clone 334-2C mRNA sequence.
JD220162 - Sequence 201186 from Patent EP1572962.
JD409192 - Sequence 390216 from Patent EP1572962.
JD396069 - Sequence 377093 from Patent EP1572962.
AK301791 - Homo sapiens cDNA FLJ56167 complete cds, highly similar to Kelch-like protein 12.
KJ899393 - Synthetic construct Homo sapiens clone ccsbBroadEn_08787 KLHL12 gene, encodes complete protein.
EU446840 - Synthetic construct Homo sapiens clone IMAGE:100070224; IMAGE:100012049; FLH258179.01L kelch-like 12 (Drosophila) (KLHL12) gene, encodes complete protein.
AB527536 - Synthetic construct DNA, clone: pF1KB5982, Homo sapiens KLHL12 gene for kelch-like protein 12, without stop codon, in Flexi system.
AF306689 - Homo sapiens clone O1-1a mRNA sequence.
JD228809 - Sequence 209833 from Patent EP1572962.
CU678428 - Synthetic construct Homo sapiens gateway clone IMAGE:100017707 5' read KLHL12 mRNA.
DQ592806 - Homo sapiens piRNA piR-59918, complete sequence.
JD085947 - Sequence 66971 from Patent EP1572962.
JD480285 - Sequence 461309 from Patent EP1572962.
JD123191 - Sequence 104215 from Patent EP1572962.
JD461593 - Sequence 442617 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q53G59 (Reactome details) participates in the following event(s):

R-HSA-1504213 DVL is bound by the CUL3:KLHL12:RBX1 ubiquitin ligase complex
R-HSA-1504190 DVL is ubiquitinated by CUL3:KLHL12:RBX1
R-HSA-4641258 Degradation of DVL
R-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-195721 Signaling by WNT
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A6NEN8, B7Z7B8, C3IP1, KLH12_HUMAN, NM_021633, NP_067646, Q53G59, Q9HBX5
UCSC ID: uc001gyo.1
RefSeq Accession: NM_021633
Protein: Q53G59 (aka KLH12_HUMAN)
CCDS: CCDS1429.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_021633.2
exon count: 12CDS single in 3' UTR: no RNA size: 3338
ORF size: 1707CDS single in intron: no Alignment % ID: 99.88
txCdsPredict score: 3614.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.