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Klhl3 kelch-like 3 [ Mus musculus (house mouse) ]

Gene ID: 100503085, updated on 21-Apr-2024

Summary

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Official Symbol
Klhl3provided by MGI
Official Full Name
kelch-like 3provided by MGI
Primary source
MGI:MGI:2445185
See related
Ensembl:ENSMUSG00000014164 AllianceGenome:MGI:2445185
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
EG627648; 7530408C15Rik
Summary
Predicted to enable cullin family protein binding activity. Predicted to be involved in several processes, including cellular protein metabolic process; distal tubule morphogenesis; and renal sodium ion absorption. Predicted to be located in cytoplasm and cytoskeleton. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytosol. Is expressed in endocrine gland; genitourinary system; heart; lung; and nervous system. Used to study pseudohypoaldosteronism. Human ortholog(s) of this gene implicated in pseudohypoaldosteronism. Orthologous to human KLHL3 (kelch like family member 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in kidney adult (RPKM 6.1), frontal lobe adult (RPKM 4.8) and 21 other tissues See more
Orthologs
human all
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Genomic context

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Location:
13 B1; 13 30.92 cM
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 13 NC_000079.7 (58148040..58271288, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 13 NC_000079.6 (58000226..58123477, complement)

Chromosome 13 - NC_000079.7Genomic Context describing neighboring genes Neighboring gene predicted gene, 33294 Neighboring gene STARR-seq mESC enhancer starr_34663 Neighboring gene sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 Neighboring gene predicted gene, 33240 Neighboring gene STARR-seq mESC enhancer starr_34665 Neighboring gene STARR-seq mESC enhancer starr_34666 Neighboring gene STARR-seq mESC enhancer starr_34669 Neighboring gene CapStarr-seq enhancer MGSCv37_chr13:58168862-58169015 Neighboring gene microRNA 874 Neighboring gene CapStarr-seq enhancer MGSCv37_chr13:58214590-58214824 Neighboring gene CapStarr-seq enhancer MGSCv37_chr13:58219145-58219254 Neighboring gene STARR-positive B cell enhancer ABC_E7243 Neighboring gene STARR-seq mESC enhancer starr_34671 Neighboring gene predicted gene, 33389 Neighboring gene predicted gene, 52040 Neighboring gene heterogeneous nuclear ribonucleoprotein A0 Neighboring gene predicted gene, 40964

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure. Jang JH, et al. Exp Mol Med, 2022 Aug. PMID 36028759, Free PMC Article
  2. Generation and analysis of pseudohypoaldosteronism type II knock-in mice caused by a nonsense KLHL3 mutation in the Kelch domain. Lin CM, et al. FASEB J, 2022 Jun. PMID 35621709
  3. Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice. Guo Q, et al. Pflugers Arch, 2021 Feb. PMID 33432425
  4. Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by KLHL3 mutation in BTB domain. Lin CM, et al. FASEB J, 2019 Jan. PMID 30148674
  5. KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3. Sasaki E, et al. Mol Cell Biol, 2017 Apr 1. PMID 28052936, Free PMC Article

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.
    Title: KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.
  2. KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure.
    Title: KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure.
  3. Generation and analysis of pseudohypoaldosteronism type II knock-in mice caused by a nonsense KLHL3 mutation in the Kelch domain.
    Title: Generation and analysis of pseudohypoaldosteronism type II knock-in mice caused by a nonsense KLHL3 mutation in the Kelch domain.
  4. Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in Mice.
    Title: Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in Mice.
  5. Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice.
    Title: Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice.
  6. Role of KLHL3 and dietary K(+) in regulating KS-WNK1 expression.
    Title: Role of KLHL3 and dietary K(+) in regulating KS-WNK1 expression.
  7. Klhl3(M131V/+) KI mice feature typical pseudohypoaldosteronism II with a simultaneous increase of WNK1 and WNK4 through the impaired KLHL3 BTB domain binding to Cul3
    Title: Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by KLHL3 mutation in BTB domain.
  8. deletion of exon 9 from Cul3 generates a protein that is itself ubiquitin-ligase defective but also capable of enhanced autophagocytic KLHL3 degradation
    Title: Dual gain and loss of cullin 3 function mediates familial hyperkalemic hypertension.
  9. decreased abundance of KLHL3 is a specific phenomenon caused by mutant CUL3 (Deltaexon9).
    Title: Decreased KLHL3 expression is involved in the pathogenesis of pseudohypoaldosteronism type II caused by cullin 3 mutation in vivo.
  10. However, phosphorylation of SPAK and NCC at distal convoluted tubules were almost completely absent even in WNK4(-/-)KLHL3(R528H/R528H) mice. In conclusion, increased WNK1 was unable to compensate for WNK4 deficiency and phosphorylate the NCC, indicating that WNK4 is indispensable for the onset of PHAII.
    Title: WNK4 is indispensable for the pathogenesis of pseudohypoaldosteronism type II caused by mutant KLHL3.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables actin binding IEA
Inferred from Electronic Annotation
more info
  
enables cullin family protein binding ISO
Inferred from Sequence Orthology
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-like ligase-substrate adaptor activity ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
involved_in distal tubule morphogenesis ISO
Inferred from Sequence Orthology
more info
  
involved_in gene expression IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in gene expression IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in monoatomic ion homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in monoatomic ion homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in monoatomic ion homeostasis ISO
Inferred from Sequence Orthology
more info
  
involved_in potassium ion homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process ISO
Inferred from Sequence Orthology
more info
  
involved_in protein K48-linked ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein K48-linked ubiquitination ISO
Inferred from Sequence Orthology
more info
  
involved_in protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein phosphorylation IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein polyubiquitination IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in protein polyubiquitination IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein ubiquitination ISO
Inferred from Sequence Orthology
more info
  
involved_in renal absorption IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in renal sodium ion absorption IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in renal sodium ion absorption IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in renal sodium ion absorption ISO
Inferred from Sequence Orthology
more info
  
involved_in ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
part_of Cul3-RING ubiquitin ligase complex ISO
Inferred from Sequence Orthology
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in cytoskeleton IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
kelch-like protein 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001362415.3 → NP_001349344.2  kelch-like protein 3 isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC165251
    Consensus CDS
    CCDS88463.1
    UniProtKB/Swiss-Prot
    E0CZ16, F7A5U9, I6L891
    Related
    ENSMUSP00000123701.3, ENSMUST00000160860.9
    Conserved Domains (4) summary
    PHA03098
    Location:50 → 566
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:431 → 476
    Kelch; KELCH repeat [structural motif]
    cd18339
    Location:29 → 149
    BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
    cd18513
    Location:147 → 276
    BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

  2. NM_001368867.2 → NP_001355796.1  kelch-like protein 3 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AC165251
    Conserved Domains (4) summary
    PHA03098
    Location:50 → 532
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:384 → 442
    Kelch; KELCH repeat [structural motif]
    cd18339
    Location:29 → 149
    BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
    cd18513
    Location:147 → 276
    BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

  3. NM_001368868.2 → NP_001355797.1  kelch-like protein 3 isoform 3

    Status: VALIDATED

    Source sequence(s)
    AC165251
    Conserved Domains (4) summary
    PHA03098
    Location:18 → 500
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:352 → 410
    Kelch; KELCH repeat [structural motif]
    cd18339
    Location:1 → 117
    BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
    cd18513
    Location:115 → 244
    BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000079.7 Reference GRCm39 C57BL/6J

    Range
    58148040..58271288 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006517010.5 → XP_006517073.1  kelch-like protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006517073.1

    Conserved Domains (4) summary
    PHA03098
    Location:18 → 534
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:399 → 444
    Kelch; KELCH repeat [structural motif]
    cd18339
    Location:1 → 117
    BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
    cd18513
    Location:115 → 244
    BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

  2. XM_006517011.5 → XP_006517074.1  kelch-like protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006517074.1

    Related
    ENSMUST00000091583.6
    Conserved Domains (4) summary
    PHA03098
    Location:18 → 534
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:399 → 444
    Kelch; KELCH repeat [structural motif]
    cd18339
    Location:1 → 117
    BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
    cd18513
    Location:115 → 244
    BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

  3. XM_006517013.4 → XP_006517076.1  kelch-like protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006517076.1

    Conserved Domains (4) summary
    PHA03098
    Location:18 → 534
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:399 → 444
    Kelch; KELCH repeat [structural motif]
    cd18339
    Location:1 → 117
    BTB_POZ_KLHL3; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 3 (KLHL3)
    cd18513
    Location:115 → 244
    BACK_KLHL3; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 3 (KLHL3)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001195075.1: Suppressed sequence

    Description
    NM_001195075.1: This RefSeq was removed because currently there is insufficient support for the transcript and protein.
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
E0CZ16.2 GenPept UniProtKB/Swiss-Prot:E0CZ16

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Chemical Information
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