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

Summary

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 and ubiquitin-like ligase-substrate adaptor activity. Involved in several processes, including potassium ion homeostasis; protein polyubiquitination; and renal sodium ion absorption. Predicted to be located in 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, Dec 2024]
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

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_000079.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
Role of KLHL3 and dietary K(+) in regulating KS-WNK1 expression.
Title: Role of KLHL3 and dietary K(+) in regulating KS-WNK1 expression.
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.
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.
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.
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)

Endonuclease-mediated (4) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables actin binding	IEA Inferred from Electronic Annotation more info
enables cullin family protein 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	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-like ligase-substrate adaptor activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin-like ligase-substrate adaptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in distal tubule morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in distal tubule morphogenesis	ISS Inferred from Sequence or Structural Similarity 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 monoatomic ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in potassium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein K48-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K48-linked ubiquitination	ISS Inferred from Sequence or Structural Similarity 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 protein ubiquitination	ISS Inferred from Sequence or Structural Similarity 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 renal sodium ion absorption	ISS Inferred from Sequence or Structural Similarity 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
involved_in ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of Cul3-RING ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of Cul3-RING ubiquitin ligase complex	ISO Inferred from Sequence Orthology more info
part_of Cul3-RING ubiquitin ligase complex	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor 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
located_in cytosol	ISS Inferred from Sequence or Structural Similarity 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)

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)
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)
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

NC_000079.7 Reference GRCm39 C57BL/6J

Range

58148040..58271288 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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)
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)
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

NM_001195075.1: Suppressed sequence

Description

NM_001195075.1: This RefSeq was removed because currently there is insufficient support for the transcript and protein.