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KLHL22 kelch like family member 22 [ Homo sapiens (human) ]

Gene ID: 84861, updated on 11-Apr-2024

Summary

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Official Symbol
KLHL22provided by HGNC
Official Full Name
kelch like family member 22provided by HGNC
Primary source
HGNC:HGNC:25888
See related
Ensembl:ENSG00000099910 MIM:618020; AllianceGenome:HGNC:25888
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
KELCHL
Summary
Enables 14-3-3 protein binding activity. Involved in several processes, including cellular protein metabolic process; cellular response to leucine; and mitotic spindle assembly checkpoint signaling. Located in several cellular components, including cytosol; intercellular bridge; and microtubule cytoskeleton. Part of Cul3-RING ubiquitin ligase complex. Colocalizes with lysosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in brain (RPKM 3.8), thyroid (RPKM 3.7) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
22q11.21
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (20441519..20495795, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (20845791..20900118, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (20795806..20850082, complement)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene VISTA enhancer hs1620 Neighboring gene RNA, U6 small nuclear 225, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr22:20783264-20783430 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:20784487-20785326 Neighboring gene uncharacterized LOC107985588 Neighboring gene scavenger receptor class F member 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:20795983-20796484 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:20796485-20796984 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62725 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62734 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62743 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:20810551-20811052 Neighboring gene KLHL12 pseudogene 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:20814017-20814215 Neighboring gene uncharacterized LOC124905085 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18678 Neighboring gene RNA, 7SL, cytoplasmic 812, pseudogene Neighboring gene RNY1 pseudogene 9 Neighboring gene keratin 18 pseudogene 5 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13496 Neighboring gene uncharacterized LOC101928824 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:20850596-20851248 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:20859501-20860000 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18679 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18680 Neighboring gene mediator complex subunit 15 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62777 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:20884447-20885434 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62783 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62800 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:20903520-20904510 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18681 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62813 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18682 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62834 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_62844 Neighboring gene uncharacterized LOC124905084

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. KLHL22 promotes malignant melanoma growth in vitro and in vivo by activating the PI3K/Akt/mTOR signaling pathway. Liu XR, et al. Neoplasma, 2020 Sep. PMID 32484697
  2. KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression. Zhou XA, et al. Proc Natl Acad Sci U S A, 2020 Nov 10. PMID 33109719, Free PMC Article
  3. CUL3 and protein kinases: insights from PLK1/KLHL22 interaction. Metzger T, et al. Cell Cycle, 2013 Jul 15. PMID 24067371, Free PMC Article
  4. XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7. Liu BQ, et al. EMBO Rep, 2023 Jan 9. PMID 36394357, Free PMC Article
  5. KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing. Chen J, et al. Nature, 2018 May. PMID 29769719

See all (47) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression.
    Title: KLHL22 maintains PD-1 homeostasis and prevents excessive T cell suppression.
  2. KLHL22 promotes malignant melanoma growth in vitro and in vivo by activating the PI3K/Akt/mTOR signaling pathway.
    Title: KLHL22 promotes malignant melanoma growth in vitro and in vivo by activating the PI3K/Akt/mTOR signaling pathway.
  3. KLHL22 plays a conserved role to mediate the activation of mTORC1 and downstream events; depletion of KLHL22 in breast cancer cells suppresses tumour growth in nude mice; therefore, pharmacological interventions targeting KLHL22 may have therapeutic potential for the treatment of breast cancer and age-related diseases
    Title: KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing.
  4. CUL3/KLHL22 may contact two distinct motifs within PLK1 protein, consistent with the bivalent mode of substrate targeting.
    Title: CUL3 and protein kinases: insights from PLK1/KLHL22 interaction.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of retinopathy in individuals without diabetes.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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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 GOA

Function Evidence Code Pubs
enables 14-3-3 protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-like ligase-substrate adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell division IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to L-leucine IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cellular response to amino acid stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in mitotic sister chromatid segregation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in mitotic spindle assembly checkpoint signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of autophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of type I interferon production IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of TORC1 signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of TORC1 signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of TORC1 signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cell growth 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 IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein monoubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein monoubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
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 IDA
Inferred from Direct Assay
more info
 PubMed 
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IC
Inferred by Curator
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in intercellular bridge IDA
Inferred from Direct Assay
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
colocalizes_with lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in microtubule cytoskeleton IDA
Inferred from Direct Assay
more info
  
is_active_in mitotic spindle IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitotic spindle IDA
Inferred from Direct Assay
more info
 PubMed 
colocalizes_with nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
colocalizes_with nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in polar microtubule IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in polar microtubule IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
kelch-like protein 22
Names
kelch-like 22

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_032775.4 → NP_116164.2  kelch-like protein 22

    See identical proteins and their annotated locations for NP_116164.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the functional protein.
    Source sequence(s)
    BC015923
    Consensus CDS
    CCDS13780.1
    UniProtKB/Swiss-Prot
    A8K3Q4, A8MTV3, B7Z2G1, D3DX30, Q53GT1, Q96B68, Q96KC6
    Related
    ENSP00000331682.4, ENST00000328879.9
    Conserved Domains (4) summary
    PHA03098
    Location:52 → 592
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:340 → 385
    Kelch; KELCH repeat [structural motif]
    cd18251
    Location:27 → 151
    BTB_POZ_KLHL22; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 22 (KLHL22)
    cd18461
    Location:147 → 250
    BACK_KLHL22; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 22 (KLHL22)

RNA

  1. NR_033825.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC007731, AK294682, BC015923

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    20441519..20495795 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017029025.2 → XP_016884514.1  kelch-like protein 22 isoform X8

    Conserved Domains (6) summary
    smart00612
    Location:370 → 416
    Kelch; Kelch domain
    smart00875
    Location:76 → 179
    BACK; BTB And C-terminal Kelch
    PHA03098
    Location:1 → 515
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:263 → 308
    Kelch; KELCH repeat [structural motif]
    pfam00651
    Location:1 → 66
    BTB; BTB/POZ domain
    pfam01344
    Location:313 → 356
    Kelch_1; Kelch motif

  2. XM_017029018.3 → XP_016884507.2  kelch-like protein 22 isoform X1

  3. XM_017029021.3 → XP_016884510.1  kelch-like protein 22 isoform X4

    UniProtKB/Swiss-Prot
    A8K3Q4, A8MTV3, B7Z2G1, D3DX30, Q53GT1, Q96B68, Q96KC6
    Conserved Domains (4) summary
    PHA03098
    Location:52 → 592
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:340 → 385
    Kelch; KELCH repeat [structural motif]
    cd18251
    Location:27 → 151
    BTB_POZ_KLHL22; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Kelch-like protein 22 (KLHL22)
    cd18461
    Location:147 → 250
    BACK_KLHL22; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 22 (KLHL22)

  4. XM_017029022.2 → XP_016884511.1  kelch-like protein 22 isoform X5

  5. XM_017029024.2 → XP_016884513.1  kelch-like protein 22 isoform X7

  6. XM_017029019.3 → XP_016884508.1  kelch-like protein 22 isoform X2

  7. XM_017029020.3 → XP_016884509.1  kelch-like protein 22 isoform X3

    Conserved Domains (4) summary
    PHA03098
    Location:84 → 624
    PHA03098; kelch-like protein; Provisional
    sd00038
    Location:372 → 417
    Kelch; KELCH repeat [structural motif]
    cd18461
    Location:179 → 282
    BACK_KLHL22; BACK (BTB and C-terminal Kelch) domain found in Kelch-like protein 22 (KLHL22)
    cl38908
    Location:59 → 183
    BTB_POZ; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain superfamily

  8. XM_017029023.2 → XP_016884512.1  kelch-like protein 22 isoform X6

RNA

  1. XR_001755341.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    20845791..20900118 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054326056.1 → XP_054182031.1  kelch-like protein 22 isoform X8

  2. XM_054326057.1 → XP_054182032.1  kelch-like protein 22 isoform X1

  3. XM_054326052.1 → XP_054182027.1  kelch-like protein 22 isoform X4

    UniProtKB/Swiss-Prot
    A8K3Q4, A8MTV3, B7Z2G1, D3DX30, Q53GT1, Q96B68, Q96KC6

  4. XM_054326053.1 → XP_054182028.1  kelch-like protein 22 isoform X5

  5. XM_054326055.1 → XP_054182030.1  kelch-like protein 22 isoform X7

  6. XM_054326049.1 → XP_054182024.1  kelch-like protein 22 isoform X2

  7. XM_054326050.1 → XP_054182025.1  kelch-like protein 22 isoform X3

  8. XM_054326054.1 → XP_054182029.1  kelch-like protein 22 isoform X6

  9. XM_054326051.1 → XP_054182026.1  kelch-like protein 22 isoform X3

RNA

  1. XR_008485415.1 RNA Sequence

  2. XR_008485414.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q53GT1.2 GenPept UniProtKB/Swiss-Prot:Q53GT1

Gene LinkOut

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