Aliases for KLHL22 Gene

Aliases for KLHL22 Gene

  • Kelch Like Family Member 22 2 3 5
  • Kelch-Like Protein 22 3 4
  • KELCHL 2 3
  • Kelch-Like 22 (Drosophila) 2
  • Kelch-Like 22 3
  • FLJ14360 2
  • KLHL22 5

External Ids for KLHL22 Gene

Previous GeneCards Identifiers for KLHL22 Gene

  • GC22M019122
  • GC22M020783
  • GC22M004059

Summaries for KLHL22 Gene

GeneCards Summary for KLHL22 Gene

KLHL22 (Kelch Like Family Member 22) is a Protein Coding gene. Diseases associated with KLHL22 include Neurogenic Bowel and Nephronophthisis 3. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. An important paralog of this gene is KLHL13.

UniProtKB/Swiss-Prot Summary for KLHL22 Gene

  • Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for chromosome alignment and localization of PLK1 at kinetochores. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. Monoubiquitination of PLK1 does not lead to PLK1 degradation (PubMed:19995937, PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway. It is therefore an amino acid-dependent activator within the amino acid-sensing branch of the TORC1 pathway, indirectly regulating different cellular processes including cell growth and autophagy (PubMed:29769719).

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLHL22 Gene

Genomics for KLHL22 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KLHL22 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLHL22 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLHL22

Top Transcription factor binding sites by QIAGEN in the KLHL22 gene promoter:
  • FOXO4
  • Ik-3
  • Lmo2
  • NRF-2
  • POU2F1
  • POU2F1a
  • SRF
  • SRF (504 AA)
  • STAT3

Genomic Locations for KLHL22 Gene

Latest Assembly
chr22:20,441,519-20,497,305
(GRCh38/hg38)
Size:
55,787 bases
Orientation:
Minus strand

Previous Assembly
chr22:20,795,806-20,850,082
(GRCh37/hg19 by Entrez Gene)
Size:
54,277 bases
Orientation:
Minus strand

chr22:20,783,528-20,850,170
(GRCh37/hg19 by Ensembl)
Size:
66,643 bases
Orientation:
Minus strand

Genomic View for KLHL22 Gene

Genes around KLHL22 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLHL22 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLHL22 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLHL22 Gene

Proteins for KLHL22 Gene

  • Protein details for KLHL22 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q53GT1-KLH22_HUMAN
    Recommended name:
    Kelch-like protein 22
    Protein Accession:
    Q53GT1
    Secondary Accessions:
    • A8K3Q4
    • A8MTV3
    • B7Z2G1
    • D3DX30
    • Q96B68
    • Q96KC6

    Protein attributes for KLHL22 Gene

    Size:
    634 amino acids
    Molecular mass:
    71667 Da
    Quaternary structure:
    • Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (PubMed:19995937). Interacts with PLK1 (PubMed:24067371, PubMed:23455478). Interacts with DEPDC5 (via DEP domain); the interaction depends on amino acid availability (PubMed:29769719). Interacts with YWHAE; required for the nuclear localization of KLHL22 upon amino acid starvation (PubMed:29769719).
    SequenceCaution:
    • Sequence=BAB55007.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
    Miscellaneous:
    • Potential oncogene that is up-regulated in breast cancer cells and promotes tumor growth.

    Alternative splice isoforms for KLHL22 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLHL22 Gene

Post-translational modifications for KLHL22 Gene

  • Ubiquitination at Lys12, Lys329, and Lys433
  • Modification sites at PhosphoSitePlus

Antibodies for research

  • Abcam antibodies for KLHL22
  • Boster Bio Antibodies for KLHL22

No data available for DME Specific Peptides for KLHL22 Gene

Domains & Families for KLHL22 Gene

Gene Families for KLHL22 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for KLHL22 Gene

InterPro:
Blocks:
  • BTB/POZ domain
  • BTB/Kelch-associated
ProtoNet:

Suggested Antigen Peptide Sequences for KLHL22 Gene

GenScript: Design optimal peptide antigens:
  • Kelch-like protein 22 (KLH22_HUMAN)
genes like me logo Genes that share domains with KLHL22: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for KLHL22 Gene

Function for KLHL22 Gene

Molecular function for KLHL22 Gene

UniProtKB/Swiss-Prot Function:
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for chromosome alignment and localization of PLK1 at kinetochores. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. Monoubiquitination of PLK1 does not lead to PLK1 degradation (PubMed:19995937, PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway. It is therefore an amino acid-dependent activator within the amino acid-sensing branch of the TORC1 pathway, indirectly regulating different cellular processes including cell growth and autophagy (PubMed:29769719).

Phenotypes From GWAS Catalog for KLHL22 Gene

Gene Ontology (GO) - Molecular Function for KLHL22 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 23455478
GO:0071889 14-3-3 protein binding IPI 29769719
genes like me logo Genes that share ontologies with KLHL22: view
genes like me logo Genes that share phenotypes with KLHL22: view

miRNA for KLHL22 Gene

miRTarBase miRNAs that target KLHL22

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLHL22

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for KLHL22 Gene

Localization for KLHL22 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLHL22 Gene

Cytoplasm, cytosol. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Nucleus. Lysosome. Note=Mainly cytoplasmic in prophase and prometaphase. Associates with the mitotic spindle as the cells reach chromosome bi-orientation. Localizes to the centrosomes shortly before cells enter anaphase After anaphase onset, predominantly associates with the polar microtubules connecting the 2 opposing centrosomes and gradually diffuses into the cytoplasm during telophase (PubMed:23455478). Localizes to the nucleus upon amino acid starvation (PubMed:29769719). Relocalizes to the cytosol and associates with lysosomes when amino acids are available (PubMed:29769719). {ECO:0000269 PubMed:23455478, ECO:0000269 PubMed:29769719}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KLHL22 gene
Compartment Confidence
cytoskeleton 5
cytosol 5
extracellular 4
nucleus 4
golgi apparatus 4
lysosome 3
plasma membrane 1
mitochondrion 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytokinetic bridge (3)
  • Mitotic spindle (3)
  • Vesicles (3)
  • Microtubules (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KLHL22 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 colocalizes_with nucleus IEA,IDA 29769719
GO:0005737 cytoplasm IEA,IDA 23455478
GO:0005764 colocalizes_with lysosome IEA,IDA 29769719
GO:0005813 centrosome IBA,IDA 23455478
GO:0005815 microtubule organizing center IEA --
genes like me logo Genes that share ontologies with KLHL22: view

Pathways & Interactions for KLHL22 Gene

genes like me logo Genes that share pathways with KLHL22: view

UniProtKB/Swiss-Prot Q53GT1-KLH22_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for KLHL22 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000070 mitotic sister chromatid segregation IMP 23455478
GO:0006513 protein monoubiquitination IEA,IDA 23455478
GO:0007049 cell cycle IEA --
GO:0007094 mitotic spindle assembly checkpoint IBA,IMP 23455478
GO:0010507 negative regulation of autophagy IMP 29769719
genes like me logo Genes that share ontologies with KLHL22: view

No data available for SIGNOR curated interactions for KLHL22 Gene

Drugs & Compounds for KLHL22 Gene

No Compound Related Data Available

Transcripts for KLHL22 Gene

mRNA/cDNA for KLHL22 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLHL22

Alternative Splicing Database (ASD) splice patterns (SP) for KLHL22 Gene

No ASD Table

Relevant External Links for KLHL22 Gene

GeneLoc Exon Structure for
KLHL22

Expression for KLHL22 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLHL22 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for KLHL22 Gene

This gene is overexpressed in Testis (8.6) and Fetal Brain (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for KLHL22 Gene



Protein tissue co-expression partners for KLHL22 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLHL22

SOURCE GeneReport for Unigene cluster for KLHL22 Gene:

Hs.517419

Evidence on tissue expression from TISSUES for KLHL22 Gene

  • Nervous system(4.9)
  • Kidney(4.2)
  • Liver(4.1)
  • Lung(2.1)
genes like me logo Genes that share expression patterns with KLHL22: view

Primer products for research

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for KLHL22 Gene

Orthologs for KLHL22 Gene

This gene was present in the common ancestor of animals.

Orthologs for KLHL22 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KLHL22 30 31
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KLHL22 30 31
  • 90.75 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Klhl22 30
  • 87.38 (n)
Mouse
(Mus musculus)
Mammalia Klhl22 30 17 31
  • 87.28 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KLHL22 30 31
  • 86.86 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia KLHL22 31
  • 76 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia KLHL22 31
  • 64 (a)
OneToOne
Chicken
(Gallus gallus)
Aves KLHL22 30 31
  • 72.4 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 65 (a)
OneToMany
-- 31
  • 58 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia klhl22 30
  • 66.61 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC100333714 30
  • 62.66 (n)
klhl22 31
  • 60 (a)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.7057 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG1812 30 31
  • 45.62 (n)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 26 (a)
OneToMany
Species where no ortholog for KLHL22 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for KLHL22 Gene

ENSEMBL:
Gene Tree for KLHL22 (if available)
TreeFam:
Gene Tree for KLHL22 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLHL22: view image

Paralogs for KLHL22 Gene

(23) SIMAP similar genes for KLHL22 Gene using alignment to 9 proteins:

  • KLH22_HUMAN
  • B7Z2G1_HUMAN
  • C9J191_HUMAN
  • C9J2T1_HUMAN
  • C9J5F8_HUMAN
  • C9JHG1_HUMAN
  • C9JLE9_HUMAN
  • C9JRG9_HUMAN
  • H7BZZ5_HUMAN
genes like me logo Genes that share paralogs with KLHL22: view

Variants for KLHL22 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLHL22 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
VAR_079854 - p.Pro20Gln

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for KLHL22 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for KLHL22 Gene

Variant ID Type Subtype PubMed ID
dgv10n35 CNV novel sequence insertion 20440878
dgv4483n100 CNV gain 25217958
dgv7993n54 CNV gain 21841781
esv3647292 CNV gain 21293372
esv3893438 CNV gain 25118596
nsv1056614 CNV loss 25217958
nsv1109451 CNV deletion 24896259
nsv1123576 CNV deletion 24896259
nsv3561 CNV insertion 18451855
nsv436864 CNV insertion 17901297
nsv479206 CNV novel sequence insertion 20440878
nsv479247 CNV novel sequence insertion 20440878
nsv509809 CNV insertion 20534489
nsv509810 CNV insertion 20534489
nsv523162 CNV loss 19592680
nsv588293 CNV gain 21841781
nsv828954 CNV gain 20364138
nsv834135 CNV gain 17160897
nsv834136 CNV loss 17160897
nsv834138 CNV loss 17160897
nsv953032 CNV deletion 24416366
nsv962758 CNV duplication 23825009
nsv966079 CNV duplication 23825009

Variation tolerance for KLHL22 Gene

Residual Variation Intolerance Score: 4.55% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.87; 18.11% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLHL22 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLHL22

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLHL22 Gene

Disorders for KLHL22 Gene

MalaCards: The human disease database

(2) MalaCards diseases for KLHL22 Gene - From: COP

Disorder Aliases PubMed IDs
neurogenic bowel
nephronophthisis 3
  • nphp3
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

KLH22_HUMAN
  • Note=Defects in KLHL22 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269 PubMed:28493397}.

Additional Disease Information for KLHL22

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with KLHL22: view

No data available for Genatlas for KLHL22 Gene

Publications for KLHL22 Gene

  1. CUL3 and protein kinases: insights from PLK1/KLHL22 interaction. (PMID: 24067371) Metzger T … Sumara I (Cell cycle (Georgetown, Tex.) 2013) 2 3 4
  2. KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing. (PMID: 29769719) Chen J … Liu Y (Nature 2018) 3 4
  3. Ubiquitylation-dependent localization of PLK1 in mitosis. (PMID: 23455478) Beck J … Sumara I (Nature cell biology 2013) 3 4
  4. The Cul3-KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis. (PMID: 19995937) Maerki S … Peter M (The Journal of cell biology 2009) 3 4
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

Products for KLHL22 Gene

Sources for KLHL22 Gene