UniProtKB - Q9UH77 (KLHL3_HUMAN)
(max 400 entries)x
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- BLAST
>sp|Q9UH77|KLHL3_HUMAN Kelch-like protein 3 OS=Homo sapiens OX=9606 GN=KLHL3 PE=1 SV=2 MEGESVKLSSQTLIQAGDDEKNQRTITVNPAHMGKAFKVMNELRSKQLLCDVMIVAEDVE IEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTAEIEVTEENV QVLLPAASLLQLMDVRQNCCDFLQSQLHPTNCLGIRAFADVHTCTDLLQQANAYAEQHFP EVMLGEEFLSLSLDQVCSLISSDKLTVSSEEKVFEAVISWINYEKETRLEHMAKLMEHVR LPLLPRDYLVQTVEEEALIKNNNTCKDFLIEAMKYHLLPLDQRLLIKNPRTKPRTPVSLP KVMIVVGGQAPKAIRSVECYDFEEDRWDQIAELPSRRCRAGVVFMAGHVYAVGGFNGSLR VRTVDVYDGVKDQWTSIASMQERRSTLGAAVLNDLLYAVGGFDGSTGLASVEAYSYKTNE WFFVAPMNTRRSSVGVGVVEGKLYAVGGYDGASRQCLSTVEQYNPATNEWIYVADMSTRR SGAGVGVLSGQLYATGGHDGPLVRKSVEVYDPGTNTWKQVADMNMCRRNAGVCAVNGLLY VVGGDDGSCNLASVEYYNPVTDKWTLLPTNMSTGRSYAGVAVIHKSL
- Align
Protein
Kelch-like protein 3
Gene
KLHL3
Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:
Annotation score:5 out of 5
<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>Select a section on the left to see content.
<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity).By similarity
<p>Manually curated information which has been propagated from a related experimentally characterized protein.</p> <p><a href="/manual/evidences#ECO:0000250">More...</a></p> Manual assertion inferred from sequence similarity toi
6 Publications<p>Manually curated information for which there is published experimental evidence.</p> <p><a href="/manual/evidences#ECO:0000269">More...</a></p> Manual assertion based on experiment ini
- Ref.6"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
Furukawa M., He Y.J., Borchers C., Xiong Y.
Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL3. - Ref.7"The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CUL3; WNK1 AND WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; VAL-340; GLN-384; PRO-387; LEU-410; ASN-432; ASN-433; THR-494; HIS-528; CYS-528 AND LYS-529. - Ref.8"Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension."
Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M., Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T., Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.
Cell Rep. 3:858-868(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.9"Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation."
Wu G., Peng J.B.
FEBS Lett. 587:1717-1722(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; PHE-164; ARG-309; PRO-387 AND CYS-528. - Ref.10"Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4."
Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK1; WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
Caution
The BCR(KLHL3) complex was initially thought to act by mediating ubiquitination of SLC12A3/NCC (PubMed:22406640). However, it was later shown that effects on SLC12A3/NCC are indirect and caused by impaired ubiquitination of WNK4 (PubMed:23387299).2 Publications
<p>Manually curated information which has been inferred by a curator based on his/her scientific knowledge or on the scientific content of an article.</p> <p><a href="/manual/evidences#ECO:0000305">More...</a></p> Manual assertion inferred by curator fromi
- Ref.7"The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CUL3; WNK1 AND WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; VAL-340; GLN-384; PRO-387; LEU-410; ASN-432; ASN-433; THR-494; HIS-528; CYS-528 AND LYS-529. - Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: protein ubiquitination
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 PublicationManual assertion based on experiment ini
- Ref.6"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
Furukawa M., He Y.J., Borchers C., Xiong Y.
Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL3.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni
- actin binding Source: UniProtKB-KW
- structural molecule activity Source: ProtInc <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementi
GO - Biological processi
- distal tubule morphogenesis Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypei
- ion homeostasis Source: UniProtKBInferred from mutant phenotypei
- post-translational protein modification Source: Reactome
- protein K48-linked ubiquitination Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayi
- protein ubiquitination Source: UniProtKBInferred from direct assayi
- renal sodium ion absorption Source: UniProtKBInferred from mutant phenotypei
- ubiquitin-dependent protein catabolic process Source: UniProtKBInferred from direct assayi
<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi
| Molecular function | Actin-binding |
| Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
Reactome - a knowledgebase of biological pathways and processes More...Reactomei | R-HSA-8951664 Neddylation R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation |
UniPathway: a resource for the exploration and annotation of metabolic pathways More...UniPathwayi | UPA00143 |
<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi | Recommended name: Kelch-like protein 3 |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi | Name:KLHL31 Publication <p>Manually curated information that is based on statements in scientific articles for which there is no experimental support.</p> <p><a href="/manual/evidences#ECO:0000303">More...</a></p> Manual assertion based on opinion ini
<p>Manually validated information which has been imported from another database.</p> <p><a href="/manual/evidences#ECO:0000312">More...</a></p> Manual assertion inferred from database entriesi Synonyms:KIAA11291 Publication Manual assertion based on opinion ini
|
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>Organismi | Homo sapiens (Human) |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri | 9606 [NCBI] |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineagei | cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo |
| <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi |
|
Organism-specific databases
Eukaryotic Pathogen Database Resources More...EuPathDBi | HostDB:ENSG00000146021.14 |
Human Gene Nomenclature Database More...HGNCi | HGNC:6354 KLHL3 |
Online Mendelian Inheritance in Man (OMIM) More...MIMi | 605775 gene |
neXtProt; the human protein knowledge platform More...neXtProti | NX_Q9UH77 |
<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi
Cytoskeleton
- cytoskeleton 1 Publication
Manual assertion based on experiment ini
- Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
- cytoskeleton 1 Publication
Cytosol
- cytosol 1 Publication
Manual assertion based on experiment ini
- Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
- cytosol 1 Publication
Cytoskeleton
- cytoskeleton Source: UniProtKB-SubCell
Cytosol
Other locations
- Cul3-RING ubiquitin ligase complex Source: UniProtKBInferred from direct assayi
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi
<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei
Pseudohypoaldosteronism 2D (PHA2D)11 PublicationsManual assertion based on experiment ini
- Ref.7"The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CUL3; WNK1 AND WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; VAL-340; GLN-384; PRO-387; LEU-410; ASN-432; ASN-433; THR-494; HIS-528; CYS-528 AND LYS-529. - Ref.8"Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension."
Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M., Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T., Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.
Cell Rep. 3:858-868(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.9"Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation."
Wu G., Peng J.B.
FEBS Lett. 587:1717-1722(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; PHE-164; ARG-309; PRO-387 AND CYS-528. - Ref.10"Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4."
Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK1; WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.11"Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3."
Yoshizaki Y., Mori Y., Tsuzaki Y., Mori T., Nomura N., Wakabayashi M., Takahashi D., Zeniya M., Kikuchi E., Araki Y., Ando F., Isobe K., Nishida H., Ohta A., Susa K., Inoue Y., Chiga M., Rai T. , Sasaki S., Uchida S., Sohara E.
Biochem. Biophys. Res. Commun. 467:229-234(2015) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-10; THR-295; THR-375; SER-376 AND SER-433, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANT PHA2D GLY-433, MUTAGENESIS OF SER-433. - Ref.12"KLHL3 knockout mice reveal the physiological role of KLHL3 and the pathophysiology of pseudohypoaldosteronism type II caused by mutant KLHL3."
Sasaki E., Susa K., Mori T., Isobe K., Araki Y., Inoue Y., Yoshizaki Y., Ando F., Mori Y., Mandai S., Zeniya M., Takahashi D., Nomura N., Rai T., Uchida S., Sohara E.
Mol. Cell. Biol. 37:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: SUBUNIT, VARIANT PHA2D HIS-528, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.15"Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities."
Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A., Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M., Gordon R.D., Semmekrot B.A., Poujol A., Valimaki M.J., De Ferrari M.E., Sanjad S.A., Gutkin M. , Karet F.E., Tucci J.R., Stockigt J.R., Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D., Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E., Nelson R.D., Trachtman H., Cole T.R., Pinsk M., Bockenhauer D., Shenoy M., Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F., Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P.
Nature 482:98-102(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; CYS-322; ILE-336; VAL-340; GLN-384; PRO-387; LEU-410; THR-427; GLN-431; ASN-432; ASN-433; THR-494; THR-501; HIS-528; CYS-528; CYS-557 AND TRP-575, VARIANT ILE-438. - Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3. - Ref.17"A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation."
Mitani M., Furuichi M., Narumi S., Hasegawa T., Chiga M., Uchida S., Sato S.
Clin. Pediatr. Endocrinol. 25:127-134(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PHA2D PRO-387. - Ref.18"A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension."
Kelly D., Rodzlan M.R., Jeunemaitre X., Wall C.
QJM 109:487-488(2016) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANT PHA2D TYR-498. - Ref.19"Familial hyperkalemia and hypertension (FHHt) and KLHL3: Description of a family with a new recessive mutation (S553L) compared to a family with a dominant mutation, Q309R, with analysis of urinary sodium chloride cotransporter."
Kliuk-Ben Bassat O., Carmon V., Hanukoglu A., Ganon L., Massalha E., Holtzman E.J., Farfel Z., Mayan H.
Nephron 137:77-84(2017) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D ARG-309 AND LEU-553.
Ref.7
"The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CUL3; WNK1 AND WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; VAL-340; GLN-384; PRO-387; LEU-410; ASN-432; ASN-433; THR-494; HIS-528; CYS-528 AND LYS-529.
Ref.8
"Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension."
Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M., Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T., Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.
Cell Rep. 3:858-868(2013) [PubMed] [Europe PMC] [Abstract]
Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M., Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T., Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.
Cell Rep. 3:858-868(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528.
Ref.9
"Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation."
Wu G., Peng J.B.
FEBS Lett. 587:1717-1722(2013) [PubMed] [Europe PMC] [Abstract]
Wu G., Peng J.B.
FEBS Lett. 587:1717-1722(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; PHE-164; ARG-309; PRO-387 AND CYS-528.
Ref.10
"Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4."
Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]
Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK1; WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528.
Ref.11
"Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3."
Yoshizaki Y., Mori Y., Tsuzaki Y., Mori T., Nomura N., Wakabayashi M., Takahashi D., Zeniya M., Kikuchi E., Araki Y., Ando F., Isobe K., Nishida H., Ohta A., Susa K., Inoue Y., Chiga M., Rai T. , Sasaki S., Uchida S., Sohara E.
Biochem. Biophys. Res. Commun. 467:229-234(2015) [PubMed] [Europe PMC] [Abstract]
Yoshizaki Y., Mori Y., Tsuzaki Y., Mori T., Nomura N., Wakabayashi M., Takahashi D., Zeniya M., Kikuchi E., Araki Y., Ando F., Isobe K., Nishida H., Ohta A., Susa K., Inoue Y., Chiga M., Rai T. , Sasaki S., Uchida S., Sohara E.
Biochem. Biophys. Res. Commun. 467:229-234(2015) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-10; THR-295; THR-375; SER-376 AND SER-433, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANT PHA2D GLY-433, MUTAGENESIS OF SER-433.
Ref.12
"KLHL3 knockout mice reveal the physiological role of KLHL3 and the pathophysiology of pseudohypoaldosteronism type II caused by mutant KLHL3."
Sasaki E., Susa K., Mori T., Isobe K., Araki Y., Inoue Y., Yoshizaki Y., Ando F., Mori Y., Mandai S., Zeniya M., Takahashi D., Nomura N., Rai T., Uchida S., Sohara E.
Mol. Cell. Biol. 37:0-0(2017) [PubMed] [Europe PMC] [Abstract]
Sasaki E., Susa K., Mori T., Isobe K., Araki Y., Inoue Y., Yoshizaki Y., Ando F., Mori Y., Mandai S., Zeniya M., Takahashi D., Nomura N., Rai T., Uchida S., Sohara E.
Mol. Cell. Biol. 37:0-0(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, VARIANT PHA2D HIS-528, CHARACTERIZATION OF VARIANT PHA2D HIS-528.
Ref.15
"Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities."
Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A., Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M., Gordon R.D., Semmekrot B.A., Poujol A., Valimaki M.J., De Ferrari M.E., Sanjad S.A., Gutkin M. , Karet F.E., Tucci J.R., Stockigt J.R., Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D., Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E., Nelson R.D., Trachtman H., Cole T.R., Pinsk M., Bockenhauer D., Shenoy M., Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F., Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P.
Nature 482:98-102(2012) [PubMed] [Europe PMC] [Abstract]
Boyden L.M., Choi M., Choate K.A., Nelson-Williams C.J., Farhi A., Toka H.R., Tikhonova I.R., Bjornson R., Mane S.M., Colussi G., Lebel M., Gordon R.D., Semmekrot B.A., Poujol A., Valimaki M.J., De Ferrari M.E., Sanjad S.A., Gutkin M. , Karet F.E., Tucci J.R., Stockigt J.R., Keppler-Noreuil K.M., Porter C.C., Anand S.K., Whiteford M.L., Davis I.D., Dewar S.B., Bettinelli A., Fadrowski J.J., Belsha C.W., Hunley T.E., Nelson R.D., Trachtman H., Cole T.R., Pinsk M., Bockenhauer D., Shenoy M., Vaidyanathan P., Foreman J.W., Rasoulpour M., Thameem F., Al-Shahrouri H.Z., Radhakrishnan J., Gharavi A.G., Goilav B., Lifton R.P.
Nature 482:98-102(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; CYS-322; ILE-336; VAL-340; GLN-384; PRO-387; LEU-410; THR-427; GLN-431; ASN-432; ASN-433; THR-494; THR-501; HIS-528; CYS-528; CYS-557 AND TRP-575, VARIANT ILE-438.
Ref.16
"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
Ref.17
"A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation."
Mitani M., Furuichi M., Narumi S., Hasegawa T., Chiga M., Uchida S., Sato S.
Clin. Pediatr. Endocrinol. 25:127-134(2016) [PubMed] [Europe PMC] [Abstract]
Mitani M., Furuichi M., Narumi S., Hasegawa T., Chiga M., Uchida S., Sato S.
Clin. Pediatr. Endocrinol. 25:127-134(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHA2D PRO-387.
Ref.18
"A novel mutation in KLHL3 gene causes familial hyperkalemic hypertension."
Kelly D., Rodzlan M.R., Jeunemaitre X., Wall C.
QJM 109:487-488(2016) [PubMed] [Europe PMC] [Abstract]
Kelly D., Rodzlan M.R., Jeunemaitre X., Wall C.
QJM 109:487-488(2016) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHA2D TYR-498.
Ref.19
"Familial hyperkalemia and hypertension (FHHt) and KLHL3: Description of a family with a new recessive mutation (S553L) compared to a family with a dominant mutation, Q309R, with analysis of urinary sodium chloride cotransporter."
Kliuk-Ben Bassat O., Carmon V., Hanukoglu A., Ganon L., Massalha E., Holtzman E.J., Farfel Z., Mayan H.
Nephron 137:77-84(2017) [PubMed] [Europe PMC] [Abstract]
Kliuk-Ben Bassat O., Carmon V., Hanukoglu A., Ganon L., Massalha E., Holtzman E.J., Farfel Z., Mayan H.
Nephron 137:77-84(2017) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHA2D ARG-309 AND LEU-553.
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive.
See also OMIM:614495| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_067501 | 77 | A → E in PHA2D; impaired interaction with CUL3. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067502 | 78 | M → V in PHA2D; impaired interaction with CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067503 | 85 | E → A in PHA2D; impaired interaction with CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067504 | 164 | C → F in PHA2D; impaired interaction with CUL3; de novo mutation. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067505 | 228 | R → G in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067506 | 309 | Q → R in PHA2D; impaired interaction with WNK1. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067507 | 322 | F → C in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067508 | 336 | R → I in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067509 | 340 | A → V in PHA2D; does not affect interaction with WNK1 or CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067510 | 361 | V → M in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067511 | 362 | R → W in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067512 | 384 | R → Q in PHA2D; impaired interaction with WNK1. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067513 | 384 | R → W in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067514 | 387 | L → P in PHA2D; abolished interaction with WNK1. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067515 | 398 | A → V in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067516 | 410 | S → L in PHA2D; impaired interaction with WNK1. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067517 | 426 | P → L in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067518 | 427 | M → T in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067519 | 431 | R → Q in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067520 | 432 | S → N in PHA2D; impaired interaction with WNK1. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067521 | 433 | S → G in PHA2D; decreased interaction with WNK4. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067522 | 433 | S → N in PHA2D. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067524 | 494 | A → T in PHA2D; does not affect interaction with WNK1 or CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_079630 | 498 | H → Y in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067525 | 500 | G → V in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067526 | 501 | P → T in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067527 | 528 | R → C in PHA2D; impaired interaction with WNK1. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067528 | 528 | R → H in PHA2D; dominant negative effect due to homodimer formation; impaired interaction with WNK1 and WNK4 and impaired ubiquitination of WNK4. 6 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067529 | 529 | N → K in PHA2D; impaired interaction with WNK1. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_079631 | 553 | S → L in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067530 | 557 | Y → C in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067531 | 575 | R → W in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi | 433 | S → E or D: Phosphomimetic mutant that shows decreased interaction with WNK4. 1 Publication Manual assertion based on experiment ini
| 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNET More...DisGeNETi | 26249 |
MalaCards human disease database More...MalaCardsi | KLHL3 |
| MIMi | 614495 phenotype |
Open Targets More...OpenTargetsi | ENSG00000146021 |
Orphanet; a database dedicated to information on rare diseases and orphan drugs More...Orphaneti | 300525 Pseudohypoaldosteronism type 2D |
The Pharmacogenetics and Pharmacogenomics Knowledge Base More...PharmGKBi | PA30144 |
Polymorphism and mutation databases
BioMuta curated single-nucleotide variation and disease association database More...BioMutai | KLHL3 |
Domain mapping of disease mutations (DMDM) More...DMDMi | 13431657 |
<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_0000119103 | 1 – 587 | Kelch-like protein 3Add BLAST | 587 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei | 10 | Phosphoserine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 295 | Phosphothreonine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 375 | Phosphothreonine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 376 | Phosphoserine1 Publication Manual assertion based on experiment ini
| 1 | |
| Modified residuei | 433 | Phosphoserine; by PKA2 Publications Manual assertion based on experiment ini
| 1 |
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi
Phosphorylation at Ser-433 by PKA decreases the interaction with WNK4, Leading to inhibit WNK4 degradation by the BCR(KLHL3) complex (PubMed:26435498, PubMed:27727489). Phosphorylation at Ser-433 is increased by insulin (PubMed:26435498).2 Publications
Manual assertion based on experiment ini
- Ref.11"Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3."
Yoshizaki Y., Mori Y., Tsuzaki Y., Mori T., Nomura N., Wakabayashi M., Takahashi D., Zeniya M., Kikuchi E., Araki Y., Ando F., Isobe K., Nishida H., Ohta A., Susa K., Inoue Y., Chiga M., Rai T. , Sasaki S., Uchida S., Sohara E.
Biochem. Biophys. Res. Commun. 467:229-234(2015) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-10; THR-295; THR-375; SER-376 AND SER-433, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANT PHA2D GLY-433, MUTAGENESIS OF SER-433. - Ref.13"Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study."
Wang L., Peng J.B.
Protein Sci. 26:163-173(2017) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-433, INTERACTION WITH WNK4.
Keywords - PTMi
PhosphoproteinProteomic databases
Encyclopedia of Proteome Dynamics More...EPDi | Q9UH77 |
PaxDb, a database of protein abundance averages across all three domains of life More...PaxDbi | Q9UH77 |
PeptideAtlas More...PeptideAtlasi | Q9UH77 |
PRoteomics IDEntifications database More...PRIDEi | Q9UH77 |
ProteomicsDB human proteome resource More...ProteomicsDBi | 84282 84283 [Q9UH77-2] 84284 [Q9UH77-3] |
PTM databases
iPTMnet integrated resource for PTMs in systems biology context More...iPTMneti | Q9UH77 |
Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat. More...PhosphoSitePlusi | Q9UH77 |
<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni
<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi
Widely expressed.1 Publication
Manual assertion based on experiment ini
- Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
Gene expression databases
Bgee dataBase for Gene Expression Evolution More...Bgeei | ENSG00000146021 Expressed in 203 organ(s), highest expression level in cerebellar vermis |
CleanEx database of gene expression profiles More...CleanExi | HS_KLHL3 |
ExpressionAtlas, Differential and Baseline Expression More...ExpressionAtlasi | Q9UH77 baseline and differential |
Genevisible search portal to normalized and curated expression data from Genevestigator More...Genevisiblei | Q9UH77 HS |
Organism-specific databases
Human Protein Atlas More...HPAi | HPA051291 |
<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni
<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei
Homodimer (PubMed:28052936). Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable) (PubMed:23453970, PubMed:23576762, PubMed:23573258). Interacts with SLC12A3 (PubMed:22406640). Interacts with WNK1 and WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23573258, PubMed:23576762, PubMed:23665031, PubMed:26435498, PubMed:27727489). Interacts with CLDN8 (By similarity).By similarity
Manual assertion inferred from sequence similarity toi
9 PublicationsManual assertion based on experiment ini
- Ref.6"Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases."
Furukawa M., He Y.J., Borchers C., Xiong Y.
Nat. Cell Biol. 5:1001-1007(2003) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL3. - Ref.7"The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH CUL3; WNK1 AND WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; VAL-78; ALA-85; PHE-164; ARG-309; VAL-340; GLN-384; PRO-387; LEU-410; ASN-432; ASN-433; THR-494; HIS-528; CYS-528 AND LYS-529. - Ref.8"Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension."
Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M., Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T., Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.
Cell Rep. 3:858-868(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.9"Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation."
Wu G., Peng J.B.
FEBS Lett. 587:1717-1722(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANTS VARIANTS PHA2D GLU-77; PHE-164; ARG-309; PRO-387 AND CYS-528. - Ref.10"Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4."
Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]Cited for: FUNCTION, IDENTIFICATION IN A BCR (BTB-CUL3-RBX1) E3 UBIQUITIN LIGASE COMPLEX, INTERACTION WITH WNK1; WNK4 AND CUL3, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.11"Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3."
Yoshizaki Y., Mori Y., Tsuzaki Y., Mori T., Nomura N., Wakabayashi M., Takahashi D., Zeniya M., Kikuchi E., Araki Y., Ando F., Isobe K., Nishida H., Ohta A., Susa K., Inoue Y., Chiga M., Rai T. , Sasaki S., Uchida S., Sohara E.
Biochem. Biophys. Res. Commun. 467:229-234(2015) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-10; THR-295; THR-375; SER-376 AND SER-433, INTERACTION WITH WNK4, CHARACTERIZATION OF VARIANT PHA2D GLY-433, MUTAGENESIS OF SER-433. - Ref.12"KLHL3 knockout mice reveal the physiological role of KLHL3 and the pathophysiology of pseudohypoaldosteronism type II caused by mutant KLHL3."
Sasaki E., Susa K., Mori T., Isobe K., Araki Y., Inoue Y., Yoshizaki Y., Ando F., Mori Y., Mandai S., Zeniya M., Takahashi D., Nomura N., Rai T., Uchida S., Sohara E.
Mol. Cell. Biol. 37:0-0(2017) [PubMed] [Europe PMC] [Abstract]Cited for: SUBUNIT, VARIANT PHA2D HIS-528, CHARACTERIZATION OF VARIANT PHA2D HIS-528. - Ref.13"Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study."
Wang L., Peng J.B.
Protein Sci. 26:163-173(2017) [PubMed] [Europe PMC] [Abstract]Cited for: PHOSPHORYLATION AT SER-433, INTERACTION WITH WNK4. - Ref.16"KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron."
Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., Delahousse M., Esnault V., Fiquet B. , Houillier P., Bagnis C.I., Koenig J., Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.
Nat. Genet. 44:456-460(2012) [PubMed] [Europe PMC] [Abstract]Cited for: VARIANTS PHA2D GLY-228; MET-361; TRP-362; TRP-384; VAL-398; LEU-410; LEU-426; ASN-432; GLY-433; VAL-500; HIS-528; CYS-528 AND LYS-529, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SLC12A3.
<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi
| With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CUL3 | Q13618 | 3 | EBI-8524663,EBI-456129 |
GO - Molecular functioni
- actin binding Source: UniProtKB-KW
Protein-protein interaction databases
The Biological General Repository for Interaction Datasets (BioGrid) More...BioGridi | 117637, 19 interactors |
CORUM comprehensive resource of mammalian protein complexes More...CORUMi | Q9UH77 |
The Eukaryotic Linear Motif resource for Functional Sites in Proteins More...ELMi | Q9UH77 |
Protein interaction database and analysis system More...IntActi | Q9UH77, 6 interactors |
Molecular INTeraction database More...MINTi | Q9UH77 |
STRING: functional protein association networks More...STRINGi | 9606.ENSP00000312397 |
<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsHide details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined beta strands within the protein sequence.<p><a href='/help/strand' target='_top'>More...</a></p>Beta strandi | 301 – 306 | Combined sources <p>Manually validated information inferred from a combination of experimental and computational evidence.</p> <p><a href="/manual/evidences#ECO:0000244">More...</a></p> Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 309 – 314 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 317 – 321 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| <p>This subsection of the ‘Structure’ section is used to indicate the positions of experimentally determined hydrogen-bonded turns within the protein sequence. These elements correspond to the DSSP secondary structure code ‘T’.<p><a href='/help/turn' target='_top'>More...</a></p>Turni | 322 – 325 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 326 – 331 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 337 – 339 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 341 – 345 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 348 – 355 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 8 | |
| Beta strandi | 357 – 368 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 12 | |
| Turni | 369 – 372 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 373 – 376 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 388 – 392 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 395 – 399 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 404 – 407 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 411 – 415 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Turni | 416 – 419 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 420 – 424 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 435 – 439 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 442 – 446 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Turni | 451 – 454 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 460 – 464 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Turni | 465 – 468 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 469 – 472 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 484 – 488 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 491 – 495 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 507 – 510 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Turni | 512 – 514 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 517 – 520 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 531 – 535 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 538 – 542 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Beta strandi | 545 – 550 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 | |
| Beta strandi | 554 – 558 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 5 | |
| Turni | 559 – 562 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 563 – 566 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 4 | |
| Beta strandi | 575 – 577 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 3 | |
| Beta strandi | 579 – 584 | Combined sources Manual assertion inferred from combination of experimental and computational evidencei | 6 |
3D structure databases
Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase More...ProteinModelPortali | Q9UH77 |
SWISS-MODEL Repository - a database of annotated 3D protein structure models More...SMRi | Q9UH77 |
Database of comparative protein structure models More...ModBasei | Search... |
MobiDB: a database of protein disorder and mobility annotations More...MobiDBi | Search... |
<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini | 50 – 117 | BTBPROSITE-ProRule annotation <p>Manual validated information which has been generated by the UniProtKB automatic annotation system.</p> <p><a href="/manual/evidences#ECO:0000255">More...</a></p> Manual assertion according to rulesi Add BLAST | 68 | |
| Domaini | 152 – 254 | BACKAdd BLAST | 103 | |
| <p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati | 302 – 347 | Kelch 1Add BLAST | 46 | |
| Repeati | 348 – 394 | Kelch 2Add BLAST | 47 | |
| Repeati | 396 – 441 | Kelch 3Add BLAST | 46 | |
| Repeati | 442 – 490 | Kelch 4Add BLAST | 49 | |
| Repeati | 491 – 537 | Kelch 5Add BLAST | 47 | |
| Repeati | 539 – 585 | Kelch 6Add BLAST | 47 |
Keywords - Domaini
Kelch repeat, RepeatPhylogenomic databases
evolutionary genealogy of genes: Non-supervised Orthologous Groups More...eggNOGi | KOG4441 Eukaryota ENOG410XNX8 LUCA |
Ensembl GeneTree More...GeneTreei | ENSGT00760000118931 |
The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms More...HOGENOMi | HOG000230814 |
The HOVERGEN Database of Homologous Vertebrate Genes More...HOVERGENi | HBG014286 |
InParanoid: Eukaryotic Ortholog Groups More...InParanoidi | Q9UH77 |
KEGG Orthology (KO) More...KOi | K10443 |
Identification of Orthologs from Complete Genome Data More...OMAi | FADLHTC |
Database of Orthologous Groups More...OrthoDBi | EOG091G04QJ |
Database for complete collections of gene phylogenies More...PhylomeDBi | Q9UH77 |
TreeFam database of animal gene trees More...TreeFami | TF329218 |
Family and domain databases
Gene3D Structural and Functional Annotation of Protein Families More...Gene3Di | 2.120.10.80, 1 hit |
Integrated resource of protein families, domains and functional sites More...InterProi | View protein in InterPro IPR011705 BACK IPR017096 BTB-kelch_protein IPR000210 BTB/POZ_dom IPR015915 Kelch-typ_b-propeller IPR006652 Kelch_1 IPR011333 SKP1/BTB/POZ_sf |
Pfam protein domain database More...Pfami | View protein in Pfam PF07707 BACK, 1 hit PF00651 BTB, 1 hit PF01344 Kelch_1, 6 hits |
PIRSF; a whole-protein classification database More...PIRSFi | PIRSF037037 Kelch-like_protein_gigaxonin, 1 hit |
Simple Modular Architecture Research Tool; a protein domain database More...SMARTi | View protein in SMART SM00875 BACK, 1 hit SM00225 BTB, 1 hit SM00612 Kelch, 6 hits |
Superfamily database of structural and functional annotation More...SUPFAMi | SSF117281 SSF117281, 1 hit SSF54695 SSF54695, 1 hit |
PROSITE; a protein domain and family database More...PROSITEi | View protein in PROSITE PS50097 BTB, 1 hit |
<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i
<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.
This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basketAdded to basketThis entry has 3 described isoforms and 2 potential isoforms that are <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>computationally mapped.iShow all
Isoform A (identifier: Q9UH77-1) [UniParc]FASTAAdd to basketAdded to basket
Also known as: KLHL3A1 Publication
Manual assertion based on opinion ini
- Ref.1"Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene."
Lai F., Orelli B.J., Till B.G., Godley L.A., Fernald A.A., Pamintuan L., Le Beau M.M.
Genomics 66:65-75(2000) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), ALTERNATIVE SPLICING.
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
« Hide
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MEGESVKLSS QTLIQAGDDE KNQRTITVNP AHMGKAFKVM NELRSKQLLC
60 70 80 90 100
DVMIVAEDVE IEAHRVVLAA CSPYFCAMFT GDMSESKAKK IEIKDVDGQT
110 120 130 140 150
LSKLIDYIYT AEIEVTEENV QVLLPAASLL QLMDVRQNCC DFLQSQLHPT
160 170 180 190 200
NCLGIRAFAD VHTCTDLLQQ ANAYAEQHFP EVMLGEEFLS LSLDQVCSLI
210 220 230 240 250
SSDKLTVSSE EKVFEAVISW INYEKETRLE HMAKLMEHVR LPLLPRDYLV
260 270 280 290 300
QTVEEEALIK NNNTCKDFLI EAMKYHLLPL DQRLLIKNPR TKPRTPVSLP
310 320 330 340 350
KVMIVVGGQA PKAIRSVECY DFEEDRWDQI AELPSRRCRA GVVFMAGHVY
360 370 380 390 400
AVGGFNGSLR VRTVDVYDGV KDQWTSIASM QERRSTLGAA VLNDLLYAVG
410 420 430 440 450
GFDGSTGLAS VEAYSYKTNE WFFVAPMNTR RSSVGVGVVE GKLYAVGGYD
460 470 480 490 500
GASRQCLSTV EQYNPATNEW IYVADMSTRR SGAGVGVLSG QLYATGGHDG
510 520 530 540 550
PLVRKSVEVY DPGTNTWKQV ADMNMCRRNA GVCAVNGLLY VVGGDDGSCN
560 570 580
LASVEYYNPV TDKWTLLPTN MSTGRSYAGV AVIHKSL
Length:587
Mass (Da):64,970
Last modified:April 27, 2001 - v2
<p>The checksum is a form of redundancy check that is calculated
from the sequence. It is useful for tracking sequence updates.</p>
<p>It should be noted that while, in theory, two different sequences could
have the same checksum value, the likelihood that this would happen
is extremely low.</p>
<p>However UniProtKB may contain entries with identical sequences in case
of multiple genes (paralogs).</p>
<p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64)
using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1.
The algorithm is described in the ISO 3309 standard.
</p>
<p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br />
<strong>Cyclic redundancy and other checksums</strong><br />
<a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p>
Checksum:iC5026A246620BEA1
Isoform B (identifier: Q9UH77-2) [UniParc]FASTAAdd to basketAdded to basket
Also known as: KLHL3B1 Publication
Manual assertion based on opinion ini
- Ref.1"Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene."
Lai F., Orelli B.J., Till B.G., Godley L.A., Fernald A.A., Pamintuan L., Le Beau M.M.
Genomics 66:65-75(2000) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), ALTERNATIVE SPLICING.
The sequence of this isoform differs from the canonical sequence as follows:
1-32: Missing.
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MGKAFKVMNE LRSKQLLCDV MIVAEDVEIE AHRVVLAACS PYFCAMFTGD
60 70 80 90 100
MSESKAKKIE IKDVDGQTLS KLIDYIYTAE IEVTEENVQV LLPAASLLQL
110 120 130 140 150
MDVRQNCCDF LQSQLHPTNC LGIRAFADVH TCTDLLQQAN AYAEQHFPEV
160 170 180 190 200
MLGEEFLSLS LDQVCSLISS DKLTVSSEEK VFEAVISWIN YEKETRLEHM
210 220 230 240 250
AKLMEHVRLP LLPRDYLVQT VEEEALIKNN NTCKDFLIEA MKYHLLPLDQ
260 270 280 290 300
RLLIKNPRTK PRTPVSLPKV MIVVGGQAPK AIRSVECYDF EEDRWDQIAE
310 320 330 340 350
LPSRRCRAGV VFMAGHVYAV GGFNGSLRVR TVDVYDGVKD QWTSIASMQE
360 370 380 390 400
RRSTLGAAVL NDLLYAVGGF DGSTGLASVE AYSYKTNEWF FVAPMNTRRS
410 420 430 440 450
SVGVGVVEGK LYAVGGYDGA SRQCLSTVEQ YNPATNEWIY VADMSTRRSG
460 470 480 490 500
AGVGVLSGQL YATGGHDGPL VRKSVEVYDP GTNTWKQVAD MNMCRRNAGV
510 520 530 540 550
CAVNGLLYVV GGDDGSCNLA SVEYYNPVTD KWTLLPTNMS TGRSYAGVAV
IHKSL
Isoform C (identifier: Q9UH77-3) [UniParc]FASTAAdd to basketAdded to basket
Also known as: KLHL3C1 Publication
Manual assertion based on opinion ini
- Ref.1"Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene."
Lai F., Orelli B.J., Till B.G., Godley L.A., Fernald A.A., Pamintuan L., Le Beau M.M.
Genomics 66:65-75(2000) [PubMed] [Europe PMC] [Abstract]Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), ALTERNATIVE SPLICING.
The sequence of this isoform differs from the canonical sequence as follows:
1-82: Missing.
« Hide
Show »10 20 30 40 50
MSESKAKKIE IKDVDGQTLS KLIDYIYTAE IEVTEENVQV LLPAASLLQL
60 70 80 90 100
MDVRQNCCDF LQSQLHPTNC LGIRAFADVH TCTDLLQQAN AYAEQHFPEV
110 120 130 140 150
MLGEEFLSLS LDQVCSLISS DKLTVSSEEK VFEAVISWIN YEKETRLEHM
160 170 180 190 200
AKLMEHVRLP LLPRDYLVQT VEEEALIKNN NTCKDFLIEA MKYHLLPLDQ
210 220 230 240 250
RLLIKNPRTK PRTPVSLPKV MIVVGGQAPK AIRSVECYDF EEDRWDQIAE
260 270 280 290 300
LPSRRCRAGV VFMAGHVYAV GGFNGSLRVR TVDVYDGVKD QWTSIASMQE
310 320 330 340 350
RRSTLGAAVL NDLLYAVGGF DGSTGLASVE AYSYKTNEWF FVAPMNTRRS
360 370 380 390 400
SVGVGVVEGK LYAVGGYDGA SRQCLSTVEQ YNPATNEWIY VADMSTRRSG
410 420 430 440 450
AGVGVLSGQL YATGGHDGPL VRKSVEVYDP GTNTWKQVAD MNMCRRNAGV
460 470 480 490 500
CAVNGLLYVV GGDDGSCNLA SVEYYNPVTD KWTLLPTNMS TGRSYAGVAV
IHKSL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| Entry | Entry name | Protein names | Gene names | Length | Annotation | ||
|---|---|---|---|---|---|---|---|
| D6RH21 | D6RH21_HUMAN | Kelch-like protein 3 Kelch-like protein 3 | KLHL3 | 400 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> | ||
| D6R9K4 | D6R9K4_HUMAN | Kelch-like protein 3 Kelch-like protein 3 | KLHL3 | 105 | Annotation score: Annotation score:1 out of 5 <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p> |
<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni
The sequence AAB97127 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAA86443 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti | 227 | T → N in AAF20938 (PubMed:10843806).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_067501 | 77 | A → E in PHA2D; impaired interaction with CUL3. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067502 | 78 | M → V in PHA2D; impaired interaction with CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067503 | 85 | E → A in PHA2D; impaired interaction with CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067504 | 164 | C → F in PHA2D; impaired interaction with CUL3; de novo mutation. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067505 | 228 | R → G in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067506 | 309 | Q → R in PHA2D; impaired interaction with WNK1. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067507 | 322 | F → C in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067508 | 336 | R → I in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067509 | 340 | A → V in PHA2D; does not affect interaction with WNK1 or CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067510 | 361 | V → M in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067511 | 362 | R → W in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067512 | 384 | R → Q in PHA2D; impaired interaction with WNK1. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067513 | 384 | R → W in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067514 | 387 | L → P in PHA2D; abolished interaction with WNK1. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067515 | 398 | A → V in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067516 | 410 | S → L in PHA2D; impaired interaction with WNK1. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067517 | 426 | P → L in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067518 | 427 | M → T in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067519 | 431 | R → Q in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067520 | 432 | S → N in PHA2D; impaired interaction with WNK1. 3 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067521 | 433 | S → G in PHA2D; decreased interaction with WNK4. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067522 | 433 | S → N in PHA2D. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067523 | 438 | V → I Found in a patient with hypertension; unknown pathological significance. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067524 | 494 | A → T in PHA2D; does not affect interaction with WNK1 or CUL3. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_079630 | 498 | H → Y in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067525 | 500 | G → V in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067526 | 501 | P → T in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067527 | 528 | R → C in PHA2D; impaired interaction with WNK1. 4 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067528 | 528 | R → H in PHA2D; dominant negative effect due to homodimer formation; impaired interaction with WNK1 and WNK4 and impaired ubiquitination of WNK4. 6 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067529 | 529 | N → K in PHA2D; impaired interaction with WNK1. 2 Publications Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_079631 | 553 | S → L in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067530 | 557 | Y → C in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 | |
| Natural variantiVAR_067531 | 575 | R → W in PHA2D. 1 Publication Manual assertion based on experiment ini
| 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| <p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_002817 | 1 – 82 | Missing in isoform C. 1 Publication Manual assertion based on opinion ini
| 82 | |
| Alternative sequenceiVSP_002816 | 1 – 32 | Missing in isoform B. 1 Publication Manual assertion based on opinion ini
| 32 |
Sequence databases
| Select the link destinations: EMBL nucleotide sequence database More...EMBLiGenBank nucleotide sequence database More...GenBankiDNA Data Bank of Japan; a nucleotide sequence database More...DDBJiLinks Updated | AF208068 mRNA Translation: AAF20938.1 AF208069 mRNA Translation: AAF20939.1 AF208070 mRNA Translation: AAF20995.1 AB032955 mRNA Translation: BAA86443.1 Different initiation. AK314707 mRNA Translation: BAG37254.1 AC004021 Genomic DNA Translation: AAB97127.1 Sequence problems. AC092318 Genomic DNA No translation available. AC106775 Genomic DNA No translation available. CH471062 Genomic DNA Translation: EAW62183.1 |
The Consensus CDS (CCDS) project More...CCDSi | CCDS4192.1 [Q9UH77-1] CCDS58969.1 [Q9UH77-3] CCDS58970.1 [Q9UH77-2] |
NCBI Reference Sequences More...RefSeqi | NP_001244123.1, NM_001257194.1 [Q9UH77-2] NP_001244124.1, NM_001257195.1 [Q9UH77-3] NP_059111.2, NM_017415.2 [Q9UH77-1] |
UniGene gene-oriented nucleotide sequence clusters More...UniGenei | Hs.655084 |
Genome annotation databases
Ensembl eukaryotic genome annotation project More...Ensembli | ENST00000309755; ENSP00000312397; ENSG00000146021 [Q9UH77-1] ENST00000506491; ENSP00000424828; ENSG00000146021 [Q9UH77-3] ENST00000508657; ENSP00000422099; ENSG00000146021 [Q9UH77-2] |
Database of genes from NCBI RefSeq genomes More...GeneIDi | 26249 |
KEGG: Kyoto Encyclopedia of Genes and Genomes More...KEGGi | hsa:26249 |
UCSC genome browser More...UCSCi | uc003lbr.6 human [Q9UH77-1] |
Keywords - Coding sequence diversityi
Alternative splicing<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi
| Protein | Similar proteins | Species | Score | Length | Source | |
|---|---|---|---|---|---|---|
| Q9UH77 | KLHL3 isoform 1 | 587 | UniRef100_Q9UH77 | |||
| Kelch like family member 3 | 587 | |||||
| Q9UH77-2 | KLHL3 isoform 5 | 555 | UniRef100_Q9UH77-2 | |||
| Kelch like family member 3 | 601 | |||||
| Isoform C of Kelch-like protein 3 | 505 | |||||
| UPI00084019F1 | 455 | |||||
| KLHL3 isoform 6 | 505 | |||||
| Q9UH77-3 | Isoform B of Kelch-like protein 3 | 555 | UniRef100_Q9UH77-2 | |||
| KLHL3 isoform 5 | 555 | |||||
| Kelch like family member 3 | 601 | |||||
| UPI00084019F1 | 455 | |||||
| KLHL3 isoform 6 | 505 |
| Protein | Similar proteins | Species | Score | Length | Source | |
|---|---|---|---|---|---|---|
| Q9UH77 | Kelch-like protein 3 | 587 | UniRef90_Q9UH77 | |||
| Kelch-like protein 3 | 587 | |||||
| Kelch-like protein 3 | 587 | |||||
| Kelch-like protein 3 | 587 | |||||
| KLHL3 isoform 1 | 587 | |||||
| +284 | ||||||
| Protein | Similar proteins | Species | Score | Length | Source | |
|---|---|---|---|---|---|---|
| Q9UH77 | Kelch-like protein 3 | 587 | UniRef50_Q9UH77 | |||
| Kelch-like protein 3 | 587 | |||||
| Kelch-like protein 3 | 587 | |||||
| Kelch-like protein 3 | 587 | |||||
| Kelch-like protein 2 | ) | 593 | ||||
| +827 | ||||||
<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi
| <p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry namei | KLHL3_HUMAN | |
| <p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>Accessioni | Q9UH77Primary (citable) accession number: Q9UH77 Secondary accession number(s): B2RBK7 , Q9UH75, Q9UH76, Q9ULU0, Q9Y6V6 | |
| <p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
| Last sequence update: | April 27, 2001 | |
| Last modified: | September 12, 2018 | |
| This is version 159 of the entry and version 2 of the sequence. See complete history. | ||
| <p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | |
