Q6TFL4 · KLH24_HUMAN
- ProteinKelch-like protein 24
- GeneKLHL24
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids600 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity (PubMed:27889062).
As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 and controls its levels during keratinocytes differentiation (PubMed:27798626).
Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity).
Has a crucial role in cardiac development and function (PubMed:30715372).
As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 and controls its levels during keratinocytes differentiation (PubMed:27798626).
Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity).
Has a crucial role in cardiac development and function (PubMed:30715372).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | adherens junction | |
Cellular Component | axon | |
Cellular Component | Cul3-RING ubiquitin ligase complex | |
Cellular Component | cytoplasm | |
Cellular Component | desmosome | |
Cellular Component | perikaryon | |
Biological Process | intermediate filament organization | |
Biological Process | protein autoubiquitination | |
Biological Process | protein ubiquitination |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameKelch-like protein 24
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6TFL4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Epidermolysis bullosa simplex 6, generalized intermediate, with or without cardiomyopathy (EBS6)
- Note
- DescriptionA form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS6 is an autosomal dominant disorder presenting at birth with extensive skin defects on the extremities, leaving behind hypopigmentation and atrophy with a whirled pattern. Cutaneous fragility and generalized blistering persist during childhood and decrease in adulthood. Adult patients have dyspigmentation and atrophy of the skin, scars, follicular atrophoderma, sparse body hair, progressive diffuse alopecia of the scalp, diffuse palmoplantar keratoderma, and nail changes.
- See alsoMIM:617294
Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies (CMH29)
- Note
- DescriptionA form of hypertrophic cardiomyopathy, a heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH29 is an autosomal recessive form associated with a poor prognosis due to lethal arrhythmias and cardiac failure. Cardiac muscle biopsies show intermyofibrillar accumulation of glycogen and polyglucosan bodies within cardiomyocytes. Intermyofibrillar glycogen accumulation is also present in skeletal muscle.
- See alsoMIM:620236
Natural variants in CMH29
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_088094 | 306 | R>H | in CMH29; loss-of-function variant unable to rescue heart defects and cardiac failure in zebrafish morphants | |
VAR_088095 | 350-600 | missing | in CMH29; loss-of-function variant unable to rescue heart defects and cardiac failure in zebrafish morphants |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 32 | Increased protein stability. | ||||
Sequence: K → R | ||||||
Mutagenesis | 90 | Weak interaction with CUL3. Weak autoubiquitination. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 175 | Weak interaction with CUL3. Weak autoubiquitination. | ||||
Sequence: A → V | ||||||
Natural variant | VAR_088094 | 306 | in CMH29; loss-of-function variant unable to rescue heart defects and cardiac failure in zebrafish morphants | |||
Sequence: R → H | ||||||
Natural variant | VAR_088095 | 350-600 | in CMH29; loss-of-function variant unable to rescue heart defects and cardiac failure in zebrafish morphants | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 585 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000261594 | 1-600 | UniProt | Kelch-like protein 24 | |||
Sequence: MVLILGRRLNREDLGVRDSPATKRKVFEMDPKSLTGHEFFDFSSGSSHAENILQIFNEFRDSRLFTDVIICVEGKEFPCHRAVLSACSSYFRAMFCNDHRESREMLVEINGILAEAMECFLQYVYTGKVKITTENVQYLFETSSLFQISVLRDACAKFLEEQLDPCNCLGIQRFADTHSLKTLFTKCKNFALQTFEDVSQHEEFLELDKDELIDYICSDELVIGKEEMVFEAVMRWVYRAVDLRRPLLHELLTHVRLPLLHPNYFVQTVEVDQLIQNSPECYQLLHEARRYHILGNEMMSPRTRPRRSTGYSEVIVVVGGCERVGGFNLPYTECYDPVTGEWKSLAKLPEFTKSEYAVCALRNDILVSGGRINSRDVWIYNSQLNIWIRVASLNKGRWRHKMAVLLGKVYVVGGYDGQNRLSSVECYDSFSNRWTEVAPLKEAVSSPAVTSCVGKLFVIGGGPDDNTCSDKVQSYDPETNSWLLRAAIPIAKRCITAVSLNNLIYVAGGLTKAIYCYDPVEDYWMHVQNTFSRQENCGMSVCNGKIYILGGRRENGEATDTILCYDPATSIITGVAAMPRPVSYHGCVTIHRYNEKCFKL | |||||||
Modified residue (large scale data) | 19 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autoubiquitinated. Autoubiquitination leads to proteasomal degradation and is necessary to control KLHL24 levels.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the skin (PubMed:27798626, PubMed:27889062).
Found in keratinocytes, dermal fibroblasts, and melanocytes (PubMed:27889062).
Basal-layer keratinocytes have lower KLHL24 expression than suprabasal keratinocytes (PubMed:27798626).
Expressed in the brain, spinal cord, liver, testis, heart and at higher levels in the skeletal muscle (PubMed:30715372).
Found in keratinocytes, dermal fibroblasts, and melanocytes (PubMed:27889062).
Basal-layer keratinocytes have lower KLHL24 expression than suprabasal keratinocytes (PubMed:27798626).
Expressed in the brain, spinal cord, liver, testis, heart and at higher levels in the skeletal muscle (PubMed:30715372).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms homodimers. Interacts with GRIK2 (By similarity).
Component of the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24. Interacts with CUL3. Interacts with KRT14 (PubMed:27798626).
Component of the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24. Interacts with CUL3. Interacts with KRT14 (PubMed:27798626).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q6TFL4 | ATP6V1C2 Q8NEY4-2 | 3 | EBI-2510117, EBI-10270867 | |
BINARY | Q6TFL4 | KLHL12 Q53G59 | 6 | EBI-2510117, EBI-740929 | |
BINARY | Q6TFL4 | NCK2 O43639 | 3 | EBI-2510117, EBI-713635 | |
BINARY | Q6TFL4 | PPP1R21 Q6ZMI0 | 2 | EBI-2510117, EBI-5235703 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 66-133 | BTB | ||||
Sequence: TDVIICVEGKEFPCHRAVLSACSSYFRAMFCNDHRESREMLVEINGILAEAMECFLQYVYTGKVKITT | ||||||
Domain | 168-270 | BACK | ||||
Sequence: CLGIQRFADTHSLKTLFTKCKNFALQTFEDVSQHEEFLELDKDELIDYICSDELVIGKEEMVFEAVMRWVYRAVDLRRPLLHELLTHVRLPLLHPNYFVQTVE | ||||||
Repeat | 314-363 | Kelch 1 | ||||
Sequence: VIVVVGGCERVGGFNLPYTECYDPVTGEWKSLAKLPEFTKSEYAVCALRN | ||||||
Repeat | 365-407 | Kelch 2 | ||||
Sequence: ILVSGGRINSRDVWIYNSQLNIWIRVASLNKGRWRHKMAVLLG | ||||||
Repeat | 408-454 | Kelch 3 | ||||
Sequence: KVYVVGGYDGQNRLSSVECYDSFSNRWTEVAPLKEAVSSPAVTSCVG | ||||||
Repeat | 456-502 | Kelch 4 | ||||
Sequence: LFVIGGGPDDNTCSDKVQSYDPETNSWLLRAAIPIAKRCITAVSLNN | ||||||
Repeat | 504-544 | Kelch 5 | ||||
Sequence: IYVAGGLTKAIYCYDPVEDYWMHVQNTFSRQENCGMSVCNG | ||||||
Repeat | 546-592 | Kelch 6 | ||||
Sequence: IYILGGRRENGEATDTILCYDPATSIITGVAAMPRPVSYHGCVTIHR |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q6TFL4-1
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.
- Name1
- Length600
- Mass (Da)68,361
- Last updated2004-07-05 v1
- Checksum54538E2BF447A56B
Q6TFL4-2
- Name2
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 489 | in Ref. 3; BAA90921 | ||||
Sequence: P → R | ||||||
Sequence conflict | 515 | in Ref. 3; BAB15447 | ||||
Sequence: Y → C | ||||||
Alternative sequence | VSP_028644 | 535-537 | in isoform 2 | |||
Sequence: ENC → VIT | ||||||
Sequence conflict | 536 | in Ref. 5; AAI42994 | ||||
Sequence: N → D | ||||||
Alternative sequence | VSP_028645 | 538-600 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY422472 EMBL· GenBank· DDBJ | AAR13703.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ925701 EMBL· GenBank· DDBJ | ABI96896.1 EMBL· GenBank· DDBJ | mRNA | ||
AK000066 EMBL· GenBank· DDBJ | BAA90921.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK026326 EMBL· GenBank· DDBJ | BAB15447.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BX648466 EMBL· GenBank· DDBJ | CAI46031.1 EMBL· GenBank· DDBJ | mRNA | ||
BX648812 EMBL· GenBank· DDBJ | CAI46002.1 EMBL· GenBank· DDBJ | mRNA | ||
BC142993 EMBL· GenBank· DDBJ | AAI42994.1 EMBL· GenBank· DDBJ | mRNA |