Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys.
Association of klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women.
Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane.
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Secreted Klotho is present in serum and cerebrospinal fluid.
"Newly established antibodies against Klotho allowed the detection of secreted Klotho, a candidate for the putative humoral factor, in sera and cerebrospinal fluid."
C-terminal tail of FGF19 determines its specificity toward Klotho co-receptors.
Large-scale proteomics and phosphoproteomics of urinary exosomes.
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein.
PI3K-containing complexes phosphorylate PIP2 to PIP3
FGFR1c binds to Klotho-bound FGF23
Autocatalytic phosphorylation of Klotho-bound FGFR1c
PI3K phosphorylates PIP2 to PIP3
PI3K inhibitors block PI3K catalytic activity
Activated FGFR1 phosphorylates PLCG1
p-4Y-PLCG1 dissociates from activated FGFR1
Activated FGFR1 binds PLCG1
Activated FGFR1:p-FRS:GRB2:SOS1 activates RAS nucleotide exchange
Activated ERK1/2 threonine-phosphorylates FGFR1-associated FRS2
Activated FGFR1 binds FRS2
Activated FGFR1 binds FRS3
Activated FGFR1 binds SHC1
Activated FGFR1 phosphorylates FRS2
Activated FGFR1 phosphorylates FRS3
Activated FGFR1 phosphorylates SHC1
Activated FGFR1:p-FRS bind to PPTN11
Activated FGFR1:p-FRS binds GRB2:SOS1
Activated FGFR1:p-FRS phosphorylates PPTN11
Activated FGFR1:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA
Activated FGFR1:p-FRS2 binds GRB2:GAB1:PIK3R1
Activated FGFR1:p-FRS2:p-PPTN11 binds GRB2:GAB1:PI3KR1
Activated FGFR1:p-FRS2:p-PPTN11:GRB2:GAB1:PIK3R1 binds PIK3CA
Activated FGFR1:p-SHC1 binds GRB2:SOS1
Activated FGFR1:p-SHC1:GRB2:SOS1 activates RAS nucleotide exchange
CBL ubiquitinates FRS2 and FGFR1
p-CBL:GRB2 binds p-FRS2:activated FGFR1
FGFR1-associated PI3K phosphorylates PIP2 to PIP3
FGFR1- and PTPN11- associated PI3K phosphorylates PIP2 to PIP3
Activated FGFR1 binds FLRT1,2,3
RAS GEFs promote RAS nucleotide exchange
α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.
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Alpha-Klotho is a non-enzymatic scaffold that tethers FGF23 and FGFR1c together.
"The structure reveals that αKlotho serves as a non-enzymatic scaffold that simultaneously tethers FGFR1c and FGF23 to implement FGF23-FGFR1c proximity and hence stability."
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The shed soluble ectodomain also works as an FGF23 co-receptor.
"demonstrating that αKlothoecto can serve as a bona fide co-receptor to support FGF23 signaling in renal proximal tubules"
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The human ectodomain has no detectable glycosidase activity and both KL domains lack a catalytic glutamate.
"Indeed, αKlothoecto failed to hydrolyze substrates for both sialidase and β-glucuronidase in vitro"
Klotho converts canonical FGF receptor into a specific receptor for FGF23.
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Klotho together with FGFR1(IIIc) reconstitutes the FGF23 receptor.
"Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor."
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Klotho binds FGF23.
"Using a renal homogenate, we found that Klotho binds to FGF23."
Regulation of fibroblast growth factor-23 signaling by klotho.
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Klotho binds multiple FGFRs and is a required cofactor for FGF23 signaling.
"Klotho binds to multiple FGFRs and functions as a cofactor necessary for FGF signaling activation by FGF23"
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FGF23 associates with FGFR1c, FGFR3c and FGFR4 only when Klotho is present.
"FGF23 was pulled down with FGFR1c, -3c, and -4 only in the presence of Klotho"
Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides.
A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis.
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Human KL loss of function impairs FGF23 bioactivity and mineral homeostasis.
"loss-of-function mutations in human KL impair FGF23 bioactivity, underscoring the essential role of KL in FGF23-mediated phosphate and vitamin D homeostasis in humans"
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The patient showed hyperphosphatemia and ectopic calcification.
"This patient exhibited defects in mineral ion homeostasis with marked hyperphosphatemia"
RNAi silencing of brain klotho potentiates cold-induced elevation of blood pressure via the endothelin pathway.
Suppression of aging in mice by the hormone Klotho.
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Klotho inhibits insulin and IGF1 signaling in mice.
"Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties."
UniProt entry Q9UEF7 (human KL)
Deep research report on human KL (provider: falcon)