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KL klotho [ Homo sapiens (human) ]

Gene ID: 9365, updated on 26-Aug-2014
Official Symbol
KLprovided by HGNC
Official Full Name
klothoprovided by HGNC
Primary source
HGNC:6344
See related
Ensembl:ENSG00000133116; HPRD:05316; MIM:604824; Vega:OTTHUMG00000017408
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]
Location:
13q12
Exon count:
6
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 13 NC_000013.11 (33016063..33066145)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (33590571..33640282)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 423 Neighboring gene translocase of outer mitochondrial membrane 22 homolog (yeast) pseudogene 3 Neighboring gene uncharacterized LOC101927403 Neighboring gene StAR-related lipid transfer (START) domain containing 13 Neighboring gene STARD13 antisense RNA Neighboring gene uncharacterized LOC102723425

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  • Adaptive Immune System, organism-specific biosystem (from REACTOME)
    Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
  • Constitutive PI3K/AKT Signaling in Cancer, organism-specific biosystem (from REACTOME)
    Constitutive PI3K/AKT Signaling in Cancer, organism-specific biosystemClass IA PI3K is a heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). In the absence of activating signa...
  • DAP12 interactions, organism-specific biosystem (from REACTOME)
    DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
  • DAP12 signaling, organism-specific biosystem (from REACTOME)
    DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Downstream signal transduction, organism-specific biosystem (from REACTOME)
    Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
  • Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Downstream signaling events of B Cell Receptor (BCR), organism-specific biosystemSecond messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RA...
  • Downstream signaling of activated FGFR, organism-specific biosystem (from REACTOME)
    Downstream signaling of activated FGFR, organism-specific biosystemSignaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that be...
  • Endocrine and other factor-regulated calcium reabsorption, organism-specific biosystem (from KEGG)
    Endocrine and other factor-regulated calcium reabsorption, organism-specific biosystemCalcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis...
  • Endocrine and other factor-regulated calcium reabsorption, conserved biosystem (from KEGG)
    Endocrine and other factor-regulated calcium reabsorption, conserved biosystemCalcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis...
  • FGFR ligand binding and activation, organism-specific biosystem (from REACTOME)
    FGFR ligand binding and activation, organism-specific biosystemThe FGFs are a family of 22 secreted glycoproteins that are sequestered in the extracellular matrix (ECM) through their interaction with heparin and heparin sulphate proteoglycans (HSPGs). Release o...
  • FGFR1c and Klotho ligand binding and activation, organism-specific biosystem (from REACTOME)
    FGFR1c and Klotho ligand binding and activation, organism-specific biosystemFGF23 is a member of the endocrine subfamily of FGFs. It is produced in bone tissue and regulates kidney functions. Klotho is essential for endogenous FGF23 function as it converts FGFR1c into a spec...
  • FRS2-mediated cascade, organism-specific biosystem (from REACTOME)
    FRS2-mediated cascade, organism-specific biosystemThe FRS family of scaffolding adaptor proteins has two members, FRS2alpha and FRS2beta (also known as FRS3 or SNT-2). Activation of FGFR tyrosine kinase allows FRS2 proteins to become phosphorylated...
  • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
    Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
  • GAB1 signalosome, organism-specific biosystem (from REACTOME)
    GAB1 signalosome, organism-specific biosystemGAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also...
  • Glucuronate pathway (uronate pathway), organism-specific biosystem (from KEGG)
    Glucuronate pathway (uronate pathway), organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Other carbohydrate metabolism
  • Glucuronate pathway (uronate pathway), conserved biosystem (from KEGG)
    Glucuronate pathway (uronate pathway), conserved biosystemPathway module; Carbohydrate and lipid metabolism; Other carbohydrate metabolism
  • IGF1R signaling cascade, organism-specific biosystem (from REACTOME)
    IGF1R signaling cascade, organism-specific biosystemAfter autophosphorylation the type 1 insulin-like growth factor receptor (IGF1R) binds and phosphorylates scaffold proteins, IRS1/2/4 and SHC1, which in turn bind effectors possessing enzymatic activ...
  • IRS-mediated signalling, organism-specific biosystem (from REACTOME)
    IRS-mediated signalling, organism-specific biosystemRelease of phospho-IRS from the insulin receptor triggers a cascade of signalling events via PI3K, SOS, RAF and the MAP kinases.
  • IRS-related events, organism-specific biosystem (from REACTOME)
    IRS-related events, organism-specific biosystemIRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned unde...
  • IRS-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
    IRS-related events triggered by IGF1R, organism-specific biosystemThe phosphorylated type 1 insulin-like growth factor receptor phosphorylates IR1, IRS2, IRS4 and possibly other IRS/DOK family members (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et a...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
    Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
  • Klotho-mediated ligand binding, organism-specific biosystem (from REACTOME)
    Klotho-mediated ligand binding, organism-specific biosystemThe endocrine FGFs (19, 21 and 23) have lower affinity for heparin and HSPG compared to their paracrine or autocrine coutnerparts. Binding of these ligands to their receptors is generally aided by t...
  • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
    NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
  • Negative regulation of FGFR signaling, organism-specific biosystem (from REACTOME)
    Negative regulation of FGFR signaling, organism-specific biosystemOnce activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-m...
  • PI-3K cascade, organism-specific biosystem (from REACTOME)
    PI-3K cascade, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...
  • PI3K Cascade, organism-specific biosystem (from REACTOME)
    PI3K Cascade, organism-specific biosystem
    PI3K Cascade
  • PI3K events in ERBB2 signaling, organism-specific biosystem (from REACTOME)
    PI3K events in ERBB2 signaling, organism-specific biosystemERBB2:ERBB3 and ERBB2:ERBB4cyt1 heterodimers activate PI3K signaling by direct binding of PI3K regulatory subunit p85 (Yang et al. 2007, Cohen et al. 1996, Kaushansky et al. 2008) to phosphorylated t...
  • PI3K events in ERBB4 signaling, organism-specific biosystem (from REACTOME)
    PI3K events in ERBB4 signaling, organism-specific biosystemThe CYT1 isoforms of ERBB4 possess a C-tail tyrosine residue that, upon trans-autophosphorylation, serves as a docking site for the p85 alpha subunit of PI3K - PIK3R1 (Kaushansky et al. 2008, Cohen e...
  • PI3K/AKT Signaling in Cancer, organism-specific biosystem (from REACTOME)
    PI3K/AKT Signaling in Cancer, organism-specific biosystemThis pathway describes how normal signaling by PI3K/AKT, presented in the contained module 'PIP3 Activates AKT Signaling' and recently reviewed by Manning and Cantley in 2007, is perturbed in cancer,...
  • PI3K/AKT activation, organism-specific biosystem (from REACTOME)
    PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...
  • PIP3 activates AKT signaling, organism-specific biosystem (from REACTOME)
    PIP3 activates AKT signaling, organism-specific biosystemSignaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimula...
  • Pentose and glucuronate interconversions, organism-specific biosystem (from KEGG)
    Pentose and glucuronate interconversions, organism-specific biosystem
    Pentose and glucuronate interconversions
  • Pentose and glucuronate interconversions, conserved biosystem (from KEGG)
    Pentose and glucuronate interconversions, conserved biosystem
    Pentose and glucuronate interconversions
  • Phospholipase C-mediated cascade, organism-specific biosystem (from REACTOME)
    Phospholipase C-mediated cascade, organism-specific biosystemPhospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 dom...
  • Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystem (from REACTOME)
    Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystemThe lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell...
  • SHC-mediated cascade, organism-specific biosystem (from REACTOME)
    SHC-mediated cascade, organism-specific biosystemThe exact role of SHC1 in FGFR signaling remains unclear. Numerous studies have shown that the p46 and p52 isoforms of SHC1 are phosphorylated in response to FGF stimulation, but direct interaction...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by EGFR, organism-specific biosystem (from REACTOME)
    Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
  • Signaling by EGFR in Cancer, organism-specific biosystem (from REACTOME)
    Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows "Signaling by constitutively active EGFR" in parallel with "Signaling by EGFR". This allows users to compare signaling by constitutively active EGFR ca...
  • Signaling by ERBB2, organism-specific biosystem (from REACTOME)
    Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
  • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
    Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
  • Signaling by FGFR, organism-specific biosystem (from REACTOME)
    Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
  • Signaling by FGFR in disease, organism-specific biosystem (from REACTOME)
    Signaling by FGFR in disease, organism-specific biosystemThe pathway 'Signaling by FGFR in disease' shows 'Signaling by FGFR mutants' in parallel with the wild-type pathway 'Signaling by FGFR', allowing users to compare disease and normal events. FGFR mut...
  • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
    Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
  • Signaling by PDGF, organism-specific biosystem (from REACTOME)
    Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
  • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
    Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
  • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
    Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
  • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
    Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Starch and sucrose metabolism, organism-specific biosystem (from KEGG)
    Starch and sucrose metabolism, organism-specific biosystem
    Starch and sucrose metabolism
  • Starch and sucrose metabolism, conserved biosystem (from KEGG)
    Starch and sucrose metabolism, conserved biosystem
    Starch and sucrose metabolism
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
beta-glucosidase activity TAS
Traceable Author Statement
more info
PubMed 
beta-glucuronidase activity IEA
Inferred from Electronic Annotation
more info
 
fibroblast growth factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
fibroblast growth factor receptor binding IEA
Inferred from Electronic Annotation
more info
 
hormone activity IEA
Inferred from Electronic Annotation
more info
 
signal transducer activity IEA
Inferred from Electronic Annotation
more info
 
vitamin D binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
acute inflammatory response IEA
Inferred from Electronic Annotation
more info
 
aging IMP
Inferred from Mutant Phenotype
more info
PubMed 
calcium ion homeostasis IEA
Inferred from Electronic Annotation
more info
 
carbohydrate metabolic process IEA
Inferred from Electronic Annotation
more info
 
energy reserve metabolic process IEA
Inferred from Electronic Annotation
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
fibroblast growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
innate immune response TAS
Traceable Author Statement
more info
 
insulin receptor signaling pathway TAS
Traceable Author Statement
more info
 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
more info
 
phosphatidylinositol-mediated signaling TAS
Traceable Author Statement
more info
 
positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
positive regulation of bone mineralization IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IEA
Inferred from Electronic Annotation
more info
 
extracellular space TAS
Traceable Author Statement
more info
PubMed 
extracellular vesicular exosome IDA
Inferred from Direct Assay
more info
PubMed 
integral component of membrane TAS
Traceable Author Statement
more info
PubMed 
integral component of plasma membrane TAS
Traceable Author Statement
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
klotho
Names
klotho
NP_004786.2

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011485.1 

    Range
    5001..54712
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_004795.3NP_004786.2  klotho precursor

    See proteins identical to NP_004786.2

    Status: REVIEWED

    Source sequence(s)
    AA890465, AB005142, AL161898
    Consensus CDS
    CCDS9347.1
    UniProtKB/Swiss-Prot
    Q9UEF7
    Related
    ENSP00000369442, OTTHUMP00000018796, ENST00000380099, OTTHUMT00000045987
    Conserved Domains (3) summary
    COG2723
    Location:582952
    Blast Score: 527
    BglB; Beta-glucosidase/6-phospho-beta-glucosidase/beta-galactosidase [Carbohydrate transport and metabolism]
    pfam00232
    Location:58506
    Blast Score: 1087
    Glyco_hydro_1; Glycosyl hydrolase family 1
    cl01046
    Location:62497
    Blast Score: 862
    BglB; Beta-glucosidase/6-phospho-beta-glucosidase/beta-galactosidase [Carbohydrate transport and metabolism]

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000013.11 

    Range
    33016063..33066145
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006719895.1XP_006719958.1  

    Conserved Domains (1) summary
    cl01046
    Location:275637
    Blast Score: 524
    BglB; Beta-glucosidase/6-phospho-beta-glucosidase/beta-galactosidase [Carbohydrate transport and metabolism]

Alternate HuRef

Genomic

  1. AC_000145.1 

    Range
    14401659..14452070
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018924.2 

    Range
    33558119..33607832
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_153683.2: Suppressed sequence

    Description
    NM_153683.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.