Tbio KL Klotho

Protein Classes

PANTHER Classes

Protein / ... / Glycosidase / Klotho

DTO Classes

Protein / Enzyme / Hydrolase / Glycosidase / Klotho

Protein Summary

Description

May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity). The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling. 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]

Uniprot Accession IDs

• Q9UEF7
• Q5VZ95
• Q96KV5
• Q96KW5
• Q9UEI9
• Q9Y4F0

Gene Name

• KL

Ensembl ID

• ENST00000380099
• ENSP00000369442
• ENSG00000133116

Symbol

• HFTC3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	0.96
molecular function	0.84
protein domain	0.73
disease	0.72
histone modification site profile	0.7

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 933.17   (req: < 5)

Gene RIFs: 288   (req: <= 3)

Antibodies: 357   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 933.17   (req: >= 5)

Gene RIFs: 288   (req: > 3)

Antibodies: 357   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Data Bank (1)

1 – 1 of 1

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (49)

Reactome (35)

KEGG (5)

PathwayCommons (2)

WikiPathways (7)

Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)

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Items per page:

5

1 – 5 of 35

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Constitutive Signaling by Aberrant PI3K in Cancer	75 targets	R-HSA-2219530
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of signal transduction	387 targets	R-HSA-5663202
Reactome	Downstream signaling of activated FGFR1	31 targets	R-HSA-5654687

Name	Explore in Pharos	Explore in Source
Constitutive Signaling by Aberrant PI3K in Cancer	75 targets	R-HSA-2219530
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Disease	1105 targets	R-HSA-1643685
Diseases of signal transduction	387 targets	R-HSA-5663202
Downstream signaling of activated FGFR1	31 targets	R-HSA-5654687

Gene Ontology Terms (26)

Functions (9)

Components (7)

Processes (10)

Items per page:

10

1 – 9 of 9

GO Term	Evidence	Assigned by
fibroblast growth factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
beta-glucosidase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
fibroblast growth factor receptor binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
1-phosphatidylinositol-3-kinase activity	Traceable Author Statement (TAS)	Reactome
phosphatidylinositol-4,5-bisphosphate 3-kinase activity	Traceable Author Statement (TAS)	Reactome
Ras guanyl-nucleotide exchange factor activity	Traceable Author Statement (TAS)	Reactome
beta-glucuronidase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-EC
hormone activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
vitamin D binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (149)

Explore Interacting Targets

1 – 10 of 149

• See Interactions on String-DB

FGF23

Tclin

Novelty: 0.00057077

Score: 0.999

Data Source: Reactome,STRINGDB

FGFR3

Tclin

Family: Kinase

Novelty: 0.00092116

Score: 0.968

Data Source: STRINGDB

GUSB

Tchem

Family: Enzyme

Novelty: 0.00074055

Score: 0.94

Data Source: STRINGDB

IGF1R

Tclin

Family: Kinase

Novelty: 0.00039695

Score: 0.935

Data Source: STRINGDB

IRS2

Tbio

Novelty: 0.00217941

Score: 0.92

Data Source: STRINGDB

AKR1A1

Tchem

Family: Enzyme

Novelty: 0.00656392

Score: 0.904

Data Source: STRINGDB

TRPV5

Tchem

Family: IC

Novelty: 0.00701642

Score: 0.879

Data Source: STRINGDB

IRS1

Tbio

Novelty: 0.00061858

Score: 0.859

Data Source: STRINGDB

FGFR1

Tclin

Family: Kinase

Novelty: 0.00068893

Score: 0.854

Data Source: Reactome,STRINGDB

INSR

Tclin

Family: Kinase

Novelty: 0.0029743

Score: 0.848

Data Source: STRINGDB

Publication Statistics

PubMed Score  933.17

PubMed score by year

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PubTator Score  520.53

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAGLFQGTFPDGFLWAVG

1-70

SAAYQTEGGWQQHGKGASIWDTFTHHPLAPPGDSRNASLPLGAPSPLQPATGDVASDSYNNVFRDTEALR

70-140

ELGVTHYRFSISWARVLPNGSAGVPNREGLRYYRRLLERLRELGVQPVVTLYHWDLPQRLQDAYGGWANR

140-210

ALADHFRDYAELCFRHFGGQVKYWITIDNPYVVAWHGYATGRLAPGIRGSPRLGYLVAHNLLLAHAKVWH

210-280

LYNTSFRPTQGGQVSIALSSHWINPRRMTDHSIKECQKSLDFVLGWFAKPVFIDGDYPESMKNNLSSILP

280-350

DFTESEKKFIKGTADFFALCFGPTLSFQLLDPHMKFRQLESPNLRQLLSWIDLEFNHPQIFIVENGWFVS

350-420

GTTKRDDAKYMYYLKKFIMETLKAIKLDGVDVIGYTAWSLMDGFEWHRGYSIRRGLFYVDFLSQDKMLLP

420-490

KSSALFYQKLIEKNGFPPLPENQPLEGTFPCDFAWGVVDNYIQVDTTLSQFTDLNVYLWDVHHSKRLIKV

490-560

DGVVTKKRKSYCVDFAAIQPQIALLQEMHVTHFRFSLDWALILPLGNQSQVNHTILQYYRCMASELVRVN

560-630

ITPVVALWQPMAPNQGLPRLLARQGAWENPYTALAFAEYARLCFQELGHHVKLWITMNEPYTRNMTYSAG

630-700

HNLLKAHALAWHVYNEKFRHAQNGKISIALQADWIEPACPFSQKDKEVAERVLEFDIGWLAEPIFGSGDY

700-770

PWVMRDWLNQRNNFLLPYFTEDEKKLIQGTFDFLALSHYTTILVDSEKEDPIKYNDYLEVQEMTDITWLN

770-840

SPSQVAVVPWGLRKVLNWLKFKYGDLPMYIISNGIDDGLHAEDDQLRVYYMQNYINEALKAHILDGINLC

840-910

GYFAYSFNDRTAPRFGLYRYAADQFEPKASMKHYRKIIDSNGFPGPETLERFCPEEFTVCTECSFFHTRK

910-980

SLLAFIAFLFFASIISLSLIFYYSKKGRRSYK

980-1012

MPASAPPRRPRPPPPSLSLLLVLLGLGGRRLRAEPGDGAQTWARFSRPPAPEAAGLFQGTFPDGFLWAVGSAAYQTEGGWQQHGKGASIWDTFTHHPLAPPGDSRNASLPLGAPSPLQPATGDVASDSYNNVFRDTEALRELGVTHYRFSISWARVLPNGSAGVPNREGLRYYRRLLERLRELGVQPVVTLYHWDLPQRLQDAYGGWANRALADHFRDYAELCFRHFGGQVKYWITIDNPYVVAWHGYATGRLAPGIRGSPRLGYLVAHNLLLAHAKVWHLYNTSFRPTQGGQVSIALSSHWINPRRMTDHSIKECQKSLDFVLGWFAKPVFIDGDYPESMKNNLSSILPDFTESEKKFIKGTADFFALCFGPTLSFQLLDPHMKFRQLESPNLRQLLSWIDLEFNHPQIFIVENGWFVSGTTKRDDAKYMYYLKKFIMETLKAIKLDGVDVIGYTAWSLMDGFEWHRGYSIRRGLFYVDFLSQDKMLLPKSSALFYQKLIEKNGFPPLPENQPLEGTFPCDFAWGVVDNYIQVDTTLSQFTDLNVYLWDVHHSKRLIKVDGVVTKKRKSYCVDFAAIQPQIALLQEMHVTHFRFSLDWALILPLGNQSQVNHTILQYYRCMASELVRVNITPVVALWQPMAPNQGLPRLLARQGAWENPYTALAFAEYARLCFQELGHHVKLWITMNEPYTRNMTYSAGHNLLKAHALAWHVYNEKFRHAQNGKISIALQADWIEPACPFSQKDKEVAERVLEFDIGWLAEPIFGSGDYPWVMRDWLNQRNNFLLPYFTEDEKKLIQGTFDFLALSHYTTILVDSEKEDPIKYNDYLEVQEMTDITWLNSPSQVAVVPWGLRKVLNWLKFKYGDLPMYIISNGIDDGLHAEDDQLRVYYMQNYINEALKAHILDGINLCGYFAYSFNDRTAPRFGLYRYAADQFEPKASMKHYRKIIDSNGFPGPETLERFCPEEFTVCTECSFFHTRKSLLAFIAFLFFASIISLSLIFYYSKKGRRSYK

Find similar targets by:

Uniprot Keyword

3D-structure
Alternative splicing
Cell membrane
Complete proteome
Disease mutation
Glycoprotein
Glycosidase
Hormone
Hydrolase
Membrane