Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:Q9UEF7-1 KL

Class:IdReferenceIsoform:190199
_chainChangeLogsignal peptide:1-33 added on Fri February 6 2015;chain:34-1012 added on Fri February 6 2015;chain:34- added on Fri February 6 2015
_displayNameUniProt:Q9UEF7-1 KL
_timestamp2025-02-21 18:48:07
chainsignal peptide:1-33
chain:34-1012
chain:34-
checksum62031BD73E322E63
commentFUNCTION 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).FUNCTION 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.CATALYTIC ACTIVITY a beta-D-glucuronoside + H2O = D-glucuronate + an alcoholSUBUNIT Homodimer. Interacts with FGF23 and FGFR1.SUBCELLULAR LOCATION Isoform 1 shedding leads to a soluble peptide.SUBCELLULAR LOCATION Present in cortical renal tubules (at protein level). Soluble peptide is present in serum and cerebrospinal fluid. Expressed in kidney, placenta, small intestine and prostate. Down-regulated in renal cell carcinomas, hepatocellular carcinomas, and in chronic renal failure kidney.DOMAIN Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 239, and the second one lacks the essential Glu active site residue at position 872.PTM N-glycosylated.POLYMORPHISM Homozygosity for KL-VS allele is associated with decreased longevity and increased cardiovascular disease risk.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Defects in KL may be a cause of chronic renal failure complications.MISCELLANEOUS Predominates over the membrane form in all tissues examined.SIMILARITY Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.ONLINE INFORMATION The thread of life - Issue 65 of December 2005
created[InstanceEdit:190200] de Bono, B, 2006-12-18 09:54:45
descriptionrecommendedName: Klotho ecNumber: 3.2.1.31 component recommendedName: Klotho peptide /component
geneNameKL
identifierQ9UEF7
isoformParent
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Cell membrane
Disease variant
Glycoprotein
Glycosidase
Hormone
Hydrolase
Membrane
Proteomics identification
Reference proteome
Repeat
Secreted
Signal
Transmembrane
Transmembrane helix
Vitamin D
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameKL
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8998954] ENSEMBL:ENSG00000133116 KL [Homo sapiens]
secondaryIdentifierKLOT_HUMAN
Q5VZ95
Q96KV5
Q96KW5
Q9UEI9
Q9Y4F0
sequenceLength1012
species[Species:48887] Homo sapiens
variantIdentifierQ9UEF7-1
(referenceEntity)[EntityWithAccessionedSequence:190198] KL-1 [plasma membrane] [Homo sapiens]
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:Q9UEF7-1 KL (190199)