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beta-klotho (betaKlotho, klotho beta-like protein, KLB)
Function:
- role in transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1 (rate-limiting enzyme in bile acid synthesis)
- probably inactive as a glycosidase
- coreceptors for endocrine FGFs, FGF19 & FGF21
Structure:
- contains 2 glycosyl hydrolase 1 regions
- 1st region lacks essential Glu active site at position 241
- 2nd region lacks essential Glu active site at position 889
- domains are predicted to be inactive.
- belongs to the glycosyl hydrolase 1 family, Klotho subfamily
Compartment: membrane
Genetics:
- genetic variants of KLB appear to confer appetite for alcohol in humans [2]
Comparative biology:
- FGF21 inhibits alcohol drinking by acting on the brain
- beta-klotho is a coreceptor for FGF21 & defects increase appetite of mice for alcohol
General
glycoprotein
membrane protein
Properties
SIZE: MW = 120 kD
entity length = 1044 aa
COMPARTMENT: cellular membrane
MOTIF: N-glycosylation site {N71}
Glycosyl hydrolase-1 1 {77-508}
MOTIF: N-glycosylation site {N120}
N-glycosylation site {N125}
N-glycosylation site {N211}
N-glycosylation site {N308}
N-glycosylation site {N391}
Glycosyl hydrolase-1 2 {517-967}
MOTIF: N-glycosylation site {N554}
N-glycosylation site {N611}
N-glycosylation site {N702}
N-glycosylation site {N706}
N-glycosylation site {N971}
transmembrane domain {997-1017}
Database Correlations
UniProt Q86Z14
Pfam PF00232
References
- UniProt :accession Q86Z14
- Schumann G, Liu C, O'Reilly P et al.
KLB is associated with alcohol drinking, and its gene product
beta-Klotho is necessary for FGF21 regulation of alcohol
preference.
Proc Natl Acad Sci U S A 2016 Dec 13; 113:14372.
PMID: 27911795