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Reviewed, UniProtKB/Swiss-Prot Q99N32 (KLOTB_MOUSE)

Last modified November 24, 2009. Version 63. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Beta-klotho
Alternative name(s):
    BetaKlotho
    Klotho beta-like protein
Gene names
Name: Klb
Synonyms: Betakl
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length1043 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 to bind FGF21. Ref.3 Ref.4

Subunit structure

Interacts with FGF19; this interaction is direct. Interacts (via C-terminus) with FGF21; this interaction is direct By similarity. Interacts with FGFR1 and FGFR4.

Subcellular location

Cell membrane; Single-pass type III membrane protein Potential.

Tissue specificity

Present in liver, muscle and white adipose tissue, but not in kidney (at protein level). Expressed in liver and pancreas, and at lower levels in skin, stomach, skeletal muscle, small intestine and lung. Ref.3 Ref.4 Ref.1

Developmental stage

Expression starts at E10.5 in hepatocytes. Expressed in the acinar cells of the pancreas and cervical brown adipose tissue at E15.5. Expressed in white adipose tissue at E19.5. Up-regulated during preadipocyte differentiation into adipocytes (at protein level). Ref.4 Ref.1

Domain

Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 887. These domains are therefore predicted to be inactive.

Disruption phenotype

Mice are viable and fertile, but have an altered bile metabolism: they have increased CYP7A1 levels, secrete more bile acids and are resistant to cholesterol gallstone formation. Ref.3

Sequence similarities

Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.

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Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Transmembrane
   PTMGlycoprotein
Gene Ontology (GO)
   Biological processcarbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functioncation binding

Inferred from electronic annotation. Source: InterPro

hydrolase activity, hydrolyzing O-glycosyl compounds

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99N32-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99N32-2)

The sequence of this isoform differs from the canonical sequence as follows:
     276-295: AHSKVWHNYDKNFRPHQKGW → VLYSWLLTRASELGGGVLGG
     296-1043: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10431043Beta-klotho
PRO_0000063906

Regions

Topological domain1 – 994994Extracellular Potential
Transmembrane995 – 101521 Potential
Topological domain1016 – 104328Cytoplasmic Potential
Region77 – 506430Glycosyl hydrolase-1 1
Region515 – 965451Glycosyl hydrolase-1 2

Amino acid modifications

Glycosylation841N-linked (GlcNAc...) Potential
Glycosylation1221N-linked (GlcNAc...) Potential
Glycosylation1611N-linked (GlcNAc...) Potential
Glycosylation2111N-linked (GlcNAc...) Potential
Glycosylation2621N-linked (GlcNAc...) Potential
Glycosylation3081N-linked (GlcNAc...) Potential
Glycosylation3891N-linked (GlcNAc...) Potential
Glycosylation5521N-linked (GlcNAc...) Potential
Glycosylation6091N-linked (GlcNAc...) Potential
Glycosylation7001N-linked (GlcNAc...) Potential
Glycosylation7041N-linked (GlcNAc...) Potential
Glycosylation8371N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence276 – 29520AHSKV…HQKGW → VLYSWLLTRASELGGGVLGG in isoform 2.
VSP_015830
Alternative sequence296 – 1043748Missing in isoform 2.
VSP_015831

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 4CBE6735F4112D5E

FASTA1,043120,189
        10         20         30         40         50         60 
MKTGCAAGSP GNEWIFFSSD ERNTRSRKTM SNRALQRSAV LSAFVLLRAV TGFSGDGKAI 

        70         80         90        100        110        120 
WDKKQYVSPV NPSQLFLYDT FPKNFSWGVG TGAFQVEGSW KTDGRGPSIW DRYVYSHLRG 

       130        140        150        160        170        180 
VNGTDRSTDS YIFLEKDLLA LDFLGVSFYQ FSISWPRLFP NGTVAAVNAQ GLRYYRALLD 

       190        200        210        220        230        240 
SLVLRNIEPI VTLYHWDLPL TLQEEYGGWK NATMIDLFND YATYCFQTFG DRVKYWITIH 

       250        260        270        280        290        300 
NPYLVAWHGF GTGMHAPGEK GNLTAVYTVG HNLIKAHSKV WHNYDKNFRP HQKGWLSITL 

       310        320        330        340        350        360 
GSHWIEPNRT DNMEDVINCQ HSMSSVLGWF ANPIHGDGDY PEFMKTGAMI PEFSEAEKEE 

       370        380        390        400        410        420 
VRGTADFFAF SFGPNNFRPS NTVVKMGQNV SLNLRQVLNW IKLEYDDPQI LISENGWFTD 

       430        440        450        460        470        480 
SYIKTEDTTA IYMMKNFLNQ VLQAIKFDEI RVFGYTAWTL LDGFEWQDAY TTRRGLFYVD 

       490        500        510        520        530        540 
FNSEQKERKP KSSAHYYKQI IQDNGFPLKE STPDMKGRFP CDFSWGVTES VLKPEFTVSS 

       550        560        570        580        590        600 
PQFTDPHLYV WNVTGNRLLY RVEGVRLKTR PSQCTDYVSI KKRVEMLAKM KVTHYQFALD 

       610        620        630        640        650        660 
WTSILPTGNL SKVNRQVLRY YRCVVSEGLK LGVFPMVTLY HPTHSHLGLP LPLLSSGGWL 

       670        680        690        700        710        720 
NMNTAKAFQD YAELCFRELG DLVKLWITIN EPNRLSDMYN RTSNDTYRAA HNLMIAHAQV 

       730        740        750        760        770        780 
WHLYDRQYRP VQHGAVSLSL HCDWAEPANP FVDSHWKAAE RFLQFEIAWF ADPLFKTGDY 

       790        800        810        820        830        840 
PSVMKEYIAS KNQRGLSSSV LPRFTAKESR LVKGTVDFYA LNHFTTRFVI HKQLNTNRSV 

       850        860        870        880        890        900 
ADRDVQFLQD ITRLSSPSRL AVTPWGVRKL LAWIRRNYRD RDIYITANGI DDLALEDDQI 

       910        920        930        940        950        960 
RKYYLEKYVQ EALKAYLIDK VKIKGYYAFK LTEEKSKPRF GFFTSDFRAK SSVQFYSKLI 

       970        980        990       1000       1010       1020 
SSSGLPAENR SPACGQPAED TDCTICSFLV EKKPLIFFGC CFISTLAVLL SITVFHHQKR 

      1030       1040 
RKFQKARNLQ NIPLKKGHSR VFS

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Isoform 2.

Checksum: 0B1C8C4453E11D19
Show »

FASTA29533,142

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References

« Hide 'large scale' references
[1]"Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein."
Ito S., Kinoshita S., Shiraishi N., Nakagawa S., Sekine S., Fujimori T., Nabeshima Y.
Mech. Dev. 98:115-119(2000) [PubMed: 11044614] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: Swiss Webster.
Tissue: Liver.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"Impaired negative feedback suppression of bile acid synthesis in mice lacking betaKlotho."
Ito S., Fujimori T., Furuya A., Satoh J., Nabeshima Y., Nabeshima Y.
J. Clin. Invest. 115:2202-2208(2005) [PubMed: 16075061] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[4]"BetaKlotho is required for metabolic activity of fibroblast growth factor 21."
Ogawa Y., Kurosu H., Yamamoto M., Nandi A., Rosenblatt K.P., Goetz R., Eliseenkova A.V., Mohammadi M., Kuro-o M.
Proc. Natl. Acad. Sci. U.S.A. 104:7432-7437(2007) [PubMed: 17452648] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INTERACTION WITH FGFR1 AND FGFR4.
+Additional computationally mapped references.

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Cross-references

Sequence databases

AF178429 mRNA. Translation: AAL01648.1. Different initiation.
AF165170 mRNA. Translation: AAK28704.1.
AF165171 mRNA. Translation: AAK28705.1.
BC138008 mRNA. Translation: AAI38009.1.
BC138010 mRNA. Translation: AAI38011.1.
IPIIPI00118044.
IPI00473391.
RefSeqNP_112457.1.
UniGeneMm.45274

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

STRINGQ99N32.

Protein family/group databases

CAZyGH1. Glycoside Hydrolase Family 1.

PTM databases

PhosphoSiteQ99N32.

Proteomic databases

PRIDEQ99N32.

Genome annotation databases

EnsemblENSMUST00000031096; ENSMUSP00000031096; ENSMUSG00000029195; Mus musculus. [Genome view]
GeneID83379.
KEGGmmu:83379.
UCSCuc008xnn.1. mouse.

Organism-specific databases

CTD83379.
MGIMGI:1932466. Klb.

Phylogenomic databases

HOGENOMQ99N32.
HOVERGENQ99N32.
OMAPGNEWIF
OrthoDBEOG91G5QB

Gene expression databases

ArrayExpressQ99N32.
BgeeQ99N32.
CleanExMM_KLB.
GenevestigatorQ99N32.
GermOnlineENSMUSG00000029195. Mus musculus.

Family and domain databases

InterProIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR017853. Glyco_hydro_catalytic_core.
IPR013781. Glyco_hydro_sg_catalytic.
[Graphical view]
Gene3DG3DSA:3.20.20.80. Glyco_hydro_cat. 2 hits.
PANTHERPTHR10353. Glyco_hydro_1. 1 hit.
PfamPF00232. Glyco_hydro_1. 2 hits.
[Graphical view]
PRINTSPR00131. GLHYDRLASE1.
PROSITEPS00572. GLYCOSYL_HYDROL_F1_1. False negative.
PS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio350499.
SOURCESearch...

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Entry information

Entry nameKLOTB_MOUSE
AccessionPrimary (citable) accession number: Q99N32
Secondary accession number(s): B2RQN8, Q920J2, Q99N31
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: June 1, 2001
Last modified: November 24, 2009
This is version 63 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents