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Protein

Beta-klotho

Gene

Klb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 FGF21.2 Publications

GO - Molecular functioni

GO - Biological processi

  • carbohydrate metabolic process Source: InterPro
  • fibroblast growth factor receptor signaling pathway Source: MGI
  • glycosyl compound metabolic process Source: GO_Central
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-109704. PI3K Cascade.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-1307965. betaKlotho-mediated ligand binding.
R-MMU-5654228. Phospholipase C-mediated cascade, FGFR4.
R-MMU-5654712. FRS-mediated FGFR4 signaling.
R-MMU-5654719. SHC-mediated cascade:FGFR4.
R-MMU-5654720. PI-3K cascade:FGFR4.
R-MMU-5654733. Negative regulation of FGFR4 signaling.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Protein family/group databases

CAZyiGH1. Glycoside Hydrolase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-klotho
Short name:
BKL
Short name:
BetaKlotho
Alternative name(s):
Klotho beta-like protein
Gene namesi
Name:Klb
Synonyms:Betakl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1932466. Klb.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 994ExtracellularSequence analysisAdd BLAST994
Transmembranei995 – 1015HelicalSequence analysisAdd BLAST21
Topological domaini1016 – 1043CytoplasmicSequence analysisAdd BLAST28

GO - Cellular componenti

  • integral component of membrane Source: MGI
  • integral component of plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000639061 – 1043Beta-klothoAdd BLAST1043

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi84N-linked (GlcNAc...)Sequence analysis1
Glycosylationi122N-linked (GlcNAc...)Sequence analysis1
Glycosylationi161N-linked (GlcNAc...)Sequence analysis1
Glycosylationi211N-linked (GlcNAc...)Sequence analysis1
Glycosylationi262N-linked (GlcNAc...)Sequence analysis1
Glycosylationi308N-linked (GlcNAc...)Sequence analysis1
Glycosylationi389N-linked (GlcNAc...)Sequence analysis1
Glycosylationi552N-linked (GlcNAc...)Sequence analysis1
Glycosylationi609N-linked (GlcNAc...)Sequence analysis1
Glycosylationi700N-linked (GlcNAc...)Sequence analysis1
Glycosylationi704N-linked (GlcNAc...)Sequence analysis1
Glycosylationi837N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ99N32.
PRIDEiQ99N32.

PTM databases

iPTMnetiQ99N32.
PhosphoSitePlusiQ99N32.

Expressioni

Tissue specificityi

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.3 Publications

Developmental stagei

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).2 Publications

Gene expression databases

BgeeiENSMUSG00000029195.
CleanExiMM_KLB.
ExpressionAtlasiQ99N32. baseline and differential.
GenevisibleiQ99N32. MM.

Interactioni

Subunit structurei

Interacts with FGF19; this interaction is direct. Interacts (via C-terminus) with FGF21; this interaction is direct (By similarity). Interacts with FGFR1 and FGFR4.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-60918N.
STRINGi10090.ENSMUSP00000031096.

Structurei

3D structure databases

ProteinModelPortaliQ99N32.
SMRiQ99N32.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni77 – 506Glycosyl hydrolase-1 1Add BLAST430
Regioni515 – 965Glycosyl hydrolase-1 2Add BLAST451

Domaini

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0626. Eukaryota.
COG2723. LUCA.
GeneTreeiENSGT00550000074452.
HOGENOMiHOG000060126.
HOVERGENiHBG081856.
InParanoidiQ99N32.
OMAiMLARMKV.
OrthoDBiEOG091G0035.
PhylomeDBiQ99N32.
TreeFamiTF314803.

Family and domain databases

Gene3Di3.20.20.80. 2 hits.
InterProiIPR001360. Glyco_hydro_1.
IPR033132. Glyco_hydro_1_N_CS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 1 hit.
PfamiPF00232. Glyco_hydro_1. 3 hits.
[Graphical view]
PRINTSiPR00131. GLHYDRLASE1.
SUPFAMiSSF51445. SSF51445. 2 hits.
PROSITEiPS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99N32-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKTGCAAGSP GNEWIFFSSD ERNTRSRKTM SNRALQRSAV LSAFVLLRAV
60 70 80 90 100
TGFSGDGKAI WDKKQYVSPV NPSQLFLYDT FPKNFSWGVG TGAFQVEGSW
110 120 130 140 150
KTDGRGPSIW DRYVYSHLRG VNGTDRSTDS YIFLEKDLLA LDFLGVSFYQ
160 170 180 190 200
FSISWPRLFP NGTVAAVNAQ GLRYYRALLD SLVLRNIEPI VTLYHWDLPL
210 220 230 240 250
TLQEEYGGWK NATMIDLFND YATYCFQTFG DRVKYWITIH NPYLVAWHGF
260 270 280 290 300
GTGMHAPGEK GNLTAVYTVG HNLIKAHSKV WHNYDKNFRP HQKGWLSITL
310 320 330 340 350
GSHWIEPNRT DNMEDVINCQ HSMSSVLGWF ANPIHGDGDY PEFMKTGAMI
360 370 380 390 400
PEFSEAEKEE VRGTADFFAF SFGPNNFRPS NTVVKMGQNV SLNLRQVLNW
410 420 430 440 450
IKLEYDDPQI LISENGWFTD SYIKTEDTTA IYMMKNFLNQ VLQAIKFDEI
460 470 480 490 500
RVFGYTAWTL LDGFEWQDAY TTRRGLFYVD FNSEQKERKP KSSAHYYKQI
510 520 530 540 550
IQDNGFPLKE STPDMKGRFP CDFSWGVTES VLKPEFTVSS PQFTDPHLYV
560 570 580 590 600
WNVTGNRLLY RVEGVRLKTR PSQCTDYVSI KKRVEMLAKM KVTHYQFALD
610 620 630 640 650
WTSILPTGNL SKVNRQVLRY YRCVVSEGLK LGVFPMVTLY HPTHSHLGLP
660 670 680 690 700
LPLLSSGGWL NMNTAKAFQD YAELCFRELG DLVKLWITIN EPNRLSDMYN
710 720 730 740 750
RTSNDTYRAA HNLMIAHAQV WHLYDRQYRP VQHGAVSLSL HCDWAEPANP
760 770 780 790 800
FVDSHWKAAE RFLQFEIAWF ADPLFKTGDY PSVMKEYIAS KNQRGLSSSV
810 820 830 840 850
LPRFTAKESR LVKGTVDFYA LNHFTTRFVI HKQLNTNRSV ADRDVQFLQD
860 870 880 890 900
ITRLSSPSRL AVTPWGVRKL LAWIRRNYRD RDIYITANGI DDLALEDDQI
910 920 930 940 950
RKYYLEKYVQ EALKAYLIDK VKIKGYYAFK LTEEKSKPRF GFFTSDFRAK
960 970 980 990 1000
SSVQFYSKLI SSSGLPAENR SPACGQPAED TDCTICSFLV EKKPLIFFGC
1010 1020 1030 1040
CFISTLAVLL SITVFHHQKR RKFQKARNLQ NIPLKKGHSR VFS
Length:1,043
Mass (Da):120,189
Last modified:June 1, 2001 - v1
Checksum:i4CBE6735F4112D5E
GO
Isoform 2 (identifier: Q99N32-2) [UniParc]FASTAAdd to basket

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

Show »
Length:295
Mass (Da):33,142
Checksum:i0B1C8C4453E11D19
GO

Sequence cautioni

The sequence AAL01648 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015830276 – 295AHSKV…HQKGW → VLYSWLLTRASELGGGVLGG in isoform 2. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_015831296 – 1043Missing in isoform 2. 1 PublicationAdd BLAST748

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS19306.1. [Q99N32-1]
RefSeqiNP_112457.1. NM_031180.2. [Q99N32-1]
UniGeneiMm.45274.

Genome annotation databases

EnsembliENSMUST00000031096; ENSMUSP00000031096; ENSMUSG00000029195. [Q99N32-1]
GeneIDi83379.
KEGGimmu:83379.
UCSCiuc008xnn.1. mouse. [Q99N32-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS19306.1. [Q99N32-1]
RefSeqiNP_112457.1. NM_031180.2. [Q99N32-1]
UniGeneiMm.45274.

3D structure databases

ProteinModelPortaliQ99N32.
SMRiQ99N32.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60918N.
STRINGi10090.ENSMUSP00000031096.

Protein family/group databases

CAZyiGH1. Glycoside Hydrolase Family 1.

PTM databases

iPTMnetiQ99N32.
PhosphoSitePlusiQ99N32.

Proteomic databases

PaxDbiQ99N32.
PRIDEiQ99N32.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000031096; ENSMUSP00000031096; ENSMUSG00000029195. [Q99N32-1]
GeneIDi83379.
KEGGimmu:83379.
UCSCiuc008xnn.1. mouse. [Q99N32-1]

Organism-specific databases

CTDi152831.
MGIiMGI:1932466. Klb.

Phylogenomic databases

eggNOGiKOG0626. Eukaryota.
COG2723. LUCA.
GeneTreeiENSGT00550000074452.
HOGENOMiHOG000060126.
HOVERGENiHBG081856.
InParanoidiQ99N32.
OMAiMLARMKV.
OrthoDBiEOG091G0035.
PhylomeDBiQ99N32.
TreeFamiTF314803.

Enzyme and pathway databases

ReactomeiR-MMU-109704. PI3K Cascade.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-1307965. betaKlotho-mediated ligand binding.
R-MMU-5654228. Phospholipase C-mediated cascade, FGFR4.
R-MMU-5654712. FRS-mediated FGFR4 signaling.
R-MMU-5654719. SHC-mediated cascade:FGFR4.
R-MMU-5654720. PI-3K cascade:FGFR4.
R-MMU-5654733. Negative regulation of FGFR4 signaling.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.

Miscellaneous databases

PROiQ99N32.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029195.
CleanExiMM_KLB.
ExpressionAtlasiQ99N32. baseline and differential.
GenevisibleiQ99N32. MM.

Family and domain databases

Gene3Di3.20.20.80. 2 hits.
InterProiIPR001360. Glyco_hydro_1.
IPR033132. Glyco_hydro_1_N_CS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 1 hit.
PfamiPF00232. Glyco_hydro_1. 3 hits.
[Graphical view]
PRINTSiPR00131. GLHYDRLASE1.
SUPFAMiSSF51445. SSF51445. 2 hits.
PROSITEiPS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKLOTB_MOUSE
AccessioniPrimary (citable) accession number: Q99N32
Secondary accession number(s): B2RQN8, Q920J2, Q99N31
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: June 1, 2001
Last modified: November 2, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.