Q99N32 (KLOTB_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-klotho
Short name=BKL
Short name=BetaKlotho

Alternative name(s):
Klotho beta-like protein

Gene names

Name:	Klb
Synonyms:	Betakl

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1043 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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. Ref.4
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.1 Ref.3 Ref.4
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.1 Ref.4
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.
Sequence caution	The sequence AAL01648.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cation binding Inferred from electronic annotation. Source: InterPro hydrolase activity, hydrolyzing O-glycosyl compounds Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1043	1043	Beta-klotho		PRO_0000063906
Regions
	Topological domain	1 – 994	994	Extracellular Potential
	Transmembrane	995 – 1015	21	Helical; Potential
	Topological domain	1016 – 1043	28	Cytoplasmic Potential
	Region	77 – 506	430	Glycosyl hydrolase-1 1
	Region	515 – 965	451	Glycosyl hydrolase-1 2
Amino acid modifications
	Glycosylation	84	1	N-linked (GlcNAc...) Potential
	Glycosylation	122	1	N-linked (GlcNAc...) Potential
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Glycosylation	211	1	N-linked (GlcNAc...) Potential
	Glycosylation	262	1	N-linked (GlcNAc...) Potential
	Glycosylation	308	1	N-linked (GlcNAc...) Potential
	Glycosylation	389	1	N-linked (GlcNAc...) Potential
	Glycosylation	552	1	N-linked (GlcNAc...) Potential
	Glycosylation	609	1	N-linked (GlcNAc...) Potential
	Glycosylation	700	1	N-linked (GlcNAc...) Potential
	Glycosylation	704	1	N-linked (GlcNAc...) Potential
	Glycosylation	837	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	276 – 295	20	AHSKV…HQKGW → VLYSWLLTRASELGGGVLGG in isoform 2.		VSP_015830
	Alternative sequence	296 – 1043	748	Missing in isoform 2.		VSP_015831

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 4CBE6735F4112D5E	FASTA	1,043	120,189
	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
	Isoform 2 [UniParc]. Checksum: 0B1C8C4453E11D19	FASTA	295	33,142
	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 NPYLVAWHGF GTGMHAPGEK GNLTAVYTVG HNLIKVLYSW LLTRASELGG GVLGG

References

	« Hide 'large scale' referencesShow '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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00118044. IPI00473391.
RefSeq	NP_112457.1. NM_031180.2.
UniGene	Mm.45274.
3D structure databases
ProteinModelPortal	Q99N32.
SMR	Q99N32. Positions 80-507, 515-961.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99N32.
Protein family/group databases
CAZy	GH1. Glycoside Hydrolase Family 1.
PTM databases
PhosphoSite	Q99N32.
Proteomic databases
PRIDE	Q99N32.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000031096; ENSMUSP00000031096; ENSMUSG00000029195.
GeneID	83379.
KEGG	mmu:83379.
UCSC	uc008xnn.1. mouse.
Organism-specific databases
CTD	152831.
MGI	MGI:1932466. Klb.
Phylogenomic databases
eggNOG	roNOG06830.
GeneTree	ENSGT00550000074452.
HOGENOM	HBG443600.
HOVERGEN	HBG081856.
InParanoid	Q99N32.
OMA	GNEWIFF.
OrthoDB	EOG451DQ0.
PhylomeDB	Q99N32.
Gene expression databases
ArrayExpress	Q99N32.
Bgee	Q99N32.
CleanEx	MM_KLB.
Genevestigator	Q99N32.
GermOnline	ENSMUSG00000029195. Mus musculus.
Family and domain databases
InterPro	IPR001360. Glyco_hydro_1. IPR018120. Glyco_hydro_1_AS. IPR013781. Glyco_hydro_subgr_catalytic. IPR017853. Glycoside_hydrolase_SF. [Graphical view]
Gene3D	G3DSA:3.20.20.80. Glyco_hydro_cat. 2 hits.
PANTHER	PTHR10353. Glyco_hydro_1. 1 hit.
Pfam	PF00232. Glyco_hydro_1. 2 hits. [Graphical view]
PRINTS	PR00131. GLHYDRLASE1.
SUPFAM	SSF51445. Glyco_hydro_cat. 2 hits.
PROSITE	PS00572. GLYCOSYL_HYDROL_F1_1. False negative. PS00653. GLYCOSYL_HYDROL_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	350499.
SOURCE	Search...

Entry information

Entry name

KLOTB_MOUSE

Accession

Primary (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:	September 21, 2011
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program