UniProtKB - O35082 (KLOT_MOUSE)
Klotho
Kl
Functioni
May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 241 and 874, 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. Essential factor for the specific interaction between FGF23 and FGFR1.
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 activityi
- EC:3.2.1.311 Publication
Activity regulationi
Kineticsi
- KM=0.249 mM for 4-methylumbelliferylglucuronide1 Publication
- KM=0.251 mM for estrone 3-beta-D-glucuronide1 Publication
- KM=0.174 mM for beta-estradiol 3-beta-D-glucuronide1 Publication
- KM=0.251 mM for estriol 3-beta-D-glucuronide1 Publication
- Vmax=0.62 µM/h/µg enzyme1 Publication
pH dependencei
GO - Molecular functioni
- beta-glucuronidase activity Source: UniProtKB-EC
- fibroblast growth factor binding Source: UniProtKB
- fibroblast growth factor receptor binding Source: UniProtKB
GO - Biological processi
- acute inflammatory response Source: MGI
- aging Source: MGI
- calcium ion homeostasis Source: MGI
- carbohydrate metabolic process Source: InterPro
- energy reserve metabolic process Source: MGI
- fibroblast growth factor receptor signaling pathway Source: GO_Central
- insulin receptor signaling pathway Source: InterPro
- negative regulation of systemic arterial blood pressure Source: MGI
- norepinephrine biosynthetic process Source: MGI
- positive regulation of bone mineralization Source: MGI
- positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Source: MGI
- response to activity Source: Ensembl
- response to angiotensin Source: Ensembl
- response to vitamin D Source: Ensembl
Keywordsi
Molecular function | Glycosidase, Hydrolase |
Enzyme and pathway databases
Reactomei | R-MMU-109704, PI3K Cascade R-MMU-1257604, PIP3 activates AKT signaling R-MMU-190374, FGFR1c and Klotho ligand binding and activation R-MMU-5654219, Phospholipase C-mediated cascade: FGFR1 R-MMU-5654687, Downstream signaling of activated FGFR1 R-MMU-5654688, SHC-mediated cascade:FGFR1 R-MMU-5654689, PI-3K cascade:FGFR1 R-MMU-5654693, FRS-mediated FGFR1 signaling R-MMU-5654726, Negative regulation of FGFR1 signaling R-MMU-5673001, RAF/MAP kinase cascade R-MMU-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
Protein family/group databases
CAZyi | GH1, Glycoside Hydrolase Family 1 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:Kl |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1101771, Kl |
VEuPathDBi | HostDB:ENSMUSG00000058488 |
Subcellular locationi
Plasma membrane
- Cell membrane 4 Publications; Single-pass type I membrane protein 1 Publication
- Apical cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication
Note: Isoform 1 shedding leads to a soluble peptide.1 Publication
Extracellular region or secreted
- Secreted 2 Publications
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: MGI
- extracellular space Source: InterPro
Plasma Membrane
- apical plasma membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 35 – 982 | ExtracellularSequence analysisAdd BLAST | 948 | |
Transmembranei | 983 – 1003 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1004 – 1014 | CytoplasmicSequence analysisAdd BLAST | 11 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 34 | Sequence analysisAdd BLAST | 34 | |
ChainiPRO_0000042247 | 35 – 1014 | KlothoAdd BLAST | 980 | |
ChainiPRO_0000042248 | 35 – ? | Klotho peptide |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 161 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 285 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 346 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 609 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 614 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 696 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | O35082 |
PaxDbi | O35082 |
PeptideAtlasi | O35082 |
PRIDEi | O35082 |
ProteomicsDBi | 264854 [O35082-1] 264855 [O35082-2] |
PTM databases
GlyGeni | O35082, 6 sites |
iPTMneti | O35082 |
PhosphoSitePlusi | O35082 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000058488, Expressed in kidney and 108 other tissues |
Genevisiblei | O35082, MM |
Interactioni
Subunit structurei
Homodimer.
Interacts with FGF23 and FGFR1.
2 PublicationsBinary interactionsi
O35082
GO - Molecular functioni
- fibroblast growth factor binding Source: UniProtKB
- fibroblast growth factor receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 200958, 8 interactors |
CORUMi | O35082 |
DIPi | DIP-39894N |
IntActi | O35082, 10 interactors |
MINTi | O35082 |
STRINGi | 10090.ENSMUSP00000077899 |
Miscellaneous databases
RNActi | O35082, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 59 – 508 | Glycosyl hydrolase-1 1Add BLAST | 450 | |
Regioni | 517 – 955 | Glycosyl hydrolase-1 2Add BLAST | 439 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0626, Eukaryota |
GeneTreei | ENSGT00940000157614 |
HOGENOMi | CLU_001859_5_2_1 |
InParanoidi | O35082 |
OMAi | LHYYRCV |
OrthoDBi | 408001at2759 |
PhylomeDBi | O35082 |
TreeFami | TF314803 |
Family and domain databases
InterProi | View protein in InterPro IPR001360, Glyco_hydro_1 IPR033132, Glyco_hydro_1_N_CS IPR017853, Glycoside_hydrolase_SF IPR028546, Klotho |
PANTHERi | PTHR10353, PTHR10353, 5 hits PTHR10353:SF10, PTHR10353:SF10, 5 hits |
Pfami | View protein in Pfam PF00232, Glyco_hydro_1, 3 hits |
PRINTSi | PR00131, GLHYDRLASE1 |
SUPFAMi | SSF51445, SSF51445, 2 hits |
PROSITEi | View protein in PROSITE PS00653, GLYCOSYL_HYDROL_F1_2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLARAPPRRP PRLVLLRLLL LHLLLLALRA RCLSAEPGQG AQTWARFARA
60 70 80 90 100
PAPEAAGLLH DTFPDGFLWA VGSAAYQTEG GWRQHGKGAS IWDTFTHHSG
110 120 130 140 150
AAPSDSPIVV APSGAPSPPL SSTGDVASDS YNNVYRDTEG LRELGVTHYR
160 170 180 190 200
FSISWARVLP NGTAGTPNRE GLRYYRRLLE RLRELGVQPV VTLYHWDLPQ
210 220 230 240 250
RLQDTYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID NPYVVAWHGY
260 270 280 290 300
ATGRLAPGVR GSSRLGYLVA HNLLLAHAKV WHLYNTSFRP TQGGRVSIAL
310 320 330 340 350
SSHWINPRRM TDYNIRECQK SLDFVLGWFA KPIFIDGDYP ESMKNNLSSL
360 370 380 390 400
LPDFTESEKR LIRGTADFFA LSFGPTLSFQ LLDPNMKFRQ LESPNLRQLL
410 420 430 440 450
SWIDLEYNHP PIFIVENGWF VSGTTKRDDA KYMYYLKKFI METLKAIRLD
460 470 480 490 500
GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY VDFLSQDKEL LPKSSALFYQ
510 520 530 540 550
KLIEDNGFPP LPENQPLEGT FPCDFAWGVV DNYVQVDTTL SQFTDPNVYL
560 570 580 590 600
WDVHHSKRLI KVDGVVAKKR KPYCVDFSAI RPQITLLREM RVTHFRFSLD
610 620 630 640 650
WALILPLGNQ TQVNHTVLHF YRCMISELVH ANITPVVALW QPAAPHQGLP
660 670 680 690 700
HALAKHGAWE NPHTALAFAD YANLCFKELG HWVNLWITMN EPNTRNMTYR
710 720 730 740 750
AGHHLLRAHA LAWHLYDDKF RAAQKGKISI ALQADWIEPA CPFSQNDKEV
760 770 780 790 800
AERVLEFDIG WLAEPIFGSG DYPRVMRDWL NQKNNFLLPY FTEDEKKLVR
810 820 830 840 850
GSFDFLAVSH YTTILVDWEK EDPMKYNDYL EVQEMTDITW LNSPSQVAVV
860 870 880 890 900
PWGLRKVLNW LRFKYGDLPM YVTANGIDDD PHAEQDSLRI YYIKNYVNEA
910 920 930 940 950
LKAYVLDDIN LCGYFAYSLS DRSAPKSGFY RYAANQFEPK PSMKHYRKII
960 970 980 990 1000
DSNGFLGSGT LGRFCPEEYT VCTECGFFQT RKSLLVFISF LVFTFIISLA
1010
LIFHYSKKGQ RSYK
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 854 | L → V in BAA25308 (PubMed:9537505).Curated | 1 | |
Sequence conflicti | 948 | K → R in BAA23381 (PubMed:9363890).Curated | 1 | |
Sequence conflicti | 948 | K → R in BAA25308 (PubMed:9537505).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015828 | 537 – 550 | DTTLS…PNVYL → SPLTKPSVGLLLPH in isoform 2. 1 PublicationAdd BLAST | 14 | |
Alternative sequenceiVSP_015829 | 551 – 1014 | Missing in isoform 2. 1 PublicationAdd BLAST | 464 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB005141 mRNA Translation: BAA23381.1 AB010088 mRNA Translation: BAA25307.1 AB010091 Genomic DNA Translation: BAA25308.1 AB010091 Genomic DNA Translation: BAA25309.1 BC138258 mRNA Translation: AAI38259.1 BC138259 mRNA Translation: AAI38260.1 |
CCDSi | CCDS19889.1 [O35082-1] |
RefSeqi | NP_038851.2, NM_013823.2 [O35082-1] |
Genome annotation databases
Ensembli | ENSMUST00000078856; ENSMUSP00000077899; ENSMUSG00000058488 [O35082-1] |
GeneIDi | 16591 |
KEGGi | mmu:16591 |
UCSCi | uc009auk.2, mouse [O35082-2] uc009aul.2, mouse [O35082-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Protein Spotlight The thread of life - Issue 65 of December 2005 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB005141 mRNA Translation: BAA23381.1 AB010088 mRNA Translation: BAA25307.1 AB010091 Genomic DNA Translation: BAA25308.1 AB010091 Genomic DNA Translation: BAA25309.1 BC138258 mRNA Translation: AAI38259.1 BC138259 mRNA Translation: AAI38260.1 |
CCDSi | CCDS19889.1 [O35082-1] |
RefSeqi | NP_038851.2, NM_013823.2 [O35082-1] |
3D structure databases
AlphaFoldDBi | O35082 |
SMRi | O35082 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200958, 8 interactors |
CORUMi | O35082 |
DIPi | DIP-39894N |
IntActi | O35082, 10 interactors |
MINTi | O35082 |
STRINGi | 10090.ENSMUSP00000077899 |
Protein family/group databases
CAZyi | GH1, Glycoside Hydrolase Family 1 |
PTM databases
GlyGeni | O35082, 6 sites |
iPTMneti | O35082 |
PhosphoSitePlusi | O35082 |
Proteomic databases
jPOSTi | O35082 |
PaxDbi | O35082 |
PeptideAtlasi | O35082 |
PRIDEi | O35082 |
ProteomicsDBi | 264854 [O35082-1] 264855 [O35082-2] |
Protocols and materials databases
ABCDi | O35082, 1 sequenced antibody |
Antibodypediai | 7860, 397 antibodies from 40 providers |
DNASUi | 16591 |
Genome annotation databases
Ensembli | ENSMUST00000078856; ENSMUSP00000077899; ENSMUSG00000058488 [O35082-1] |
GeneIDi | 16591 |
KEGGi | mmu:16591 |
UCSCi | uc009auk.2, mouse [O35082-2] uc009aul.2, mouse [O35082-1] |
Organism-specific databases
CTDi | 9365 |
MGIi | MGI:1101771, Kl |
VEuPathDBi | HostDB:ENSMUSG00000058488 |
Phylogenomic databases
eggNOGi | KOG0626, Eukaryota |
GeneTreei | ENSGT00940000157614 |
HOGENOMi | CLU_001859_5_2_1 |
InParanoidi | O35082 |
OMAi | LHYYRCV |
OrthoDBi | 408001at2759 |
PhylomeDBi | O35082 |
TreeFami | TF314803 |
Enzyme and pathway databases
Reactomei | R-MMU-109704, PI3K Cascade R-MMU-1257604, PIP3 activates AKT signaling R-MMU-190374, FGFR1c and Klotho ligand binding and activation R-MMU-5654219, Phospholipase C-mediated cascade: FGFR1 R-MMU-5654687, Downstream signaling of activated FGFR1 R-MMU-5654688, SHC-mediated cascade:FGFR1 R-MMU-5654689, PI-3K cascade:FGFR1 R-MMU-5654693, FRS-mediated FGFR1 signaling R-MMU-5654726, Negative regulation of FGFR1 signaling R-MMU-5673001, RAF/MAP kinase cascade R-MMU-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
Miscellaneous databases
BioGRID-ORCSi | 16591, 9 hits in 73 CRISPR screens |
PROi | PR:O35082 |
RNActi | O35082, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000058488, Expressed in kidney and 108 other tissues |
Genevisiblei | O35082, MM |
Family and domain databases
InterProi | View protein in InterPro IPR001360, Glyco_hydro_1 IPR033132, Glyco_hydro_1_N_CS IPR017853, Glycoside_hydrolase_SF IPR028546, Klotho |
PANTHERi | PTHR10353, PTHR10353, 5 hits PTHR10353:SF10, PTHR10353:SF10, 5 hits |
Pfami | View protein in Pfam PF00232, Glyco_hydro_1, 3 hits |
PRINTSi | PR00131, GLHYDRLASE1 |
SUPFAMi | SSF51445, SSF51445, 2 hits |
PROSITEi | View protein in PROSITE PS00653, GLYCOSYL_HYDROL_F1_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KLOT_MOUSE | |
Accessioni | O35082Primary (citable) accession number: O35082 Secondary accession number(s): B2RR78, O70175, O70621 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 11, 2005 |
Last sequence update: | July 27, 2011 | |
Last modified: | May 25, 2022 | |
This is version 165 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- 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 - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries