Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Klotho

Gene

Kl

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

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

A beta-D-glucuronoside + H2O = D-glucuronate + an alcohol.1 Publication

Activity regulationi

Inhibited by D-saccharic acid 1,4-lactone and taurocholic acid.1 Publication

Kineticsi

  1. KM=0.249 mM for 4-methylumbelliferylglucuronide1 Publication
  2. KM=0.251 mM for estrone 3-beta-D-glucuronide1 Publication
  3. KM=0.174 mM for beta-estradiol 3-beta-D-glucuronide1 Publication
  4. KM=0.251 mM for estriol 3-beta-D-glucuronide1 Publication
  1. Vmax=0.62 µM/h/µg enzyme1 Publication

pH dependencei

Optimum pH is 5.5.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase

Enzyme and pathway databases

ReactomeiR-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-5654700 FRS-mediated FGFR2 signaling
R-MMU-5654706 FRS-mediated FGFR3 signaling
R-MMU-5654712 FRS-mediated FGFR4 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

CAZyiGH1 Glycoside Hydrolase Family 1

Names & Taxonomyi

Protein namesi
Recommended name:
Klotho (EC:3.2.1.31)
Cleaved into the following chain:
Gene namesi
Name:Kl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1101771 Kl

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 982ExtracellularSequence analysisAdd BLAST948
Transmembranei983 – 1003HelicalSequence analysisAdd BLAST21
Topological domaini1004 – 1014CytoplasmicSequence analysisAdd BLAST11

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Mice display a syndrome resembling to human aging, with short lifespan, infertility, atherosclerosis, skin atrophy, osteoporosis and emphysema. They have various metabolic abnormalities, including increased insulin sensitivity and decreased insulin production. Mice overexpressing Kl have increased resistance to insulin and IGF1, a lifespan extended of more than 20%, and generate fewer offspring.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000004224735 – 1014KlothoAdd BLAST980
ChainiPRO_000004224835 – ?Klotho peptide

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi161N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi285N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi346N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi609N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi614N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi696N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO35082
PeptideAtlasiO35082
PRIDEiO35082

PTM databases

iPTMnetiO35082
PhosphoSitePlusiO35082

Expressioni

Tissue specificityi

Membrane-bound protein is present in distal renal tubules, inner ear, ependymal cells of brain choroid plexus, elongating spermatids and mature oocytes (at protein level). Soluble peptide is present in serum (100 pM) and cerebrospinal fluid. Expressed strongly in kidney, moderately in brain choroid plexus, and at low levels in pituitary, placenta, skeletal muscle, urinary bladder, aorta, pancreas, testis, ovary, colon, thyroid gland and adipocytes.8 Publications

Developmental stagei

Not expressed in the embryo. Expressed in the kidney of newborns.1 Publication

Inductioni

Induced by 1,25-dihydroxyvitamin D3 in kidney. Down-regulated by angiotensin II and up-regulated by statins through modulation of the RhoA pathway in epithelial cells (in vitro). Isoform 1 (but not isoform 2) is up-regulated by thyroid hormone in adipocytes.3 Publications

Gene expression databases

BgeeiENSMUSG00000058488 Expressed in 72 organ(s), highest expression level in kidney
CleanExiMM_KL
GenevisibleiO35082 MM

Interactioni

Subunit structurei

Homodimer. Interacts with FGF23 and FGFR1.2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200958, 5 interactors
CORUMiO35082
DIPiDIP-39894N
IntActiO35082, 10 interactors
MINTiO35082
STRINGi10090.ENSMUSP00000077899

Structurei

3D structure databases

ProteinModelPortaliO35082
SMRiO35082
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni59 – 508Glycosyl hydrolase-1 1Add BLAST450
Regioni517 – 955Glycosyl hydrolase-1 2Add BLAST439

Domaini

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0626 Eukaryota
COG2723 LUCA
GeneTreeiENSGT00550000074452
HOGENOMiHOG000060126
HOVERGENiHBG081856
InParanoidiO35082
KOiK14756
OMAiYYLKKFI
OrthoDBiEOG091G0035
TreeFamiTF314803

Family and domain databases

InterProiView protein in InterPro
IPR001360 Glyco_hydro_1
IPR033132 Glyco_hydro_1_N_CS
IPR017853 Glycoside_hydrolase_SF
IPR028546 Klotho
PANTHERiPTHR10353 PTHR10353, 6 hits
PTHR10353:SF10 PTHR10353:SF10, 6 hits
PfamiView protein in Pfam
PF00232 Glyco_hydro_1, 3 hits
PRINTSiPR00131 GLHYDRLASE1
SUPFAMiSSF51445 SSF51445, 2 hits
PROSITEiView protein in PROSITE
PS00653 GLYCOSYL_HYDROL_F1_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O35082-1) [UniParc]FASTAAdd to basket
Also known as: Membrane-bound

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
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
Note: Predominates over the secreted form by more than 10 times in all tissues examined.
Length:1,014
Mass (Da):116,398
Last modified:July 27, 2011 - v2
Checksum:i24BD772A1F81B8EC
GO
Isoform 2 (identifier: O35082-2) [UniParc]FASTAAdd to basket
Also known as: Secreted

The sequence of this isoform differs from the canonical sequence as follows:
     537-550: DTTLSQFTDPNVYL → SPLTKPSVGLLLPH
     551-1014: Missing.

Show »
Length:550
Mass (Da):62,348
Checksum:iE59AF8F24871BDC8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti854L → V in BAA25308 (PubMed:9537505).Curated1
Sequence conflicti948K → R in BAA23381 (PubMed:9363890).Curated1
Sequence conflicti948K → R in BAA25308 (PubMed:9537505).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015828537 – 550DTTLS…PNVYL → SPLTKPSVGLLLPH in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_015829551 – 1014Missing in isoform 2. 1 PublicationAdd BLAST464

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
CCDSiCCDS19889.1 [O35082-1]
RefSeqiNP_038851.2, NM_013823.2 [O35082-1]
UniGeneiMm.6500

Genome annotation databases

EnsembliENSMUST00000078856; ENSMUSP00000077899; ENSMUSG00000058488 [O35082-1]
GeneIDi16591
KEGGimmu:16591
UCSCiuc009auk.2 mouse [O35082-2]
uc009aul.2 mouse [O35082-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS19889.1 [O35082-1]
RefSeqiNP_038851.2, NM_013823.2 [O35082-1]
UniGeneiMm.6500

3D structure databases

ProteinModelPortaliO35082
SMRiO35082
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200958, 5 interactors
CORUMiO35082
DIPiDIP-39894N
IntActiO35082, 10 interactors
MINTiO35082
STRINGi10090.ENSMUSP00000077899

Protein family/group databases

CAZyiGH1 Glycoside Hydrolase Family 1

PTM databases

iPTMnetiO35082
PhosphoSitePlusiO35082

Proteomic databases

PaxDbiO35082
PeptideAtlasiO35082
PRIDEiO35082

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000078856; ENSMUSP00000077899; ENSMUSG00000058488 [O35082-1]
GeneIDi16591
KEGGimmu:16591
UCSCiuc009auk.2 mouse [O35082-2]
uc009aul.2 mouse [O35082-1]

Organism-specific databases

CTDi9365
MGIiMGI:1101771 Kl

Phylogenomic databases

eggNOGiKOG0626 Eukaryota
COG2723 LUCA
GeneTreeiENSGT00550000074452
HOGENOMiHOG000060126
HOVERGENiHBG081856
InParanoidiO35082
KOiK14756
OMAiYYLKKFI
OrthoDBiEOG091G0035
TreeFamiTF314803

Enzyme and pathway databases

ReactomeiR-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-5654700 FRS-mediated FGFR2 signaling
R-MMU-5654706 FRS-mediated FGFR3 signaling
R-MMU-5654712 FRS-mediated FGFR4 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

PROiPR:O35082
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000058488 Expressed in 72 organ(s), highest expression level in kidney
CleanExiMM_KL
GenevisibleiO35082 MM

Family and domain databases

InterProiView protein in InterPro
IPR001360 Glyco_hydro_1
IPR033132 Glyco_hydro_1_N_CS
IPR017853 Glycoside_hydrolase_SF
IPR028546 Klotho
PANTHERiPTHR10353 PTHR10353, 6 hits
PTHR10353:SF10 PTHR10353:SF10, 6 hits
PfamiView protein in Pfam
PF00232 Glyco_hydro_1, 3 hits
PRINTSiPR00131 GLHYDRLASE1
SUPFAMiSSF51445 SSF51445, 2 hits
PROSITEiView protein in PROSITE
PS00653 GLYCOSYL_HYDROL_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiKLOT_MOUSE
AccessioniPrimary (citable) accession number: O35082
Secondary accession number(s): B2RR78, O70175, O70621
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 145 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  4. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again