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Protein

Klotho

Gene

Kl

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).By similarity
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.By similarity

Catalytic activityi

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Enzyme and pathway databases

ReactomeiREACT_291658. PI3K Cascade.
REACT_299102. PIP3 activates AKT signaling.
REACT_341391. FGFR1c and Klotho ligand binding and activation.
REACT_357272. Phospholipase C-mediated cascade: FGFR1.
REACT_359276. Negative regulation of FGFR1 signaling.
REACT_359641. PI-3K cascade:FGFR1.
REACT_360887. FRS-mediated FGFR1 signaling.
REACT_361671. SHC-mediated cascade:FGFR1.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 12

Organism-specific databases

RGDi620396. Kl.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 983949ExtracellularSequence AnalysisAdd
BLAST
Transmembranei984 – 100421HelicalSequence AnalysisAdd
BLAST
Topological domaini1005 – 101410CytoplasmicSequence Analysis

GO - Cellular componenti

  • extracellular exosome Source: Ensembl
  • extracellular space Source: InterPro
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3434Sequence AnalysisAdd
BLAST
Chaini35 – 1014980KlothoPRO_0000042249Add
BLAST
Chaini35 – ?Klotho peptideBy similarityPRO_0000042250

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi161 – 1611N-linked (GlcNAc...)Sequence Analysis
Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence Analysis
Glycosylationi346 – 3461N-linked (GlcNAc...)Sequence Analysis
Glycosylationi609 – 6091N-linked (GlcNAc...)Sequence Analysis
Glycosylationi614 – 6141N-linked (GlcNAc...)Sequence Analysis
Glycosylationi696 – 6961N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9Z2Y9.
PRIDEiQ9Z2Y9.

Expressioni

Tissue specificityi

Present in cortical renal tubules and the parathyroid (at protein level). Strongly expressed in kidney. Expressed at low levels in brain, lung, intestine and ovaries.3 Publications

Developmental stagei

Expressed faintly from E18 in the kidney. Expression increases in the kidney after 4 days of age.1 Publication

Inductioni

Down-regulated by angiotensin II and iron overload (at protein level). Down-regulated by acute inflammatory stress, and in models for long-term hypertension, diabetes mellitus and chronic renal failure.5 Publications

Gene expression databases

GenevestigatoriQ9Z2Y9.

Interactioni

Subunit structurei

Homodimer. Interacts with FGF23 and FGFR1.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001449.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2Y9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni59 – 508450Glycosyl hydrolase-1 1Add
BLAST
Regioni517 – 955439Glycosyl hydrolase-1 2Add
BLAST

Domaini

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2723.
GeneTreeiENSGT00550000074452.
HOGENOMiHOG000060126.
HOVERGENiHBG081856.
InParanoidiQ9Z2Y9.
KOiK14756.
OMAiALSSHWI.
OrthoDBiEOG7MH0XV.
PhylomeDBiQ9Z2Y9.
TreeFamiTF314803.

Family and domain databases

Gene3Di3.20.20.80. 2 hits.
InterProiIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 1 hit.
PTHR10353:SF10. PTHR10353:SF10. 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]

Sequencei

Sequence statusi: Complete.

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

Q9Z2Y9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPARAPPRRL PRLLLLRLLS LHLLLLTLRA RCLSAEPGQG AQTWARFARP
60 70 80 90 100
PVPEASGLLH DTFPDGFLWA VGSAAYQTEG GWRQHGKGAS IWDTFTHHPR
110 120 130 140 150
AIPEDSPIVM APSGAPLPPL PSTGDVASDS 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 WRLYNTSFRP TQGGRVSIAL
310 320 330 340 350
GSHWITPRRM TDYHIRECQK SLDFVLGWFA KPIFIDGDYP KSMKNNLSSL
360 370 380 390 400
LPDFTESEKR FIRGTADFFA LSFGPTLSFQ LLDPSMKFRQ LESPSLRQLL
410 420 430 440 450
SWIDLEYNHP QIFIVENGWF VSGTTRRDDA KYMYYLKKFI MESLKAIRLD
460 470 480 490 500
GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY VDFLSQDKEL LPKSSALFYQ
510 520 530 540 550
KLIENNGFPP LPENQPLEGT FPCDFAWGVV DNYIQVDPTL SQFTDPNVYL
560 570 580 590 600
WDVHHSKRLI KVDGVVAKKR KPYCVDFSAI RPQITLLREM RVTHFRFSLD
610 620 630 640 650
WALILPLGNQ TQVNRTVLHF YRCMVSELVH ANITPVVALW QPATPHQGLP
660 670 680 690 700
HALAKHGAWE NPHTALAFAD YANLCFEELG HWVKFWITIN EPNSRNMTYR
710 720 730 740 750
AGHHLLKAHA LAWHLYDDKF RAAQKGKISI ALQVDWIEPA CPFSQKDKEV
760 770 780 790 800
AERVLEFDVG WLAEPIFGSG DYPHVMREWL NQKNNFLLPY FTEDEKKLIR
810 820 830 840 850
GSFDFLALSH YTTILVDWEK EDPIKYNDYL EVQEMTDITW LNSPNQVAVV
860 870 880 890 900
PWGLRKALNW LRFKYGDLPM FVTANGIDDD PHAEQDSLRM YYIKNYVNEA
910 920 930 940 950
LKAYVLDGIN LCGYFAYSLS DRSVPKSGFY RYAANQFEPK PSIKHYRKII
960 970 980 990 1000
DNNGFLGSGT LGRFCPEEYT VCTGCGFFQT RKSLLAFISF LVFAFVTSLA
1010
LIYYYSKKGR RRYK
Length:1,014
Mass (Da):116,800
Last modified:May 1, 1999 - v1
Checksum:i16F3B57581AC1DF0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017820 mRNA. Translation: BAA34740.1.
PIRiJE0333.
RefSeqiNP_112626.1. NM_031336.1.
UniGeneiRn.30061.

Genome annotation databases

EnsembliENSRNOT00000001449; ENSRNOP00000001449; ENSRNOG00000001092.
GeneIDi83504.
KEGGirno:83504.
UCSCiRGD:620396. rat.

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
AB017820 mRNA. Translation: BAA34740.1.
PIRiJE0333.
RefSeqiNP_112626.1. NM_031336.1.
UniGeneiRn.30061.

3D structure databases

ProteinModelPortaliQ9Z2Y9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001449.

Protein family/group databases

CAZyiGH1. Glycoside Hydrolase Family 1.

Proteomic databases

PaxDbiQ9Z2Y9.
PRIDEiQ9Z2Y9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000001449; ENSRNOP00000001449; ENSRNOG00000001092.
GeneIDi83504.
KEGGirno:83504.
UCSCiRGD:620396. rat.

Organism-specific databases

CTDi9365.
RGDi620396. Kl.

Phylogenomic databases

eggNOGiCOG2723.
GeneTreeiENSGT00550000074452.
HOGENOMiHOG000060126.
HOVERGENiHBG081856.
InParanoidiQ9Z2Y9.
KOiK14756.
OMAiALSSHWI.
OrthoDBiEOG7MH0XV.
PhylomeDBiQ9Z2Y9.
TreeFamiTF314803.

Enzyme and pathway databases

ReactomeiREACT_291658. PI3K Cascade.
REACT_299102. PIP3 activates AKT signaling.
REACT_341391. FGFR1c and Klotho ligand binding and activation.
REACT_357272. Phospholipase C-mediated cascade: FGFR1.
REACT_359276. Negative regulation of FGFR1 signaling.
REACT_359641. PI-3K cascade:FGFR1.
REACT_360887. FRS-mediated FGFR1 signaling.
REACT_361671. SHC-mediated cascade:FGFR1.

Miscellaneous databases

NextBioi615928.
PROiQ9Z2Y9.

Gene expression databases

GenevestigatoriQ9Z2Y9.

Family and domain databases

Gene3Di3.20.20.80. 2 hits.
InterProiIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 1 hit.
PTHR10353:SF10. PTHR10353:SF10. 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...

Publicationsi

  1. "Molecular cloning of rat klotho cDNA: markedly decreased expression of klotho by acute inflammatory stress."
    Ohyama Y., Kurabayashi M., Masuda H., Nakamura T., Aihara Y., Kaname T., Suga T., Arai M., Aizawa H., Matsumura Y., Kuro-o M., Nabeshima Y., Nagai R.
    Biochem. Biophys. Res. Commun. 251:920-925(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, DEVELOPMENTAL STAGE.
    Tissue: Lung.
  2. Cited for: INDUCTION.
  3. Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  4. "Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases."
    Nagai R., Saito Y., Ohyama Y., Aizawa H., Suga T., Nakamura T., Kurabayashi M., Kuroo M.
    Cell. Mol. Life Sci. 57:738-746(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  5. "In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage."
    Mitani H., Ishizaka N., Aizawa T., Ohno M., Usui S., Suzuki T., Amaki T., Mori I., Nakamura Y., Sato M., Nangaku M., Hirata Y., Nagai R.
    Hypertension 39:838-843(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  6. "Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat."
    Saito K., Ishizaka N., Mitani H., Ohno M., Nagai R.
    FEBS Lett. 551:58-62(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  7. Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiKLOT_RAT
AccessioniPrimary (citable) accession number: Q9Z2Y9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 1, 1999
Last modified: May 27, 2015
This is version 112 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. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.