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Q9Z2Y9 (KLOT_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Klotho

EC=3.2.1.31

Cleaved into the following chain:

  1. Klotho peptide
Gene names
Name:Kl
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1014 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

The Klotho peptide generated by cleavage of the membrane-bound isoform maybe an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling By similarity.

Catalytic activity

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

Subunit structure

Homodimer By similarity. Interacts with FGF23 and FGFR1 By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Note: Its shedding leads to a soluble peptide. Ref.3

Klotho peptide: Secreted By similarity Ref.3.

Tissue specificity

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. Ref.1 Ref.3 Ref.7

Developmental stage

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

Induction

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. Ref.1 Ref.2 Ref.4 Ref.5 Ref.6

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 874.

Post-translational modification

N-glycosylated By similarity.

Sequence similarities

Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434 Potential
Chain35 – 1014980Klotho
PRO_0000042249
Chain35 – ?Klotho peptide By similarityPRO_0000042250

Regions

Topological domain35 – 983949Extracellular Potential
Transmembrane984 – 100421Helical; Potential
Topological domain1005 – 101410Cytoplasmic Potential
Region59 – 508450Glycosyl hydrolase-1 1
Region517 – 955439Glycosyl hydrolase-1 2

Amino acid modifications

Glycosylation1611N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation3461N-linked (GlcNAc...) Potential
Glycosylation6091N-linked (GlcNAc...) Potential
Glycosylation6141N-linked (GlcNAc...) Potential
Glycosylation6961N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
Q9Z2Y9 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 16F3B57581AC1DF0

FASTA1,014116,800
        10         20         30         40         50         60 
MPARAPPRRL PRLLLLRLLS LHLLLLTLRA RCLSAEPGQG AQTWARFARP PVPEASGLLH 

        70         80         90        100        110        120 
DTFPDGFLWA VGSAAYQTEG GWRQHGKGAS IWDTFTHHPR AIPEDSPIVM APSGAPLPPL 

       130        140        150        160        170        180 
PSTGDVASDS YNNVYRDTEG LRELGVTHYR FSISWARVLP NGTAGTPNRE GLRYYRRLLE 

       190        200        210        220        230        240 
RLRELGVQPV VTLYHWDLPQ RLQDTYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID 

       250        260        270        280        290        300 
NPYVVAWHGY ATGRLAPGVR GSSRLGYLVA HNLLLAHAKV WRLYNTSFRP TQGGRVSIAL 

       310        320        330        340        350        360 
GSHWITPRRM TDYHIRECQK SLDFVLGWFA KPIFIDGDYP KSMKNNLSSL LPDFTESEKR 

       370        380        390        400        410        420 
FIRGTADFFA LSFGPTLSFQ LLDPSMKFRQ LESPSLRQLL SWIDLEYNHP QIFIVENGWF 

       430        440        450        460        470        480 
VSGTTRRDDA KYMYYLKKFI MESLKAIRLD GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY 

       490        500        510        520        530        540 
VDFLSQDKEL LPKSSALFYQ KLIENNGFPP LPENQPLEGT FPCDFAWGVV DNYIQVDPTL 

       550        560        570        580        590        600 
SQFTDPNVYL WDVHHSKRLI KVDGVVAKKR KPYCVDFSAI RPQITLLREM RVTHFRFSLD 

       610        620        630        640        650        660 
WALILPLGNQ TQVNRTVLHF YRCMVSELVH ANITPVVALW QPATPHQGLP HALAKHGAWE 

       670        680        690        700        710        720 
NPHTALAFAD YANLCFEELG HWVKFWITIN EPNSRNMTYR AGHHLLKAHA LAWHLYDDKF 

       730        740        750        760        770        780 
RAAQKGKISI ALQVDWIEPA CPFSQKDKEV AERVLEFDVG WLAEPIFGSG DYPHVMREWL 

       790        800        810        820        830        840 
NQKNNFLLPY FTEDEKKLIR GSFDFLALSH YTTILVDWEK EDPIKYNDYL EVQEMTDITW 

       850        860        870        880        890        900 
LNSPNQVAVV PWGLRKALNW LRFKYGDLPM FVTANGIDDD PHAEQDSLRM YYIKNYVNEA 

       910        920        930        940        950        960 
LKAYVLDGIN LCGYFAYSLS DRSVPKSGFY RYAANQFEPK PSIKHYRKII DNNGFLGSGT 

       970        980        990       1000       1010 
LGRFCPEEYT VCTGCGFFQT RKSLLAFISF LVFAFVTSLA LIYYYSKKGR RRYK 

« Hide

References

[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]"Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats."
Aizawa H., Saito Y., Nakamura T., Inoue M., Imanari T., Ohyama Y., Matsumura Y., Masuda H., Oba S., Mise N., Kimura K., Hasegawa A., Kurabayashi M., Kuro-o M., Nabeshima Y., Nagai R.
Biochem. Biophys. Res. Commun. 249:865-871(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[3]"Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys."
Kato Y., Arakawa E., Kinoshita S., Shirai A., Furuya A., Yamano K., Nakamura K., Iida A., Anazawa H., Koh N., Iwano A., Imura A., Fujimori T., Kuro-o M., Hanai N., Takeshige K., Nabeshima Y.
Biochem. Biophys. Res. Commun. 267:597-602(2000) [PubMed] [Europe PMC] [Abstract]
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]"The parathyroid is a target organ for FGF23 in rats."
Ben-Dov I.Z., Galitzer H., Lavi-Moshayoff V., Goetz R., Kuro-o M., Mohammadi M., Sirkis R., Naveh-Many T., Silver J.
J. Clin. Invest. 117:4003-4008(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The thread of life - Issue 65 of December 2005

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB017820 mRNA. Translation: BAA34740.1.
PIRJE0333.
RefSeqNP_112626.1. NM_031336.1.
UniGeneRn.30061.

3D structure databases

ProteinModelPortalQ9Z2Y9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000001449.

Protein family/group databases

CAZyGH1. Glycoside Hydrolase Family 1.

Proteomic databases

PaxDbQ9Z2Y9.
PRIDEQ9Z2Y9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000001449; ENSRNOP00000001449; ENSRNOG00000001092.
GeneID83504.
KEGGrno:83504.
UCSCRGD:620396. rat.

Organism-specific databases

CTD9365.
RGD620396. Kl.

Phylogenomic databases

eggNOGCOG2723.
GeneTreeENSGT00550000074452.
HOGENOMHOG000060126.
HOVERGENHBG081856.
InParanoidQ9Z2Y9.
KOK14756.
OMAALSSHWI.
OrthoDBEOG7MH0XV.
TreeFamTF314803.

Gene expression databases

GenevestigatorQ9Z2Y9.

Family and domain databases

Gene3D3.20.20.80. 2 hits.
InterProIPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
[Graphical view]
PANTHERPTHR10353. PTHR10353. 1 hit.
PTHR10353:SF10. PTHR10353:SF10. 1 hit.
PfamPF00232. Glyco_hydro_1. 3 hits.
[Graphical view]
PRINTSPR00131. GLHYDRLASE1.
SUPFAMSSF51445. SSF51445. 2 hits.
PROSITEPS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio615928.
PROQ9Z2Y9.

Entry information

Entry nameKLOT_RAT
AccessionPrimary (citable) accession number: Q9Z2Y9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 1, 1999
Last modified: February 19, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries