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Q9Z2Y9

- KLOT_RAT

UniProt

Q9Z2Y9 - KLOT_RAT

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Protein
Klotho
Gene
Kl
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.
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

  1. beta-glucuronidase activity Source: UniProtKB-EC
  2. signal transducer activity Source: InterPro

GO - Biological processi

  1. acute inflammatory response Source: RGD
  2. aging Source: RGD
  3. calcium ion homeostasis Source: Ensembl
  4. carbohydrate metabolic process Source: InterPro
  5. energy reserve metabolic process Source: Ensembl
  6. insulin receptor signaling pathway Source: InterPro
  7. positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Source: Ensembl
  8. positive regulation of bone mineralization Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Enzyme and pathway databases

ReactomeiREACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198995. Negative regulation of FGFR signaling.
REACT_202034. Phospholipase C-mediated cascade.
REACT_79133. SHC-mediated cascade.

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: Chromosome 12

Organism-specific databases

RGDi620396. Kl.

Subcellular locationi

Cell membrane; Single-pass type I membrane protein By similarity
Note: Its shedding leads to a soluble peptide.1 Publication
Chain Klotho peptide : Secreted By similarity 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 983949Extracellular Reviewed prediction
Add
BLAST
Transmembranei984 – 100421Helical; Reviewed prediction
Add
BLAST
Topological domaini1005 – 101410Cytoplasmic Reviewed prediction

GO - Cellular componenti

  1. extracellular space Source: InterPro
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: RGD
  4. 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 – 3434 Reviewed prediction
Add
BLAST
Chaini35 – 1014980Klotho
PRO_0000042249Add
BLAST
Chaini35 – ?Klotho peptide By similarityPRO_0000042250

Amino acid modifications

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

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 By similarity. Interacts with FGF23 and FGFR1 By similarity.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001449.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2Y9.

Family & Domainsi

Region

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

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MPARAPPRRL PRLLLLRLLS LHLLLLTLRA RCLSAEPGQG AQTWARFARP     50
PVPEASGLLH DTFPDGFLWA VGSAAYQTEG GWRQHGKGAS IWDTFTHHPR 100
AIPEDSPIVM APSGAPLPPL PSTGDVASDS YNNVYRDTEG LRELGVTHYR 150
FSISWARVLP NGTAGTPNRE GLRYYRRLLE RLRELGVQPV VTLYHWDLPQ 200
RLQDTYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID NPYVVAWHGY 250
ATGRLAPGVR GSSRLGYLVA HNLLLAHAKV WRLYNTSFRP TQGGRVSIAL 300
GSHWITPRRM TDYHIRECQK SLDFVLGWFA KPIFIDGDYP KSMKNNLSSL 350
LPDFTESEKR FIRGTADFFA LSFGPTLSFQ LLDPSMKFRQ LESPSLRQLL 400
SWIDLEYNHP QIFIVENGWF VSGTTRRDDA KYMYYLKKFI MESLKAIRLD 450
GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY VDFLSQDKEL LPKSSALFYQ 500
KLIENNGFPP LPENQPLEGT FPCDFAWGVV DNYIQVDPTL SQFTDPNVYL 550
WDVHHSKRLI KVDGVVAKKR KPYCVDFSAI RPQITLLREM RVTHFRFSLD 600
WALILPLGNQ TQVNRTVLHF YRCMVSELVH ANITPVVALW QPATPHQGLP 650
HALAKHGAWE NPHTALAFAD YANLCFEELG HWVKFWITIN EPNSRNMTYR 700
AGHHLLKAHA LAWHLYDDKF RAAQKGKISI ALQVDWIEPA CPFSQKDKEV 750
AERVLEFDVG WLAEPIFGSG DYPHVMREWL NQKNNFLLPY FTEDEKKLIR 800
GSFDFLALSH YTTILVDWEK EDPIKYNDYL EVQEMTDITW LNSPNQVAVV 850
PWGLRKALNW LRFKYGDLPM FVTANGIDDD PHAEQDSLRM YYIKNYVNEA 900
LKAYVLDGIN LCGYFAYSLS DRSVPKSGFY RYAANQFEPK PSIKHYRKII 950
DNNGFLGSGT LGRFCPEEYT VCTGCGFFQT RKSLLAFISF LVFAFVTSLA 1000
LIYYYSKKGR RRYK 1014
Length:1,014
Mass (Da):116,800
Last modified:May 1, 1999 - v1
Checksum:i16F3B57581AC1DF0
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AB017820 mRNA. Translation: BAA34740.1 .
PIRi JE0333.
RefSeqi NP_112626.1. NM_031336.1.
UniGenei Rn.30061.

3D structure databases

ProteinModelPortali Q9Z2Y9.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000001449.

Protein family/group databases

CAZyi GH1. Glycoside Hydrolase Family 1.

Proteomic databases

PaxDbi Q9Z2Y9.
PRIDEi Q9Z2Y9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000001449 ; ENSRNOP00000001449 ; ENSRNOG00000001092 .
GeneIDi 83504.
KEGGi rno:83504.
UCSCi RGD:620396. rat.

Organism-specific databases

CTDi 9365.
RGDi 620396. Kl.

Phylogenomic databases

eggNOGi COG2723.
GeneTreei ENSGT00550000074452.
HOGENOMi HOG000060126.
HOVERGENi HBG081856.
InParanoidi Q9Z2Y9.
KOi K14756.
OMAi ALSSHWI.
OrthoDBi EOG7MH0XV.
PhylomeDBi Q9Z2Y9.
TreeFami TF314803.

Enzyme and pathway databases

Reactomei REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198995. Negative regulation of FGFR signaling.
REACT_202034. Phospholipase C-mediated cascade.
REACT_79133. SHC-mediated cascade.

Miscellaneous databases

NextBioi 615928.
PROi Q9Z2Y9.

Gene expression databases

Genevestigatori Q9Z2Y9.

Family and domain databases

Gene3Di 3.20.20.80. 2 hits.
InterProi IPR001360. Glyco_hydro_1.
IPR018120. Glyco_hydro_1_AS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
[Graphical view ]
PANTHERi PTHR10353. PTHR10353. 1 hit.
PTHR10353:SF10. PTHR10353:SF10. 1 hit.
Pfami PF00232. Glyco_hydro_1. 3 hits.
[Graphical view ]
PRINTSi PR00131. GLHYDRLASE1.
SUPFAMi SSF51445. SSF51445. 2 hits.
PROSITEi PS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 106 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

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