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Q9Z2Y9

- KLOT_RAT

UniProt

Q9Z2Y9 - KLOT_RAT

Protein

Klotho

Gene

Kl

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    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

    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 bone mineralization Source: Ensembl
    8. positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Source: Ensembl

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

    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

    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...

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei984 – 100421HelicalSequence AnalysisAdd
    BLAST

    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

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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: October 1, 2014
    This is version 107 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