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Q8WP17

- KLOT_MACFA

UniProt

Q8WP17 - KLOT_MACFA

Protein

Klotho

Gene

KL

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 72 (01 Oct 2014)
      Sequence version 1 (01 Mar 2002)
      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. aging Source: InterPro
    2. carbohydrate metabolic process Source: InterPro
    3. fibroblast growth factor receptor signaling pathway Source: InterPro
    4. insulin receptor signaling pathway Source: InterPro

    Keywords - Molecular functioni

    Glycosidase, Hydrolase

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Klotho (EC:3.2.1.31)
    Cleaved into the following chain:
    Gene namesi
    Name:KL
    OrganismiMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
    Taxonomic identifieri9541 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

    Subcellular locationi

    Isoform 1 : Cell membrane By similarity; Single-pass type I membrane protein By similarity
    Note: Isoform 1 shedding leads to a soluble peptide.
    Isoform 2 : Secreted By similarity

    GO - Cellular componenti

    1. extracellular space Source: InterPro
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3535Sequence AnalysisAdd
    BLAST
    Chaini36 – 1014979KlothoPRO_0000042245Add
    BLAST
    Chaini36 – ?Klotho peptideBy similarityPRO_0000042246

    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

    Keywords - PTMi

    Glycoprotein

    Interactioni

    Subunit structurei

    Homodimer. Interacts with FGF23 and FGFR1.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ8WP17.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini36 – 983948ExtracellularSequence 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

    HOVERGENiHBG081856.

    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]

    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. Align

    Isoform 1 (identifier: Q8WP17-1) [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

    MPASAPPRRP RPPPPSLSLS LLLVLLGLAG RRLRAEPGDG AQTWARFARP     50
    PAPEAAGLFQ GTFPDGFLWA VGSAAYQTEG GWQQHGKGAS IWDTFTHHPL 100
    APPGDSRIAN VPSGAPSPLQ PATGDVASDS YNNVFRDTEA LRELGVTHYR 150
    FSISWARVLP NGSAGVPNRE GLRYYRRLLE RLRELGVQPV VTLYHWDLPQ 200
    RLQDAYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID NPYVVAWHGY 250
    ATGRLAPGIR GSPRLGYLVA HNLLLAHAKV WHLYNTSFRP TQGGQVSIAL 300
    SSHWINPRRM TDHSIKECQK SLDFVLGWFA KPIFIDGDYP ESMKNNLSSL 350
    LPDFTESEKK FIKGTADFFA LSFGPTLSFQ LLDPHMKFRQ LESPSLRQLL 400
    SWIDLEYNHP QIFIVENGWF VSGTTKRDDA KYMYYLKKFI METLKAIKLD 450
    GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY VDFLSQEKTL LPKSSALFYQ 500
    KLIEKNGFPP LPENQPLEGT FPCDFAWGIV DNYIQVDTTL SQFTDLNVYL 550
    WDVHHSKRLI KVDGVVTKKR KSYCVDFAAI QPQITLLQEM HVTHFRFSLD 600
    WALILPLGNQ SQVNHTILQY YRCMVSELVR VNITPVVALW QPVAPNQGLP 650
    RLLARQGAWE NPYTALAFAE YARLCFQELG HHVKLWITMN EPYTRNMTYS 700
    AGHNLLKAHA LAWHVYNEKF RHAQNGKISI ALQADWIEPA CPFSQKDKEV 750
    AERVLEFDIG WLAEPIFGSG DYPWVMRDWL NQRNNFLLPY FTEDEKKLIQ 800
    GTFDFLALSH YTTILVDSEK EDPIKYNDYL EVQEMTDITW LNSPSQVAVV 850
    PWGLRKVLNW LKFKYGDLPM YIISNGIDDG LHAEDDQLRV YYMQNYINEA 900
    LKAHILDGIN LCGYFAYSFN DRTAPRFGLY RFAADQFEPK PSMKHYRKII 950
    DSNGFPGPET LEKFCPEEFT VCTECSFFHT RKPLVAFIAF LFFAFIVSLS 1000
    LIFYYSKKGR RRYQ 1014
    Length:1,014
    Mass (Da):116,469
    Last modified:March 1, 2002 - v1
    Checksum:i00669CD244A4DD0F
    GO
    Isoform 2 (identifier: Q8WP17-2) [UniParc]FASTAAdd to Basket

    Also known as: Secreted

    The sequence of this isoform differs from the canonical sequence as follows:
         537-551: DTTLSQFTDLNVYLW → SQLAKPISSLTKPYH
         552-1014: Missing.

    Show »
    Length:551
    Mass (Da):62,274
    Checksum:i45F4EAD2358DDBAA
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei537 – 55115DTTLS…NVYLW → SQLAKPISSLTKPYH in isoform 2. 1 PublicationVSP_015826Add
    BLAST
    Alternative sequencei552 – 1014463Missing in isoform 2. 1 PublicationVSP_015827Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF064053 mRNA. Translation: AAC77917.1.
    AF064054 mRNA. Translation: AAC77918.1.

    Keywords - Coding sequence diversityi

    Alternative splicing

    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
    AF064053 mRNA. Translation: AAC77917.1 .
    AF064054 mRNA. Translation: AAC77918.1 .

    3D structure databases

    ProteinModelPortali Q8WP17.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    HOVERGENi HBG081856.

    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. Koh N., Fujimori T., Nabeshima Y.
      Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).

    Entry informationi

    Entry nameiKLOT_MACFA
    AccessioniPrimary (citable) accession number: Q8WP17
    Secondary accession number(s): Q8WP18
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 11, 2005
    Last sequence update: March 1, 2002
    Last modified: October 1, 2014
    This is version 72 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    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