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Q8WP17 (KLOT_MACFA) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Klotho

EC=3.2.1.31

Cleaved into the following chain:

  1. Klotho peptide
Gene names
Name:KL
OrganismMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Taxonomic identifier9541 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

Protein attributes

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

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

Isoform 2: Secreted By similarity.

Klotho peptide: Secreted By similarity.

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.

Sequence similarities

Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8WP17-1)

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.
Isoform 2 (identifier: Q8WP17-2)

Also known as: Secreted;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Potential
Chain36 – 1014979Klotho
PRO_0000042245
Chain36 – ?Klotho peptide By similarityPRO_0000042246

Regions

Topological domain36 – 983948Extracellular 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

Natural variations

Alternative sequence537 – 55115DTTLS…NVYLW → SQLAKPISSLTKPYH in isoform 2.
VSP_015826
Alternative sequence552 – 1014463Missing in isoform 2.
VSP_015827

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Membrane-bound) [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 00669CD244A4DD0F

FASTA1,014116,469
        10         20         30         40         50         60 
MPASAPPRRP RPPPPSLSLS LLLVLLGLAG RRLRAEPGDG AQTWARFARP PAPEAAGLFQ 

        70         80         90        100        110        120 
GTFPDGFLWA VGSAAYQTEG GWQQHGKGAS IWDTFTHHPL APPGDSRIAN VPSGAPSPLQ 

       130        140        150        160        170        180 
PATGDVASDS YNNVFRDTEA LRELGVTHYR FSISWARVLP NGSAGVPNRE GLRYYRRLLE 

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

       250        260        270        280        290        300 
NPYVVAWHGY ATGRLAPGIR GSPRLGYLVA HNLLLAHAKV WHLYNTSFRP TQGGQVSIAL 

       310        320        330        340        350        360 
SSHWINPRRM TDHSIKECQK SLDFVLGWFA KPIFIDGDYP ESMKNNLSSL LPDFTESEKK 

       370        380        390        400        410        420 
FIKGTADFFA LSFGPTLSFQ LLDPHMKFRQ LESPSLRQLL SWIDLEYNHP QIFIVENGWF 

       430        440        450        460        470        480 
VSGTTKRDDA KYMYYLKKFI METLKAIKLD GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY 

       490        500        510        520        530        540 
VDFLSQEKTL LPKSSALFYQ KLIEKNGFPP LPENQPLEGT FPCDFAWGIV DNYIQVDTTL 

       550        560        570        580        590        600 
SQFTDLNVYL WDVHHSKRLI KVDGVVTKKR KSYCVDFAAI QPQITLLQEM HVTHFRFSLD 

       610        620        630        640        650        660 
WALILPLGNQ SQVNHTILQY YRCMVSELVR VNITPVVALW QPVAPNQGLP RLLARQGAWE 

       670        680        690        700        710        720 
NPYTALAFAE YARLCFQELG HHVKLWITMN EPYTRNMTYS AGHNLLKAHA LAWHVYNEKF 

       730        740        750        760        770        780 
RHAQNGKISI ALQADWIEPA CPFSQKDKEV AERVLEFDIG WLAEPIFGSG DYPWVMRDWL 

       790        800        810        820        830        840 
NQRNNFLLPY FTEDEKKLIQ GTFDFLALSH YTTILVDSEK EDPIKYNDYL EVQEMTDITW 

       850        860        870        880        890        900 
LNSPSQVAVV PWGLRKVLNW LKFKYGDLPM YIISNGIDDG LHAEDDQLRV YYMQNYINEA 

       910        920        930        940        950        960 
LKAHILDGIN LCGYFAYSFN DRTAPRFGLY RFAADQFEPK PSMKHYRKII DSNGFPGPET 

       970        980        990       1000       1010 
LEKFCPEEFT VCTECSFFHT RKPLVAFIAF LFFAFIVSLS LIFYYSKKGR RRYQ 

« Hide

Isoform 2 (Secreted) [UniParc].

Checksum: 45F4EAD2358DDBAA
Show »

FASTA55162,274

References

[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).

Web resources

Protein Spotlight

The thread of life - Issue 65 of December 2005

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF064053 mRNA. Translation: AAC77917.1.
AF064054 mRNA. Translation: AAC77918.1.

3D structure databases

ProteinModelPortalQ8WP17.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG081856.

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...

Entry information

Entry nameKLOT_MACFA
AccessionPrimary (citable) accession number: Q8WP17
Secondary accession number(s): Q8WP18
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: March 1, 2002
Last modified: February 19, 2014
This is version 71 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