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Protein

Klotho

Gene

KL

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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).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

GO - Biological processi

Complete GO annotation...

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
  • Apical cell membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: Isoform 1 shedding leads to a soluble peptide.By similarity
Isoform 2 :
  • Secreted By similarity
Klotho peptide :
  • Secreted By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini36 – 983ExtracellularSequence analysisAdd BLAST948
Transmembranei984 – 1004HelicalSequence analysisAdd BLAST21
Topological domaini1005 – 1014CytoplasmicSequence analysis10

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 35Sequence analysisAdd BLAST35
ChainiPRO_000004224536 – 1014KlothoAdd BLAST979
ChainiPRO_000004224636 – ?Klotho peptideBy similarity

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi161N-linked (GlcNAc...)Sequence analysis1
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Glycosylationi346N-linked (GlcNAc...)Sequence analysis1
Glycosylationi609N-linked (GlcNAc...)Sequence analysis1
Glycosylationi614N-linked (GlcNAc...)Sequence analysis1
Glycosylationi696N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Interactioni

Subunit structurei

Homodimer. Interacts with FGF23 and FGFR1.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ8WP17.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni59 – 508Glycosyl hydrolase-1 1Add BLAST450
Regioni517 – 955Glycosyl hydrolase-1 2Add BLAST439

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.
IPR033132. Glyco_hydro_1_N_CS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 2 hits.
PTHR10353:SF10. PTHR10353:SF10. 2 hits.
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. AlignAdd to basket

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

        10         20         30         40         50
MPASAPPRRP RPPPPSLSLS LLLVLLGLAG RRLRAEPGDG AQTWARFARP
60 70 80 90 100
PAPEAAGLFQ GTFPDGFLWA VGSAAYQTEG GWQQHGKGAS IWDTFTHHPL
110 120 130 140 150
APPGDSRIAN VPSGAPSPLQ PATGDVASDS YNNVFRDTEA LRELGVTHYR
160 170 180 190 200
FSISWARVLP NGSAGVPNRE GLRYYRRLLE RLRELGVQPV VTLYHWDLPQ
210 220 230 240 250
RLQDAYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID NPYVVAWHGY
260 270 280 290 300
ATGRLAPGIR GSPRLGYLVA HNLLLAHAKV WHLYNTSFRP TQGGQVSIAL
310 320 330 340 350
SSHWINPRRM TDHSIKECQK SLDFVLGWFA KPIFIDGDYP ESMKNNLSSL
360 370 380 390 400
LPDFTESEKK FIKGTADFFA LSFGPTLSFQ LLDPHMKFRQ LESPSLRQLL
410 420 430 440 450
SWIDLEYNHP QIFIVENGWF VSGTTKRDDA KYMYYLKKFI METLKAIKLD
460 470 480 490 500
GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY VDFLSQEKTL LPKSSALFYQ
510 520 530 540 550
KLIEKNGFPP LPENQPLEGT FPCDFAWGIV DNYIQVDTTL SQFTDLNVYL
560 570 580 590 600
WDVHHSKRLI KVDGVVTKKR KSYCVDFAAI QPQITLLQEM HVTHFRFSLD
610 620 630 640 650
WALILPLGNQ SQVNHTILQY YRCMVSELVR VNITPVVALW QPVAPNQGLP
660 670 680 690 700
RLLARQGAWE NPYTALAFAE YARLCFQELG HHVKLWITMN EPYTRNMTYS
710 720 730 740 750
AGHNLLKAHA LAWHVYNEKF RHAQNGKISI ALQADWIEPA CPFSQKDKEV
760 770 780 790 800
AERVLEFDIG WLAEPIFGSG DYPWVMRDWL NQRNNFLLPY FTEDEKKLIQ
810 820 830 840 850
GTFDFLALSH YTTILVDSEK EDPIKYNDYL EVQEMTDITW LNSPSQVAVV
860 870 880 890 900
PWGLRKVLNW LKFKYGDLPM YIISNGIDDG LHAEDDQLRV YYMQNYINEA
910 920 930 940 950
LKAHILDGIN LCGYFAYSFN DRTAPRFGLY RFAADQFEPK PSMKHYRKII
960 970 980 990 1000
DSNGFPGPET LEKFCPEEFT VCTECSFFHT RKPLVAFIAF LFFAFIVSLS
1010
LIFYYSKKGR RRYQ
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015826537 – 551DTTLS…NVYLW → SQLAKPISSLTKPYH in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_015827552 – 1014Missing in isoform 2. 1 PublicationAdd BLAST463

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF064053 mRNA. Translation: AAC77917.1.
AF064054 mRNA. Translation: AAC77918.1.
UniGeneiMfa.6119.

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:
EMBLi
GenBanki
DDBJi
Links Updated
AF064053 mRNA. Translation: AAC77917.1.
AF064054 mRNA. Translation: AAC77918.1.
UniGeneiMfa.6119.

3D structure databases

ProteinModelPortaliQ8WP17.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG081856.

Family and domain databases

Gene3Di3.20.20.80. 2 hits.
InterProiIPR001360. Glyco_hydro_1.
IPR033132. Glyco_hydro_1_N_CS.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
[Graphical view]
PANTHERiPTHR10353. PTHR10353. 2 hits.
PTHR10353:SF10. PTHR10353:SF10. 2 hits.
PfamiPF00232. Glyco_hydro_1. 3 hits.
[Graphical view]
PRINTSiPR00131. GLHYDRLASE1.
SUPFAMiSSF51445. SSF51445. 2 hits.
PROSITEiPS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: May 11, 2016
This is version 78 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.