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Q8WP17

- KLOT_MACFA

UniProt

Q8WP17 - KLOT_MACFA

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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

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
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
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-KW
Complete GO annotation...

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

        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)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 29, 2014
This is version 73 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