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Protein

Klotho

Gene

Kl

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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

  • acute inflammatory response Source: RGD
  • aging Source: RGD
  • carbohydrate metabolic process Source: InterPro
  • fibroblast growth factor receptor signaling pathway Source: GO_Central
  • glycosyl compound metabolic process Source: GO_Central
  • insulin receptor signaling pathway Source: InterPro
  • negative regulation of systemic arterial blood pressure Source: RGD
  • norepinephrine biosynthetic process Source: RGD
  • response to activity Source: RGD
  • response to angiotensin Source: RGD
  • response to fibroblast growth factor Source: RGD
  • response to vitamin D Source: RGD

Keywordsi

Molecular functionGlycosidase, Hydrolase

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620396. Kl.

Subcellular locationi

  • 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: Its shedding leads to a soluble peptide.By similarity
Klotho peptide :
  • Secreted By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 983ExtracellularSequence analysisAdd BLAST949
Transmembranei984 – 1004HelicalSequence analysisAdd BLAST21
Topological domaini1005 – 1014CytoplasmicSequence analysis10

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • extracellular space Source: InterPro
  • integral component of plasma membrane Source: GO_Central
  • membrane Source: RGD

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000004224935 – 1014KlothoAdd BLAST980
ChainiPRO_000004225035 – ?Klotho peptideBy similarity

Amino acid modifications

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

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

BgeeiENSRNOG00000001092.
GenevisibleiQ9Z2Y9. RN.

Interactioni

Subunit structurei

Homodimer. Interacts with FGF23 and FGFR1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000001449.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2Y9.
SMRiQ9Z2Y9.
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

eggNOGiKOG0626. Eukaryota.
COG2723. LUCA.
HOGENOMiHOG000060126.
HOVERGENiHBG081856.
InParanoidiQ9Z2Y9.
KOiK14756.
OrthoDBiEOG091G0035.
PhylomeDBiQ9Z2Y9.
TreeFamiTF314803.

Family and domain databases

InterProiView protein in InterPro
IPR001360. Glyco_hydro_1.
IPR033132. Glyco_hydro_1_N_CS.
IPR017853. Glycoside_hydrolase_SF.
IPR028546. Klotho.
PANTHERiPTHR10353. PTHR10353. 1 hit.
PTHR10353:SF88. PTHR10353:SF88. 1 hit.
PfamiView protein in Pfam
PF00232. Glyco_hydro_1. 3 hits.
PRINTSiPR00131. GLHYDRLASE1.
SUPFAMiSSF51445. SSF51445. 2 hits.
PROSITEiView protein in PROSITE
PS00653. GLYCOSYL_HYDROL_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Z2Y9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPARAPPRRL PRLLLLRLLS LHLLLLTLRA RCLSAEPGQG AQTWARFARP
60 70 80 90 100
PVPEASGLLH DTFPDGFLWA VGSAAYQTEG GWRQHGKGAS IWDTFTHHPR
110 120 130 140 150
AIPEDSPIVM APSGAPLPPL PSTGDVASDS YNNVYRDTEG LRELGVTHYR
160 170 180 190 200
FSISWARVLP NGTAGTPNRE GLRYYRRLLE RLRELGVQPV VTLYHWDLPQ
210 220 230 240 250
RLQDTYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID NPYVVAWHGY
260 270 280 290 300
ATGRLAPGVR GSSRLGYLVA HNLLLAHAKV WRLYNTSFRP TQGGRVSIAL
310 320 330 340 350
GSHWITPRRM TDYHIRECQK SLDFVLGWFA KPIFIDGDYP KSMKNNLSSL
360 370 380 390 400
LPDFTESEKR FIRGTADFFA LSFGPTLSFQ LLDPSMKFRQ LESPSLRQLL
410 420 430 440 450
SWIDLEYNHP QIFIVENGWF VSGTTRRDDA KYMYYLKKFI MESLKAIRLD
460 470 480 490 500
GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY VDFLSQDKEL LPKSSALFYQ
510 520 530 540 550
KLIENNGFPP LPENQPLEGT FPCDFAWGVV DNYIQVDPTL SQFTDPNVYL
560 570 580 590 600
WDVHHSKRLI KVDGVVAKKR KPYCVDFSAI RPQITLLREM RVTHFRFSLD
610 620 630 640 650
WALILPLGNQ TQVNRTVLHF YRCMVSELVH ANITPVVALW QPATPHQGLP
660 670 680 690 700
HALAKHGAWE NPHTALAFAD YANLCFEELG HWVKFWITIN EPNSRNMTYR
710 720 730 740 750
AGHHLLKAHA LAWHLYDDKF RAAQKGKISI ALQVDWIEPA CPFSQKDKEV
760 770 780 790 800
AERVLEFDVG WLAEPIFGSG DYPHVMREWL NQKNNFLLPY FTEDEKKLIR
810 820 830 840 850
GSFDFLALSH YTTILVDWEK EDPIKYNDYL EVQEMTDITW LNSPNQVAVV
860 870 880 890 900
PWGLRKALNW LRFKYGDLPM FVTANGIDDD PHAEQDSLRM YYIKNYVNEA
910 920 930 940 950
LKAYVLDGIN LCGYFAYSLS DRSVPKSGFY RYAANQFEPK PSIKHYRKII
960 970 980 990 1000
DNNGFLGSGT LGRFCPEEYT VCTGCGFFQT RKSLLAFISF LVFAFVTSLA
1010
LIYYYSKKGR RRYK
Length:1,014
Mass (Da):116,800
Last modified:May 1, 1999 - v1
Checksum:i16F3B57581AC1DF0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017820 mRNA. Translation: BAA34740.1.
PIRiJE0333.
RefSeqiNP_112626.1. NM_031336.1.
UniGeneiRn.30061.

Genome annotation databases

GeneIDi83504.
KEGGirno:83504.
UCSCiRGD:620396. rat.

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.

Entry informationi

Entry nameiKLOT_RAT
AccessioniPrimary (citable) accession number: Q9Z2Y9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: May 1, 1999
Last modified: May 10, 2017
This is version 126 of the entry and version 1 of the sequence. See 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