KLOT_MACFA
ID KLOT_MACFA Reviewed; 1014 AA.
AC Q8WP17; Q8WP18;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 25-MAY-2022, entry version 94.
DE RecName: Full=Klotho;
DE EC=3.2.1.31;
DE Contains:
DE RecName: Full=Klotho peptide;
DE Flags: Precursor;
GN Name=KL;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Koh N., Fujimori T., Nabeshima Y.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: May have weak glycosidase activity towards glucuronylated
CC steroids. However, it lacks essential active site Glu residues at
CC positions 241 and 874, suggesting it may be inactive as a glycosidase
CC in vivo. May be involved in the regulation of calcium and phosphorus
CC homeostasis by inhibiting the synthesis of active vitamin D (By
CC similarity). Essential factor for the specific interaction between
CC FGF23 and FGFR1 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The Klotho peptide generated by cleavage of the membrane-
CC bound isoform may be an anti-aging circulating hormone which would
CC extend life span by inhibiting insulin/IGF1 signaling. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucuronoside + H2O = an alcohol + D-glucuronate;
CC Xref=Rhea:RHEA:17633, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC ChEBI:CHEBI:58720, ChEBI:CHEBI:83411; EC=3.2.1.31;
CC -!- SUBUNIT: Homodimer. Interacts with FGF23 and FGFR1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000250|UniProtKB:O35082}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:O35082}. Apical cell membrane
CC {ECO:0000250|UniProtKB:O35082}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:O35082}. Note=Isoform 1 shedding leads to a
CC soluble peptide. {ECO:0000250|UniProtKB:O35082}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC {ECO:0000250|UniProtKB:O35082}.
CC -!- SUBCELLULAR LOCATION: [Klotho peptide]: Secreted
CC {ECO:0000250|UniProtKB:O35082}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Membrane-bound;
CC IsoId=Q8WP17-1; Sequence=Displayed;
CC Name=2; Synonyms=Secreted;
CC IsoId=Q8WP17-2; Sequence=VSP_015826, VSP_015827;
CC -!- DOMAIN: Contains 2 glycosyl hydrolase 1 regions. However, the first
CC region lacks the essential Glu active site residue at position 241, and
CC the second one lacks the essential Glu active site residue at position
CC 874.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 1 family. Klotho
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The thread of life - Issue
CC 65 of December 2005;
CC URL="https://web.expasy.org/spotlight/back_issues/065";
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DR EMBL; AF064053; AAC77917.1; -; mRNA.
DR EMBL; AF064054; AAC77918.1; -; mRNA.
DR AlphaFoldDB; Q8WP17; -.
DR SMR; Q8WP17; -.
DR STRING; 9541.XP_005586019.1; -.
DR eggNOG; KOG0626; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004566; F:beta-glucuronidase activity; IEA:UniProtKB-EC.
DR GO; GO:0007568; P:aging; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:InterPro.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:InterPro.
DR InterPro; IPR001360; Glyco_hydro_1.
DR InterPro; IPR033132; Glyco_hydro_1_N_CS.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR028546; Klotho.
DR PANTHER; PTHR10353; PTHR10353; 5.
DR PANTHER; PTHR10353:SF10; PTHR10353:SF10; 5.
DR Pfam; PF00232; Glyco_hydro_1; 3.
DR PRINTS; PR00131; GLHYDRLASE1.
DR SUPFAM; SSF51445; SSF51445; 2.
DR PROSITE; PS00653; GLYCOSYL_HYDROL_F1_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Glycoprotein; Glycosidase; Hydrolase;
KW Membrane; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..1014
FT /note="Klotho"
FT /id="PRO_0000042245"
FT CHAIN 36..?
FT /note="Klotho peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000042246"
FT TOPO_DOM 36..983
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 984..1004
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1005..1014
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 59..508
FT /note="Glycosyl hydrolase-1 1"
FT REGION 517..955
FT /note="Glycosyl hydrolase-1 2"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 285
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 609
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 614
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 696
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 537..551
FT /note="DTTLSQFTDLNVYLW -> SQLAKPISSLTKPYH (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_015826"
FT VAR_SEQ 552..1014
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_015827"
SQ SEQUENCE 1014 AA; 116469 MW; 00669CD244A4DD0F CRC64;
MPASAPPRRP RPPPPSLSLS LLLVLLGLAG RRLRAEPGDG AQTWARFARP PAPEAAGLFQ
GTFPDGFLWA VGSAAYQTEG GWQQHGKGAS IWDTFTHHPL APPGDSRIAN VPSGAPSPLQ
PATGDVASDS YNNVFRDTEA LRELGVTHYR FSISWARVLP NGSAGVPNRE GLRYYRRLLE
RLRELGVQPV VTLYHWDLPQ RLQDAYGGWA NRALADHFRD YAELCFRHFG GQVKYWITID
NPYVVAWHGY ATGRLAPGIR GSPRLGYLVA HNLLLAHAKV WHLYNTSFRP TQGGQVSIAL
SSHWINPRRM TDHSIKECQK SLDFVLGWFA KPIFIDGDYP ESMKNNLSSL LPDFTESEKK
FIKGTADFFA LSFGPTLSFQ LLDPHMKFRQ LESPSLRQLL SWIDLEYNHP QIFIVENGWF
VSGTTKRDDA KYMYYLKKFI METLKAIKLD GVDVIGYTAW SLMDGFEWHR GYSIRRGLFY
VDFLSQEKTL LPKSSALFYQ KLIEKNGFPP LPENQPLEGT FPCDFAWGIV DNYIQVDTTL
SQFTDLNVYL WDVHHSKRLI KVDGVVTKKR KSYCVDFAAI QPQITLLQEM HVTHFRFSLD
WALILPLGNQ SQVNHTILQY YRCMVSELVR VNITPVVALW QPVAPNQGLP RLLARQGAWE
NPYTALAFAE YARLCFQELG HHVKLWITMN EPYTRNMTYS AGHNLLKAHA LAWHVYNEKF
RHAQNGKISI ALQADWIEPA CPFSQKDKEV AERVLEFDIG WLAEPIFGSG DYPWVMRDWL
NQRNNFLLPY FTEDEKKLIQ GTFDFLALSH YTTILVDSEK EDPIKYNDYL EVQEMTDITW
LNSPSQVAVV PWGLRKVLNW LKFKYGDLPM YIISNGIDDG LHAEDDQLRV YYMQNYINEA
LKAHILDGIN LCGYFAYSFN DRTAPRFGLY RFAADQFEPK PSMKHYRKII DSNGFPGPET
LEKFCPEEFT VCTECSFFHT RKPLVAFIAF LFFAFIVSLS LIFYYSKKGR RRYQ