Reviewed, UniProtKB/Swiss-Prot Q8WP17 (KLOT_MACFA)

Names and origin

Protein names

Recommended name:
    Klotho
    EC=3.2.1.31
Cleaved into the following 1 chains:
    1- Recommended name:
            Klotho peptide

Gene names

Name:

KL

Organism

Macaca fascicularis (Crab eating macaque) (Cynomolgus monkey)

Taxonomic identifier

9541 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca

Protein attributes

Sequence length	1014 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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 activity	A beta-D-glucuronoside + H(2)O = D-glucuronate + an alcohol.
Subunit structure	Homodimer By similarity.
Subcellular location	Isoform 1: Cell membrane; Single-pass type I membrane proteinBy similarity. Note= Isoform 1 shedding leads to a soluble peptide. Isoform 2: SecretedBy 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane
Molecular function	Glycosidase Hydrolase
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
None. [Check GOA]

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.

Notes: Isoform 1 shedding leads to a soluble peptide.

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 key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 35	35	Potential
	Chain	36 – 1014	979	Klotho
	Chain	36 – ?		Klotho peptide By similarity
Regions
	Topological domain	36 – 983	948	Extracellular Potential
	Transmembrane	984 – 1004	21	Potential
	Topological domain	1005 – 1014	10	Cytoplasmic Potential
	Region	59 – 508	450	Glycosyl hydrolase-1 1
	Region	517 – 955	439	Glycosyl hydrolase-1 2
Amino acid modifications
	Modified residue	499	1	Phosphotyrosine By similarity
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Glycosylation	285	1	N-linked (GlcNAc...) Potential
	Glycosylation	346	1	N-linked (GlcNAc...) Potential
	Glycosylation	609	1	N-linked (GlcNAc...) Potential
	Glycosylation	614	1	N-linked (GlcNAc...) Potential
	Glycosylation	696	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	537 – 551	15	DTTLS…NVYLW → SQLAKPISSLTKPYH in isoform 2.
	Alternative sequence	552 – 1014	463	Missing in isoform 2.

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Membrane-bound) [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 00669CD244A4DD0F	FASTA	1,014	116,469
	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
	Isoform 2 (Secreted) [UniParc]. Checksum: 45F4EAD2358DDBAA		551	62,274
	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 DNYIQVSQLA 550 KPISSLTKPY H

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
EMBLGenBankDDBJ	AF064053 mRNA. Translation: AAC77917.1. AF064054 mRNA. Translation: AAC77918.1.
3D structure databases
HSSP	HSSP built from PDB template 1OIF based on UniProtKB Q08638.
ModBase	Search...
Phylogenomic databases
HOVERGEN	Q8WP17.
Family and domain databases
InterPro	IPR001360. Glyco_hydro_1. IPR013781. Glyco_hydro_sub_cat. [Graphical view]
Gene3D	G3DSA:3.20.20.80. Glyco_hydro_cat. 2 hits.
PANTHER	PTHR10353. Glyco_hydro_1. 1 hit.
Pfam	PF00232. Glyco_hydro_1. 3 hits. [Graphical view]
PRINTS	PR00131. GLHYDRLASE1.
ProDom	PD000650. Glyco_hydro_euk. 2 hits. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00572. GLYCOSYL_HYDROL_F1_1. False negative. PS00653. GLYCOSYL_HYDROL_F1_2. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
ProtoNet	Search...

Entry information

Entry name

KLOT_MACFA

Accession

Primary (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:	September 2, 2008
This is version 45 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)