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Entry version 159 (18 Sep 2019)
Sequence version 2 (11 Oct 2005)
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Protein

Klotho

Gene

KL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, 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

Miscellaneous

Defects in KL may be a cause of chronic renal failure complications.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionGlycosidase, Hormone, Hydrolase
LigandVitamin D

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-109704 PI3K Cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-190374 FGFR1c and Klotho ligand binding and activation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654219 Phospholipase C-mediated cascade: FGFR1
R-HSA-5654687 Downstream signaling of activated FGFR1
R-HSA-5654688 SHC-mediated cascade:FGFR1
R-HSA-5654689 PI-3K cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Protein family/group databases

Carbohydrate-Active enZymes

More...
CAZyi
GH1 Glycoside Hydrolase Family 1

Transport Classification Database

More...
TCDBi
8.A.49.1.1 the klotho auxiliary protein (klotho) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Klotho (EC:3.2.1.31)
Cleaved into the following chain:
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:KL
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 13

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:6344 KL

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
604824 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q9UEF7

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini34 – 981ExtracellularSequence analysisAdd BLAST948
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei982 – 1002HelicalSequence analysisAdd BLAST21
Topological domaini1003 – 1012CytoplasmicSequence analysis10

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Tumoral calcinosis, hyperphosphatemic, familial, 3 (HFTC3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hyperphosphatemic tumoral calcinosis, a rare autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients have recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_064554193H → R in HFTC3; impairs the ability to form a ternary complex with FGF23 and FGFR1c; impairs KL-dependent FGF23 signaling. 1 PublicationCorresponds to variant dbSNP:rs121908423EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
9365

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...
GeneReviewsi
KL

MalaCards human disease database

More...
MalaCardsi
KL
MIMi617994 phenotype

Open Targets

More...
OpenTargetsi
ENSG00000133116

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
306661 Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA30130

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
KL

Domain mapping of disease mutations (DMDM)

More...
DMDMi
77416517

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 33Sequence analysisAdd BLAST33
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000004224334 – 1012KlothoAdd BLAST979
ChainiPRO_000004224434 – ?Klotho peptideBy similarity

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi106N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi159N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi283N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi344N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi607N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi612N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi694N-linked (GlcNAc...) asparagineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...
MassIVEi
Q9UEF7

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q9UEF7

PeptideAtlas

More...
PeptideAtlasi
Q9UEF7

PRoteomics IDEntifications database

More...
PRIDEi
Q9UEF7

ProteomicsDB human proteome resource

More...
ProteomicsDBi
84144 [Q9UEF7-1]
84145 [Q9UEF7-2]

PTM databases

GlyConnect protein glycosylation platform

More...
GlyConnecti
1435

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q9UEF7

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q9UEF7

Miscellaneous databases

CutDB - Proteolytic event database

More...
PMAP-CutDBi
Q9UEF7

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Present in cortical renal tubules (at protein level). Soluble peptide is present in serum and cerebrospinal fluid. Expressed in kidney, placenta, small intestine and prostate. Down-regulated in renal cell carcinomas, hepatocellular carcinomas, and in chronic renal failure kidney.5 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000133116 Expressed in 149 organ(s), highest expression level in nephron tubule

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q9UEF7 HS

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

Interacts with FGF23 and FGFR1.

By similarity

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
114766, 1 interactor

Protein interaction database and analysis system

More...
IntActi
Q9UEF7, 1 interactor

STRING: functional protein association networks

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STRINGi
9606.ENSP00000369442

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11012
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q9UEF7

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni57 – 506Glycosyl hydrolase-1 1Add BLAST450
Regioni515 – 953Glycosyl hydrolase-1 2Add BLAST439

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG0626 Eukaryota
COG2723 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000157614

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000060126

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q9UEF7

KEGG Orthology (KO)

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KOi
K14756

Identification of Orthologs from Complete Genome Data

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OMAi
YVVAWHG

Database of Orthologous Groups

More...
OrthoDBi
408001at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q9UEF7

TreeFam database of animal gene trees

More...
TreeFami
TF314803

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR001360 Glyco_hydro_1
IPR033132 Glyco_hydro_1_N_CS
IPR017853 Glycoside_hydrolase_SF
IPR028546 Klotho

The PANTHER Classification System

More...
PANTHERi
PTHR10353 PTHR10353, 3 hits
PTHR10353:SF10 PTHR10353:SF10, 3 hits

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00232 Glyco_hydro_1, 3 hits

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00131 GLHYDRLASE1

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF51445 SSF51445, 2 hits

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00653 GLYCOSYL_HYDROL_F1_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9UEF7-1) [UniParc]FASTAAdd to basket
Also known as: Membrane-bound

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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 RPPPPSLSLL LVLLGLGGRR LRAEPGDGAQ TWARFSRPPA
60 70 80 90 100
PEAAGLFQGT FPDGFLWAVG SAAYQTEGGW QQHGKGASIW DTFTHHPLAP
110 120 130 140 150
PGDSRNASLP LGAPSPLQPA TGDVASDSYN NVFRDTEALR ELGVTHYRFS
160 170 180 190 200
ISWARVLPNG SAGVPNREGL RYYRRLLERL RELGVQPVVT LYHWDLPQRL
210 220 230 240 250
QDAYGGWANR ALADHFRDYA ELCFRHFGGQ VKYWITIDNP YVVAWHGYAT
260 270 280 290 300
GRLAPGIRGS PRLGYLVAHN LLLAHAKVWH LYNTSFRPTQ GGQVSIALSS
310 320 330 340 350
HWINPRRMTD HSIKECQKSL DFVLGWFAKP VFIDGDYPES MKNNLSSILP
360 370 380 390 400
DFTESEKKFI KGTADFFALC FGPTLSFQLL DPHMKFRQLE SPNLRQLLSW
410 420 430 440 450
IDLEFNHPQI FIVENGWFVS GTTKRDDAKY MYYLKKFIME TLKAIKLDGV
460 470 480 490 500
DVIGYTAWSL MDGFEWHRGY SIRRGLFYVD FLSQDKMLLP KSSALFYQKL
510 520 530 540 550
IEKNGFPPLP ENQPLEGTFP CDFAWGVVDN YIQVDTTLSQ FTDLNVYLWD
560 570 580 590 600
VHHSKRLIKV DGVVTKKRKS YCVDFAAIQP QIALLQEMHV THFRFSLDWA
610 620 630 640 650
LILPLGNQSQ VNHTILQYYR CMASELVRVN ITPVVALWQP MAPNQGLPRL
660 670 680 690 700
LARQGAWENP YTALAFAEYA RLCFQELGHH VKLWITMNEP YTRNMTYSAG
710 720 730 740 750
HNLLKAHALA WHVYNEKFRH AQNGKISIAL QADWIEPACP FSQKDKEVAE
760 770 780 790 800
RVLEFDIGWL AEPIFGSGDY PWVMRDWLNQ RNNFLLPYFT EDEKKLIQGT
810 820 830 840 850
FDFLALSHYT TILVDSEKED PIKYNDYLEV QEMTDITWLN SPSQVAVVPW
860 870 880 890 900
GLRKVLNWLK FKYGDLPMYI ISNGIDDGLH AEDDQLRVYY MQNYINEALK
910 920 930 940 950
AHILDGINLC GYFAYSFNDR TAPRFGLYRY AADQFEPKAS MKHYRKIIDS
960 970 980 990 1000
NGFPGPETLE RFCPEEFTVC TECSFFHTRK SLLAFIAFLF FASIISLSLI
1010
FYYSKKGRRS YK
Length:1,012
Mass (Da):116,181
Last modified:October 11, 2005 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i62031BD73E322E63
GO
Isoform 2 (identifier: Q9UEF7-2) [UniParc]FASTAAdd to basket
Also known as: Secreted

The sequence of this isoform differs from the canonical sequence as follows:
     535-549: DTTLSQFTDLNVYLW → SQLTKPISSLTKPYH
     550-1012: Missing.

Note: Predominates over the membrane form in all tissues examined.
Show »
Length:549
Mass (Da):62,135
Checksum:iCAD8D74DB71C49C6
GO

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Homozygosity for KL-VS allele is associated with decreased longevity and increased cardiovascular disease risk.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02358215P → Q1 PublicationCorresponds to variant dbSNP:rs1052018Ensembl.1
Natural variantiVAR_02358345F → V1 PublicationCorresponds to variant dbSNP:rs1052019Ensembl.1
Natural variantiVAR_064554193H → R in HFTC3; impairs the ability to form a ternary complex with FGF23 and FGFR1c; impairs KL-dependent FGF23 signaling. 1 PublicationCorresponds to variant dbSNP:rs121908423EnsemblClinVar.1
Natural variantiVAR_023584352F → V in allele KL-VS; associated with S-370. 2 PublicationsCorresponds to variant dbSNP:rs9536314EnsemblClinVar.1
Natural variantiVAR_023585370C → S in allele KL-VS; associated with V-352. 2 PublicationsCorresponds to variant dbSNP:rs9527025EnsemblClinVar.1
Natural variantiVAR_049295514P → S. Corresponds to variant dbSNP:rs3752472EnsemblClinVar.1
Natural variantiVAR_036449954P → L in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs139939367Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_015824535 – 549DTTLS…NVYLW → SQLTKPISSLTKPYH in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_015825550 – 1012Missing in isoform 2. 1 PublicationAdd BLAST463

Sequence databases

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EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AB005142 mRNA Translation: BAA23382.1
AB009667 Genomic DNA Translation: BAA24940.1
AB009667 Genomic DNA Translation: BAA24941.1
AL161898 Genomic DNA No translation available.
Z92540 Genomic DNA Translation: CAC94767.1
Z84483 Genomic DNA Translation: CAC94773.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS9347.1 [Q9UEF7-1]

Protein sequence database of the Protein Information Resource

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PIRi
JC5925
JC5926

NCBI Reference Sequences

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RefSeqi
NP_004786.2, NM_004795.3 [Q9UEF7-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000380099; ENSP00000369442; ENSG00000133116 [Q9UEF7-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
9365

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:9365

UCSC genome browser

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UCSCi
uc001uus.3 human [Q9UEF7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Protein Spotlight

The thread of life - Issue 65 of December 2005

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB005142 mRNA Translation: BAA23382.1
AB009667 Genomic DNA Translation: BAA24940.1
AB009667 Genomic DNA Translation: BAA24941.1
AL161898 Genomic DNA No translation available.
Z92540 Genomic DNA Translation: CAC94767.1
Z84483 Genomic DNA Translation: CAC94773.1
CCDSiCCDS9347.1 [Q9UEF7-1]
PIRiJC5925
JC5926
RefSeqiNP_004786.2, NM_004795.3 [Q9UEF7-1]

3D structure databases

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Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5W21X-ray3.00A1-981[»]
SMRiQ9UEF7
ModBaseiSearch...

Protein-protein interaction databases

BioGridi114766, 1 interactor
IntActiQ9UEF7, 1 interactor
STRINGi9606.ENSP00000369442

Protein family/group databases

CAZyiGH1 Glycoside Hydrolase Family 1
TCDBi8.A.49.1.1 the klotho auxiliary protein (klotho) family

PTM databases

GlyConnecti1435
iPTMnetiQ9UEF7
PhosphoSitePlusiQ9UEF7

Polymorphism and mutation databases

BioMutaiKL
DMDMi77416517

Proteomic databases

MassIVEiQ9UEF7
PaxDbiQ9UEF7
PeptideAtlasiQ9UEF7
PRIDEiQ9UEF7
ProteomicsDBi84144 [Q9UEF7-1]
84145 [Q9UEF7-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380099; ENSP00000369442; ENSG00000133116 [Q9UEF7-1]
GeneIDi9365
KEGGihsa:9365
UCSCiuc001uus.3 human [Q9UEF7-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
9365
DisGeNETi9365

GeneCards: human genes, protein and diseases

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GeneCardsi
KL
GeneReviewsiKL
HGNCiHGNC:6344 KL
MalaCardsiKL
MIMi604824 gene
617994 phenotype
neXtProtiNX_Q9UEF7
OpenTargetsiENSG00000133116
Orphaneti306661 Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis syndrome
PharmGKBiPA30130

GenAtlas: human gene database

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GenAtlasi
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Phylogenomic databases

eggNOGiKOG0626 Eukaryota
COG2723 LUCA
GeneTreeiENSGT00940000157614
HOGENOMiHOG000060126
InParanoidiQ9UEF7
KOiK14756
OMAiYVVAWHG
OrthoDBi408001at2759
PhylomeDBiQ9UEF7
TreeFamiTF314803

Enzyme and pathway databases

ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-190374 FGFR1c and Klotho ligand binding and activation
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654219 Phospholipase C-mediated cascade: FGFR1
R-HSA-5654687 Downstream signaling of activated FGFR1
R-HSA-5654688 SHC-mediated cascade:FGFR1
R-HSA-5654689 PI-3K cascade:FGFR1
R-HSA-5654693 FRS-mediated FGFR1 signaling
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Miscellaneous databases

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
Klotho_(biology)

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
9365

Pharos

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Pharosi
Q9UEF7
PMAP-CutDBiQ9UEF7

Protein Ontology

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PROi
PR:Q9UEF7

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
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Gene expression databases

BgeeiENSG00000133116 Expressed in 149 organ(s), highest expression level in nephron tubule
GenevisibleiQ9UEF7 HS

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, 3 hits
PTHR10353:SF10 PTHR10353:SF10, 3 hits
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

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiKLOT_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q9UEF7
Secondary accession number(s): Q5VZ95
, Q96KV5, Q96KW5, Q9UEI9, Q9Y4F0
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: October 11, 2005
Last modified: September 18, 2019
This is version 159 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  4. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  5. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  8. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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