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UniProtKB - P05186 (PPBT_HUMAN)

Entry version 233 (07 Apr 2021)
Sequence version 4 (21 Jun 2005)
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Protein

Alkaline phosphatase, tissue-nonspecific isozyme

Gene

ALPL

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

This isozyme plays a key role in skeletal mineralization by regulating levels of diphosphate (PPi).2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi60MagnesiumBy similarity1
Metal bindingi60Zinc 1By similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei110Phosphoserine intermediateBy similarity1
Metal bindingi110Zinc 1By similarity1
Metal bindingi173MagnesiumBy similarity1
Metal bindingi332MagnesiumBy similarity1
Metal bindingi337Zinc 2By similarity1
Metal bindingi341Zinc 2; via tele nitrogenBy similarity1
Metal bindingi378Zinc 1By similarity1
Metal bindingi379Zinc 1; via tele nitrogenBy similarity1
Metal bindingi454Zinc 2; via tele nitrogenBy similarity1

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 functionHydrolase
Biological processBiomineralization
LigandMagnesium, Metal-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		3.1.3.1, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P05186

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-163125, Post-translational modification: synthesis of GPI-anchored proteins

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		P05186

SIGNOR Signaling Network Open Resource

More...SIGNORi		P05186

<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%5Fand%5Ftaxonomy%5Fsection">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:
Alkaline phosphatase, tissue-nonspecific isozyme (EC:3.1.3.12 Publications)
Short name:
AP-TNAP
Short name:
TNSALP
Alternative name(s):
Alkaline phosphatase liver/bone/kidney isozyme
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:ALPL
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fmanual">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 1

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:438, ALPL

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		171760, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P05186

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000162551.13

<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

Keywords - Cellular componenti

Cell membrane, Membrane

<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

Hypophosphatasia (HOPS)29 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia).
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_02590317S → F in HOPS. 1 Publication1
Natural variantiVAR_00614733A → V in HOPS; 7.2% of wild-type activity. 2 PublicationsCorresponds to variant dbSNP:rs121918005EnsemblClinVar.1
Natural variantiVAR_01108140A → V in HOPS; 2% of activity. 5 PublicationsCorresponds to variant dbSNP:rs770093969Ensembl.1
Natural variantiVAR_02590451A → S in HOPS. 1 Publication1
Natural variantiVAR_01397351A → V in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1470389268Ensembl.1
Natural variantiVAR_00614862M → L in HOPS; moderate; 27% of activity. 2 Publications1
Natural variantiVAR_02590562M → V in HOPS. 1 Publication1
Natural variantiVAR_02590663G → R in HOPS. 1 Publication1
Natural variantiVAR_01397463G → V in HOPS; loss of activity. 1 Publication1
Natural variantiVAR_00614971R → C in HOPS; 35% of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918001EnsemblClinVar.1
Natural variantiVAR_01397571R → H in HOPS; loss of alkaline phosphatase activity. 3 PublicationsCorresponds to variant dbSNP:rs121918003EnsemblClinVar.1
Natural variantiVAR_00615071R → P in HOPS. 1 PublicationCorresponds to variant dbSNP:rs121918003EnsemblClinVar.1
Natural variantiVAR_01397675G → S in HOPS; severe; 3.5% of activity. 2 PublicationsCorresponds to variant dbSNP:rs1304394441Ensembl.1
Natural variantiVAR_02590976Q → R in HOPS. Corresponds to variant dbSNP:rs1057521085EnsemblClinVar.1
Natural variantiVAR_025910108P → L in HOPS; 0.4% of alkaline phosphatase activity; severe allele; no effect on subcellular location; fails to assemble into dimeric structure; dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs121918015EnsemblClinVar.1
Natural variantiVAR_006151111A → T in HOPS; odonto; 50% of alkaline phosphatase activity. 6 PublicationsCorresponds to variant dbSNP:rs773257111EnsemblClinVar.1
Natural variantiVAR_025911114A → G in HOPS. 1 Publication1
Natural variantiVAR_013977116A → T in HOPS; loss of alkaline phosphatase activity. 4 PublicationsCorresponds to variant dbSNP:rs121918013EnsemblClinVar.1
Natural variantiVAR_013978120G → R in HOPS. 2 PublicationsCorresponds to variant dbSNP:rs954135116Ensembl.1
Natural variantiVAR_025912128V → M in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1159854007Ensembl.1
Natural variantiVAR_013979129G → R in HOPS. 2 Publications1
Natural variantiVAR_013146132A → V in HOPS. 1 Publication1
Natural variantiVAR_025913134T → H in HOPS; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs786204530EnsemblClinVar.1
Natural variantiVAR_011082134T → N in HOPS; 9% of activity. 1 PublicationCorresponds to variant dbSNP:rs780583917Ensembl.1
Natural variantiVAR_006152136R → H in HOPS; moderate; 33% of activity. 5 PublicationsCorresponds to variant dbSNP:rs121918011EnsemblClinVar.1
Natural variantiVAR_025914148T → I in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1376937780Ensembl.1
Natural variantiVAR_013980152R → H in HOPS; lethal form; benign variant. 2 PublicationsCorresponds to variant dbSNP:rs149344982EnsemblClinVar.1
Natural variantiVAR_025915162G → S in HOPS. 1 PublicationCorresponds to variant dbSNP:rs760029254Ensembl.1
Natural variantiVAR_006153162G → V in HOPS; severe; 1% of activity. 2 PublicationsCorresponds to variant dbSNP:rs121918012EnsemblClinVar.1
Natural variantiVAR_013981170N → D in HOPS. 2 Publications1
Natural variantiVAR_025916171H → R in HOPS. Corresponds to variant dbSNP:rs778232217Ensembl.1
Natural variantiVAR_006154171H → Y in HOPS; severe; 2% of activity. 2 Publications1
Natural variantiVAR_011083176A → T in HOPS; 30% of alkaline phosphatase activity. 4 PublicationsCorresponds to variant dbSNP:rs121918019EnsemblClinVar.1
Natural variantiVAR_006155177A → T in HOPS and HOPSC; moderate allele. 2 PublicationsCorresponds to variant dbSNP:rs199669988EnsemblClinVar.1
Natural variantiVAR_006156179A → T in HOPS. 2 PublicationsCorresponds to variant dbSNP:rs121918000EnsemblClinVar.1
Natural variantiVAR_013982181S → L in HOPS; 1% of activity. 1 PublicationCorresponds to variant dbSNP:rs199590449EnsemblClinVar.1
Natural variantiVAR_013983184R → W in HOPS; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs763159520EnsemblClinVar.1
Natural variantiVAR_025917189D → E in HOPS. 1 Publication1
Natural variantiVAR_006157191E → G in HOPS; odonto. 1 Publication1
Natural variantiVAR_006158191E → K in HOPS; moderate; frequent mutation in European countries; 56% of alkaline phosphatase activity. 8 PublicationsCorresponds to variant dbSNP:rs121918007EnsemblClinVar.1
Natural variantiVAR_006159201C → Y in HOPS; weak alkaline phosphatase activity; severely affects homodimerization; reduced cell surface expression. 3 Publications1
Natural variantiVAR_006160207Q → P in HOPS. 1 PublicationCorresponds to variant dbSNP:rs121918004EnsemblClinVar.1
Natural variantiVAR_013984211N → D in HOPS. 1 Publication1
Natural variantiVAR_025918212I → F in HOPS. 1
Natural variantiVAR_025919220G → A in HOPS. 1 Publication1
Natural variantiVAR_013985220G → V in HOPS; odonto. 1 Publication1
Natural variantiVAR_025920223R → Q in HOPS. 2 PublicationsCorresponds to variant dbSNP:rs199665722EnsemblClinVar.1
Natural variantiVAR_013986223R → W in HOPS and HOPSC; 3% of activity; severe allele. 6 PublicationsCorresponds to variant dbSNP:rs766076920EnsemblClinVar.1
Natural variantiVAR_013987235E → G in HOPS. 1 Publication1
Natural variantiVAR_011085246R → S in HOPS; 4% of activity. 2 PublicationsCorresponds to variant dbSNP:rs1223142821Ensembl.1
Natural variantiVAR_013988249G → V in HOPS; partial loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs121918018EnsemblClinVar.1
Natural variantiVAR_025921272R → H in HOPS; 6.8% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs781272386EnsemblClinVar.1
Natural variantiVAR_025922272R → L in HOPS. 1 PublicationCorresponds to variant dbSNP:rs781272386EnsemblClinVar.1
Natural variantiVAR_006162289L → F in HOPS. 1 Publication1
Natural variantiVAR_013989291E → K in HOPS; moderate; 8% of activity. 3 PublicationsCorresponds to variant dbSNP:rs786204473EnsemblClinVar.1
Natural variantiVAR_025924292P → T in HOPS; 4% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs765458125Ensembl.1
Natural variantiVAR_025925293 – 294Missing in HOPS. 2
Natural variantiVAR_006163294D → A in HOPS. 3 PublicationsCorresponds to variant dbSNP:rs121918002EnsemblClinVar.1
Natural variantiVAR_013990294D → Y in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1553414079EnsemblClinVar.1
Natural variantiVAR_025926295M → T in HOPS; 8.5% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs1220125702Ensembl.1
Natural variantiVAR_025927297Y → D in HOPS; 1.3% of wild-type activity. 1 Publication1
Natural variantiVAR_025929299L → P in HOPS. 1 Publication1
Natural variantiVAR_006164306D → V in HOPS. 2 Publications1
Natural variantiVAR_025930311E → K in HOPS. 1 PublicationCorresponds to variant dbSNP:rs763457259Ensembl.1
Natural variantiVAR_013991326G → R in HOPS; in a patient carrying also K-291. 1 Publication1
Natural variantiVAR_013992327F → G in HOPS; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_006165327F → L in HOPS and HOPSI. 2 PublicationsCorresponds to variant dbSNP:rs121918010EnsemblClinVar.1
Natural variantiVAR_025931327Missing in HOPS. 1 Publication1
Natural variantiVAR_006166334G → D in HOPS; loss of alkaline phosphatase activity. 5 PublicationsCorresponds to variant dbSNP:rs121918009EnsemblClinVar.1
Natural variantiVAR_075557334G → R in HOPS; weak alkaline phosphatase activity. 1 Publication1
Natural variantiVAR_025932339G → R in HOPS; loss of alkaline phosphatase activity. 2 Publications1
Natural variantiVAR_011086348A → T in HOPS. 2 PublicationsCorresponds to variant dbSNP:rs1553414563EnsemblClinVar.1
Natural variantiVAR_025933354E → D in HOPS. Corresponds to variant dbSNP:rs1553414568EnsemblClinVar.1
Natural variantiVAR_006167378D → V in HOPS; loss of activity. 4 PublicationsCorresponds to variant dbSNP:rs121918008EnsemblClinVar.1
Natural variantiVAR_011087381H → R in HOPS. 1 Publication1
Natural variantiVAR_006168382V → I in HOPS; loss of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs771540767EnsemblClinVar.1
Natural variantiVAR_013993391R → C in HOPS; moderate; 4-10% of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs371243939EnsemblClinVar.1
Natural variantiVAR_025934391R → H in HOPSC and HOPS; severe allele; loss of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs1442918125EnsemblClinVar.1
Natural variantiVAR_013994399A → S in HOPS. 1 Publication1
Natural variantiVAR_011088406D → G in HOPS; 15% of activity. 1 Publication1
Natural variantiVAR_025935411T → A in HOPS; absence of residual enzymatic activity. 1 Publication1
Natural variantiVAR_025936414L → M in HOPS; loss of alkaline phosphatase activity. 3 Publications1
Natural variantiVAR_025937417N → S in HOPS; very low alkaline phosphatase activity; does not affect subcellular location; fails to assemble into dimeric structure. 2 PublicationsCorresponds to variant dbSNP:rs121918014EnsemblClinVar.1
Natural variantiVAR_075558420G → A in HOPS; very low alkaline phosphatase activity; does not affect subcellular location. 2 Publications1
Natural variantiVAR_075559420G → S in HOPS; very low alkaline phosphatase activity; does not affect subcellular location. 1 Publication1
Natural variantiVAR_013995423V → A in HOPS; 16% alkaline of phosphatase activity. 2 Publications1
Natural variantiVAR_025938426G → D in HOPS. 1 Publication1
Natural variantiVAR_006169436Y → H in HOPS. 1 PublicationCorresponds to variant dbSNP:rs121918006EnsemblClinVar.1
Natural variantiVAR_013996445S → P in HOPS; severe; 2% of activity. 2 PublicationsCorresponds to variant dbSNP:rs1553415041EnsemblClinVar.1
Natural variantiVAR_013997450R → C in HOPS; severe; 4% of activity. 2 PublicationsCorresponds to variant dbSNP:rs138690664Ensembl.1
Natural variantiVAR_011090450R → H in HOPS. 1 PublicationCorresponds to variant dbSNP:rs150799088EnsemblClinVar.1
Natural variantiVAR_025939452E → K in HOPS; loss of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs966212736Ensembl.1
Natural variantiVAR_075560459V → L in HOPS; loss of alkaline phosphatase activity. 1 Publication1
Natural variantiVAR_025940468A → T in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1196976671Ensembl.1
Natural variantiVAR_013999473G → S in HOPS. 2 Publications1
Natural variantiVAR_075561476E → A in HOPS; loss of alkaline phosphatase activity. 1 Publication1
Natural variantiVAR_006170476E → K in HOPS. 3 Publications1
Natural variantiVAR_011092478N → I in HOPS; 9% of activity. 2 Publications1
Natural variantiVAR_011093489C → S in HOPS; reduces alkaline phosphatase activity. 2 Publications1
Natural variantiVAR_014000490I → F in HOPS; odonto; partial loss of activity. 1 Publication1
Natural variantiVAR_014001491G → R in HOPS. 2 PublicationsCorresponds to variant dbSNP:rs1413274209EnsemblClinVar.1
Hypophosphatasia childhood type (HOPSC)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02590768T → M in HOPSC; severe allele. 1 Publication1
Natural variantiVAR_02590871R → S in HOPSC; severe allele. 1 PublicationCorresponds to variant dbSNP:rs121918001EnsemblClinVar.1
Natural variantiVAR_006155177A → T in HOPS and HOPSC; moderate allele. 2 PublicationsCorresponds to variant dbSNP:rs199669988EnsemblClinVar.1
Natural variantiVAR_013986223R → W in HOPS and HOPSC; 3% of activity; severe allele. 6 PublicationsCorresponds to variant dbSNP:rs766076920EnsemblClinVar.1
Natural variantiVAR_025923275L → P in HOPSC; severe allele. 1 PublicationCorresponds to variant dbSNP:rs1237252052Ensembl.1
Natural variantiVAR_025934391R → H in HOPSC and HOPS; severe allele; loss of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs1442918125EnsemblClinVar.1
Hypophosphatasia infantile type (HOPSI)4 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA severe bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Three more or less distinct types of infantile hypophosphatasia can be identified: (1) type 1 with onset in utero or in early postnatal life, craniostenosis, severe skeletal abnormalities, hypercalcemia, and death in the first year or so of life; (2) type 2 with later, more gradual development of symptoms, moderately severe 'rachitic' skeletal changes and premature loss of teeth; (3) type 3 with no symptoms, the condition being determined on routine studies.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01397228Y → C in HOPSI; 7% of activity. 1 Publication1
Natural variantiVAR_011084224K → E in HOPSI; partial loss of activity. 1 PublicationCorresponds to variant dbSNP:rs1226800998EnsemblClinVar.1
Natural variantiVAR_025928298E → K in HOPSI. 1 PublicationCorresponds to variant dbSNP:rs121918017EnsemblClinVar.1
Natural variantiVAR_006165327F → L in HOPS and HOPSI. 2 PublicationsCorresponds to variant dbSNP:rs121918010EnsemblClinVar.1
Natural variantiVAR_011089426G → C in HOPSI; partial loss of activity. 1 Publication1
Natural variantiVAR_011091456G → R in HOPSI; loss of activity. 1 PublicationCorresponds to variant dbSNP:rs121918016EnsemblClinVar.1
Natural variantiVAR_013998459V → M in HOPSI. 1 PublicationCorresponds to variant dbSNP:rs1054159992EnsemblClinVar.1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		249

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

More...GeneReviewsi		ALPL

MalaCards human disease database

More...MalaCardsi		ALPL
MIMi146300, phenotype
241500, phenotype
241510, phenotype

Open Targets

More...OpenTargetsi		ENSG00000162551

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

More...Orphaneti		247676, Adult hypophosphatasia
247667, Childhood-onset hypophosphatasia
247651, Infantile hypophosphatasia
247685, Odontohypophosphatasia
247623, Perinatal lethal hypophosphatasia
247638, Prenatal benign hypophosphatasia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA24729

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P05186, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL5979

Drug and drug target database

More...DrugBanki		DB01143, Amifostine
DB06716, Fospropofol
DB09338, Mersalyl
DB00165, Pyridoxine
DB09498, Strontium chloride Sr-89

DrugCentral

More...DrugCentrali		P05186

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		ALPL

Domain mapping of disease mutations (DMDM)

More...DMDMi		68067533

<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 – 172 PublicationsAdd BLAST17
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000002402318 – 501Alkaline phosphatase, tissue-nonspecific isozymeAdd BLAST484
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_0000024024502 – 524Removed in mature formCuratedAdd BLAST23

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei110PhosphoserineBy similarity1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi139 ↔ 201By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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>Glycosylationi140N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi230N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi271N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi303N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi430N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi489 ↔ 497By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi501GPI-anchor amidated serineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P05186

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P05186

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P05186

MaxQB - The MaxQuant DataBase

More...MaxQBi		P05186

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

More...PaxDbi		P05186

PeptideAtlas

More...PeptideAtlasi		P05186

PRoteomics IDEntifications database

More...PRIDEi		P05186

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		51821 [P05186-1]
51822 [P05186-2]
6645

PTM databases

DEPOD human dephosphorylation database

More...DEPODi		ALPL

GlyConnect protein glycosylation platform

More...GlyConnecti		1916, 7 N-Linked glycans (2 sites)

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P05186, 8 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P05186

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

More...PhosphoSitePlusi		P05186

<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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000162551, Expressed in blood and 160 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P05186, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P05186, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000162551, Tissue enhanced (blood, liver, lung)

<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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		106750, 18 interactors

Protein interaction database and analysis system

More...IntActi		P05186, 10 interactors

Molecular INTeraction database

More...MINTi		P05186

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000363973

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P05186

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P05186, protein

<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

3D structure databases

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

More...SMRi		P05186

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

<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

Belongs to the alkaline phosphatase family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG4126, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00950000183063

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_008539_4_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P05186

Identification of Orthologs from Complete Genome Data

More...OMAi		PRTDCKV

Database for complete collections of gene phylogenies

More...PhylomeDBi		P05186

TreeFam database of animal gene trees

More...TreeFami		TF323513

Family and domain databases

Conserved Domains Database

More...CDDi		cd16012, ALP, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.40.720.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR001952, Alkaline_phosphatase
IPR018299, Alkaline_phosphatase_AS
IPR017850, Alkaline_phosphatase_core_sf

The PANTHER Classification System

More...PANTHERi		PTHR11596, PTHR11596, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00245, Alk_phosphatase, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00113, ALKPHPHTASE

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00098, alkPPc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF53649, SSF53649, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00123, ALKALINE_PHOSPHATASE, 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%5Flength">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 (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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 3 <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. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P05186-1) [UniParc]FASTAAdd to basket

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
MISPFLVLAI GTCLTNSLVP EKEKDPKYWR DQAQETLKYA LELQKLNTNV 
        60         70         80         90        100
AKNVIMFLGD GMGVSTVTAA RILKGQLHHN PGEETRLEMD KFPFVALSKT 
       110        120        130        140        150
YNTNAQVPDS AGTATAYLCG VKANEGTVGV SAATERSRCN TTQGNEVTSI 
       160        170        180        190        200
LRWAKDAGKS VGIVTTTRVN HATPSAAYAH SADRDWYSDN EMPPEALSQG 
       210        220        230        240        250
CKDIAYQLMH NIRDIDVIMG GGRKYMYPKN KTDVEYESDE KARGTRLDGL 
       260        270        280        290        300
DLVDTWKSFK PRYKHSHFIW NRTELLTLDP HNVDYLLGLF EPGDMQYELN 
       310        320        330        340        350
RNNVTDPSLS EMVVVAIQIL RKNPKGFFLL VEGGRIDHGH HEGKAKQALH 
       360        370        380        390        400
EAVEMDRAIG QAGSLTSSED TLTVVTADHS HVFTFGGYTP RGNSIFGLAP 
       410        420        430        440        450
MLSDTDKKPF TAILYGNGPG YKVVGGEREN VSMVDYAHNN YQAQSAVPLR 
       460        470        480        490        500
HETHGGEDVA VFSKGPMAHL LHGVHEQNYV PHVMAYAACI GANLGHCAPA 
       510        520 
SSAGSLAAGP LLLALALYPL SVLF
Length:524
Mass (Da):57,305
Last modified:June 21, 2005 - v4
<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:i71B45F17F6211900
GO
Isoform 2 (identifier: P05186-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: MISPFLVLAI...DKFPFVALSK → MPWSFRSSTPTWLRMSSCSWEM

Show »
Length:447
Mass (Da):48,909
Checksum:i4433599B70DBDB88
GO
Isoform 3 (identifier: P05186-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.

Show »
Length:469
Mass (Da):51,045
Checksum:iD57207402F616985
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1ANL0B1ANL0_HUMAN
Alkaline phosphatase
ALPL
216Annotation score:

Annotation score:2 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>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAD93051 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti29W → A AA sequence (PubMed:3954357).Curated1
Sequence conflicti104N → K in CAA32376 (PubMed:2928120).Curated1
Sequence conflicti361Q → H in BAA32129 (PubMed:3532105).Curated1
Sequence conflicti446A → P in BAA32129 (PubMed:3532105).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02590317S → F in HOPS. 1 Publication1
Natural variantiVAR_01397228Y → C in HOPSI; 7% of activity. 1 Publication1
Natural variantiVAR_00614733A → V in HOPS; 7.2% of wild-type activity. 2 PublicationsCorresponds to variant dbSNP:rs121918005EnsemblClinVar.1
Natural variantiVAR_01108140A → V in HOPS; 2% of activity. 5 PublicationsCorresponds to variant dbSNP:rs770093969Ensembl.1
Natural variantiVAR_02590451A → S in HOPS. 1 Publication1
Natural variantiVAR_01397351A → V in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1470389268Ensembl.1
Natural variantiVAR_00614862M → L in HOPS; moderate; 27% of activity. 2 Publications1
Natural variantiVAR_02590562M → V in HOPS. 1 Publication1
Natural variantiVAR_02590663G → R in HOPS. 1 Publication1
Natural variantiVAR_01397463G → V in HOPS; loss of activity. 1 Publication1
Natural variantiVAR_02590768T → M in HOPSC; severe allele. 1 Publication1
Natural variantiVAR_00614971R → C in HOPS; 35% of alkaline phosphatase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918001EnsemblClinVar.1
Natural variantiVAR_01397571R → H in HOPS; loss of alkaline phosphatase activity. 3 PublicationsCorresponds to variant dbSNP:rs121918003EnsemblClinVar.1
Natural variantiVAR_00615071R → P in HOPS. 1 PublicationCorresponds to variant dbSNP:rs121918003EnsemblClinVar.1
Natural variantiVAR_02590871R → S in HOPSC; severe allele. 1 PublicationCorresponds to variant dbSNP:rs121918001EnsemblClinVar.1
Natural variantiVAR_01397675G → S in HOPS; severe; 3.5% of activity. 2 PublicationsCorresponds to variant dbSNP:rs1304394441Ensembl.1
Natural variantiVAR_02590976Q → R in HOPS. Corresponds to variant dbSNP:rs1057521085EnsemblClinVar.1
Natural variantiVAR_025910108P → L in HOPS; 0.4% of alkaline phosphatase activity; severe allele; no effect on subcellular location; fails to assemble into dimeric structure; dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs121918015EnsemblClinVar.1
Natural variantiVAR_006151111A → T in HOPS; odonto; 50% of alkaline phosphatase activity. 6 PublicationsCorresponds to variant dbSNP:rs773257111EnsemblClinVar.1
Natural variantiVAR_025911114A → G in HOPS. 1 Publication1
Natural variantiVAR_013977116A → T in HOPS; loss of alkaline phosphatase activity. 4 PublicationsCorresponds to variant dbSNP:rs121918013EnsemblClinVar.1
Natural variantiVAR_013978120G → R in HOPS. 2 PublicationsCorresponds to variant dbSNP:rs954135116Ensembl.1
Natural variantiVAR_025912128V → M in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1159854007Ensembl.1
Natural variantiVAR_013979129G → R in HOPS. 2 Publications1
Natural variantiVAR_013146132A → V in HOPS. 1 Publication1
Natural variantiVAR_025913134T → H in HOPS; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs786204530EnsemblClinVar.1
Natural variantiVAR_011082134T → N in HOPS; 9% of activity. 1 PublicationCorresponds to variant dbSNP:rs780583917Ensembl.1
Natural variantiVAR_006152136R → H in HOPS; moderate; 33% of activity. 5 PublicationsCorresponds to variant dbSNP:rs121918011EnsemblClinVar.1
Natural variantiVAR_025914148T → I in HOPS. 1 PublicationCorresponds to variant dbSNP:rs1376937780Ensembl.1
Natural variantiVAR_013980152R → H in HOPS; lethal form; benign variant. 2 PublicationsCorresponds to variant dbSNP:rs149344982EnsemblClinVar.1
Natural variantiVAR_025915162G → S in HOPS. 1 PublicationCorresponds to variant dbSNP:rs760029254Ensembl.1
Natural variantiVAR_006153162G → V in HOPS; severe; 1% of activity. 2 PublicationsCorresponds to variant dbSNP:rs121918012EnsemblClinVar.1
Natural variantiVAR_013981170N → D in HOPS. 2 Publications1
Natural variantiVAR_025916171H → R in HOPS. Corresponds to variant dbSNP:rs778232217Ensembl.1
Natural variantiVAR_006154171H → Y in HOPS; severe; 2% of activity. 2 Publications1
Natural variantiVAR_011083176A → T in HOPS; 30% of alkaline phosphatase activity. 4 Publications