ALPL
Alkaline phosphatase, tissue-nonspecific isozyme
Also known as: HOPS, PPBT_HUMAN, TNALP, TNAP, TNSALP
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P05186
- Gene
- ALPL
- Ensembl
- ENSG00000162551
- Chromosome
- 1
- Canonical length
- 524 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
- Subcellular location
- Cytosol
- Secretome location
- Intracellular and membrane
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a member of the alkaline phosphatase family of proteins. There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The first three are located together on chromosome 2, while the tissue non-specific form is located on chromosome 1. The product of this gene is a membrane bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This enzyme may play a role in bone mineralization. Mutations in this gene have been linked to hypophosphatasia, a disorder that is characterized by hypercalcemia and skeletal defects. [provided by RefSeq, Oct 2015]
Canonical amino-acid sequenceUniProt
524 residues, UniProt reviewed canonical sequence.
>P05186|ALPL
1 MISPFLVLAI GTCLTNSLVP EKEKDPKYWR DQAQETLKYA LELQKLNTNV AKNVIMFLGD
61 GMGVSTVTAA RILKGQLHHN PGEETRLEMD KFPFVALSKT YNTNAQVPDS AGTATAYLCG
121 VKANEGTVGV SAATERSRCN TTQGNEVTSI LRWAKDAGKS VGIVTTTRVN HATPSAAYAH
181 SADRDWYSDN EMPPEALSQG CKDIAYQLMH NIRDIDVIMG GGRKYMYPKN KTDVEYESDE
241 KARGTRLDGL DLVDTWKSFK PRYKHSHFIW NRTELLTLDP HNVDYLLGLF EPGDMQYELN
301 RNNVTDPSLS EMVVVAIQIL RKNPKGFFLL VEGGRIDHGH HEGKAKQALH EAVEMDRAIG
361 QAGSLTSSED TLTVVTADHS HVFTFGGYTP RGNSIFGLAP MLSDTDKKPF TAILYGNGPG
421 YKVVGGEREN VSMVDYAHNN YQAQSAVPLR HETHGGEDVA VFSKGPMAHL LHGVHEQNYV
481 PHVMAYAACI GANLGHCAPA SSAGSLAAGP LLLALALYPL SVLFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ALPL can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.25
- Highest tissue expression
- 58 nTPM
Expression across tissuesHPA
Tissue
- adrenal gland: 58 nTPM
- lung: 54 nTPM
- liver: 52 nTPM
- spleen: 45 nTPM
- kidney: 43 nTPM
- appendix: 26 nTPM
Single-cell type
- neutrophils: 1,574 nCPM
- alveolar cells type 2: 811 nCPM
- transitional alveolar cells: 201 nCPM
- breast myoepithelial cells: 150 nCPM
- respiratory secretory cells: 136 nCPM
- respiratory deuterosomal cells: 117 nCPM
Immune cell
- neutrophil: 381 nTPM
- eosinophil: 4.2 nTPM
- memory B-cell: 2.7 nTPM
- naive B-cell: 0.5 nTPM
- total PBMC: 0.1 nTPM
- basophil: 0 nTPM
Brain region
- choroid plexus: 34 nTPM
- pons: 26 nTPM
- medulla oblongata: 24 nTPM
- thalamus: 24 nTPM
- cerebral cortex: 23 nTPM
- amygdala: 19 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ALPL.
Disease | AllUniProt
Conditions ALPL is implicated in, by any mechanism.
- Hypophosphatasia (HOPS) MIM:146300
- Hypophosphatasia, childhood (HPPC) MIM:241510
- Hypophosphatasia, infantile (HPPI) MIM:241500
Disease | GeneticClinVar
533 pathogenic / likely-pathogenic of 1,598 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Hypophosphatasia
- Adult hypophosphatasia
- Infantile hypophosphatasia
- Childhood hypophosphatasia
- ALPL-related disorder
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.69
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.27
- DepMap mean gene effect
- -0.01
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- bone mineralization
- calcium ion homeostasis
- cellular homeostasis
- cementum mineralization
- developmental process involved in reproduction
- endochondral ossification
- futile creatine cycle
- inhibition of non-skeletal tissue mineralization
- osteoblast differentiation
- phosphate ion homeostasis
- positive regulation of cold-induced thermogenesis
- response to antibiotic
- response to glucocorticoid
- response to insulin
- response to lipopolysaccharide
- response to macrophage colony-stimulating factor
- response to sodium phosphate
- response to vitamin B6
- response to vitamin D
- skeletal system development
- pyridoxal phosphate metabolic process
Molecular functions
- ADP phosphatase activity
- alkaline phosphatase activity
- ATP hydrolysis activity
- calcium ion binding
- inorganic diphosphate phosphatase activity
- phosphoethanolamine phosphatase activity
- pyridoxal phosphatase activity
- pyrophosphatase activity
- phosphoamidase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ALPL as an antibody target. Whether an autoantibody or antibody against ALPL could matter depends on whether native ALPL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ALPL is annotated at the cell surface, where native ALPL is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label ALPL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...