General Information of Target

Target ID LDTP02099
Target Name Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)
Gene Name ALPL
Gene ID 249
Synonyms
Alkaline phosphatase, tissue-nonspecific isozyme; AP-TNAP; TNS-ALP; TNSALP; EC 3.1.3.1; Alkaline phosphatase liver/bone/kidney isozyme; Phosphoamidase; Phosphocreatine phosphatase; EC 3.9.1.1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MISPFLVLAIGTCLTNSLVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGD
GMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCG
VKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAH
SADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDE
KARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELN
RNNVTDPSLSEMVVVAIQILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIG
QAGSLTSSEDTLTVVTADHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPG
YKVVGGERENVSMVDYAHNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYV
PHVMAYAACIGANLGHCAPASSAGSLAAGPLLLALALYPLSVLF
Target Type
Successful
Target Bioclass
Enzyme
Family
Alkaline phosphatase family
Subcellular location
Cell membrane
Function
Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis. Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates. Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration. Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix. Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner. Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters. Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors. Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation. During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work.
TTD ID
T09538
Uniprot ID
P05186
DrugMap ID
TTMR5UV
Ensemble ID
ENST00000374832.5
HGNC ID
HGNC:438
ChEMBL ID
CHEMBL5979

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
KYSE180 SNV: p.D306N .
LNCaP clone FGC SNV: p.H381N .
MOLT4 SNV: p.R71H .
NCIH358 SNV: p.T366N .
RT112 SNV: p.P26S .
SCC25 SNV: p.Y263C .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
OPA-S-S-alkyne
 Probe Info 
K346(0.56); K241(3.23); K74(6.22)  LDD3494  [1]
DBIA
 Probe Info 
C64(1.60)  LDD3414  [2]
Acrolein
 Probe Info 
N.A.  LDD0217  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa H78(0.00); H79(0.00)  LDD0222  [3]
 LDCM0107  IAA HeLa N.A.  LDD0221  [3]
 LDCM0022  KB02 CAL-72 C64(1.59)  LDD2290  [2]
 LDCM0023  KB03 CAL-72 C64(2.27)  LDD2707  [2]
 LDCM0024  KB05 SAOS-2 C64(1.60)  LDD3414  [2]
 LDCM0109  NEM HeLa N.A.  LDD0223  [3]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Mitogen-activated protein kinase kinase kinase 14 (MAP3K14) STE Ser/Thr protein kinase family Q99558

The Drug(s) Related To This Target

Approved
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Amifostine Small molecular drug DB01143
Levamisole Small molecular drug D0CF2Q
Pyridoxine Small molecular drug DB00165
Asfotase Alfa . D05XSJ
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Mersalyl . DB09338

References

1 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
3 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.