PPBT_BOVIN
ID PPBT_BOVIN Reviewed; 524 AA.
AC P09487; Q17QS5;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Alkaline phosphatase, tissue-nonspecific isozyme {ECO:0000303|PubMed:19098289};
DE Short=AP-TNAP;
DE Short=TNAP {ECO:0000303|PubMed:19098289};
DE Short=TNSALP;
DE EC=3.1.3.1 {ECO:0000250|UniProtKB:P05186};
DE AltName: Full=Alkaline phosphatase liver/bone/kidney isozyme;
DE AltName: Full=Phosphoamidase {ECO:0000305};
DE AltName: Full=Phosphocreatine phosphatase {ECO:0000250|UniProtKB:P09242};
DE EC=3.9.1.1 {ECO:0000250|UniProtKB:P09242};
DE Flags: Precursor;
GN Name=ALPL;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3436527; DOI=10.1016/0378-1119(87)90264-2;
RA Garattini E., Hua J.-C., Udenfriend S.;
RT "Cloning and sequencing of bovine kidney alkaline phosphatase cDNA.";
RL Gene 59:41-46(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 18-50.
RX PubMed=3458202; DOI=10.1073/pnas.83.8.2368;
RA Hua J.-C., Berger J., Pan Y.C.E., Hulmes J.D., Udenfriend S.;
RT "Partial sequencing of human adult, human fetal, and bovine intestinal
RT alkaline phosphatases: comparison with the human placental and liver
RT isozymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:2368-2372(1986).
RN [4]
RP FUNCTION.
RX PubMed=19098289; DOI=10.1074/jbc.m803205200;
RA Price P.A., Toroian D., Chan W.S.;
RT "Tissue-nonspecific alkaline phosphatase is required for the calcification
RT of collagen in serum: a possible mechanism for biomineralization.";
RL J. Biol. Chem. 284:4594-4604(2009).
CC -!- FUNCTION: Alkaline phosphatase that metabolizes various phosphate
CC compounds and plays a key role in skeletal mineralization and adaptive
CC thermogenesis (By similarity). Has broad substrate specificity and can
CC hydrolyze a considerable variety of compounds: however, only a few
CC substrates, such as diphosphate (inorganic pyrophosphate; PPi),
CC pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural
CC substrates (By similarity). Plays an essential role in skeletal and
CC dental mineralization via its ability to hydrolyze extracellular
CC diphosphate, a potent mineralization inhibitor, to phosphate: it
CC thereby promotes hydroxyapatite crystal formation and increases
CC inorganic phosphate concentration (PubMed:19098289). Acts in a non-
CC redundant manner with PHOSPHO1 in skeletal mineralization: while
CC PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in
CC the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of
CC hydroxyapatite crystallization in the extracellular matrix (By
CC similarity). Also promotes dephosphorylation of osteopontin (SSP1), an
CC inhibitor of hydroxyapatite crystallization in its phosphorylated
CC state; it is however unclear whether ALPL/TNAP mediates SSP1
CC dephosphorylation via a direct or indirect manner (By similarity).
CC Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable
CC form of vitamin B6, in order to provide a sufficient amount of PLP in
CC the brain, an essential cofactor for enzymes catalyzing the synthesis
CC of diverse neurotransmitters (By similarity). Additionally, also able
CC to mediate ATP degradation in a stepwise manner to adenosine, thereby
CC regulating the availability of ligands for purinergic receptors (By
CC similarity). Also capable of dephosphorylating microbial products, such
CC as lipopolysaccharides (LPS) as well as other phosphorylated small-
CC molecules, such as poly-inosine:cytosine (poly I:C) (By similarity).
CC Acts as a key regulator of adaptive thermogenesis as part of the futile
CC creatine cycle: localizes to the mitochondria of thermogenic fat cells
CC and acts by mediating hydrolysis of N-phosphocreatine to initiate a
CC futile cycle of creatine dephosphorylation and phosphorylation (By
CC similarity). During the futile creatine cycle, creatine and N-
CC phosphocreatine are in a futile cycle, which dissipates the high energy
CC charge of N-phosphocreatine as heat without performing any mechanical
CC or chemical work (By similarity). {ECO:0000250|UniProtKB:P05186,
CC ECO:0000250|UniProtKB:P09242, ECO:0000269|PubMed:19098289}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a phosphate monoester + H2O = an alcohol + phosphate;
CC Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.1;
CC Evidence={ECO:0000250|UniProtKB:P09242, ECO:0000255|PROSITE-
CC ProRule:PRU10042};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15018;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphosphate + H2O = H(+) + 2 phosphate; Xref=Rhea:RHEA:24576,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:43474; Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24577;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + pyridoxal 5'-phosphate = phosphate + pyridoxal;
CC Xref=Rhea:RHEA:20533, ChEBI:CHEBI:15377, ChEBI:CHEBI:17310,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:597326;
CC Evidence={ECO:0000250|UniProtKB:P05186};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20534;
CC Evidence={ECO:0000250|UniProtKB:P05186};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + phosphoethanolamine = ethanolamine + phosphate;
CC Xref=Rhea:RHEA:16089, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57603, ChEBI:CHEBI:58190;
CC Evidence={ECO:0000250|UniProtKB:P05186};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16090;
CC Evidence={ECO:0000250|UniProtKB:P05186};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-phosphocreatine = creatine + phosphate;
CC Xref=Rhea:RHEA:12977, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57947, ChEBI:CHEBI:58092; EC=3.9.1.1;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12978;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP + H2O = AMP + H(+) + phosphate; Xref=Rhea:RHEA:61436,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61437;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AMP + H2O = adenosine + phosphate; Xref=Rhea:RHEA:29375,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16335, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456215; Evidence={ECO:0000250|UniProtKB:P09242};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29376;
CC Evidence={ECO:0000250|UniProtKB:P09242};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P05187};
CC Note=Binds 1 Mg(2+) ion. {ECO:0000250|UniProtKB:P05187};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P05187};
CC Note=Binds 2 Zn(2+) ions. {ECO:0000250|UniProtKB:P05187};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P05186};
CC -!- ACTIVITY REGULATION: Phosphatase activity is specifically inhibited by
CC 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425).
CC {ECO:0000250|UniProtKB:P09242}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P05186}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P05186};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P05186}. Extracellular
CC vesicle membrane {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-
CC anchor {ECO:0000250|UniProtKB:P09242}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:P09242}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P09242}. Mitochondrion intermembrane space
CC {ECO:0000250|UniProtKB:P09242}. Note=Localizes to special class of
CC extracellular vesicles, named matrix vesicles (MVs), which are released
CC by osteogenic cells. Localizes to the mitochondria of thermogenic fat
CC cells: tethered to mitochondrial membranes via a GPI-anchor and
CC probably resides in the mitochondrion intermembrane space.
CC {ECO:0000250|UniProtKB:P09242}.
CC -!- DOMAIN: Calcium-binding is structural and does not influence the
CC alkaline phosphatase activity. At very high concentrations, calcium can
CC however substitute for zinc at zinc-binding sites, leading to strongly
CC reduced enzyme activity. {ECO:0000250|UniProtKB:P05186}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P05186}.
CC -!- SIMILARITY: Belongs to the alkaline phosphatase family. {ECO:0000305}.
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DR EMBL; M18443; AAA30380.1; -; mRNA.
DR EMBL; BC118208; AAI18209.1; -; mRNA.
DR PIR; A29600; A29600.
DR RefSeq; NP_789828.2; NM_176858.2.
DR AlphaFoldDB; P09487; -.
DR SMR; P09487; -.
DR STRING; 9913.ENSBTAP00000011783; -.
DR BindingDB; P09487; -.
DR ChEMBL; CHEMBL2406894; -.
DR DrugCentral; P09487; -.
DR PaxDb; P09487; -.
DR PRIDE; P09487; -.
DR Ensembl; ENSBTAT00000011783; ENSBTAP00000011783; ENSBTAG00000008951.
DR Ensembl; ENSBTAT00000066596; ENSBTAP00000065772; ENSBTAG00000008951.
DR Ensembl; ENSBTAT00000071091; ENSBTAP00000063499; ENSBTAG00000008951.
DR Ensembl; ENSBTAT00000071575; ENSBTAP00000067523; ENSBTAG00000008951.
DR GeneID; 280994; -.
DR KEGG; bta:280994; -.
DR CTD; 249; -.
DR VEuPathDB; HostDB:ENSBTAG00000008951; -.
DR VGNC; VGNC:25850; ALPL.
DR eggNOG; KOG4126; Eukaryota.
DR GeneTree; ENSGT00950000183063; -.
DR HOGENOM; CLU_008539_4_0_1; -.
DR InParanoid; P09487; -.
DR OMA; RIMSKGM; -.
DR OrthoDB; 416703at2759; -.
DR TreeFam; TF323513; -.
DR BRENDA; 3.1.3.1; 908.
DR PRO; PR:P09487; -.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000008951; Expressed in olfactory segment of nasal mucosa and 104 other tissues.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0065010; C:extracellular membrane-bounded organelle; IDA:AgBase.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043262; F:adenosine-diphosphatase activity; IEA:RHEA.
DR GO; GO:0004035; F:alkaline phosphatase activity; IDA:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004427; F:inorganic diphosphatase activity; IEA:RHEA.
DR GO; GO:0050187; F:phosphoamidase activity; ISS:UniProtKB.
DR GO; GO:0052732; F:phosphoethanolamine phosphatase activity; IEA:Ensembl.
DR GO; GO:0033883; F:pyridoxal phosphatase activity; ISS:UniProtKB.
DR GO; GO:0016462; F:pyrophosphatase activity; ISS:UniProtKB.
DR GO; GO:0031214; P:biomineral tissue development; IDA:AgBase.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0019725; P:cellular homeostasis; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0016311; P:dephosphorylation; IBA:GO_Central.
DR GO; GO:0003006; P:developmental process involved in reproduction; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR GO; GO:0010259; P:multicellular organism aging; IEA:Ensembl.
DR GO; GO:0055062; P:phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:UniProtKB.
DR GO; GO:0042822; P:pyridoxal phosphate metabolic process; IEA:Ensembl.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:1904383; P:response to sodium phosphate; IEA:Ensembl.
DR GO; GO:0034516; P:response to vitamin B6; IEA:Ensembl.
DR GO; GO:0033280; P:response to vitamin D; IEA:Ensembl.
DR CDD; cd16012; ALP; 1.
DR Gene3D; 3.40.720.10; -; 1.
DR InterPro; IPR001952; Alkaline_phosphatase.
DR InterPro; IPR018299; Alkaline_phosphatase_AS.
DR InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR PANTHER; PTHR11596; PTHR11596; 1.
DR Pfam; PF00245; Alk_phosphatase; 1.
DR PRINTS; PR00113; ALKPHPHTASE.
DR SMART; SM00098; alkPPc; 1.
DR SUPFAM; SSF53649; SSF53649; 1.
DR PROSITE; PS00123; ALKALINE_PHOSPHATASE; 1.
PE 1: Evidence at protein level;
KW Biomineralization; Calcium; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein;
KW Magnesium; Membrane; Metal-binding; Mitochondrion; Phosphoprotein;
KW Reference proteome; Signal; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:3458202"
FT CHAIN 18..499
FT /note="Alkaline phosphatase, tissue-nonspecific isozyme"
FT /id="PRO_0000024019"
FT PROPEP 500..524
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024020"
FT ACT_SITE 110
FT /note="Phosphoserine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P05187,
FT ECO:0000255|PROSITE-ProRule:PRU10042"
FT BINDING 60
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P05186"
FT BINDING 290
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P05186"
FT BINDING 291
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P05186"
FT BINDING 306
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P05186"
FT BINDING 332
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 341
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 379
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT BINDING 454
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09242"
FT LIPID 499
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 430
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 139..201
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT DISULFID 489..497
FT /evidence="ECO:0000250|UniProtKB:P05187"
FT CONFLICT 210
FT /note="H -> Y (in Ref. 1; AAA30380)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="H -> Q (in Ref. 1; AAA30380)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 524 AA; 57193 MW; 21A66F10E8ADDFC2 CRC64;
MISPFLLLAI GTCFASSLVP EKEKDPKYWR DQAQQTLKNA LRLQTLNTNV AKNVIMFLGD
GMGVSTVTAA RILKGQLHHS PGEETKLEMD KFPYVALSKT YNTNAQVPDS AGTATAYLCG
VKANEGTVGV SAATQRSQCN TTQGNEVTSI LRWAKDAGKS VGIVTTTRVN HATPSASYAH
SADRDWYSDN EMPPEALSQG CKDIAYQLMH NIKDIEVIMG GGRKYMFPKN RTDVEYELDE
KARGTRLDGL NLIDIWKSFK PKHKHSHYVW NRTDLLALDP HSVDYLLGLF EPGDMQYELN
RNNATDPSLS EMVEMAIRIL NKNPKGFFLL VEGGRIDHGH HEGKAKQALH EAVEMDQAIG
QAGAMTSVED TLTVVTADHS HVFTFGGYTP RGNSIFGLAP MVSDTDKKPF TAILYGNGPG
YKVVGGEREN VSMVDYAHNN YQAQSAVPLR HETHGGEDVA VFAKGPMAHL LHGVHEQNYI
PHVMAYAACI GANRDHCASA SSSGSPSPGP LLLLLALLPL GSLF
