PPBT_FELCA
ID PPBT_FELCA Reviewed; 524 AA.
AC Q29486;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Alkaline phosphatase, tissue-nonspecific isozyme {ECO:0000303|PubMed:7574682};
DE Short=AP-TNAP;
DE Short=TNSALP;
DE EC=3.1.3.1 {ECO:0000269|PubMed:7574682};
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 Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY,
RP AND SUBCELLULAR LOCATION.
RX PubMed=7574682; DOI=10.1006/abbi.1995.1458;
RA Ghosh A.K., Mullins J.I.;
RT "cDNA encoding a functional feline liver/bone/kidney-type alkaline
RT phosphatase.";
RL Arch. Biochem. Biophys. 322:240-249(1995).
CC -!- FUNCTION: Alkaline phosphatase that metabolizes various phosphate
CC compounds and plays a key role in skeletal mineralization and adaptive
CC thermogenesis. Has broad substrate specificity and can hydrolyze a
CC considerable variety of compounds: however, only a few substrates, such
CC as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate
CC (PLP) and N-phosphocreatine are natural substrates. Plays an essential
CC role in skeletal and dental mineralization via its ability to hydrolyze
CC extracellular diphosphate, a potent mineralization inhibitor, to
CC phosphate: it thereby promotes hydroxyapatite crystal formation and
CC increases inorganic phosphate concentration. Acts in a non-redundant
CC manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1
CC mediates the initiation of hydroxyapatite crystallization in the matrix
CC vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite
CC crystallization in the extracellular matrix. Also promotes
CC dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite
CC crystallization in its phosphorylated state; it is however unclear
CC whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or
CC indirect manner. Catalyzes dephosphorylation of PLP to pyridoxal (PL),
CC the transportable form of vitamin B6, in order to provide a sufficient
CC amount of PLP in the brain, an essential cofactor for enzymes
CC catalyzing the synthesis of diverse neurotransmitters. Additionally,
CC also able to mediate ATP degradation in a stepwise manner to adenosine,
CC thereby regulating the availability of ligands for purinergic receptors
CC (By similarity). Also capable of dephosphorylating microbial products,
CC such as lipopolysaccharides (LPS) as well as other phosphorylated
CC small-molecules, such as poly-inosine:cytosine (poly I:C) (By
CC similarity). Acts as a key regulator of adaptive thermogenesis as part
CC of the futile creatine cycle: localizes to the mitochondria of
CC thermogenic fat cells and acts by mediating hydrolysis of N-
CC phosphocreatine to initiate a futile cycle of creatine
CC dephosphorylation and phosphorylation. During the futile creatine
CC cycle, creatine and N-phosphocreatine are in a futile cycle, which
CC dissipates the high energy charge of N-phosphocreatine as heat without
CC performing any mechanical or chemical work (By similarity).
CC {ECO:0000250|UniProtKB:P05186, ECO:0000250|UniProtKB:P09242}.
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:0000255|PROSITE-ProRule:PRU10042,
CC ECO:0000269|PubMed:7574682};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15018;
CC Evidence={ECO:0000269|PubMed:7574682};
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:0000269|PubMed:7574682};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:7574682}. 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; U31569; AAA82993.1; -; mRNA.
DR PIR; S66467; S66467.
DR RefSeq; NP_001036028.1; NM_001042563.1.
DR AlphaFoldDB; Q29486; -.
DR SMR; Q29486; -.
DR STRING; 9685.ENSFCAP00000002729; -.
DR GeneID; 727689; -.
DR KEGG; fca:727689; -.
DR CTD; 249; -.
DR eggNOG; KOG4126; Eukaryota.
DR InParanoid; Q29486; -.
DR OrthoDB; 416703at2759; -.
DR TreeFam; TF323513; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:UniProtKB.
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:UniProtKB.
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:RHEA.
DR GO; GO:0033883; F:pyridoxal phosphatase activity; ISS:UniProtKB.
DR GO; GO:0016462; F:pyrophosphatase activity; ISS:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:UniProtKB.
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:7574682"
FT CHAIN 18..499
FT /note="Alkaline phosphatase, tissue-nonspecific isozyme"
FT /id="PRO_0000024021"
FT PROPEP 500..524
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000024022"
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 302
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"
SQ SEQUENCE 524 AA; 57345 MW; F4863A03C7882A72 CRC64;
MISPFLVLAI GTCLTNSLVP EKEKDPKYWR DQAQQTLKNA LRLQKLNTNV VKNVIMFLGD
GMGVSTVTAA RILKGQLHHN PGEETRLEMD KFPYVALSKT YNTNAQVPDS AGTATAYLCG
VKANEGTVGV SAATQRTQCN TTQGNEVTSI LRWAKDSGKS VGIVTTTRVN HATPSAAYAH
SADRDWYSDN EMPPEALSQG CKDIAYQLMH NVRDIEVIMG GGRKYMFPKN RTDVEYEMDE
KARGTRLDGL NLVDIWKSFK PRHKHSHYVW NRTELLTLDP YGVDYLLGLF EPGDMQYELN
RNSTTDPSLS EMVEIAIKIL SKNPKGFFLL VEGGRIDHGH HEGKAKQALH EAVEMDQAIG
RAGAMTSVED TLTIVTADHS HVFTFGGYTP RGNSIFGLAP MVSDTDKKPF TSILYGNGPG
YKVVGGEREN VSMVDYAHNN YQAQSAVPLR HETHGGEDVA VFAKGPMAHL LHGVHEQNYI
PHVMAYAACI GANLDHCASA SSAGGPSPGP LFLLLALPSL GILF
