Reviewed, UniProtKB/Swiss-Prot P05186 (PPBT_HUMAN)

Names and origin

Protein names

Recommended name:
    Alkaline phosphatase, tissue-nonspecific isozyme
    EC=3.1.3.1
Alternative name(s):
    AP-TNAP
    TNSALP
    Alkaline phosphatase liver/bone/kidney isozyme

Gene names

Name:

ALPL

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This isozyme may play a role in skeletal mineralization.
Catalytic activity	A phosphate monoester + H2O = an alcohol + phosphate.
Cofactor	Binds 1 magnesium ion By similarity. Binds 2 zinc ions By similarity.
Subunit structure	Homodimer.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Ref.10 Ref.11
Post-translational modification	Glycosylated. Ref.9 Ref.12
Involvement in disease	Defects in ALPL are a cause of hypophosphatasia infantile (hypophosphatasia) [MIM:241500]; an inherited metabolic bone disease characterized by defective skeletal mineralization. Four hypophosphatasia 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. Patients with only premature loss of deciduous teeth, but with no bone disease are regarded as having odontohypophosphatasia (odonto). Defects in ALPL are a cause of hypophosphatasia childhood (hypophosphatasia) [MIM:241510]. Defects in ALPL are a cause of hypophosphatasia adult type (hypophosphatasia) [MIM:146300].
Miscellaneous	In most mammals there are four different isozymes: placental, placental-like, intestinal and tissue non-specific (liver/bone/kidney).
Sequence similarities	Belongs to the alkaline phosphatase family.

Ontologies

Keywords
Biological process	Biomineralization
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane
Ligand	Magnesium Metal-binding Zinc
Molecular function	Hydrolase
PTM	GPI-anchor Glycoprotein Lipoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	biomineral formation Inferred from electronic annotation. Source: UniProtKB-KW metabolic process Inferred from electronic annotation. Source: InterPro response to vitamin D Inferred from expression pattern. Source: UniProtKB skeletal system development Ref.18 Traceable author statement. Source: ProtInc
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	alkaline phosphatase activity Inferred from electronic annotation. Source: EC magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Ref.9 Ref.8
	Chain	18 – 502	485	Alkaline phosphatase, tissue-nonspecific isozyme		PRO_0000024023
	Propeptide	503 – 524	22	Removed in mature form Probable		PRO_0000024024
Sites
	Active site	110	1	Phosphoserine intermediate
	Metal binding	60	1	Magnesium Potential
	Metal binding	60	1	Zinc 2 Potential
	Metal binding	173	1	Magnesium Potential
	Metal binding	332	1	Magnesium Potential
	Metal binding	337	1	Zinc 1 Potential
	Metal binding	341	1	Zinc 1 Potential
	Metal binding	378	1	Zinc 2 Potential
	Metal binding	379	1	Zinc 2 Potential
	Metal binding	454	1	Zinc 1 Potential
Amino acid modifications
	Lipidation	502	1	GPI-anchor amidated serine Probable
	Glycosylation	140	1	N-linked (GlcNAc...) Potential
	Glycosylation	230	1	N-linked (GlcNAc...) Potential
	Glycosylation	271	1	N-linked (GlcNAc...) Potential
	Glycosylation	303	1	N-linked (GlcNAc...) Potential
	Glycosylation	430	1	N-linked (GlcNAc...) Ref.12
Natural variations
	Natural variant	17	1	S → F in hypophosphatasia. Ref.18		VAR_025903
	Natural variant	28	1	Y → C in hypophosphatasia; infantile; 7% of activity. Ref.27		VAR_013972
	Natural variant	33	1	A → V in hypophosphatasia; 7.2% of wild-type activity. Ref.14 Ref.35		VAR_006147
	Natural variant	40	1	A → V in hypophosphatasia; 2% of activity. Ref.18 Ref.27 Ref.20 Ref.23 Ref.26		VAR_011081
	Natural variant	51	1	A → S in hypophosphatasia. Ref.31		VAR_025904
	Natural variant	51	1	A → V in hypophosphatasia. Ref.27		VAR_013973
	Natural variant	62	1	M → L in hypophosphatasia; moderate; 27% of activity. Ref.20 Ref.21		VAR_006148
	Natural variant	62	1	M → V in hypophosphatasia. Ref.32		VAR_025905
	Natural variant	63	1	G → R in hypophosphatasia. Ref.32		VAR_025906
	Natural variant	63	1	G → V in hypophosphatasia; loss of activity. Ref.26		VAR_013974
	Natural variant	68	1	T → M in hypophosphatasia; childhood-type; severe allele. Ref.28		VAR_025907
	Natural variant	71	1	R → C in hypophosphatasia. Ref.14		VAR_006149
	Natural variant	71	1	R → H in hypophosphatasia. Ref.27 Ref.31		VAR_013975
	Natural variant	71	1	R → P in hypophosphatasia. Ref.14		VAR_006150
	Natural variant	71	1	R → S in hypophosphatasia; childhood-type; severe allele. Ref.28		VAR_025908
	Natural variant	75	1	G → S in hypophosphatasia; severe; 3.5% of activity. Ref.18 Ref.20		VAR_013976
	Natural variant	76	1	Q → R in hypophosphatasia.		VAR_025909
	Natural variant	108	1	P → L in hypophosphatasia; 0.4% of wild-type activity; severe allele. Ref.33		VAR_025910
	Natural variant	111	1	A → T in hypophosphatasia; odonto. Ref.20 Ref.23 Ref.31 Ref.32 Ref.19		VAR_006151
	Natural variant	114	1	A → G in hypophosphatasia. Ref.34		VAR_025911
	Natural variant	116	1	A → T in hypophosphatasia; loss of activity. Ref.27 Ref.26 Ref.33		VAR_013977
	Natural variant	120	1	G → R in hypophosphatasia. Ref.18 Ref.20		VAR_013978
	Natural variant	128	1	V → M in hypophosphatasia. Ref.31		VAR_025912
	Natural variant	129	1	G → R in hypophosphatasia. Ref.18 Ref.20		VAR_013979
	Natural variant	132	1	A → V in hypophosphatasia. Ref.29		VAR_013146
	Natural variant	134	1	T → H in hypophosphatasia; requires 2 nucleotide substitutions. Ref.31		VAR_025913
	Natural variant	134	1	T → N in hypophosphatasia; 9% of activity. Ref.23		VAR_011082
	Natural variant	136	1	R → H in hypophosphatasia; moderate; 33% of activity. Ref.27 Ref.35 Ref.20 Ref.31 Ref.21		VAR_006152
	Natural variant	148	1	T → I in hypophosphatasia. Ref.32		VAR_025914
	Natural variant	152	1	R → H in hypophosphatasia. Ref.27 Ref.5		VAR_013980
	Natural variant	162	1	G → S in hypophosphatasia. Ref.32		VAR_025915
	Natural variant	162	1	G → V in hypophosphatasia; severe; 1% of activity. Ref.20 Ref.21		VAR_006153
	Natural variant	170	1	N → D in hypophosphatasia. Ref.18 Ref.20		VAR_013981
	Natural variant	171	1	H → R in hypophosphatasia.		VAR_025916
	Natural variant	171	1	H → Y in hypophosphatasia; severe; 2% of activity. Ref.20 Ref.21		VAR_006154
	Natural variant	176	1	A → T in hypophosphatasia. Ref.27 Ref.23 Ref.31		VAR_011083
	Natural variant	177	1	A → T in hypophosphatasia; adult type; moderate allele. Ref.28 Ref.19		VAR_006155
	Natural variant	179	1	A → T in hypophosphatasia. Ref.27 Ref.13		VAR_006156
	Natural variant	181	1	S → L in hypophosphatasia; 1% OF activity. Ref.26		VAR_013982
	Natural variant	184	1	R → W in hypophosphatasia; loss of activity. Ref.18 Ref.20 Ref.26		VAR_013983
	Natural variant	189	1	D → E in hypophosphatasia. Ref.32		VAR_025917
	Natural variant	191	1	E → G in hypophosphatasia; odonto. Ref.19		VAR_006157
	Natural variant	191	1	E → K in hypophosphatasia; moderate; frequent mutation in European countries. Ref.18 Ref.27 Ref.14 Ref.20 Ref.23 Ref.31 Ref.21		VAR_006158
	Natural variant	201	1	C → Y in hypophosphatasia. Ref.23 Ref.21		VAR_006159
	Natural variant	207	1	Q → P in hypophosphatasia. Ref.14		VAR_006160
	Natural variant	211	1	N → D in hypophosphatasia. Ref.27		VAR_013984
	Natural variant	212	1	I → F in hypophosphatasia.		VAR_025918
	Natural variant	220	1	G → A in hypophosphatasia. Ref.32		VAR_025919
	Natural variant	220	1	G → V in hypophosphatasia; odonto. Ref.27		VAR_013985
	Natural variant	223	1	R → Q in hypophosphatasia. Ref.35 Ref.31		VAR_025920
	Natural variant	223	1	R → W in hypophosphatasia; 3% of activity; severe allele. Ref.18 Ref.35 Ref.20 Ref.26 Ref.31 Ref.28		VAR_013986
	Natural variant	224	1	K → E in hypophosphatasia; infantile; partial loss of activity. Ref.22		VAR_011084
	Natural variant	235	1	E → G in hypophosphatasia. Ref.27		VAR_013987
	Natural variant	246	1	R → S in hypophosphatasia; 4% of activity. Ref.23 Ref.31		VAR_011085
	Natural variant	249	1	G → V in hypophosphatasia; partial loss of activity. Ref.20 Ref.26 Ref.21		VAR_013988
	Natural variant	263	1	Y → H Common polymorphism. dbSNP rs3200254. Ref.18 Ref.14 Ref.31 Ref.3 Ref.7		VAR_006161
	Natural variant	272	1	R → H in hypophosphatasia; 6.8% of wild-type activity. Ref.35		VAR_025921
	Natural variant	272	1	R → L in hypophosphatasia. Ref.32		VAR_025922
	Natural variant	275	1	L → P in hypophosphatasia; childhood-type; severe allele. Ref.28		VAR_025923
	Natural variant	289	1	L → F in hypophosphatasia. Ref.4		VAR_006162
	Natural variant	291	1	E → K in hypophosphatasia; moderate; 8% of activity. Ref.18 Ref.20 Ref.30		VAR_013989
	Natural variant	292	1	P → T in hypophosphatasia; 4% of wild-type activity. Ref.35		VAR_025924
	Natural variant	293 – 294	2	Missing in hypophosphatasia.		VAR_025925
	Natural variant	294	1	D → A in hypophosphatasia. Ref.14 Ref.35 Ref.31		VAR_006163
	Natural variant	294	1	D → Y in hypophosphatasia. Ref.27		VAR_013990
	Natural variant	295	1	M → T in hypophosphatasia; 8.5% of wild-type activity. Ref.35		VAR_025926
	Natural variant	297	1	Y → D in hypophosphatasia; 1.3% of wild-type activity. Ref.35		VAR_025927
	Natural variant	298	1	E → K in hypophosphatasia. Ref.16		VAR_025928
	Natural variant	299	1	L → P in hypophosphatasia. Ref.31		VAR_025929
	Natural variant	306	1	D → V in hypophosphatasia. Ref.20 Ref.21		VAR_006164
	Natural variant	311	1	E → K in hypophosphatasia. Ref.32		VAR_025930
	Natural variant	326	1	G → R in hypophosphatasia; in a patient carrying also lys-291. Ref.30		VAR_013991
	Natural variant	327	1	F → G in hypophosphatasia; requires 2 nucleotide substitutions. Ref.27		VAR_013992
	Natural variant	327	1	F → L in hypophosphatasia; childhood. Ref.19 Ref.17		VAR_006165
	Natural variant	327	1	Missing in hypophosphatasia.		VAR_025931
	Natural variant	334	1	G → D in hypophosphatasia. Ref.18 Ref.35 Ref.20 Ref.15		VAR_006166
	Natural variant	339	1	G → R in hypophosphatasia. Ref.31		VAR_025932
	Natural variant	348	1	A → T in hypophosphatasia. Ref.23 Ref.31		VAR_011086
	Natural variant	354	1	E → D in hypophosphatasia.		VAR_025933
	Natural variant	378	1	D → V in hypophosphatasia; loss of activity. Ref.14 Ref.26 Ref.31 Ref.24		VAR_006167
	Natural variant	381	1	H → R in hypophosphatasia. Ref.23		VAR_011087
	Natural variant	382	1	V → I in hypophosphatasia. Ref.19		VAR_006168
	Natural variant	391	1	R → C in hypophosphatasia; moderate; 10% of activity. Ref.20		VAR_013993
	Natural variant	391	1	R → H in hypophosphatasia; childhood-type; severe allele. Ref.28		VAR_025934
	Natural variant	399	1	A → S in hypophosphatasia. Ref.27		VAR_013994
	Natural variant	406	1	D → G in hypophosphatasia; 15% of activity. Ref.23		VAR_011088
	Natural variant	411	1	T → A in hypophosphatasia; absence of residual enzymatic activity. Ref.35		VAR_025935
	Natural variant	414	1	L → M in hypophosphatasia. Ref.31 Ref.33		VAR_025936
	Natural variant	417	1	N → S in hypophosphatasia. Ref.25		VAR_025937
	Natural variant	423	1	V → A in hypophosphatasia; 16% of activity. Ref.27		VAR_013995
	Natural variant	426	1	G → C in hypophosphatasia; infantile; partial loss of activity. Ref.22		VAR_011089
	Natural variant	426	1	G → D in hypophosphatasia. Ref.31		VAR_025938
	Natural variant	436	1	Y → H in hypophosphatasia. Ref.14		VAR_006169
	Natural variant	445	1	S → P in hypophosphatasia; severe; 2% of activity. Ref.18 Ref.20		VAR_013996
	Natural variant	450	1	R → C in hypophosphatasia; severe; 4% of activity. Ref.18 Ref.20		VAR_013997
	Natural variant	450	1	R → H in hypophosphatasia. Ref.23		VAR_011090
	Natural variant	452	1	E → K in hypophosphatasia. Ref.32		VAR_025939
	Natural variant	456	1	G → R in hypophosphatasia; loss of activity. Ref.17		VAR_011091
	Natural variant	459	1	V → M in hypophosphatasia; infantile. Ref.27		VAR_013998
	Natural variant	468	1	A → T in hypophosphatasia. Ref.32		VAR_025940
	Natural variant	473	1	G → S in hypophosphatasia. Ref.18 Ref.20		VAR_013999
	Natural variant	476	1	E → K in hypophosphatasia. Ref.20 Ref.31 Ref.21		VAR_006170
	Natural variant	478	1	N → I in hypophosphatasia; 9% of activity. Ref.23 Ref.26		VAR_011092
	Natural variant	489	1	C → S in hypophosphatasia; 9% of activity. Ref.23		VAR_011093
	Natural variant	490	1	I → F in hypophosphatasia; odonto; partial loss of activity. Ref.26		VAR_014000
	Natural variant	491	1	G → R in hypophosphatasia. Ref.18 Ref.20		VAR_014001
	Natural variant	522	1	V → A: dbSNP rs34605986. Ref.31 Ref.28 Ref.24		VAR_011094
Experimental info
	Sequence conflict	29	1	W → A AA sequence Ref.8
	Sequence conflict	104	1	N → K in CAA32376. Ref.3
	Sequence conflict	361	1	Q → H in BAA32129. Ref.1
	Sequence conflict	446	1	A → P in BAA32129. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P05186-1 [UniParc]. Last modified June 21, 2005. Version 4. Checksum: 71B45F17F6211900	FASTA	524	57,305
	10 20 30 40 50 60 MISPFLVLAI GTCLTNSLVP EKEKDPKYWR DQAQETLKYA LELQKLNTNV AKNVIMFLGD 70 80 90 100 110 120 GMGVSTVTAA RILKGQLHHN PGEETRLEMD KFPFVALSKT YNTNAQVPDS AGTATAYLCG 130 140 150 160 170 180 VKANEGTVGV SAATERSRCN TTQGNEVTSI LRWAKDAGKS VGIVTTTRVN HATPSAAYAH 190 200 210 220 230 240 SADRDWYSDN EMPPEALSQG CKDIAYQLMH NIRDIDVIMG GGRKYMYPKN KTDVEYESDE 250 260 270 280 290 300 KARGTRLDGL DLVDTWKSFK PRYKHSHFIW NRTELLTLDP HNVDYLLGLF EPGDMQYELN 310 320 330 340 350 360 RNNVTDPSLS EMVVVAIQIL RKNPKGFFLL VEGGRIDHGH HEGKAKQALH EAVEMDRAIG 370 380 390 400 410 420 QAGSLTSSED TLTVVTADHS HVFTFGGYTP RGNSIFGLAP MLSDTDKKPF TAILYGNGPG 430 440 450 460 470 480 YKVVGGEREN VSMVDYAHNN YQAQSAVPLR HETHGGEDVA VFSKGPMAHL LHGVHEQNYV 490 500 510 520 PHVMAYAACI GANLGHCAPA SSAGSLAAGP LLLALALYPL SVLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase." Weiss M.J., Henthorn P.S., Lafferty M.A., Slaughter C., Raducha M., Harris H. Proc. Natl. Acad. Sci. U.S.A. 83:7182-7186(1986) [PubMed: 3532105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Osteosarcoma.
[2]	"Structure of the human liver/bone/kidney alkaline phosphatase gene." Weiss M.J., Ray K., Henthorn P.S., Lamb B., Kadesch T., Harris H. J. Biol. Chem. 263:12002-12010(1988) [PubMed: 3165380] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Osteosarcoma.
[3]	"Nucleotide sequence of the human liver-type alkaline phosphatase cDNA." Kishi F., Matsuura S., Kajii T. Nucleic Acids Res. 17:2129-2129(1989) [PubMed: 2928120] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-263. Tissue: Liver.
[4]	"A novel missense mutation of the tissue-nonspecific alkaline phosphatase gene detected in a patient with hypophosphatasia." Sugimoto N., Iwamoto S., Hoshino Y., Kajii E. J. Hum. Genet. 43:160-164(1998) [PubMed: 9747027] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HYPOPHOSPHATASIA PHE-289.
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-152. Tissue: Brain.
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-263. Tissue: Brain, Cerebellum, Lymphoma and Peripheral nerve.
[8]	"Human liver alkaline phosphatase, purification and partial sequencing: homology with the placental isozyme." Garattini E., Hua J.-C., Pan Y.C.E., Udenfriend S. Arch. Biochem. Biophys. 245:331-337(1986) [PubMed: 3954357] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-49. Tissue: Liver.
[9]	"Chemical nature of intestinal-type alkaline phosphatase in human kidney." Nishihara Y., Hayashi Y., Adachi T., Koyama I., Stigbrand T., Hirano K. Clin. Chem. 38:2539-2542(1992) [PubMed: 1458595] [Abstract] Cited for: PROTEIN SEQUENCE OF 18-32, GLYCOSYLATION.
[10]	"Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins." Elortza F., Nuehse T.S., Foster L.J., Stensballe A., Peck S.C., Jensen O.N. Mol. Cell. Proteomics 2:1261-1270(2003) [PubMed: 14517339] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment." Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N. J. Proteome Res. 5:935-943(2006) [PubMed: 16602701] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-430, MASS SPECTROMETRY. Tissue: Liver.
[13]	"A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia." Weiss M.J., Cole D.E.C., Ray K., Whyte M.P., Lafferty M.A., Mulivor R.A., Harris H. Proc. Natl. Acad. Sci. U.S.A. 85:7666-7669(1988) [PubMed: 3174660] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA THR-179.
[14]	"Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia." Henthorn P.S., Raducha M., Fedde K.N., Lafferty M.A., Whyte M.P. Proc. Natl. Acad. Sci. U.S.A. 89:9924-9928(1992) [PubMed: 1409720] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-33; CYS-71; PRO-71; LYS-191; PRO-207; ALA-294; VAL-378 AND HIS-436, VARIANT HIS-263.
[15]	"A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites." Greenberg C.R., Taylor C.L., Haworth J.C., Seargeant L.E., Philipps S., Triggs-Raine B., Chodirker B.N. Genomics 17:215-217(1993) [PubMed: 8406453] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA ASP-334.
[16]	"Novel missense and frameshift mutations in the tissue-nonspecific alkaline phosphatase gene in a Japanese patient with hypophosphatasia." Orimo H., Hayashi Z., Watanabe A., Hirayama T., Hirayama T., Shimada T. Hum. Mol. Genet. 3:1683-1684(1994) [PubMed: 7833929] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA LYS-298.
[17]	"Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia." Ozono K., Yamagata M., Michigami T., Nakajima S., Sakai N., Cai G., Satomura K., Yasui N., Okada S., Nakayama M. J. Clin. Endocrinol. Metab. 81:4458-4461(1996) [PubMed: 8954059] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LEU-327 AND ARG-456.
[18]	"Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia." Mornet E., Taillandier A., Peyramaure S., Kaper F., Muller F., Brenner R., Bussiere P., Freisinger P., Godard J., Le Merrer M., Oury J.F., Plauchu H., Puddu R., Rival J.M., Superti-Furga A., Touraine R.L., Serre J.L., Simon-Bouy B. Eur. J. Hum. Genet. 6:308-314(1998) [PubMed: 9781036] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA PHE-17; VAL-40; SER-75; ARG-120; ARG-129; ASP-170; TRP-184; LYS-191; TRP-223; LYS-291; ASP-334; PRO-445; CYS-450; SER-473 AND ARG-491, VARIANT HIS-263.
[19]	"Hypophosphatasia: identification of five novel missense mutations (G507A, G705A, A748G, T1155C, G1320A) in the tissue-nonspecific alkaline phosphatase gene among Japanese patients." Goseki-Sone M., Orimo H., Iimura T., Takagi Y., Watanabe H., Taketa K., Sato S., Mayanagi H., Shimada T., Oida S. Hum. Mutat. Suppl. 1:S263-S267(1998) [PubMed: 9452105] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA THR-111; THR-177; GLY-191; LEU-327 AND ILE-382.
[20]	"Correlations of genotype and phenotype in hypophosphatasia." Zurutuza L., Muller F., Gibrat J.F., Taillandier A., Simon-Bouy B., Serre J.L., Mornet E. Hum. Mol. Genet. 8:1039-1046(1999) [PubMed: 10332035] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-40; LEU-62; SER-75; THR-111; ARG-120; ARG-129; HIS-136; VAL-162; ASP-170; TYR-171; TRP-184; LYS-191; TRP-223; VAL-249; LYS-291; VAL-306; ASP-334; CYS-391; PRO-445; CYS-450; SER-473; LYS-476 AND ARG-491, 3D-STRUCTURE MODELING, CHARACTERIZATION OF VARIANTS.
[21]	"Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia." Taillandier A., Zurutuza L., Muller F., Simon-Bouy B., Serre J.L., Bird L., Brenner R., Boute O., Cousin J., Gaillard D., Heidemann P.H., Steinmann B., Wallot M., Mornet E. Hum. Mutat. 13:171-172(1999) [PubMed: 10094560] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LEU-62; HIS-136; VAL-162; TYR-171; LYS-191; TYR-201; VAL-249; VAL-306 AND LYS-476.
[22]	"Severe hypercalcaemia and respiratory insufficiency associated with infantile hypophosphatasia caused by two novel mutations of the tissue-nonspecific alkaline phosphatase gene." Mochizuki H., Saito M., Michigami T., Ohashi H., Koda N., Yamaguchi S., Ozono K. Eur. J. Pediatr. 159:375-379(2000) [PubMed: 10834525] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA GLU-224 AND CYS-426.
[23]	"Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia." Taillandier A., Cozien E., Muller F., Merrien Y., Bonnin E., Fribourg C., Simon-Bouy B., Serre J.L., Bieth E., Brenner R., Cordier M.P., De Bie S., Fellmann F., Freisinger P., Hesse V., Hennekam R.C.M., Josifova D., Kerzin-Storrar L. , Leporrier N., Zabot M.-T., Mornet E. Hum. Mutat. 15:293-293(2000) [PubMed: 10679946] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-40; THR-111; ASN-134; THR-176; LYS-191; TYR-201; SER-246; THR-348; ARG-381; GLY-406; HIS-450; ILE-478 AND SER-489.
[24]	"Asp361Val mutant of alkaline phosphatase found in patients with dominantly inherited hypophosphatasia inhibits the activity of the wild-type enzyme." Mueller H.L., Yamazaki M., Michigami T., Kageyama T., Schoenau E., Schneider P., Ozono K. J. Clin. Endocrinol. Metab. 85:743-747(2000) [PubMed: 10690885] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA VAL-378, VARIANT ALA-522.
[25]	"Perinatal hypophosphatasia: radiology, pathology and molecular biology studies in a family harboring a splicing mutation (648+1A) and a novel missense mutation (N400S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene." Sergi C., Mornet E., Troeger J., Voigtlaender T. Am. J. Med. Genet. 103:235-240(2001) [PubMed: 11745997] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA SER-417.
[26]	"A molecular approach to dominance in hypophosphatasia." Lia-Baldini A.S., Muller F., Taillandier A., Gibrat J.F., Mouchard M., Robin B., Simon-Bouy B., Serre J.L., Aylsworth A.S., Bieth E., Delanote S., Freisinger P., Hu J.C.-C., Krohn H.-P., Nunes M.E., Mornet E. Hum. Genet. 109:99-108(2001) [PubMed: 11479741] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS HYPOPHOSPHATASIA VAL-40; VAL-63; THR-116; LEU-181; TRP-184; TRP-223; VAL-249; VAL-378; ILE-478 AND PHE-490.
[27]	"Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia." Taillandier A., Lia-Baldini A.S., Mouchard M., Robin B., Muller F., Simon-Bouy B., Serre J.L., Bera-Louville A., Bonduelle M., Eckhardt J., Gaillard D., Myhre A.G., Koertge-Jung S., Larget-Piet L., Malou E., Sillence D., Temple I.K., Viot G., Mornet E. Hum. Mutat. 18:83-84(2001) [PubMed: 11438998] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA CYS-28; VAL-40; VAL-51; HIS-71; THR-116; HIS-136; HIS-152; THR-176; THR-179; LYS-191; ASP-211; VAL-220; GLY-235; TYR-294; GLY-327; SER-399; ALA-423 AND MET-459.
[28]	"Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia." Orimo H., Girschick H.J., Goseki-Sone M., Ito M., Oda K., Shimada T. J. Bone Miner. Res. 16:2313-2319(2001) [PubMed: 11760847] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA MET-68; SER-71; THR-177; TRP-223; PRO-275 AND HIS-391, CHARACTERIZATION OF VARIANTS HYPOPHOSPHATASIA MET-68; SER-71; THR-177; TRP-223; PRO-275 AND HIS-391, VARIANT ALA-522, CHARACTERIZATION OF VARIANT ALA-522.
[29]	"A novel point mutation (C571T) in the tissue-non-specific alkaline phosphatase gene in a case of adult-type hypophosphatasia." Watanabe H., Hashimoto-Uoshima M., Goseki-Sone M., Orimo H., Ishikawa I. Oral Dis. 7:331-335(2001) [PubMed: 11834095] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA VAL-132.
[30]	"Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions." Litmanovitz I., Reish O., Dolfin T., Arnon S., Regev R., Grinshpan G., Yamazaki M., Ozono K. J. Inherit. Metab. Dis. 25:35-40(2002) [PubMed: 11999978] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LYS-291 AND ARG-326.
[31]	"Denaturing gradient gel electrophoresis analysis of the tissue nonspecific alkaline phosphatase isoenzyme gene in hypophosphatasia." Mumm S., Jones J., Finnegan P., Henthorn P.S., Podgornik M.N., Whyte M.P. Mol. Genet. Metab. 75:143-153(2002) [PubMed: 11855933] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA SER-51; HIS-71; THR-111; MET-128; HIS-134; HIS-136; THR-176; LYS-191; GLN-223; TRP-223; SER-246; ALA-294; PRO-299; PHE-327 DEL; ARG-339; THR-348; VAL-378; MET-414; ASP-426 AND LYS-476, VARIANTS HIS-263 AND ALA-522.
[32]	"Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene." Spentchian M., Merrien Y., Herasse M., Dobbie Z., Glaeser D., Holder S.E., Ivarsson S.-A., Kostiner D., Mansour S., Norman A., Roth J., Stipoljev F., Taillemite J.-L., van der Smagt J.J., Serre J.-L., Simon-Bouy B., Taillandier A., Mornet E. Hum. Mutat. 22:105-106(2003) [PubMed: 12815606] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-62; ARG-63; THR-111; ILE-148; SER-162; GLU-189; ALA-220; LEU-272; GLY-293-294-ASP DEL; LYS-311; LYS-452 AND THR-468.
[33]	"Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene." Herasse M., Spentchian M., Taillandier A., Keppler-Noreuil K., Fliorito A.N.M., Bergoffen J., Wallerstein R., Muti C., Simon-Bouy B., Mornet E. J. Med. Genet. 40:605-609(2003) [PubMed: 12920074] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA LEU-108; THR-116 AND MET-414, CHARACTERIZATION OF VARIANT HYPOPHOSPHATASIA LEU-108.
[34]	"Childhood hypophosphatasia: a case report due to a novel mutation." Draguet C., Gillerot Y., Mornet E. Arch. Pediatr. 11:440-443(2004) [PubMed: 15135428] [Abstract] Cited for: VARIANT HYPOPHOSPHATASIA GLY-114.
[35]	"Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations." Brun-Heath I., Taillandier A., Serre J.-L., Mornet E. Mol. Genet. Metab. 84:273-277(2005) [PubMed: 15694177] [Abstract] Cited for: VARIANTS HYPOPHOSPHATASIA VAL-33; HIS-136; GLN-223; TRP-223; HIS-272; THR-292; ALA-294; THR-295; ASP-297; ASP-334 AND ALA-411, CHARACTERIZATION OF VARIANTS HYPOPHOSPHATASIA VAL-33; HIS-272; THR-292; THR-295; ASP-297 AND ALA-411.
+	Additional computationally mapped references.

Web resources

ALPL

Tissue nonspecific alkaline phosphatase gene mutations database

GeneReviews

Wikipedia

Alkaline phosphatase entry

Cross-references

Sequence databases
EMBLGenBankDDBJ	M24439 , M24429, M24430, M24431, M24432, M24433, M24434, M24435, M24436, M24437, M24438 Genomic DNA. Translation: AAB59378.1. X14174 mRNA. Translation: CAA32376.1. AB011406 mRNA. Translation: BAA32129.1. AB209814 mRNA. Translation: BAD93051.1. Different initiation. AL592309, AL359815 Genomic DNA. Translation: CAH72079.1. AL359815, AL592309 Genomic DNA. Translation: CAI16259.1. BC021289 mRNA. Translation: AAH21289.3. BC066116 mRNA. Translation: AAH66116.2. BC090861 mRNA. Translation: AAH90861.2. BC110909 mRNA. Translation: AAI10910.2. BC126165 mRNA. Translation: AAI26166.1. BC136325 mRNA. Translation: AAI36326.1.
IPI	IPI00419916.
PIR	PAHUH. S03613.
RefSeq	NP_000469.3. NP_001120973.1.
UniGene	Hs.75431
3D structure databases
HSSP	HSSP built from PDB template 1EW2 based on UniProtKB P05187.
ModBase	Search...
Protein-protein interaction databases
IntAct	P05186. 1 interaction.
STRING	P05186.
Proteomic databases
PeptideAtlas	P05186.
PRIDE	P05186.
Genome annotation databases
Ensembl	ENST00000374829; ENSP00000363962; ENSG00000162551; Homo sapiens. [Genome view] ENST00000374830; ENSP00000363963; ENSG00000162551; Homo sapiens. [Genome view] ENST00000374832; ENSP00000363965; ENSG00000162551; Homo sapiens. [Genome view] ENST00000374840; ENSP00000363973; ENSG00000162551; Homo sapiens. [Genome view] ENST00000425315; ENSP00000394765; ENSG00000162551; Homo sapiens. [Genome view]
GeneID	249.
KEGG	hsa:249.
NMPDR	fig|9606.3.peg.484.
UCSC	uc001bet.1. human.
Organism-specific databases
CTD	249.
GeneCards	GC01P021708.
H-InvDB	HIX0000225.
HGNC	HGNC:438. ALPL.
HPA	CAB020829. HPA007105. HPA008765.
MIM	146300. phenotype. 171760. gene. 241500. phenotype. 241510. phenotype.
Orphanet	436. Hypophosphatasia.
PharmGKB	PA24729.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P05186.
OMA	MISPFLV.
Enzyme and pathway databases
BRENDA	3.1.3.1. 247.
Gene expression databases
ArrayExpress	P05186.
Bgee	P05186.
Genevestigator	P05186.
GermOnline	ENSG00000162551. Homo sapiens.
Family and domain databases
InterPro	IPR017849. Alkaline_Pase-like_a/b/a. IPR001952. Alkaline_phosphatase. IPR018299. Alkaline_phosphatase_AS. [Graphical view]
Gene3D	G3DSA:3.40.720.10. Alk_phosphtse. 1 hit.
Pfam	PF00245. Alk_phosphatase. 1 hit. [Graphical view]
PRINTS	PR00113. ALKPHPHTASE.
SMART	SM00098. alkPPc. 1 hit. [Graphical view]
PROSITE	PS00123. ALKALINE_PHOSPHATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB01143. Amifostine.
NextBio	997.
SOURCE	Search...

Entry information

Entry name

PPBT_HUMAN

Accession

Primary (citable) accession number: P05186
Secondary accession number(s): A1A4E7 , B2RMP8, O75090, Q2TAI7, Q59EJ7, Q5BKZ5, Q5VTG5, Q6NZI8, Q8WU32, Q9UBK0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	June 21, 2005
Last modified:	November 3, 2009
This is version 129 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.