P05187 (PPB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alkaline phosphatase, placental type
EC=3.1.3.1

Alternative name(s):
Alkaline phosphatase Regan isozyme
Placental alkaline phosphatase 1
Short name=PLAP-1

Gene names

Name:	ALPP
Synonyms:	PLAP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	535 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)

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.
Polymorphism	Placental ALP is highly polymorphic, there are at least three common alleles.
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.
Sequence caution	The sequence AAA51708.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Magnesium Metal-binding Zinc
Molecular function	Hydrolase
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from direct assay PubMed 12493773PubMed 15907827. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	alkaline phosphatase activity Inferred from direct assay PubMed 2017684. Source: UniProtKB metal 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 – 22

22

Ref.7

Chain

23 – 506

484

Alkaline phosphatase, placental type

PRO_0000024031

Propeptide

507 – 535

29

Removed in mature form

PRO_0000024032

Regions

Transmembrane

513 – 529

17

Helical

Sites

Active site

114

1

Phosphoserine intermediate

Metal binding

64

1

Magnesium Potential

Metal binding

64

1

Zinc 2 Potential

Metal binding

333

1

Magnesium Potential

Metal binding

338

1

Zinc 1 Potential

Metal binding

342

1

Zinc 1 Potential

Metal binding

379

1

Zinc 2 Potential

Metal binding

380

1

Zinc 2 Potential

Metal binding

454

1

Zinc 1 Potential

Amino acid modifications

Lipidation

506

1

GPI-anchor amidated aspartate Ref.10 Ref.11

Glycosylation

144

1

N-linked (GlcNAc...) Potential

Glycosylation

271

1

N-linked (GlcNAc...) Potential

Disulfide bond

143 ↔ 205

Ref.12

Disulfide bond

489 ↔ 496

Ref.12

Natural variations

Natural variant

25

1

P → L. Ref.3 Ref.6
Corresponds to variant rs1130335 [ dbSNP | Ensembl ].

VAR_017419

Natural variant

89

1

I → L. Ref.5
Corresponds to variant rs13026692 [ dbSNP | Ensembl ].

VAR_050520

Natural variant

231

1

R → P. Ref.2
Corresponds to variant rs1048988 [ dbSNP | Ensembl ].

VAR_050521

Natural variant

263

1

R → H. Ref.3
Corresponds to variant rs2853378 [ dbSNP | Ensembl ].

VAR_050522

Natural variant

451

1

E → G.
Corresponds to variant rs1048994 [ dbSNP | Ensembl ].

VAR_050523

Experimental info

Sequence conflict

66

1

M → V in AAA51709. Ref.3

Sequence conflict

261 – 262

2

AK → GE in AAA51706. Ref.6

Sequence conflict

277

1

Q → R in AAA51709. Ref.3

Sequence conflict

285

1

T → A in AAA51709. Ref.3

Sequence conflict

324

1

N → H in AAA51706. Ref.6

Sequence conflict

389

1

Y → C in AAA51709. Ref.3

Sequence conflict

394

1

S → G in AAA51709. Ref.3

Sequence conflict

396 – 397

2

IF → FI in AAA51706. Ref.6

Sequence conflict

401

1

P → A in AAA51706. Ref.6

Sequence conflict

436

1

S → T Ref.8

Secondary structure

1

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535

Helix Strand Turn

Details...

Helix

26 – 29

4

Helix

31 – 47

17

Beta strand

56 – 63

8

Helix

68 – 81

14

Helix

93 – 95

3

Beta strand

97 – 103

7

Helix

114 – 123

10

Beta strand

132 – 134

3

Helix

143 – 145

3

Helix

154 – 160

7

Beta strand

164 – 172

9

Helix

176 – 179

4

Turn

180 – 182

3

Helix

193 – 195

3

Helix

198 – 202

5

Helix

208 – 214

7

Beta strand

219 – 224

6

Helix

226 – 229

4

Helix

243 – 245

3

Beta strand

249 – 251

3

Helix

255 – 261

7

Beta strand

266 – 269

4

Helix

272 – 279

8

Beta strand

285 – 290

6

Beta strand

292 – 295

4

Helix

299 – 301

3

Turn

304 – 306

3

Helix

310 – 321

12

Beta strand

328 – 334

7

Helix

337 – 342

6

Helix

346 – 366

21

Turn

369 – 371

3

Beta strand

372 – 379

8

Beta strand

381 – 386

6

Beta strand

411 – 418

8

Helix

433 – 436

4

Beta strand

445 – 447

3

Beta strand

459 – 465

7

Helix

468 – 470

3

Beta strand

473 – 476

4

Helix

479 – 487

9

Helix

491 – 493

3

Sequences

	Sequence		Length	Mass (Da)
	P05187 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: 13C136679A70C76B	FASTA	535	57,954
	10 20 30 40 50 60 MLGPCMLLLL LLLGLRLQLS LGIIPVEEEN PDFWNREAAE ALGAAKKLQP AQTAAKNLII 70 80 90 100 110 120 FLGDGMGVST VTAARILKGQ KKDKLGPEIP LAMDRFPYVA LSKTYNVDKH VPDSGATATA 130 140 150 160 170 180 YLCGVKGNFQ TIGLSAAARF NQCNTTRGNE VISVMNRAKK AGKSVGVVTT TRVQHASPAG 190 200 210 220 230 240 TYAHTVNRNW YSDADVPASA RQEGCQDIAT QLISNMDIDV ILGGGRKYMF RMGTPDPEYP 250 260 270 280 290 300 DDYSQGGTRL DGKNLVQEWL AKRQGARYVW NRTELMQASL DPSVTHLMGL FEPGDMKYEI 310 320 330 340 350 360 HRDSTLDPSL MEMTEAALRL LSRNPRGFFL FVEGGRIDHG HHESRAYRAL TETIMFDDAI 370 380 390 400 410 420 ERAGQLTSEE DTLSLVTADH SHVFSFGGYP LRGSSIFGLA PGKARDRKAY TVLLYGNGPG 430 440 450 460 470 480 YVLKDGARPD VTESESGSPE YRQQSAVPLD EETHAGEDVA VFARGPQAHL VHGVQEQTFI 490 500 510 520 530 AHVMAFAACL EPYTACDLAP PAGTTDAAHP GRSVVPALLP LLAGTLLLLE TATAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the human placental alkaline phosphatase gene. Evolution of the 5' flanking region by deletion/substitution." Knoll B.J., Rothblum K.N., Longley M.A. J. Biol. Chem. 263:12020-12027(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Molecular cloning and sequence analysis of human placental alkaline phosphatase." Millan J.L. J. Biol. Chem. 261:3112-3115(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-231.
[3]	"Products of two common alleles at the locus for human placental alkaline phosphatase differ by seven amino acids." Henthorn P.S., Knoll B.J., Raducha M., Rothblum K.N., Slaughter C., Weiss M., Lafferty M.A., Fischer T., Harris H. Proc. Natl. Acad. Sci. U.S.A. 83:5597-5601(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANTS LEU-25 AND HIS-263.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-89. Tissue: Cervix and Placenta.
[6]	"Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA." Kam W., Clauser E., Kim Y.S., Kan Y.W., Rutter W.J. Proc. Natl. Acad. Sci. U.S.A. 82:8715-8719(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-535, VARIANT LEU-25.
[7]	"Purification and partial sequencing of human placental alkaline phosphatase." Ezra E., Blacher R., Udenfriend S. Biochem. Biophys. Res. Commun. 116:1076-1083(1983) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-64.
[8]	"Expression of different-sized placental alkaline phosphatase mRNAs in placenta and choriocarcinoma cells." Ovitt C.E., Strauss A.W., Alpers D.H., Chou J.Y., Boime I. Proc. Natl. Acad. Sci. U.S.A. 83:3781-3785(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 382-535.
[9]	"Aspartic acid-484 of nascent placental alkaline phosphatase condenses with a phosphatidylinositol glycan to become the carboxyl terminus of the mature enzyme." Micanovic R., Bailey C.A., Brink L., Gerber L., Pan Y.C.E., Hulmes J.D., Udenfriend S. Proc. Natl. Acad. Sci. U.S.A. 85:1398-1402(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 485-535.
[10]	"Selectivity of the cleavage/attachment site of phosphatidylinositol-glycan-anchored membrane proteins determined by site-specific mutagenesis at Asp-484 of placental alkaline phosphatase." Micanovic R., Gerber L.D., Berger J., Kodukula K., Udenfriend S. Proc. Natl. Acad. Sci. U.S.A. 87:157-161(1990) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR AT ASP-506.
[11]	"Site-specific mutations in the COOH-terminus of placental alkaline phosphatase: a single amino acid change converts a phosphatidylinositol-glycan-anchored protein to a secreted protein." Lowe M.E. J. Cell Biol. 116:799-807(1992) [PubMed] [Europe PMC] [Abstract] Cited for: EFFECT OF MUTAGENESIS OF C-TERMINAL PEPTIDE ON GPI-ANCHORING.
[12]	"Function assignment to conserved residues in mammalian alkaline phosphatases." Kozlenkov A., Manes T., Hoylaerts M.F., Millan J.L. J. Biol. Chem. 277:22992-22999(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"Crystal structure of alkaline phosphatase from human placenta at 1.8 A resolution. Implication for a substrate specificity." Le Du M.H., Stigbrand T., Taussig M.J., Menez A., Stura E.A. J. Biol. Chem. 276:9158-9165(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 56-535.
+	Additional computationally mapped references.

Web resources

Wikipedia

Alkaline phosphatase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M19159 Genomic DNA. Translation: AAA51710.1.
M13077 mRNA. Translation: AAC97139.1.
M14169 mRNA. Translation: AAA51708.1. Different initiation.
M14170 mRNA. Translation: AAA51709.1.
AC068134 Genomic DNA. Translation: AAY24087.1.
BC009647 mRNA. Translation: AAH09647.1.
BC068501 mRNA. Translation: AAH68501.1.
BC094743 mRNA. Translation: AAH94743.1.
M12551 mRNA. Translation: AAA51706.1.

IPI

IPI00007289.

PIR

PAHUA. A31074.

RefSeq

NP_001623.3. NM_001632.3.

UniGene

Hs.284255.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EW2	X-ray	1.82	A	23-535	[»]
1ZEB	X-ray	1.90	A	23-506	[»]
1ZED	X-ray	1.57	A	23-506	[»]
1ZEF	X-ray	1.90	A	23-506	[»]
2GLQ	X-ray	1.60	A	23-506	[»]
3MK0	X-ray	1.90	A	23-506	[»]
3MK1	X-ray	1.57	A	23-506	[»]
3MK2	X-ray	1.89	A	23-506	[»]

ProteinModelPortal

P05187.

ModBase

Search...

Protein-protein interaction databases

IntAct

P05187. 6 interactions.

MINT

MINT-4054397.

STRING

9606.ENSP00000375881.

PTM databases

PhosphoSite

P05187.

Polymorphism databases

DMDM

130737.

Proteomic databases

PaxDb

P05187.

PRIDE

P05187.

Protocols and materials databases

DNASU

250.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000392027; ENSP00000375881; ENSG00000163283.

GeneID

250.

KEGG

hsa:250.

UCSC

uc002vsq.3. human.

Organism-specific databases

CTD

250.

GeneCards

GC02P233244.

HGNC

HGNC:439. ALPP.

MIM

171800. gene.

neXtProt

NX_P05187.

PharmGKB

PA24730.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1785.

HOGENOM

HOG000099118.

HOVERGEN

HBG007345.

InParanoid

P05187.

KO

K01077.

OMA

EIPLAMD.

OrthoDB

EOG4HDSTC.

PhylomeDB

P05187.

Gene expression databases

Bgee

P05187.

CleanEx

HS_ALPP.

Genevestigator

P05187.

GermOnline

ENSG00000163283. Homo sapiens.

Family and domain databases

Gene3D

3.40.720.10. 1 hit.

InterPro

IPR017849. Alkaline_Pase-like_a/b/a.
IPR001952. Alkaline_phosphatase.
IPR018299. Alkaline_phosphatase_AS.
IPR017850. Alkaline_phosphatase_core.
[Graphical view]

Pfam

PF00245. Alk_phosphatase. 1 hit.
[Graphical view]

PRINTS

PR00113. ALKPHPHTASE.

SMART

SM00098. alkPPc. 1 hit.
[Graphical view]

SUPFAM

SSF53649. Alkaline_phosphatase_core. 1 hit.

PROSITE

PS00123. ALKALINE_PHOSPHATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P05187.

ChEMBL

CHEMBL4458.

ChiTaRS

ALPP. human.

EvolutionaryTrace

P05187.

GenomeRNAi

250.

NextBio

1001.

SOURCE

Search...

Entry information

Entry name

PPB1_HUMAN

Accession

Primary (citable) accession number: P05187
Secondary accession number(s): P05188 , P06861, Q53S78, Q96DB7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 158 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.